The present work introduces an open-source graphical user interface (GUI) computer program called DynamicMC. The present program has the ability to generate ORNL phantom input script for the Monte Carlo N-Particle (MCNP) package. The relative dynamic movement of the radiation source with respect to the ORNL phantom can be modeled, which essentially resembles the dynamic movement of source-to-target (i.e., human phantom) distance in a 3-dimensional radiation field. The present program makes the organ-based dosimetry of the human body much easier, as users are not required to write lengthy scripts or deal with any programming that many may find tedious, time consuming, and error prone. In this paper, we have demonstrated that the present program can successfully model simple and complex relative dynamic movements (i.e., those involving rotation of source and human phantom in a 3-dimensional field). The present program would be useful for organ-based dosimetry and could also be used as a tool for teaching nuclear radiation physics and its interaction with the human body.

OBJECTIVE: Genistein is an isoflavone molecule with a high affinity for estrogen receptors (ER), which could lead to the mechanism of selective estrogen receptor modulators (SERMs) in breast cancer. Genistein labeling with technetium-99m can be a new promising strategy for diagnostic breast cancer. In this research, we evaluate the physicochemical characteristics of the [99mTc]Tc-genistein complex and describe the optimal labeling method parameters. We also calculated density functional theory to study the stability constants to support complex formation analysis (DFT). METHODS: The genistein was directly labeled with 99mTc, and its stability as well as its potential for usage as a radiotracer were all investigated. DFT calculations with thermodynamic cycles to determine chemical coordination models and calculate thermodynamic constants of complex more accurately. RESULTS: The radiochemical purity of [99mTc]Tc-genistein showed a high yield of 93.25% ± 0.30% and had good physicochemical properties. The stability of the Tc(IV)-genistein complex was confirmed by DFT calculations at a value of 99.0822. CONCLUSIONS: As a result, [99mTc]Tc-genistein could be a potential radiotracer kit for SPECT imaging of breast cancer.

The present work reports the theoretical investigation of the scattering of electrons and positrons by the ethane (C2H6) molecule over the energy range 1 eV-1 MeV. The investigation was carried out by taking into account the screening correction arising from a semiclassical analysis of the atomic geometrical overlapping of the scattering observables calculated in the independent atom approximation. The study is presented through the calculations of a broad spectrum of observable quantities, namely differential, integrated elastic, momentum transfer, viscosity, inelastic, grand total, and total ionization cross-sections and the Sherman functions. A comparative study was carried out between scattering observables for electron impact with those for positron impact to exhibit the similarity and dissimilarity arising out of the difference of the collisions of impinging projectiles with the target. Partial-wave decomposition of the scattering states within the Dirac relativistic framework employing a free-atom complex optical model potential was used to calculate the corresponding observable quantities of the constituent atoms. The results, calculated using our recipe, were compared with the experimental and theoretical works available in the literature. The Sherman function for a e±-C2H6 scattering system is presented for the first time in the literature. The addition of the screening correction to the independent atom approximation method was found to substantially reduce the scattering cross-sections, particularly at forward angles for lower incident energies.

Abstract In nuclear medicine, the development of portable imaging devices that provide high imaging resolution and sensitivity, capable of imaging gamma rays with a wide energy range and multiple radioisotopes tracing capabilities, is so important. These goals have been possible thanks to developing a compact Compton camera, a collimatorless detector coupled to compact silicon photomultiplier(SiPM) array, using scintillator crystal. In this study, the portable segmented GAGG:Ce scintillator-based Compton camera (CC) is optimized with the GATE, a Monte Carlo simulation toolkit based on Geant4, to maximize its performance for a wide range of gamma-ray energy (364–1000 keV). The geometrical parameters are selected as optimization parameters to investigate their effects on CC's performance, including imaging resolution and absolute detection efficiency (DE_a). The geometry parameters of CC include the planner area of scatterer and absorber detectors, their thicknesses, and the distance between them. The results for the energy range of 364–1000 keV show that the most important contributions to the spatial resolution and DE_a of the camera are SAD (scatterer to absorber distance) and the scatterer area while changing absorber area (A_A) showed the most negligible impact. In the short SADs, imaging resolution and DE_a are significantly affected by the detector's size and thickness. On the other hand, in the long SADs (> 4 cm), both spatial resolution and DE_a are significantly affected by the detector's area but less affected by the detector's thickness. Decreasing the scatterer's thickness and the absorber's size or thickness improves imaging resolution without significantly reducing DE_a. The simulation study's findings presented here will provide valuable guidelines for researchers choosing a desired CC's design according to particular objectives, manufacturing limitations in scintillator growth, cost, etc.

Abstract The purpose of this study is to evaluate the effect of a lead radiation shield on the ability of a beam imaging device consist of an imaging plate (IP) and a collimator by Monte Carlo simulations. Simulations were performed using PHITS. A carbon-ion beam was injected to an acrylic target. A tungsten collimator having a pinhole was placed at the distance of 31.2 cm from the beam. A lead radiation shield was placed on the tungsten collimator. An IP was placed under the collimator. Beam images were acquired by recording the position distribution of energy deposition on the IP. We confirmed that therapeutic carbon-ion beam images could be acquired using the imaging device combining the IP and collimator. It was found that removal of the lead shield had no effect on the imaging results.

The present work introduced a framework to investigate the effectiveness of proton boron fusion therapy (PBFT) at the cellular level. The framework consisted of a cell array generator program coupled with PHITS Monte Carlo package with a dedicated terminal-based code editor that was developed in this work. The framework enabled users to model large cell arrays with normal, all boron, and random boron filled cytoplasm, to investigate the underlying mechanism of PBFT. It was found that alpha particles and neutrons could be produced in absence of boron mainly because of nuclear reaction induced by proton interaction with 16O, 12C and 14N nuclei. The effectiveness of PBFT is highly dependent on the incident proton energy, source size, cell array size, buffer medium thickness layer, concentration and distribution of boron in the cell array. To quantitatively assess the effectiveness of PBFT, of the total energy deposition by alpha particle for different cases were determined. The number of alpha particle hits in cell cytoplasm and nucleus for normal and 100 ppm boron were determined. The obtained results and the developed tools would be useful for future development of PBFT to objectively determine the effectiveness of this treatment modality.

Abstract In our previous work, a cost-effective Compton camera (CC) using Ce doped Gd₃(Al,Ga)₅O₁₂(Ce:GAGG) scintillator consisting of two detectors, scatterer (20.8 × 20.8 × 5 mm³) and absorber (41.7 × 41.7 × 10 mm³), was developed to image gamma rays having energy more than 511 keV. This study fabricated a newly developed CC with a larger scatterer and thinner absorber. The system consists of two detectors: a scatterer and an absorber of Ce:GAGG scintillator. The size of the scatterer and absorber is the same; a 40-mm × 40-mm × 5-mm array block consists of 40 × 40 pixels. The size of each scintillator pixel is 0.85 mm × 0.85 mm for both systems. Imaging experiments of Na-22 and Cs-137 point sources were performed to investigate the imaging capability of the new camera, and then the obtained data were compared to the previous CC. The current CC's absolute detection efficiency (DE_a) and photopeak detection efficiency (DE_p) are improved by 1.6 and 2 times greater than the previous one. At the same time, both systems' spatial and angular resolutions are almost the same value at 511 keV. The Compton camera module (CCMod) in GATE v9.0 was employed for Monte Carlo simulations to reproduce the experimental data showing a good agreement.

Proton irradiations are highly sensitive to spatial variations, mainly due to their high linear energy transfer (LET) and densely ionizing nature. In realistic clinical applications, the targets of ionizing radiation are inhomogeneous in terms of geometry and chemical composition (i.e., organs in the human body). One of the main methods for proton range monitoring is to utilize the production of proton induced positron emitting radionuclides; these could be measured precisely with positron emission tomography (PET) systems. One main positron emitting radionuclide that could be used for proton range monitoring and verification was found to be 13N that produces a peak close to the Bragg peak. In the present work, we have employed the Monte Carlo method and Spectral Analysis (SA) technique to investigate the feasibility of utilizing the 13N peak for proton range monitoring and verification in inhomogeneous targets. Two different phantom types, namely, (1) ordinary slab and (2) MIRD anthropomorphic phantoms, were used. We have found that the generated 13N peak in such highly inhomogeneous targets (ordinary slab and human phantom) is close to the actual Bragg peak, when irradiated by incident proton beam. The feasibility of using the SA technique to estimate the distribution of positron emitter was also investigated. The current findings and the developed tools in the present work would be helpful in proton range monitoring and verification in realistic clinical radiation therapy using proton beams.

Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses.

The Monte Carlo (MC) method is a powerful tool for modeling nuclear radiation interaction with matter. A variety of MC software packages has been developed, especially for applications in radiation therapy. Most widely used MC packages require users to write their own input scripts for their systems, which can be a time consuming and error prone process and requires extensive user experience. In the present work, we have developed a graphical user interface (GUI) bundled with a custom-made 3D OpenGL visualizer for PHITS MC package. The current version focuses on modeling proton induced positron emitting radioisotopes, which in turn can be used for verification of proton ranges in proton therapy. The developed GUI program does not require extensive user experience. The present open-source program is distributed under GPLv3 license that allows users to freely download, modify, recompile and redistribute the program.

PURPOSE: Small animal PET provides the biodistribution of administrated radiotracer in vivo and have a potential to contribute on dosimetry study. The aim of this study is to investigate the effect of region-of-interest (ROI)-delineation in whole-body rat PET image toward non-invasive estimation of human dosimetry of 18F-FDG. METHOD: After administration of 18F-FDG (averaged 11.7 MBq), 3.5-h PET and 20-min CT scans were sequentially performed for three rats by Clairvivo PET/CT system. Seven source organs, and the remainder of the body, were studied to extrapolate %ID(t) and estimate time-integrated activity coefficients [kBq-h/MBq] in human. The mean absorbed dose in each target organ and the effective dose were estimated by MIRD method. Effects of ROI-definitions on both extrapolated %ID(t) in human and estimated doses were also investigated by using (i) small ROIs of high uptake region and (ii) whole organ ROIs. RESULTS: Averaged effective doses of 18F-FDG in human by using high-uptake and whole-organ ROIs were 27.8 ± 6.54 and 19.3 ± 2.72 μSv/MBq, respectively. CONCLUSION: The use of small animal PET scanner, which allows repeatedly PET scans, have a potential to contribute on the reduction of the number of experimental animals. However, the ways of ROI drawing influences on the estimated effective dose and safe-side ROI definition may be preferred.

OBJECTIVE: Transarterial Radioembolization (TARE) with 90Y-loaded glass microspheres is a locoregional treatment option for Hepatocellular Carcinoma (HCC). Post-treatment 90Y bremsstrahlung imaging using Single-Photon Emission Tomography (SPECT) is currently a gold-standard imaging modality for quantifying the delivered dose. However, the nature of bremsstrahlung photons causes difficulty for dose estimation using SPECT imaging. This work aimed to investigate the possibility of using glass microspheres loaded with 90Y and Nanoparticles (NPs) to improve the quantification of delivered doses. METHODS: The Monte Carlo codes were used to simulate the post-TARE 90Y planar imaging. Planar images from bremsstrahlung photons and characteristic X-rays are acquired when 0, 1.2 mol/L, 2.4 mol/L, and 4.8 mol/L of Gold (Au), Hafnium (Hf), and Gadolinium (Gd) NPs are incorporated into the glass microspheres. We evaluated the quality of acquired images by calculating sensitivity and Signal-to-Background Ratio (SBR). Therapeutic effects of NPs were evaluated by calculation of Dose Enhancement Ratio (DER) in tumoral and non-tumoral liver tissues. RESULTS: The in silico results showed that the sensitivity values of bremsstrahlung and characteristic X-ray planar images increased significantly as the NPs concentration increased in the glass microspheres. The SBR values decreased as the NPs concentration increased for the bremsstrahlung planar images. In contrast, the SBR values increased for the characteristic X-ray planar images when Hf and Gd were incorporated into the glass microspheres. The DER values decreased in the tumoral and non-tumoral liver tissues as the NPs concentration increased. The maximum dose reduction was observed at the NPs concentration of 4.8 mol/L (≈ 7%). CONCLUSIONS: The incorporation of Au, Hf, and Gd NPs into the glass microspheres improved the quality and quantity of post-TARE planar images. Also, treatment efficiency was decreased significantly at NPs concentration > 4.8 mol/L.

Not only visual interpretation for lesion detection, staging, and characterization, but also quantitative treatment response assessment are key roles for 18F-FDG PET in oncology. In multicenter oncology PET studies, image quality standardization and SUV harmonization are essential to obtain reliable study outcomes. Standards for image quality and SUV harmonization range should be regularly updated according to progress in scanner performance. Accordingly, the first aim of this study was to propose new image quality reference levels to ensure small lesion detectability. The second aim was to propose a new SUV harmonization range and an image noise criterion to minimize the inter-scanner and intra-scanner SUV variabilities. We collected a total of 37 patterns of images from 23 recent PET/CT scanner models using the NEMA NU2 image quality phantom. PET images with various acquisition durations of 30-300 s and 1800 s were analyzed visually and quantitatively to derive visual detectability scores of the 10-mm-diameter hot sphere, noise-equivalent count (NECphantom), 10-mm sphere contrast (QH,10 mm), background variability (N10 mm), contrast-to-noise ratio (QH,10 mm/N10 mm), image noise level (CVBG), and SUVmax and SUVpeak for hot spheres (10-37 mm diameters). We calculated a reference level for each image quality metric, so that the 10-mm sphere can be visually detected. The SUV harmonization range and the image noise criterion were proposed with consideration of overshoot due to point-spread function (PSF) reconstruction. We proposed image quality reference levels as follows: QH,10 mm/N10 mm ≥ 2.5 and CVBG ≤ 14.1%. The 10th-90th percentiles in the SUV distributions were defined as the new SUV harmonization range. CVBG ≤ 10% was proposed as the image noise criterion, because the intra-scanner SUV variability significantly depended on CVBG. We proposed new image quality reference levels to ensure small lesion detectability. A new SUV harmonization range (in which PSF reconstruction is applicable) and the image noise criterion were also proposed for minimizing the SUV variabilities. Our proposed new standards will facilitate image quality standardization and SUV harmonization of multicenter oncology PET studies. The reliability of multicenter oncology PET studies will be improved by satisfying the new standards.

Artificial intelligence (AI) has been applied to various medical imaging tasks, such as computer-aided diagnosis. Specifically, deep learning techniques such as convolutional neural network (CNN) and generative adversarial network (GAN) have been extensively used for medical image generation. Image generation with deep learning has been investigated in studies using positron emission tomography (PET). This article reviews studies that applied deep learning techniques for image generation on PET. We categorized the studies for PET image generation with deep learning into three themes as follows: (1) recovering full PET data from noisy data by denoising with deep learning, (2) PET image reconstruction and attenuation correction with deep learning and (3) PET image translation and synthesis with deep learning. We introduce recent studies based on these three categories. Finally, we mention the limitations of applying deep learning techniques to PET image generation and future prospects for PET image generation.

The interaction of ionizing radiation with matter is a stochastic process and statistical analysis of such a process would be a crucial step in understanding radioactivity. Geiger-Müller (GM) counter is a widely used radiation detector used in nuclear radiation surveying, which produces counts upon exposure to a radioactive source. There are a variety of multi-purpose software that can be used to perform statistical analysis of measured counts from a GM counter. However, statistical analysis is a lengthy, error prone and time-consuming process, which gets more tedious when the number of measurements increases. In the present work, we have developed an open-source and easy-to-use graphical user interface (GUI) computer program named RadStat for statistical analysis of counts measured by a GM counter. RadStat has its own scripting syntaxes and bundled with gnuplot for quick visualization of output results. We believe the present open-source GUI program would be a useful tool for research and teaching of nuclear radiation physics.

The Monte Carlo method is employed in this study to simulate the proton irradiation of a water-gel phantom. Positron-emitting radionuclides such as 11C, 15O, and 13N are scored using the Particle and Heavy Ion Transport Code System Monte Carlo code package. Previously, it was reported that as a result of 16O(p,2p2n)13N nuclear reaction, whose threshold energy is relatively low (5.660 MeV), a 13N peak is formed near the actual Bragg peak. Considering the generated 13N peak, we obtain offset distance values between the 13N peak and the actual Bragg peak for various incident proton energies ranging from 45 to 250 MeV, with an energy interval of 5 MeV. The offset distances fluctuate between 1.0 and 2.0 mm. For example, the offset distances between the 13N peak and the Bragg peak are 2.0, 2.0, and 1.0 mm for incident proton energies of 80, 160, and 240 MeV, respectively. These slight fluctuations for different incident proton energies are due to the relatively stable energy-dependent cross-section data for the 16O(p,2p2n)13N nuclear reaction. Hence, we develop an open-source computer program that performs linear and non-linear interpolations of offset distance data against the incident proton energy, which further reduces the energy interval from 5 to 0.1 MeV. In addition, we perform spectral analysis to reconstruct the 13N Bragg peak, and the results are consistent with those predicted from Monte Carlo computations. Hence, the results are used to generate three-dimensional scatter plots of the 13N radionuclide distribution in the modeled phantom. The obtained results and the developed methodologies will facilitate future investigations into proton range monitoring for therapeutic applications.

<jats:title>Abstract</jats:title> <jats:p>Astatine-211 is one of the promising radioisotopes for targeted alpha therapy. Optimising treatment strategies as well as determining the suitability of a given agent for a particular patient requires to image the time-dependent distribution of the targeted radiotherapeutic agent both in tumours and in normal tissues. Since the biodistribution of astatine is different from that of iodine, imaging astatine-211 directly is essential. In the previous study of astatine-211 Compton imaging, random coincidence events due to polonium K-shell X-rays were dominant and seemed to cause saturation of counts. Thus optimisation of the coincidence time windows is important to reduce random coincidence events. In this study, we have optimised the coincidence time windows of a Compton camera and improved the sensitivity, noise and spatial resolution of astatine-211 imaging.</jats:p>

<title>Abstract</title><italic>Pteris vittata</italic> is an arsenic (As) hyperaccumulator plant that accumulates a large amount of As into fronds and rhizomes (around 16,000 mg/kg in both after 16 weeks hydroponic cultivation with 30 mg/L arsenate). However, the sequence of long-distance transport of As in this hyperaccumulator plant is unclear. In this study, we used a positron-emitting tracer imaging system (PETIS) for the first time to obtain noninvasive serial images of As behavior in living plants with positron-emitting ⁷⁴As-labeled tracer. We found that As kept accumulating in rhizomes as in fronds of <italic>P. vittata</italic>, whereas As was retained in roots of a non-accumulator plant <italic>Arabidopsis thaliana</italic>. Autoradiograph results of As distribution in <italic>P</italic>. <italic>vittata</italic> showed that with low As exposure, As was predominantly accumulated in young fronds and the midrib and rachis of mature fronds. Under high As exposure, As accumulation shifted from young fronds to mature fronds, especially in the margin of pinna, which resulted in necrotic symptoms, turning the marginal color to gray and then brown. Our results indicated that the function of rhizomes in <italic>P. vittata</italic> was As accumulation and the regulation of As translocation to the mature fronds to protect the young fronds under high As exposure.

Radioprotective effects of vitamin C and vitamin E as a water-soluble and a lipid-soluble agent, respectively, were investigated at the molecular level during the imposition of gamma radiation-induced structural changes to bovine serum albumin (BSA) at the therapeutic dose of 3 Gy. Secondary and tertiary structural changes of control and irradiated BSA samples were investigated using circular dichroism and fluorescence spectroscopy. The preirradiation tests showed nonspecific and reversible binding of vitamins C and E to BSA. Secondary and tertiary structures of irradiated BSA considerably changed in the absence of the vitamins. Upon irradiation, α-helices of BSA transitioned to beta motifs and random coils, and the fluorescence emission intensity decreased relative to nonirradiated BSA. In the presence of the vitamins C or E, however, the irradiated BSA was protected from these structural changes caused by reactive oxygen species (ROS). The two vitamins exhibited different patterns of attachment to the protein surface, as inspected by blind docking, and their mechanisms of protection were different. The hydrophilicity of vitamin C resulted in the predominant scavenging of ROS in the solvent, whereas hydrophobic vitamin E localized on the nonpolar patches of the BSA surface, where it did not only form a barrier for diffusing ROS but also encountered them as an antioxidant and neutralized them thanks to the moderate BSA binding constant. Very low concentrations of vitamins C or E (0.005 mg/mL) appear to be sufficient to prevent the oxidative damage of BSA.

<jats:title>Abstract</jats:title> <jats:p>Simulations and numerical analysis of physical problems are important steps toward understanding underlying mechanisms of the processes. Important examples would be medical physics and medical imaging. Compartmental modeling has been found useful for estimating the transport and temporal variations of drugs/contaminants (commonly used in medical physics and medical imaging) in different organs, given that different organs would be modeled as compartments. Recycling among these modeled compartments (i.e., organs) was allowed through defining sets of constant transfer rates. In order to mathematically define these systems, one needs to use sets of differential equations (depending on the number of compartments) which would in fact be time-consuming and prone to mathematical error. Considering these issues, there is a need for a versatile computer program that is accurate, robust, and user-friendly to perform the required computations automatically. In the present work, we developed and benchmarked an open-source computer program entitled CompVision that was able to simulate five-compartmental systems. The present software had an easy-to-use graphical user interface (GUI) for the users. The executable program and the source codes were made available publicly under GPLv3 license, which would allow everyone to use, modify, and distribute without any restriction. The present program would be useful in a variety of research fields and applications.</jats:p>

To evaluate tumor blood flow using 15O-water positron emission tomography (PET) in patients with non-small cell lung cancer (NSCLC) before and after chemotherapy with bevacizumab, and to investigate the effects of bevacizumab on tumor blood flow changes and progression-free survival (PFS). Twelve patients with NSCLC were enrolled. Six patients underwent chemotherapy with bevacizumab and the other six without bevacizumab. 15O-water dynamic PET scans were performed within 1 week before the start of chemotherapy and within 1 week after the first day of chemotherapy. Tumor blood flow was analyzed quantitatively using a single one-tissue compartment model with the correction of pulmonary circulation blood volume and arterial blood volume via an image-derived input function. In the bevacizumab group, mean tumor blood flow was statistically significantly reduced post-chemotherapy (pre-chemotherapy 0.27 ± 0.14 mL/cm3/min, post-chemotherapy 0.18 ± 0.12 mL/cm3/min). In the no bevacizumab group, there was no significant difference between mean tumor perfusion pre-chemotherapy (0.42 ± 0.42 mL/cm3/min) and post-chemotherapy (0.40 ± 0.27 mL/cm3/min). In the bevacizumab group, there was a positive correlation between the blood flow ratio (tumor blood flow post-chemotherapy/tumor blood flow pre-chemotherapy) and PFS (correlation coefficient 0.94). Mean tumor blood flow decreases after bevacizumab administration and was positively correlated with longer PFS.

This work presents the calculations of differential, integrated elastic and momentum transfer cross sections for the elastic scattering of electrons from the ions of xenon isonuclear series over the incident energy range 1 eV–1000 eV. Coulomb glory, the amplification of elastic backscattering of electrons from positive ions owing to the electrostatic screening of nuclear potential by atomic electrons, is investigated throughout the ionic series of xenon, argon and neon. Cross sections for the angular distribution of elastically scattered positron from selected xenon ions are also calculated. Energy dependency of differential cross sections and Sherman functions are predicted for both the projectiles and a comparison is presented to exhibit the dissimilarity arising out of the difference of the interactions of the projectiles with ions. The theoretical methodology of this work employs the Dirac relativistic partial wave analysis using a complex optical potential, comprising static, exchange, polarization and imaginary components, and a pure Coulomb potential. The results obtained show reasonable agreements with the available experimental data and other theoretical calculations.

【目的】モノアミン酸化酵素B(MAO-B)は様々な臓器に分布して多様な機能を果たしているが、ヒトの全身分布の詳細はまだ十分に明らかにされていない。また最近では、アルツハイマー病患者の脳における神経炎症の一所見として増大する反応性アストロサイトにもMAO-Bが高発現することが知られている。我々は、MAO-Bに特異的に結合する新規PET診断薬剤¹⁸F-SMBT-1を開発し、ヒトにおいて脳を含む全身臓器のMAO-B分布に関する基礎データを構築するために初期臨床試験を開始した。【方法】健常成人男性4名(20～50歳代)を対象として、¹⁸F-SMBT-1のトレーサーを約185 MBq投与して、適宜休憩をはさみながら約5時間の全身PET測定を断続的に行った。PET画像をMRI画像に重ね合わせて各臓器への集積値を計測し、その時間的変化のパターンを調べた。 【結果・考察】PET薬剤¹⁸F-SMBT-1は、薬剤投与初期（最初の5分間）にすみやかに脳、心臓、胃、腎臓、消化管等に分布し、投与後から30分までは比較的高い取り込みを示しつつ、徐々に減少した。その後、肝臓および胆嚢に強い集積が観察され、薬剤投与後期には胆嚢、小腸～大腸、膀胱等に強い集積を示した。胆嚢の集積ピーク値は膀胱の10倍程度となった。また、全身の主要臓器における薬剤集積の変化に被験者間で大きな差異は認められなかった。小腸～大腸の集積所見については、胆汁排泄により薬剤が総肝管を経由し腸管に移動することが結果に影響している可能性が考えられ、生理的集積と排泄に伴う消化管集積が混在していると推測された。【結論】¹⁸F-SMBT-1は胆汁排泄の割合が高い薬剤であることがわかった。また、全身臓器のMAO-Bマッピングの目的に十分利用可能な薬剤であるとともに、脳マッピングのために十分な量の脳内分布があることがわかった。

Some concepts in nuclear radiation physics are abstract and intellectually demanding. In the present paper, an "MCHP platform" (MCHP was an acronym for Monte Carlo simulations + Human Phantoms) was proposed to provide assistance to the students through visualization. The platform involved Monte Carlo simulations of interactions between ionizing radiations and the Oak Ridge National Laboratory (ORNL) adult male human phantom. As an example to demonstrate the benefits of the proposed MCHP platform, the present paper investigated the variation of the absorbed photon dose per photon from a 137Cs source in three selected organs, namely, brain, spine and thyroid of an adult male for concrete and lead shields with varying thicknesses. The results were interesting but not readily comprehensible without direct visualization. Graphical visualization snapshots as well as video clips of real time interactions between the photons and the human phantom were presented for the involved cases, and the results were explained with the help of such snapshots and video clips. It is envisaged that, if the platform is found useful and effective by the readers, the readers can also propose examples to be gradually added onto this platform in future, with the ultimate goal of enhancing students' understanding and learning the concepts in an undergraduate nuclear radiation physics course or a related course.

Background: Novel partial volume correction (PVC) algorithms have been validated by assuming ideal conditions of image processing; however, in real clinical PET studies, the input datasets include error sources which cause error propagation to the corrected outcome. Methods: We aimed to evaluate error propagations of seven PVCs algorithms for brain PET imaging with [ F]THK-5351 and to discuss the reliability of those algorithms for clinical applications. In order to mimic brain PET imaging of [ F]THK-5351, pseudo-observed SUVR images for one healthy adult and one adult with Alzheimer’s disease were simulated from individual PET and MR images. The partial volume effect of pseudo-observed PET images were corrected by using Müller-Gärtner (MG), the geometric transfer matrix (GTM), Labbé (LABBE), regional voxel-based (RBV), iterative Yang (IY), structural functional synergy for resolution recovery (SFS-RR), and modified SFS-RR algorithms with incorporation of error sources in the datasets for PVC processing. Assumed error sources were mismatched FWHM, inaccurate image-registration, and incorrectly segmented anatomical volume. The degree of error propagations in ROI values was evaluated by percent differences (%diff) of PV-corrected SUVR against true SUVR. Results: Uncorrected SUVRs were underestimated against true SUVRs (− 15.7 and − 53.7% in hippocampus for HC and AD conditions), and application of each PVC algorithm reduced the %diff. Larger FWHM mismatch led to larger %diff of PVC-SUVRs against true SUVRs for all algorithms. Inaccurate image registration showed systematic propagation for most algorithms except for SFS-RR and modified SFS-RR. Incorrect segmentation of the anatomical volume only resulted in error propagations in limited local regions. Conclusions: We demonstrated error propagation by numerical simulation of THK-PET imaging. Error propagations of 7 PVC algorithms for brain PET imaging with [ F]THK-5351 were significant. Robust algorithms for clinical applications must be carefully selected according to the study design of clinical PET data. 18 18 18

Visualizing the dynamics of cesium (Cs) is desirable to understand the impact of radiocesium when accidentally ingested or inhaled by humans. However, visualization of radiocesium in vivo is currently limited to plants. Herein, we describe a method for the production and purification of Cs and its use in visualizing Cs dynamics in a living animal. The positron-emitting nuclide Cs was produced using the I (α, 4n) Cs reaction, which was induced by irradiation of sodium iodide with a He beam from a cyclotron. We excluded sodium ions by using a material that specifically adsorbs Cs as a purification column and successfully eluted Cs by flowing a solution of ammonium sulfate into the column. We injected the purified Cs tracer solution into living rats and the dynamics of Cs were visualized using positron emission tomography; the distributional images showed the same tendency as the results of previous studies using disruptive methods. Thus, this method is useful for the non-invasive investigation of radiocesium in a living animal. 127 127 127 127 4 2+ 127 127

Objective: Genistein is an isoflavone compound that has been proven to have anticancer activity and is capable of binding to estrogen β receptors with Selective Estrogen Receptor Modulators (SERMs) properties, and has a strong affinity to inhibit the development of cancer cells. This study is to determine the optimum conditions of the reaction in the synthesis process of compounds labeled I-genestein which can be potential for application of breast cancer diagnosis. Methods: Synthesis of I-Genistein compound labeling using the Chloramine-T iodination method. This method uses several parameter optimizations, including: pH conditions, the amount of chloramine-T oxidizer and sodium metabisulfite reducing agent. The radiochemical purity of the I-Genistein compound was determined using thin layer chromatography TLC-SG F , and measured by SCA (Single Channel Analyzer). The radiochemical purity of labeled compounds must fulfill the requirements of the United States of Pharmacopeia. Results: Optimization of the synthesis conditions of the I-Genistein compound was obtained at pH 8, the amount of chloramine-T 0.225 mg, and the amount of Na-Metabisulfite 0.342 mg, with 30 min reaction time. This optimum condition produces radiochemical purity of 95.02 ± 0.76%. Conclusion: Products labeled I-Genistein meet radiochemical purity requirements according to USP requirements. The labeled compound is expected to be able to be used to detect breast cancer through a binding mechanism with estrogen receptors β. 131 131 131 131 131 254

This work reports on differential, integrated and momentum transfer cross sections for the elastic scattering of electrons and positrons off the ions of nitrogen isonuclear series (N+ - N7+) over the energy range 1-500 eV. Calculations of these observable quantities involve the solution of Dirac relativistic wave equation employing a pure Coulomb potential and a short range potential. The latter comprises static, exchange, polarization and absorption potentials. Effects of these individual potentials on angular distribution of elastically scattered electrons are investigated throughout this ionic series. Differential cross sections for electron and positron scattering are compared with each other to demonstrate the difference of their collision dynamics. A satisfactory agreement between our predictions and other available data, experimental and theoretical, is observed.

: Functional near infrared spectroscopy (fNIRS) is an imaging system that can measure hemodynamic changes of the brain. However, the system incapability to measure beyond the brain cortex region make it usage less appealing for in-depth brain studies. To overcome this, many researchers combine fNIRS with other imaging modalities to gain better understanding of the brain activities. In this paper, we described the theory of the registering fNIRS signals and positron emission tomography (PET) image method and performed experiments to validate it. The registration method was validated using specially designed phantom for fNIRS and PET. Polaris system was used to track the position of the phantom which is based on the Polaris markers during fNIRS and PET procedures. The Polaris markers share the same coordinate, thus the fNIRS and PET were calibrated to each other through these markers. To register the fNIRS signal on the PET image, the phantom position in fNIRS coordinate is translated to PET coordinate which allow the probe and the markers being coordinated in PET. Polaris markers were used as the references marker to determine the transformation matrices. The result shows that the fNIRS channel can be viewed on the PET image of the phantom. The transformation error from Polaris to PET is less than 1.00 mm and the precision test is less than 0.1mm while the accuracy is less than 2.8 mm. This result suggests that our theory on the registration method could be used for multimodal image registration between fNIRS and other modalities.

Functional near-infrared spectroscopy (fNIRS) is an optical imaging tool to study brain activities. Moreover, many researchers combined fNIRS with other modalities to gain a better understanding of the brain. This paper provides an overview of the combination of fNIRS with other imaging modalities in the detection and measurement of the cerebral hemodynamic. Cerebral haemodynamic such as the cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral blood oxygenation (CBO) are the important parameters in many neuroimaging studies. Cerebral hemodynamic had been studied by various medical imaging modalities.  Initially, Xenon enhanced Computed Tomography (Xenon CT), Computed Tomography (CT) perfusion; Single Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET) are used to measure the cerebral hemodynamic. Recently, fNIRS is used to optically observe the changes in cerebral haemodynamic during brain activities and the combination of fNIRS with other modalities also become an interest to study the relations within brain activities and the cerebral hemodynamic. Therefore, this paper provides an overview of existing multimodal fNIRS in detection of cerebral haemodynamic changes and provides an important insight on how multimodal fNIRS aid in advancing modern investigations of human brain function.&#x0D;  &#x0D;  &#x0D;  &#x0D; Keywords: multimodal imaging, fNIRS-fMRI, fNIRS-PET, fNIRS-EEG

(R,S)-ketamine exerts robust antidepressant effects in patients with depression when given at sub-anesthetic doses. Each of the enantiomers in this racemic mixture, (R)-ketamine and (S)-ketamine, have been reported to exert antidepressant effects individually. However, the neuropharmacological effects of these enantiomers and the mechanisms underlying their antidepressive actions have not yet been fully elucidated. Therefore, we investigated the effect of (R,S)-, (R)-, and (S)-ketamine on brain activity by functional MRI (fMRI) in conscious rats and compared these with that of N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 (n = 5~7). We also assessed their pharmacokinetic profiles (n = 4) and their behavioral effects (n = 7~9). This pharmacological MRI study revealed a significant positive response to (S)-ketamine specifically in the cortex, nucleus accumbens and striatum. In contrast, negative fMRI responses were observed in various brain regions after (R)-ketamine administration. (R,S)-ketamine, evoked significant positive fMRI responses specifically in the cortex, nucleus accumbens and striatum, and this fMRI response pattern was comparable with that of (S)-ketamine. MK-801-induced similar fMRI response pattern to (S)-ketamine. The fMRI responses to (S)-ketamine and MK-801 showed differential temporal profiles, which corresponded with brain concentration profiles. (S)-ketamine and MK-801 significantly increased locomotor activity, while (R)-ketamine produced no noticeable change. (R,S)-ketamine tended to increase locomotor activity. Our novel fMRI findings show that (R)-ketamine and (S)-ketamine induce completely different fMRI response patterns on rat, and that the response produced by the latter is similar to that elicited by an NMDAR antagonist. Our findings provide insight into the antidepressant mechanism of (R,S)-ketamine.

The D-shuttle dosimeter technique is a convenient approach for estimating the radiation dosimetry in a positron emission tomography (PET) study that employs multiple D-shuttle dosimeters attached to the body surface of a patient. To bring this technique into clinical usage, it is very important to evaluate its performance by investigating the bias associated with D-shuttle dosimeter positioning and by comparing the estimates with those of the whole-body dynamic PET imaging technique. The torso cavity and six spheres of the NEMA body phantom were filled with F-FDG solution, and then, the phantom was imaged for 1 h. We assumed the mislocated positioning of the D-shuttle dosimeters by shifting them in the z-direction (upper) in a range of 1–5 cm from the original positions. The cumulative radioactivities, absorbed doses, and effective dose were estimated using accurate and mislocated positions of the D-shuttle dosimeters. For comparison, the cumulative radioactivities were also estimated from the PET images, and then, the absorbed doses and effective dose were computed. The maximum bias of the average estimated cumulated radioactivities and the effective doses was − 15.0% and − 19.7% for the 1 cm shifted positions, respectively. The ratios of absorbed doses obtained from D-shuttle and PET measurement against the actual values were between 0.9 and 1.3, and 0.7 and 1.0, respectively. The bias associated with the D-shuttle dosimeter positions was significant and probably consistent, and both dosimetric techniques exhibited good performance in this phantom study. 18

Bone scintigraphy is difficult to understand the anatomical structure and quantitatively evaluate functions due to two-dimensional image, especially in the region such as sternum and pelvis, while bone SPECT providing three-dimensional image is useful for them. However, the imaging time of SPECT using many projection data is long. Shortening of the SPECT imaging time is desired. The aim of this study is to apply the image reconstruction method using total variation (TV) regularization to bone SPECT, and to examine the feasibility of bone SPECT from a small number of projections. In the image reconstruction, we used the expectation maximization-TV (EM-TV) algorithm consisting of the L1 norm regularization called TV, one of the methods of compressed sensing, and the maximum likelihood-expectation maximization (ML-EM) method, which is a statistical iterative image reconstruction method. First, it was validated by numerical phantom simulation that EM-TV algorithm could reconstruct a small number of projection data successfully. Next, bone SPECT imaging with Tc-MDP was performed using clinical SPECT-CT scanner, and image reconstruction was performed with equally spaced 12 out of 72 directions as projection data of a small number, and comparison with the conventional method, ML-EM, was performed. From results of bone SPECT study, the artifact which appears on the image reconstructed by ML-EM was dramatically improved by EM-TV reconstruction. In addition, EM-TV reconstruction significantly improved the quantitative accuracy in the region such as the pelvis. In conclusion, this study suggested the feasibility of bone SPECT with a small number of projections by EM-TV image reconstruction method. 99m

Background: Multi-modal brain image registration is a prerequisite for accurate mapping of brain structure and function in neuroscience. Image registration is commonly performed using automated software; however, its accuracy decreases when images differ in modality, contrast, uniformity, and resolution. This limitation could be overcome by using an external reference point; however, high-contrast agents in multi-modal imaging have not been previously reported. New methods: Here, we propose a novel multi-modal fiducial marker that contains Tungsten solution and provides high contrast in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). The basic characteristics of this multi-modal marker were investigated by assessing major sources of image contrast in the following modalities: density and T1-, T2-relaxivity in comparison with conventional contrast agents. Results: Tungsten solution had lower T1- and T2-relaxivity and high solubility, and showed high contrast in T1- and T2-weighted MR and CT images at a high-density concentration (˜3.0 g/mL), whereas other conventional solutions did not show sufficient contrast in either CT or MRI. Comparison with existing methods: The use of this Tungsten-based multi-modal marker allowed more accurate registration than a software-only method in phantom and animal experiments. Application of this method demonstrated accurate cortical surface mapping of neurotransmitter function (dopamine transporter, DAT) using PET and MRI, and provided a neurobiologically relevant cortical distribution consistent with previous literature on histology-based DAT immunoreactivity. Conclusions: The Tungsten-based multi-modal fiducial marker is non-radioactive, easy to handle, and aids precise registration across different modalities of brain imaging.

Image statistics are frequently used for functional and molecular imaging research in which images from a patient group with a specific diagnosis are compared with images from a healthy control group who have been matched for demographic variables. The success of image statistics for brain imaging has encouraged us to develop a method for obtaining volumetrically normalized kidney to perform image statistics so that we can locally visualize the statistical significant difference comparing voxel by voxel between certain groups in terms kidney blood flow kinetic parameters. For the development of this evolutionary process, we first volumetrically normalized all subjects, which include healthy control (HC) and chronic renal failure (CRF) patients, 15O water PET image with respect to one HC subject's MRI image using affine transformation. Then 15O kinetic parametric images of normalized kidneys were obtained through the basis function method. Finally, the statistical map of these parametric images was produced using the threshold-free cluster enhancement based permutation method. Kinetic parameters of kidney namely, uptake rate constant (K1), clearance rate constant (k2) and blood volume (Va), were found to be notably lower in CRF than those of in HC and k2 parameter was found to be more stable compared to K1 and Va. The statistical map of these parametric images allowed us to visualize local significant differences statistically (P<0.05) between HC and CRF groups. Though PET and MRI techniques have enormous potentiality for functional and molecular imaging of kidney, these are, at best, in experimental level. It is speculated that statistical mapping of kidney could play a significant role in the successful implementation of functional and molecular kidney imaging. However, more research involving a larger sample size and improved normalization technique will be needed for the robustness of the process.

In nuclear-medical imaging, most clinically applied gamma rays have energies less than or equal to 511 keV. There is growing interest in the applications of radioisotopes emitting higher-energy gamma rays for pretherapeutic and therapeutic imaging. Compton cameras have the capability of imaging gamma rays with a wide range of energies. Since sensitivity of Compton cameras decrease with increase in gamma-ray energy, high sensitivity is required to image such radioisotopes. In this study, we developed a cost-effective Compton camera using high-sensitive inorganic scintillators and a commercially available data acquisition system for a positron emission tomography camera. An imaging experiment of a Mn point source was performed to demonstrate the imaging capability for the camera, and the source was successfully imaged. 54

With the increasing incidence of dementia worldwide, the frequent use of amyloid and tau positron emission tomography imaging requires low-dose protocols for the differential diagnoses of various neurodegenerative diseases and the monitoring of disease progression. In this study, we investigated the feasibility to reduce the PET dose without a significant loss of quantitative accuracy in 3D dynamic row action maximum likelihood algorithm-reconstructed PET images using [ C]PIB and [ F]THK5351. Eighteen cognitively normal young controls, cognitively normal elderly controls, and patients with probable Alzheimer’s disease (n = 6 each), were included. Reduced doses were simulated by randomly sampling half and quarter of the full counts in list mode data for one independent realization at each simulated dose. Bias was evaluated between the reduced dose from the full dose of standardized uptake value ratio (SUVR), distribution volume ratio (DVR) from reference Logan, and non-displaceable binding potential (BP ) from simplified reference tissue model (SRTM). DVR yielded the least bias at low dose compared to SUVR and BP , and thus, is highly recommended. The dose of [ F]THK5351 and [ C]PIB can be reduced to a quarter of the full dose using DVR for evaluation, whereas the dose can only be reduced to half and a quarter of the full dose for [ F]THK5351 and [ C]PIB using SUVR. BP showed inconsistent trend and large bias at low dose. The feasibility of dose reduction was dependent on the selected parameters of interest, reconstruction algorithms, reference regions, and to a lesser degree by motion effects. 11 18 18 11 18 11 ND ND ND

With the aim of providing critical nuclear data of primary knock-on atoms (PKAs) created from proton-induced spallation reactions, a new detection system was designed and dedicated to the PKA measurement that requires lower measurement threshold energies and superior mass resolution than the conventional experimental setups. Such requirements can be fulfilled by employing the TOF-E and dE-E methods, and this new PKA detection system, which consists of two fast timing detectors and one dE-E gas ionization detector. The design of the detectors and the experimental setup, along with the estimated system performed are briefly described in this paper.

Purpose: Internal radiation dosimetry plays an important role in ensuring the safe use of positron emission tomography (PET) technology and is a legal requirement in most countries. We propose a new technique to estimate the internal radiation dose in PET studies by means of multiple D-shuttle dosimeters attached on the body surface of the patient. Methods: Radioactivity in a source organ was estimated iteratively using measurements from multiple D-shuttle dosimeters with a maximum-likelihood expectation-maximization (MLEM) algorithm with dose response from a source to a D-shuttle dosimeter computed by Monte Carlo simulation. To validate our technique, we performed a phantom study using a National Electrical Manufacturers Association (NEMA) body phantom. The fillable compartments (torso cavity and six spheres) of the phantom were filled with F-FDG mixed with pure water using an 800:1 sphere-to-background radioactivity concentration ratio. The radioactivity concentrations present in the torso cavity and six spheres were 0.00165 MBq/mL and 1.32 MBq/mL, respectively. The initial radioactivities of the torso cavity and six spheres (treated as source organs) were 15.9 MBq (torso cavity), 34.7 MBq (37 mm sphere), 15.1 MBq (28 mm sphere), 7.27 MBq (22 mm sphere), 3.26 MBq (17 mm sphere), 1.54 MBq (13 mm sphere), and 0.697 MBq (10 mm sphere). Eleven D-shuttle dosimeters were attached to the NEMA body phantom surface to obtain information on body surface dose and a mathematical NEMA body phantom has been modeled in the Heavy Ion Transport Code System (PHITS) Monte Carlo simulation code. Results: Radioactivity was estimated in 2 min intervals over a 110-min total dose time using our proposed technique. A significant correlation (R = 0.992) was found between actual radioactivity and estimated radioactivity at every 2 min interval for each source organ. The estimated initial radioactivity (mean with standard deviation) was 16.5 ± 0.311 MBq (torso cavity), 33.0 ± 0.624 MBq (37 mm sphere), 15.7 ± 0.189 MBq (28 mm sphere), 7.11 ± 0.738 MBq (22 mm sphere), 4.17 ± 0.083 MBq (17 mm sphere), 1.48 ± 0.469 MBq (13 mm sphere), and 0.865 ± 0.313 MBq (10 mm sphere), which were very close to the actual initial radioactivity measurements for each source organ. Conclusions: The phantom study showed that our technique worked successfully. This technique could be used to estimate internal radiation dosimetry in a clinical PET study. 18 2

Astatine-211 is a promising radionuclide for targeted radiotherapy. It is required to image the distribution of targeted radiotherapeutic agents in a patient's body for optimization of treatment strategies. We proposed to image At with high-energy photons to overcome some problems in conventional planar or single-photon emission computed tomography imaging. We performed an imaging experiment of a point-like At source using a Compton camera, and demonstrated the capability of imaging At with the high-energy photons for the first time. 211 211 211

We proposed use of astatine-210 in preclinical study. Astatine-210 has higher yield of production and is easier to quantify than astatine-211. We produced astatine-210 with Bi target and 40 MeV alpha beam accelerated by cyclotron, free astatine-210 was separated and injected to normal rats. Three male rats (blocking group) were injected non-radioactive iodide before injection of astatine-210. Compared with the control group, the astatine-210 accumulations in the blocking group decreased to 24% in the thyroid.

OBJECTIVES We previously reported that cell sheet transplantation combined with an omentopexy (OP) procedure is more effective for repairing heart damage when compared with cell sheet transplantation alone. However, a simultaneous (conventional) laparotomy as part of the OP may adversely affect the general condition of critically ill heart failure patients who would otherwise benefit from cell sheet transplantation, which is a paradox to be reconciled before this treatment can be applied in a clinical setting. We devised a novel endoscopic approach termed 'transphrenic peritoneoscopy' (TPP) for minimal access to abdominal organs from the thoracic cavity. Herein, we evaluated the feasibility and safety of TPP with an OP in a porcine myocardial infarction model. METHODS Myocardial infarction was induced in 4 mini pigs by placing an ameroid constrictor around the left anterior descending artery. One month later, a left thoracotomy was performed in 2 randomly selected mini pigs, and a laparoscopic port was placed on the left diaphragm to gain access into the abdominal cavity. Using a low-pressure pneumoperitoneum, a flexible gastrointestinal endoscope was advanced, then the omentum was partially grasped with endoscopic forceps and brought back into the thoracic cavity via the diaphragm. Skeletal myoblast cell sheets were then implanted over the impaired myocardium, followed by placing the omentum over the sheets. RESULTS TPP-assisted OP was accomplished in 2 post-myocardial infarction mini pigs with severe heart failure with an intra-abdominal pressure ≤8 mmHg within 30 min (22 and 27 min, respectively). Necropsy findings revealed a viable omentum flap and pedicle in both animals, with no evidence of procedure-related complications. Angiographic and histological analyses confirmed vessel communication between the omentum and the left ventricle. CONCLUSIONS Our TPP approach was shown to be feasible and safe with a low-pressure pneumoperitoneum, while the omentum flap was durable. This successful combination of techniques may provide less-invasive endoscopic intervention and regenerative therapy.

Objectives: We aimed to determine whether high-resolution specimen-positron emission mammography (PEM) using fluorodeoxyglucose ( F-FDG) can reveal extension of breast cancer in breast-conserving surgery (BCS), and assess the safety of radiation exposure to medical staff. Methods: Sixteen patients underwent positron emission tomography, and then BCS with intraoperative frozen section analysis on the same day. Resected specimens with remaining F-FDG accumulation were scanned by high-resolution PEM. At least 1 day after surgery, tumour extension was evaluated by three independent experienced readers and by binarized images from the specimen-PEM data. Intraoperative exposure of medical staff to F-FDG was measured. Results: Specimen-PEM evaluations of binarized images and the three investigators detected all (100 %, 12/12) invasive lesions and 94.4 % (17/18) of in situ lesions using both methods. The positive predictive value of the accumulated lesions was 74.4 % (29/39) for the binarized images and 82.9 % (29/35) for the three investigators. Analysis of intraoperative frozen sections detected 100 % (2/2) of the margin-positive cases, also detected by both specimen-PEM evaluation methods with no false-positive margin cases. The mean exposure of the medical staff to F was 18 μSv. Conclusions: Specimen-PEM detected invasive and in situ lesions with high accuracy and allowable radiation exposure. Key points: • Specimen-PEM detected invasive and in situ lesions with high accuracy. • Specimen-PEM predicted complete resection with the same accuracy as frozen section analysis. • Breast-conserving surgery after fluorodeoxyglucose injection was performed with low medical staff exposure. 18 18 18 18

ObjectiveAntihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration.MethodsIn this double-blind, placebo-controlled, three-way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5mg and diphenhydramine 50mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two-back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [F-18]fluorodeoxyglucose. Regional hemodynamic responses were measured using near-infrared spectroscopy.ResultsEnergy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness.ConclusionsPhysiological coupling between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.

In clinical situations, various breast-dedicated positron emission tomography (PET) systems have been used. However, clinical breast-dedicated PET systems have polygonal detector ring. Polygonal detector ring sometimes causes image artifact, so complicated reconstruction algorithm is needed to reduce artifact. Consequently, we developed a circular detector ring for breast-dedicated PET to obtain images without artifact using a simple reconstruction algorithm. We used Lu1.9Gd0.1SiO5 (LGSO) scintillator block which was made of 1.5 x 1.9 x 15 mm pixels that were arranged in an 8 x 24 matrix. As photodetectors, we used silicon photomultiplier (Si-PM) arrays whose channel size was 3 x 3 mm. A detector unit was composed of four scintillator blocks, 16 Si-PM arrays and a light guide. The developed detector unit had angled configuration since the light guide was bending. A detector unit had three gaps with an angle of 5.625° between scintillator blocks. With these configurations, we could arrange 64 scintillator blocks in nearly circular shape (regular 64-sided polygon) using 16 detector units. The use of the smaller number of detector units could reduce the size of the front–end electronics circuits. The inner diameter of the developed detector ring was 260 mm. This size was similar to those of brain PET systems, so our breast-dedicated PET detector ring can measure not only breast but also brain. Measured radial, tangential and axial spatial resolution of the detector ring reconstructed by the filtered back-projection (FBP) algorithm were 2.1 mm FWHM, 2.0 mm FWHM and 1.7 mm FWHM at center of field of view (FOV), respectively. The sensitivity was 2.0% at center of the axial FOV. With the developed detector ring, we could obtain high resolution image of the breast phantom and the brain phantom. We conclude that our developed Si-PM-based detector ring is promising for a high resolution breast-dedicated PET system that can also be used for brain PET system.

<p> Supply Platform of Short-lived Radioisotopes for Fundamental Research has been started since 2016. Purpose of this program is to provide non-commercial RIs from accelerator facilities to researchers of various scientific fields after approving the research projects. The suppliers are domestic 4 large accelerator facilities, which have permission to use radiation generating apparatus under "Act on Prevention of Radiation Hazards due to Radioisotopes, etc.". However, it is an open question whether these facilities can provide RIs without legal notification of dealing businesses. In this paper, we report the record of how to make to be realized this platform under legal permission of use.</p>

The purpose of this study is to evaluate the feasibility of extending a previously developed amyloid biomathematical screening methodology to support the screening of tau radiotracers during compound development. 22 tau-related PET radiotracers were investigated. For each radiotracer, in silico MLogP, Vx, and in vitro KD were input into the model to predict the in vivo K1, k2, and BPND under healthy control (HC), mild cognitive impaired (MCI), and Alzheimer's disease (AD) conditions. These kinetic parameters were used to simulate the time activity curves (TACs) in the target regions of HC, MCI, and AD and a reference region. Standardized uptake value ratios (SUVR) were determined from the integrated area under the TACs of the target region over the reference region within a default time window of 90-110 min. The predicted K1, k2, and BPND values were compared with the clinically observed values. The TACs and SUVR distributions were also simulated with population variations and noise. Finally, the clinical usefulness index (CUI) ranking was compared with clinical comparison results. The TACs and SUVR distributions differed for tau radiotracers with lower tau selectivity. The CUI values ranged from 0.0 to 16.2, with 6 out of 9 clinically applied tau radiotracers having CUI values higher than the recommend CUI value of 3.0. The differences between the clinically observed TACs and SUVR results showed that the evaluation of the clinical usefulness of tau radiotracer based on single target binding could not fully reflect in vivo tau binding. The screening methodology requires further study to improve the accuracy of screening tau radiotracers. However, the higher CUI rankings of clinically applied tau radiotracers with higher signal-to-noise ratio supported the use of the screening methodology in radiotracer development by allowing comparison of candidate radiotracers with clinically applied radiotracers based on SUVR, with respect to binding to a single target.

Molecular imaging serves as an important tool for researchers and clinicians to visualize and investigate complex biochemical phenomena using specialized instruments; these instruments are either used individually or in combination with targeted imaging agents to obtain images related to specific diseases with high sensitivity, specificity, and signal-to-noise ratios. However, molecular imaging, which is a multidisciplinary research field, faces several challenges, including the integration of imaging informatics with bioinformatics and medical informatics, requirement of reliable and robust image analysis algorithms, effective quality control of imaging facilities, and those related to individualized disease mapping, data sharing, software architecture, and knowledge management. As a cost-effective and open-source approach to address these challenges related to molecular imaging, we develop a flexible, transparent, and secure infrastructure, named MIRA, which stands for Molecular Imaging Repository and Analysis, primarily using the Python programming language, and a MySQL relational database system deployed on a Linux server. MIRA is designed with a centralized image archiving infrastructure and information database so that a multicenter collaborative informatics platform can be built. The capability of dealing with metadata, image file format normalization, and storing and viewing different types of documents and multimedia files make MIRA considerably flexible. With features like logging, auditing, commenting, sharing, and searching, MIRA is useful as an Electronic Laboratory Notebook for effective knowledge management. In addition, the centralized approach for MIRA facilitates on-the-fly access to all its features remotely through any web browser. Furthermore, the open-source approach provides the opportunity for sustainable continued development. MIRA offers an infrastructure that can be used as cross-boundary collaborative MI research platform for the rapid achievement in cancer diagnosis and therapeutics.

Introduction: To facilitate radiotracers' development, a screening methodology using a biomathematical model and clinical usefulness index (CUI) was proposed to evaluate radiotracers' diagnostic capabilities. Methods: A total of 31 amyloid positron emission tomography radiotracers were evaluated. A previously developed biomathematical model was used to simulate 1000 standardized uptake value ratios with population and noise simulations, which were used to determine the integrated receiver operating characteristics curve (Az), effect size (Es), and standardized uptake value ratio (Sr) of conditions-pairs of healthy control-mild cognitive impaired and mild cognitive impaired-Alzheimer's disease. CUI was obtained from the product of averaged [Formula: see text], [Formula: see text], and [Formula: see text]. Results: The relationships of [Formula: see text], [Formula: see text], and [Formula: see text] with CUI were different, suggesting that they assessed different radiotracer properties. The combination of Az, Es, and Sr complemented each other and resulted in CUI of 0.10 to 5.72, with clinically applied amyloid positron emission tomography radiotracers having CUI greater than 3.0. Discussion: The CUI rankings of clinically applied radiotracers were close to their reported clinical results, attesting to the applicability of the screening methodology.

Attenuation correction (AC) is required for accurate quantitative evaluation of small animal PET data. Our objective was to compare three AC methods in the small animal Clairvivo-PET scanner. The three AC methods involve applying attenuation coefficient maps generated by simulating a cylindrical map (SAC), segmenting the emission data (ESAC), and segmenting the transmission data (TSAC), imaged using a 137Cs single-photon source. Investigation was carried out using a 65 mm uniform cylinder and an NEMA NU4 2008 mouse phantom, filled with water or tungsten liquid, to mimic bone. Evaluation was carried out using the difference of the segmented map volume from the known cylindrical phantom volume, the recovery of the radioactivity concentration, and the line profiles. The optimal transmission scan time for achieving accurate AC using TSAC was determined using 5, 10, 15, 20, and 25 min transmission scan time. The effects of scatter correction and reconstruction algorithms on ESAC were investigated. SAC showed the best performance but was unable to correct for different tissues and the scanner bed, and faced difficulty with correct positioning of the attenuation coefficient map. ESAC was affected by scatter correction and reconstruction algorithm, and may result in poor boundary delineation, and hence was unreliable. TSAC showed reasonable performance but required further optimization of the default segmentation setting. A minimum transmission scan time of 20 min is recommended for Clairvivo-PET using 137Cs source to ensure that sufficient transmission counts are obtained to generate accurate attenuation coefficient map.

OBJECTIVE: Although coronary perivascular adipose tissue (PVAT) may play important roles as a source of inflammation, the association of coronary PVAT inflammation and coronary hyperconstricting responses remains to be examined. We addressed this important issue in a porcine model of coronary hyperconstricting responses after drug-eluting stent implantation with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomographic imaging. APPROACH AND RESULTS: An everolimus-eluting stent (EES) was randomly implanted in pigs into the left anterior descending or the left circumflex coronary artery while nonstented coronary artery was used as a control. After 1 month, coronary vasoconstricting responses to intracoronary serotonin (10 and 100 μg/kg) were examined by coronary angiography in vivo, followed by in vivo and ex vivo 18F-FDG positron emission tomographic/computed tomographic imaging. Coronary vasoconstricting responses to serotonin were significantly enhanced at the EES edges compared with the control site (P<0.01; n=40). Notably, in vivo and ex vivo 18F-FDG positron emission tomographic/computed tomographic imaging and autoradiography showed enhanced 18F-FDG uptake and its accumulation in PVAT at the EES edges compared with the control site, respectively (both P<0.05). Furthermore, histological and reverse transcription polymerase chain reaction analysis showed that inflammatory changes of coronary PVAT were significantly enhanced at the EES edges compared with the control site (all P<0.01). Importantly, Rho-kinase expressions (ROCK1/ROCK2) and Rho-kinase activity (phosphorylated myosin phosphatase target subunit-1) at the EES edges were significantly enhanced compared with the control site. CONCLUSIONS: These results indicate for the first time that inflammatory changes of coronary PVAT are associated with drug-eluting stent-induced coronary hyperconstricting responses in pigs in vivo and that 18F-FDG positron emission tomographic imaging is useful for assessment of coronary PVAT inflammation.

Our study aimed to develop a method to mathematically predict the kinetic parameters K-1 (influx rate constant), k(2) (efflux rate constant), and BPND (nondisplaceable binding potential) of amyloid PET tracers and obtain SUV ratios (SUVRs) from predicted timeactivity curves of target and reference regions. Methods: We investigated 10 clinically applied amyloid PET radioligands: C-11-Pittsburgh compound B, C-11-BF-227, C-11-AZD2184, C-11-SB-13, F-18-FACT, F-18-florbetapir, F-18-florbetaben, F-18-flutemetamol, F-18-FDDNP, and F-18-AZD4694. For each tracer, time-activity curves of both target and reference regions were generated using a simplified 1-tissue-compartment model, with an arterial plasma input function and the predicted kinetic parameters. K-1, k(2), and BPND were derived from the lipophilicity (logP), apparent volume, free fraction in plasma, free fraction in tissue, dissociation constant, and density of amyloid beta using biomathematic modeling. Density was fixed at 3 nM to represent healthy control conditions and 50 nM to represent severe Alzheimer disease (AD). Predicted SUVRs for the healthy and AD groups were then obtained by dividing the integrated time-activity curve of the target region by that of the reference region. To validate the presented method, the predicted K-1, k(2), BPND, and SUVR for the healthy and AD groups were compared with the respective clinically observed values. Results: The correlation between predicted and clinical kinetic parameters had an R-2 value of 0.73 for K-1 in the healthy group, 0.71 for K-1 in the AD group, 0.81 for k(2) in the healthy group, 0.85 for k(2) in the AD group, and 0.63 for BPND in the AD group. The regression relationship between the predicted SUVR (y) and the clinical SUVR (x) for the healthy and the AD groups was y 5 2.73x - 2.11 (R-2 = 0.72). Conclusion: The proposed method showed a good correlation between predicted and clinical SUVR for the 10 clinically applied amyloid tracers.

Purpose To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study. Methods We investigated two of the most commonly used PVC methods, Muller-Gartner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [F-18]THK5351 and [C-11]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labb, (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data. Results In regions of high uptake of [F-18]THK5351 and [C-11]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition. Conclusions Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.

We recently found that luminescence was emitted from water during proton irradiation at lower energy than the Cerenkov-light threshold and imaging was possible by using a CCD camera. However, since the measured distributions were projection images of the luminescence, precise dose estimations from the images were not possible. If the 3 dimensional images can be formed from the projection images, more precise dose information could be obtained. For this purpose, we calculate the 3-dimensional distribution of the proton beams from the luminescence images and use them for beam width estimations. We assumed that the proton beams have circular shape and the transverse images were reconstructed from the projection images using the filtered backprojection (FBP) algorithm for positron emission tomography (PET). The reconstructed images were compared to estimate the proton-beam widths with those obtained from the projection images and simulation results. We obtained 3-dimensional distributions of the proton beams from the projection images and also the reconstructed sagittal, coronal, and transverse images as well as volume rendering images. The estimated beam widths from the reconstructed images, which were slightly smaller than those obtained from the projection images, were identical to those calculated with the simulation. The 3-dimensional distributions of the luminescence images of water of proton beams could be reconstructed from the projection images and showed improved accuracy in estimating the beam widths of the proton beams.

High-resolution images of radiocesium (Cs-137) distribution are required to study cesium kinetics in plants. A Cherenkov light imaging system can visualize fine distributions of radionuclides emitting beta particles using an optical camera. To evaluate the linearity of the system, an imaging test was performed with point sources of Cs-137, with a radioactivity of 10-2000 kBq. The results indicated that the system has a good linearity between the image intensity and the radioactivity of Cs-137. We developed an imaging system for plants using this system to study radiocesium movement in intact plants. To demonstrate the ability to image radiocesium in a plant, an experiment was performed with an intact soybean plant for four days. The root of an 11-day-old soybean plant was dipped in 20 mL of a culture solution containing Cs-137 with a radioactivity of 10 MBq without potassium. After one day, the solution was replaced with one with potassium but no Cs-137. The soybean plant was in healthy condition in the system, and the high-resolution serial images indicated that Cs-137 was transported to the shoot and accumulated in the node. Therefore, Cherenkov light imaging is promising for imaging radiocesium in intact plants.

Objective: The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI. Materials and methods: Twenty male C57/BL6 mice aged 8 weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6 weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6 weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (T-max) and half-life of elimination RE (T-1/2) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained. Results: Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6 weeks, but significant fibrosis was observed only in mice fed MCD for 6 weeks. Gd-EOB-DTPA-enhanced MRI showed that T-max was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0 +/- 0.7 min; MCD 6w, 12.1 +/- 1.6 min), although there was no alteration in the 2- and 4-week groups. T-1/2 was significantly prolonged in mice fed MCD for 4 and 6 weeks compared to the control group (control, 19.9 +/- 2.0 min; MCD 4w, 46.7 +/- 8.7 min; MCD 6w, 65.4 +/- 8.8 min). The parameters of Gd-EOB-DTPA kinetics (T-max and T-1/2) in the liver were positively correlated with the liver histopathological score (steatosis vs T-max, rho = 0.69, P = 0.0007; inflammation vs T-max, rho = 0.66, P = 0.00155; steatosis vs T-1/2, rho = 0.77, P &lt; 0.0001; inflammation vs T-1/2, rho = 0.73, P = 0.0003). Conclusions: The liver kinetics of Gd-EOB-DTPA correlated well with the inflammation score in the mouse model of NASH, suggesting the possibility of detecting the steatohepatitis stage without fibrosis by Gd-EOB-DTPA-enhanced MR imaging. (C) 2016 Elsevier Inc. All rights reserved.

In this chapter, we explain how positron emission tomography (PET) data are analyzed to estimate behavior of radiotracer injected. For this purpose, compartmental model and its kinetic parameters are introduced, and concept, mathematical basis, and biological interpretation of the compartmental model and the kinetic parameters are described. General form of the compartmental model is brought for comprehensive understanding of the model. Several approaches for fast estimation of the kinetic parameters are introduced based on general compartmental model. The input function for the compartmental model is important for quantitative analysis of PET data, and the reference region model is one approach to avoid acquisition of the input function.

The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10min after intravenous injection of F-18(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415kcps at 14.6MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.

We developed a new gamma camera specifically for plant nutritional research and successfully performed live imaging of the uptake and partitioning of Cs-137 in intact plants. The gamma camera was specially designed for high-energy gamma photons from Cs-137 (662 key). To obtain reliable images, a pinhole collimator made of tungsten heavy alloy was used to reduce penetration and scattering of gamma photons. A single-crystal scintillator, Ce-doped Gd3Al2Ga3O12, with high sensitivity, no natural radioactivity, and no hygroscopicity was used. The array block of the scintillator was coupled to a high-quantum efficiency position sensitive photomultiplier tube to obtain accurate images. The completed gamma camera had a sensitivity of 0.83 count s(-1) MBq(-1) for Cs-137 with an energy window from 600 keV to 730 keV, and a spatial resolution of 23.5 mm. We used this gamma camera to study soybean plants that were hydroponically grown and fed with 2.0 MBq of Cs-137 for 6 days to visualize and investigate the transport dynamics in aerial plant parts. Cs-137 gradually appeared in the shoot several hours after feeding, and then accumulated preferentially and intensively in growing pods and seeds; very little accumulation was observed in mature leaves. Our results also suggested that this gamma-camera method may serve as a practical analyzing tool for breeding crops and improving cultivation techniques resulting in low accumulation of radiocesium into the consumable parts of plants. (C) 2015 The Authors. Published by Elsevier Ltd.

Introduction: The purpose of this study was to compare two amyloid imaging agents, [C-11]BF227 and [F-18]FACT (derivative from [C-11]BF227) through quantitative pharmacokinetics analysis in human brain. Methods: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [C-11]BF227 and 10 HC subjects and 10 probable AD patients with [F-18]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients. Results: For [C-11]BF227, there were no significant difference of V-T (2TCM, 1TCM) and SUV in all regions (Student t-test; p &lt; 0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p &lt; 0.05) between the HC and AD groups. For [F-18]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p &lt; 0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different. Conclusion: This study revealed that although the PET amyloid imaging agents [C-11]BF227 and [F-18]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers. (C) 2015 Elsevier Inc. All rights reserved.

A PET system for small animals requires a small detector ring to obtain high-spatial resolution images, However, when we use a relatively large size of photodetector such as a position-sensitive photomultiplier tube (PSPMT), the detector ring is arranged in a hexagonal-or octagonal-shape, and the PET system has large gaps between the block detectors. The large gaps produce image distortion, and the reconstruction algorithm is difficult. To solve these problems, we proposed to arrange two scintillator blocks on one PSPMT using two angled optical fiber-based image guides. We could set two scintillator blocks angled at 22.5 degrees on a PSPMT so that these scintillator blocks are arranged in a nearly circular (hexadecagonal) shape with eight developed block detectors. We used Gd2SiO5 (GSO) scintillators with Ce concentrations of 1.5 mol% (decay time: 39 ns) and 0.4 mol% (decay time: 63 ns). Sizes of these GSO cells were 1.6 x 2.4 x 7.0 mm(3) and 1.6 x 2.4 x 8.0 mm(3) for 1.5 mol% a and 0.4 mol% Ce, respectively. These two types of GSO were arranged in an 11 x 15 matrix and optically coupled in the depth direction to form a depth-of-interaction (DOI) detector. Two GSO blocks and two optical fiber-based image guides were optically coupled to a 2-in. PSPMT (Hamamatsu Photonics H8500: 8 x 8 anodes). We measured the performances of the block detector with Cs-137 gamma photons (662-key). We could resolve almost all pixels clearly in a two-dimensional position histogram. The average peak-to-valley ratios (P/Vs) of the two-dimensional position histogram along profiles were 2.6 and 4.8 in horizontal and vertical directions, respectively. The energy resolution was 28.4% full-width at half-maximum (FWHM). The pulse shape spectra showed good separation with a P/V of 5.2. The developed block detector performed well and shows promise for the development of high-sensitivity and high-spatial resolution PET systems. (C) 2015 Elsevier B.V. All rights reserved.

Pharmacological magnetic resonance imaging (phMRI) is a powerful tool for imaging the effects of drugs on brain activity. In preclinical phMRI studies, general anesthesia used for minimizing head movements is thought to influence the phMRI responses to drugs. In this study we investigated the phMRI responses to a selective dopamine transporter (DAT) inhibitor, GBR12909, and a dopamine (DA) releaser, D-amphetamine (AMPH), in the isoflurane anesthetized and awake rats using a relative cerebral blood volume (rCBV) method. AMPH (1 mg/kg i.p.) caused an increase in rCBV in the dopaminergic circuitry in the both anesthetized and awake rats. The striatal rCBV change was correlated with the change of the striatal DA concentration induced by AMPH in the both anesthetized and awake rats. GBR12909 (10 mg/kg i.p.) caused a positive rCBV response and showed a similar regional pattern of rCBV response to AMPH in the awake rats, and the correlation between the change of the striatal rCBV and the striatal DA concentration was observed. However, in the anesthetized rats, GBR12909 induced a widespread negative rCBV response, whereas an increase in striatal DA concentration was observed. These findings indicate that phMRI responses to activation of DA neurotransmission by GBR12909 or AMPH are overall identical in the awake state, while the phMRI response to a DAT inhibitor, GBR12909 but not to AMPH was changed by isoflurane anesthesia. For the evaluation of neuroactive drugs using phMRI, isoflurane anesthesia might be complicated the interpretation of pharmacodynamic effects of drugs in preclinical studies. (C) 2015 Wiley Periodicals, Inc

Optical fiber is a promising material for integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) PET/ MRI systems. Because its material is plastic, it has no interference betweenMRI. However, it is unclear whether this material can also be used for a single photon emission tomography (SPECT)/MRI system. For this purpose, we developed an optical fiber-based block detector for a SPECT/MRI system and tested its performance by combining mm (YSO) pixels into a block and was coupled it to an optical fiber image guide that used was 0.5-mm in diameter with 80-cm long double clad fibers. The image guide had mm rectangular input and an equal size output. The input of the optical fiber-based image guide was bent at 90 degrees, aotomultiplier tube (HQE-PSPMT). The parallel hole, 7-mm-thick collimator made of tungsten plastic was mounted on a YSO block. The diameter of the collimator holes was 0.8 mm which was positioned one-to-one coupled to the YSO pixels. We evaluated the intrinsic and system performances. We resolved most of the YSO pixels in a two-dimensional histogram for Co-57 gamma photons (122-keV) with an average peak-to-value ratio of 1.5. The energy resolution was 38% full-width at half-maximum (FWHM). The system resolution was 1.7-mm FWHM, 1.5 mm from the collimator surface, and the sensitivity was 0.06%. Images of a Co-57 point source could be successfully obtained inside 0.3 T MRI without serious interference. We concnd the output was optically coupled to a 1-in square high quantum efficiency position sensitive phlude that the developed optical fiber-based YSO block detector is promising for SPECT/MRI systems.

Cell-sheet transplantation induces angiogenesis for chronic myocardial infarction (MI), though insufficient capillary maturation and paucity of arteriogenesis may limit its therapeutic effects. Omentum has been used clinically to promote revascularization and healing of ischemic tissues. We hypothesized that cell-sheet transplantation covered with an omentum-flap would effectively establish mature blood vessels and improve coronary microcirculation physiology, enhancing the therapeutic effects of cell-sheet therapy. Rats were divided into four groups after coronary ligation; skeletal myoblast cell-sheet plus omentum-flap (combined), cell-sheet only, omentum-flap only, and sham operation. At 4 weeks after the treatment, the combined group showed attenuated cardiac hypertrophy and fibrosis, and a greater amount of functionally (CD31(+)/lectin(+)) and structurally (CD31(+)/α-SMA(+)) mature blood vessels, along with myocardial upregulation of relevant genes. Synchrotron-based microangiography revealed that the combined procedure increased vascularization in resistance arterial vessels with better dilatory responses to endothelium-dependent agents. Serial (13)N-ammonia PET showed better global coronary flow reserve in the combined group, mainly attributed to improvement in the basal left ventricle. Consequently, the combined group had sustained improvements in cardiac function parameters and better functional capacity. Cell-sheet transplantation with an omentum-flap better promoted arteriogenesis and improved coronary microcirculation physiology in ischemic myocardium, leading to potent functional recovery in the failing heart.

Cerenkov-light imaging provides inherently high resolution because the light is emitted near the positron radionuclide. However, the magnitude for the high spatial resolution of Cerenkov-light imaging is unclear. Its potential molecular imaging applications also remain unclear. We developed an ultrahigh-resolution Cerenkov-light imaging system, measured its spatial resolution, and explored its applications to molecular imaging research. Our Cerenkov-light imaging system consists of a high-sensitivity charged-coupled device camera (Hamamatsu Photonics ORCA2-ER) and a bright lens (Xenon 0.95/25). An extension ring was inserted between them to magnify the subject. A similar to 100-mu m-diameter Na-22 point source was made and imaged by the system. For applications of Cerenkov-light imaging, we conducted F-18-FDG administered in vivo, ex vivo whole brain, and sliced brain imaging of rats. We obtained spatial resolution of similar to 220 mu m for a Na-22 point source with our developed imaging system. The F-18-FDG rat head images showed high light intensity in the eyes for the Cerenkov-light images, although there was no accumulation in these parts in the PET images. The sliced rat brain showed much higher spatial resolution for the Cerenkov-light images compared with CdWO4 scintillator-based autoradiography, although some contrast decrease was observed for them. Even though the Cerenkov-light images showed ultrahigh resolution of similar to 220 mu m, their distribution and contrast were sometimes different from the actual positron accumulation in the subjects. Care must be taken when evaluating positron distribution from Cerenkov-light images. However, the ultrahigh resolution of Cerenkov-light imaging will be useful for transparent subjects including phantom studies.

Purpose: Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered C-11-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. Methods: The distribution of C-11-DNP was investigated by PET/ CT in 6 normal male Wistar rats (8 weeks old, body weight = 220 +/- 8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of C-11-DNP (45.0 +/- 10.7 MBq). The whole-body distribution of the C-11-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. Results: The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of C-11-DNP in the body (following the liver) (13.33 +/- 1.08 and 19.43 +/- 1.29 ml/ cm(3), respectively), indicating that the distribution of C-11-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9 +/- 1.6, 83.1 +/- 3.0, and 38.5 +/- 8.1 mU/ mg, respectively), indicating high activity of AChE in the adrenal glands. Conclusions: We demonstrated the whole-body distribution of C-11-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of C-11-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

Purpose: Cerenkov-light imaging is a new molecular imaging technology that detects visible photons from high-speed electrons using a high sensitivity optical camera. However, the merit of Cerenkov-light imaging remains unclear. If a PET/Cerenkov-light hybrid imaging system were developed, the merit of Cerenkov-light imaging would be clarified by directly comparing these two imaging modalities. Methods: The authors developed and tested a PET/Cerenkov-light hybrid imaging system that consists of a dual-head PET system, a reflection mirror located above the subject, and a high sensitivity charge coupled device (CCD) camera. The authors installed these systems inside a black box for imaging the Cerenkov-light. The dual-head PET system employed a 1.2 x 1.2 x 10 mm(3) GSO arranged in a 33 x 33 matrix that was optically coupled to a position sensitive photomultiplier tube to form a GSO block detector. The authors arranged two GSO block detectors 10 cm apart and positioned the subject between them. The Cerenkov-light above the subject is reflected by the mirror and changes its direction to the side of the PET system and is imaged by the high sensitivity CCD camera. Results: The dual-head PET system had a spatial resolution of similar to 1.2 mm FWHM and sensitivity of similar to 0.31% at the center of the FOV. The Cerenkov-light imaging system's spatial resolution was similar to 275 mu m for a Na-22 point source. Using the combined PET/Cerenkov-light hybrid imaging system, the authors successfully obtained fused images from simultaneously acquired images. The image distributions are sometimes different due to the light transmission and absorption in the body of the subject in the Cerenkov-light images. In simultaneous imaging of rat, the authors found that F-18-FDG accumulation was observed mainly in the Harderian gland on the PET image, while the distribution of Cerenkov-light was observed in the eyes. Conclusions: The authors conclude that their developed PET/Cerenkov-light hybrid imaging system is useful to evaluate the merits and the limitations of Cerenkov-light imaging in molecular imaging research. (C) 2014 American Association of Physicists in Medicine.

Positron emission tomography (PET) with [F-18]-FDG can display cancerous activity depending on glucose uptake. Consequently, different PET tracers with different metabolisms are needed for further indication. We have developed multifunctional PET agents by combining Zn-62(2+) ion with laserphyrin (R) and bisglycosylated 5,10,15,20-tetrakis (pentafluorophenyl)porphyrins (H(2)Glccis-2 and H(2)Glctrans-2), which can be easily synthesized and have a half-life of 9 h. Zn-62-Labeled chemicals were successfully detected as PET signals in vivo and showed PDT-induced cell death by photoirradiation.

Using Ce-doped Gd2SiO5 (GSO) of different Ce concentrations, three-layer DOI block detectors were developed to reduce the parallax error at the edges of a pinhole gamma camera for high-energy gamma photons. GSOs with Ce concentrations of 1.5 mol% (decay time ~40 ns), 0.5 mol% crystal (~60 ns), 0.4 mol% (~80 ns) were selected for the depth of interaction (DOI) detectors. These three types of GSOs were optically coupled in the depth direction, arranged in a 22×22 matrix and coupled to a flat panel photomultiplier tube (FP-PMT, Hamamatsu H8500). Sizes of these GSO cells were 1.9 mm×1.9 mm×4 mm, 1.9 mm×1.9 mm×5 mm, and 1.9 mm×1.9 mm×6 mm for 1.5 mol%, 0.5 mol%, and 0.4 mol%, respectively. With these combinations of GSOs, all spots corresponding to GSO cells were clearly resolved in the position histogram. Pulse shape spectra showed three peaks for these three decay times of GSOs. The block detector was contained in a 2-cm-thick tungsten shield, and a pinhole collimator with a 0.5-mm aperture was mounted. With pulse shape discrimination, we separated the point source images of the Cs-137 for each DOI layer. The point source image of the lower layer was detected at the most central part of the field-of-view, and the distribution was the smallest. The point source image of the higher layer was detected at the most peripheral part of the field-of-view, and the distribution was widest. With this information, the spatial resolution of the pinhole gamma camera can be improved. We conclude that DOI detection is effective for pinhole gamma cameras for high energy gamma photons. © 2014 Elsevier B.V.

Positron-emission tomography (PET) can be used to visualize active stage cancer. Fluorine-18 ([F-18])labeled 2-([F-18]) 2-deoxy-2-fluoroglucose (([F-18])-FDG), which accumulates in glucose-dependent tissues, is a good cancer-targeting tracer. However, ([F-18])-FDG is obscured in glucose-dependent normal tissues. In this study, we assessed the cancer-selective accumulation of zinc-labeled glycoconjugated 5,10,15, 20-tetrakis(pentafluorophenyl) porphyrin (ZnGlc1-4), both in vitro and in vivo. Experiments using both normal and cancer cells confirmed the relationship between cancer cell-selective accumulation and the substitution numbers and orientations of glycoconjugated porphyrins. ZnGlctrans-2 accumulated at greater levels in cancer cells compared with other glycoconjugated porphyrins. PET imaging showed that ZnGlctrans-2 accumulated in tumor. (C) 2014 Elsevier Ltd. All rights reserved.

BACKGROUND: The cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy. METHODS: Twenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control. RESULTS: At 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05). CONCLUSIONS: The combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure.

Positron emission tomography (PET) is an imaging technology used to visualize distribution of particular ligands inside living organisms. The ligand is labeled by a positron-emitting isotope, such as 11C, 15O, 13N and 18F, and injected into subjects. By detecting γ-rays emitted from the ligand, in vivo biodistribution and kinetics of the ligand can be depicted with high sensitivity. By altering the target ligand for PET, one can see different distributions and time courses of the target. PET provides several biological and functional images inside the body, rather than simply an anatomical image. Therefore, PET can potentially detect biological changes that occur long before anatomical changes begin. PET has been widely used for neuroreceptor and neurotransmitter studies by tracing radioligands, which have selective affinity for a particular site. For example, the dopamine and serotonin receptors are highly related to brain disorders. By analyzing the pharmacokinetics of these ligands using PET, it is possible to noninvasively detect abnormalities in the brain. However, signals from PET contain many different types of information, and it is important to interpret the signals appropriately and choose the proper technique to analyze PET data. This chapter discusses several analytical methods for PET data.

Objective: YSO (Ce-doped Y2SiO5) is a promising scintillator for a single-photon imaging system since it has relatively high light output and does not contain any natural radioactivity. Since YSO is not hygroscopic, it may be possible to fabricate a block with small pixels for a high-resolution system. For this purpose, we developed a high-resolution gamma camera system that employs smaller than 1-mm YSO pixels. Methods: The gamma camera's detector used 0.8 × 0.8 × 7-mm YSO pixels. All the surfaces of these YSO pixels were mechanically polished, combined with a 0.1-mm-thick BaSO4 reflector to form a 48 × 48 matrix, and optically coupled to a high quantum efficiency, 2-inch square position sensitive photomultiplier tube (Hamamatsu Photonics H10966 A-100). The YSO block was 43.2 × 43.2 mm. The YSO gamma camera was encased in a 5-mm-thick tungsten container, and a parallel collimator was mounted on its front. The parallel hole collimator was made of a 3-layer (each layer was 5-mm thick) tungsten plate, and each plate had 48 × 48, 0.6-mm holes that were positioned by one-to-one coupling with the YSO pixels. Results: Even with the 0.8-mm YSO pixels, we clearly resolved most of the pixels in a 2-dimensional histogram with a peak-to-valley ratio of 2.9 for the 122-keV gamma photons. The energy resolution was 20.4 % FWHM. The spatial resolutions with a parallel hole collimator 2 mm from the collimator surface were 0.7- and 1.3-mm FWHM for the 122- and ∼35-keV gamma photons, respectively. We successfully obtained phantoms and small animal images with our YSO gamma camera system. Conclusion: Our high-resolution system has a potential to be useful for molecular imaging research. © 2014 The Japanese Society of Nuclear Medicine.

Since a high resolution PET system is needed for small animal imaging, especially for mouse studies, we developed a new small animal PET system that decreased the size of the scintillators to less than 1 mm. Our developed PET system used 0.5 x 0.7 x 5 mm(3) LYSO pixels arranged in an 11 x 13 matrix to form a block with a 0.1 mm BaSO4 reflector between the pixels. Two LYSO blocks were optically coupled to two optical fiber based angled image guides. These LYSO blocks and image guides were coupled to a Si-PM array (Hamamatsu MPPC S11064-050P) to form a block detector. Eight block detectors (16 LYSO blocks) were arranged in a 34 mm inner diameter ring to form a small animal PET system. The block detector showed good separation for the 22 x 13 LYSO pixels in the two-dimensional position histogram. The energy resolution was 20% full-with at half-maximum (FWHM) for 511 keV gamma photons. The transaxial resolution reconstructed by filtered backprojection was 0.71 to 0.75 mm FWHM and the axial resolution was 0.70 mm. The point source sensitivity was 0.24% at the central axial field-of-view. High resolution mouse images were obtained using our PET system. The developed ultrahigh resolution PET system showed attractive images for small animal studies and has a potential to provide new findings in molecular imaging researches.

Polymeric nanoparticles (NPs) comprised of hydrophilic poly(gamma-glutamic acid) in the main chain and hydrophobic phenylalanine in the side chain (gamma-PGA-Phe) are a promising vaccine carrier for various kinds of diseases. However, little is known about the fate of subcutaneously administered gamma-PGA-Phe NPs. Therefore, we newly synthesized gamma-PGA graft phenylalanine and tyrosine conjugates (gamma-PGA-Phe-Tyr), and then gamma-PGA-Phe-Tyr NPs were labeled with I-125 for monitoring their biodistribution (gamma-PGA-Phe-Tyr(I-125) NPs). Dynamic light scattering (DLS) measurements showed that gamma-PGA-Phe-Tyr(I-125) NPs showed 200 nm in diameter and a negative zeta-potential, which was comparable to those of their precursors. gamma-scintigraphic images showed that in mice, subcutaneously injected gamma-PGA-Phe-Tyr(I-125) NPs were mainly observed at the site of injection (SOI), but not other organs 1 h after administration. However, gamma-PGA-PheTyr(I-125) NPs were almost undetectable at the SOI and other organs at 11 days postinjection. Similar results were observed when gamma-PGA-Phe-Tyr(I-125) NPs were subcutaneously injected into rats. Furthermore, at 11 days postinjection, 73 +/- 3% of the injected dose of gamma-PGA-Phe-Tyr(I-125) NPs was detected in the feces (14 +/- 1%) and urine (59 +/- 1%). These results clearly showed that subcutaneously injected gamma-PGA-Phe-Tyr(I-125) NPs were cleared from the body, and gamma-PGA-Phe NPs were safe and effective vaccine carriers. (C) 2013 Elsevier Ltd. All rights reserved.

A silicon photomultiplier (Si-PM) is a promising photodetector for high resolution PET systems due to its small channel size and high gain. Using Si-PMs, it will be possible to develop a high resolution imaging systems. For this purpose, we developed a small field-of-view (FOV) ultrahigh-resolution Si-PM-based dual-head coincidence imaging system for small animals and plant research. A new scintillator, Ce doped Gd3Al12Ga3O12 (GAGG), was selected because of its high light output and its emission wavelength matched with the Si-PM arrays and contained no radioactivity. Each coincidence imaging block detector consists of 0.5 x 0.5 x 5 mm(3) GAGG pixels combined with a 0.1-mm thick reflector to form a 20 x 17 matrix that was optically coupled to a Si-PM array (Hamamatsu MPPC S11064-050P) with a 1.5-mm thick light guide. The GAGG block size was 12.0 x 10.2 mm(2). Two GAGG block detectors were positioned face to face and set on a flexible arm based detector stand. All 0.5 mm GAGG pixels in the block detectors were clearly resolved in the 2-dimensional position histogram. The energy resolution was 14.4% FWHM for the Cs-137 gamma ray. The spatial resolution was 0.7 mm FWHM measured using a 0.25 mm diameter Na-22 point source. Small animal and plant images were successfully obtained. We conclude that our developed ultrahigh-resolution Si-PM-based dual-head coincidence imaging system is promising for small animal and plant imaging research. (C) 2012 Elsevier B.V. All rights reserved.

Positron emission tomography (PET) with O-15 tracers provides essential information in patients with cerebral vascular disorders, such as cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO2). However, most of techniques require an additional (CO)-O-15 scan for compensating cerebral blood volume (CBV). We aimed to establish a technique to calculate all functional images only from a single dynamic PET scan, without losing accuracy or statistical certainties. The technique was an extension of previous dual-tracer autoradiography (DARG) approach, but based on the basis function method (DBFM), thus estimating all functional parametric images from a single session of dynamic scan acquired during the sequential administration of (H2O)-O-15 and O-15(2). Validity was tested on six monkeys by comparing global OEF by PET with those by arteriovenous blood sampling, and tested feasibility on young healthy subjects. The mean DBFM-derived global OEF was 0.57 +/- 0.06 in monkeys, in an agreement with that by the arteriovenous method (0.54 +/- 0.06). Image quality was similar and no significant differences were seen from DARG; 3.57%+/- 6.44% and 3.84%+/- 3.42% for CBF, and -2.79%+/- 11.2% and -6.68%+/- 10.5% for CMRO2. A simulation study demonstrated similar error propagation between DBFM and DARG. The DBFM method enables accurate assessment of CBF and CMRO2 without additional CBV scan within significantly shortened examination period, in clinical settings. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 440-448; doi: 10.1038/jcbfm.2012.188; published online 12 December 2012

PET with O-15 gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in humans. However, several technical difficulties limit its use in experiments on small animals. Herein, we describe the application of the O-15 gas steady-state inhalation method for normal anesthetized rats. Methods: Eight normal male Sprague-Dawley rats (mean body weight +/- SD, 268 +/- 14 g) under anesthesia were investigated by O-15-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm(3); frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with O-15-CO2 and O-15-O-2 gases delivered through the radioactive gas stabilizer. CBV was measured by O-15-CO gas inhalation and corrected for the intravascular hemoglobinbound O-15-O-2. Arterial blood sampling was performed during each study to measure the radioactivity of the whole blood and plasma. MR image was performed with the same acrylic animal holder immediately after the PET. Regions of interest were placed on the whole brain of the PET images with reference to the semiautomatically coregistered PET/MR fused images. Results: The data acquisition time for the whole PET experiment in each rat was 73.3 +/- 5.8 (range, 68-85) min. In both the O-15-CO2 and the O-15-O-2 studies, the radioactivity count of the brain reached a steady state by approximately 10 min after the start of continuous inhalation of the gas. The quantitative PET data of the whole brain were as follows: CBF, 32.3 +/- 4.5 mL/100 mL/min; CMRO2, 3.23 +/- 0.42 mL/100 mL/min; OEF, 64.6% +/- 9.1%; and CBV, 5.05 +/- 0.45 mL/100 mL. Conclusion: Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO2 using the original steady-state inhalation method of O-15-CO2 and O-15-O-2 gases and measurement of CBV using the O-15-CO gas inhalation method in the brain of normal anesthetized rats.

Background: Neurodegenerative diseases including Parkinson's and Alzheimer's diseases progress slowly and steadily over years or decades. They show significant between-subject variation in progress and clinical symptoms, which makes it difficult to predict the course of long-term disease progression with or without treatments. Recent technical advances in biomarkers have facilitated earlier, preclinical diagnoses of neurodegeneration by measuring or imaging molecules linked to pathogenesis. However, there is no established "biomarker model" by which one can quantitatively predict the progress of neurodegeneration. Here, we show predictability of a model with risk-based kinetics of neurodegeneration, whereby neurodegeneration proceeds as probabilistic events depending on the risk. Results: We used five experimental glaucomatous animals, known for causality between the increased intraocular pressure (IOP) and neurodegeneration of visual pathways, and repeatedly measured IOP as well as white matter integrity by diffusion tensor imaging (DTI) as a biomarker of axonal degeneration. The IOP in the glaucomatous eye was significantly increased than in normal and was varied across time and animals thus we tested whether this measurement is useful to predict kinetics of the integrity. Among four kinds of models of neurodegeneration, constant-rate, constant-risk, variable-risk and heterogeneity models, goodness of fit of the model and F-test for model selection showed that the time course of optic nerve integrity was best explained by the variable-risk model, wherein neurodegeneration kinetics is expressed in an exponential function across cumulative risk based on measured IOP. The heterogeneity model with stretched exponential decay function also fit well to the data, but without statistical superiority to the variable-risk model. The variable-risk model also predicted the number of viable axons in the optic nerve, as assessed by immunohistochemistry, which was also confirmed to be correlated with the pre-mortem integrity of the optic nerve. In addition, the variable-risk model identified the disintegrity in the higher-order visual pathways, known to underlie the transsynaptic degeneration in this disease. Conclusions: These findings indicate that the variable-risk model, using a risk-related biomarker, could predict the spatiotemporal progression of neurodegeneration. This model, virtually equivalent to survival analysis, may allow us to estimate possible effect of neuroprotection in delaying progress of neurodegeneration. © 2013 Hayashi et al licensee BioMed Central Ltd.

Background: [C-11] methionine (MET) has been used to monitor amino acid metabolism in tumors, the pancreas, liver, and myocardium. The aim of the present study was to standardize [C-11] MET positron emission tomography (PET) by optimizing the timing of initiation of the scan and applying correction to the plasma concentrations of neutral amino acids (NAAs), where necessary. Methods: Sequential whole-body MET PET/computed tomography (CT) was performed in 11 normal adults after they had fasted for at least 4 h. After whole-body CT for attenuation correction and intravenous bolus injection of MET, the subjects were scanned from the parietal to the groin. The scanning was repeated six to seven times. Decay of radioactivity during the PET scan was corrected to the time of initiation of the first scan. The standardized uptake values (SUVs) were evaluated in various organs by setting regions of interest on the tomographic images. Plasma concentrations of NAAs were examined in relation to the SUV values. Results: The SUVs in the pancreas reached their plateau from 6.5 to 11 min after the MET injection, and in the brain, lung, and myocardium, they reached their plateau from 19.6 to 24.1 min. The MET uptake in the spleen and kidney peaked early after the injection and steadily decreased thereafter. The SUVs in the liver and stomach wall rapidly increased during the first 0 to 4.5 min and gradually elevated thereafter during the scan period. Urinary radioactivity in the bladder reached its plateau from 26.1 to 30.6 min after the MET injection. There were no correlations between the plasma concentrations of NAAs and the maximal SUV in any organs. Conclusions: The present study revealed the times taken to reach the plateau of MET uptake in various important organs, and little effects of the plasma neutral amino acid concentrations on the SUVs in PET studies conducted after the patients had fasted for at least 4 h. In the MET PET study, 4 h fasting period before MET administration and the scan initiation 20 min after MET administration provide the SUV values independent of scan initiation time and the plasma neutral amino acid concentrations.

A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson's disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [C-11]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson's disease.

Purpose: Recently, photomultiplier tubes (PMTs) and position sensitive PMTs (PSPMTs) with higher quantum efficiencies (HQE) have been developed. However, it remains unclear whether they actually improve such performances as the energy and spatial resolution for PET and SPECT detectors. Methods: The authors evaluated the quantum efficiencies (QEs) for PMTs and PSPMTs and measured the energy resolution of a 3-in. round HQE PMT combined with various scintillators and compared the results with a conventional normal quantum efficiency (NQE) PMT of the same type. The authors also measured the position and energy performance of a 2-in. square HQE PSPMT combined with scintillator blocks and compared them with a NQE PSPMT of the same size. Results: The energy resolution of the 3-in. round HQE PMT showed higher energy resolution than the NQE with all scintillators. The improvement of the energy resolution was smaller, for all measurements, than the expected value from the quantum efficiency of the PMT but was higher for the scintillators with smaller light outputs. The energy and position performance of the HQE PSPMT based block detectors showed higher position and energy performance than those with NQE. Conclusions: From these results, the authors conclude that both HQE PMT and PSPMT contribute to improve the energy and position performance for PET and SPECT detectors. Significant performance improvements will be expected in PET and SPECT systems by the use of the HQE PMTs or PSPMTs. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4760991]

Purpose: The simultaneous measurement of PET and magnetic resonance imaging (MRI) is an emerging field for molecular imaging research. Although optical fiber based PET/MRI systems have advantages on less interference between PET and MRI, there is a drawback in reducing the scintillation light due to the fiber. To reduce the problem, the authors newly developed flexible optical fiber bundle based block detectors and employed them for a high resolution integrated PET/MRI system. Methods: The flexible optical fiber bundle used 0.5 mm diameter, 80 cm long double clad fibers which have dual 12 mm x 24 mm rectangular inputs and a single 24 mm x 24 mm rectangular output. In the input surface, LGSO scintillators of 0.025 mol.% (decay time: similar to 31 ns: 0.9 mm x 1.3 mm x 5 mm) and 0.75 mol.% (decay time: similar to 46 ns: 0.9 mm x 1.3 mm x 6 mm) were optically coupled in depth direction to form depth-of-interaction detector, arranged in 11 x 13 matrix and optically coupled to the fiber bundle. The two inputs of the bundle are bent for 90 degrees, bound to one, and are optically coupled to a Hamamatsu 1-in. square position sensitive photomultiplier tube. Results: Light loss due to the fiber bundle could be reduced and the performance of the block detectors was improved. Eight optical fiber based block detectors (16 LGSO blocks) were arranged in a 56 mm diameter ring to form a PET system. Spatial resolution and sensitivity were 1.2 mm full-width at half-maximum and 1.2% at the central field-of-view, respectively. Sensitivity change was less than 1% for 2 degrees C temperature changes. This PET system was integrated with a 0.3 T permanent magnet MRI system which has 17 cm diameter hole at the yoke area for insertion of the PET detector ring. There was no observable interference between PET and MRI. Simultaneous imaging of PET and MRI was successfully performed for small animal studies. Conclusions: The authors confirmed that the developed high resolution PET/MRI system is promising for molecular imaging research. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4757911]

In clinical cardiac positron emission tomography using O-15-water, significant tracer accumulation is observed not only in the heart but also in the liver and lung, which are partially outside the field-of-view. In this work, we investigated the effects of scatter on quantitative myocardium blood flow (MBF) and perfusable tissue fraction (PTF) by a precise Monte Carlo simulation (Geant4) and a numerical human model. We assigned activities to the heart, liver, and lung of the human model with varying ratios of organ activities according to an experimental time activity curve and created dynamic sinograms. The sinogram data were reconstructed by filtered backprojection. By comparing a scatter-corrected image (SC) with a true image (TRUE), we evaluated the accuracy of the scatter correction. TRUE was reconstructed using a scatter-eliminated sinogram, which can be obtained only in simulations. A scatter-uncorrected image (W/O SC) and an attenuation-uncorrected image (W/O AC) were also constructed. Finally, we calculated MBF and PTF with a single tissue-compartment model for four types of images. As a result, scatter was corrected accurately, and MBFs derived from all types of images were consistent with the MBF obtained from TRUE. Meanwhile, the PTF of only the SC was in agreement with the PTF of TRUE. From the simulation results, we concluded that quantitative MBF is less affected by scatter and absorption in 3D-PET using O-15-water. However, scatter correction is essential for accurate PTF.

Introduction: Measurement of regional cerebral blood flow (rCBF) in rodents can provide knowledge of pathophysiology of the cerebral circulation, but generally requires blood sampling for analysis during positron emission tomography (PET). We therefore tested the feasibility of using an arteriovenous (AV) shunt in rats for less invasive blood analysis. Methods: Six anesthetized rats received [O-15]H2O and [O-15]CO PET scans with their femoral artery and vein connected by an AV shunt, the activity within which was measured with a germanium ortho-oxysilicate scintillation detector. The [O-15]H2O was intravenously injected either at a faster or slower injection rate, while animals were placed either with their head or heart centered in the gantry. The time activity curve (TAG) from the AV shunt was compared with that from the cardiac ventricle in PET image. The rCBF values were calculated by a nonlinear least-square method using the dispersion-corrected AV-shunt TAG as an input. Results: The AV-shunt TAG had higher signal-to-noise ratio, but also had delay and dispersion compared with the image-derived TAG. The delay time between the AV-shunt TAG and image-based TAG ranged from 11 to 21 s, while the dispersion was estimated to be similar to 5 s as a time constant of the dispersion model of exponential function, and both were properly corrected. In a steady-state condition of [O-15]CO PET, the blood activity concentration by AV-shunt TAG was also comparable in height with the image-based TAG corrected for partial volume. Whole-brain CBF values measured by [O-15]H2O were 0.37+/-0.04 (mean+/-S.D.) ml/g/min, partition coefficient was 0.73+/-0.04 ml/g, and the CBF varied in a linear relationship with partial pressure of carbon dioxide during each scan. Conclusions: The AV-shunt technique allows less invasive, quantitative and reproducible measurement of rCBF in [O-15]H2O PET studies in rats than direct blood sampling and radioassay. (C) 2012 Elsevier Inc. All rights reserved.

Patient movement has been considered an important source of errors in cardiac PET. This study was aimed at evaluating the effects of such movement on myocardial blood flow (MBF) and perfusable tissue fraction (PTF) measurements in intravenous O-15-water PET. Nineteen O-15-water scans were performed on ten healthy volunteers and three patients with severe cardiac dysfunction under resting conditions. Motions of subjects during scans were estimated by monitoring locations of markers on their chests using an optical motion-tracking device. Each sinogram of the dynamic emission frames was corrected for subject motion. Variation of regional MBF and PTF with and without the motion corrections was evaluated. In nine scans, motions during O-15-water scan (inter-frame (IF) motion) and misalignments relative to the transmission scan (inter-scan (IS) motion) larger than the spatial resolution of the PET scanner (4.0 mm) were both detected by the optical motion-tracking device. After correction for IF motions, MBF values changed from 0.845 +/- A 0.366 to 0.780 +/- A 0.360 mL/minute/g (P &lt; .05). In four scans with only IS motion detected, PTF values changed significantly from 0.465 +/- A 0.118 to 0.504 +/- A 0.087 g/mL (P &lt; .05), but no significant change was found in MBF values. This study demonstrates that IF motion during O-15-water scan at rest can be source of error in MBF measurement. Furthermore, estimated MBF is less sensitive than PTF values to misalignment between transmission and O-15-water emission scans.

The objective of this study was to evaluate a resolution recovery (RR) method using a variety of simulated human brain [C-11] raclopride positron emission tomography (PET) images. Simulated datasets of 15 numerical human phantoms were processed by a wavelet-based RR method using an anatomical prior. The anatomical prior was in the form of a hybrid segmented atlas, which combined an atlas for anatomical labelling and a PET image for functional labelling of each anatomical structure. We applied RR to both 60 min static and dynamic PET images. Recovery was quantified in 84 regions, comparing the typical 'true' value for the simulation, as obtained in normal subjects, simulated and RR PET images. The radioactivity concentration in the white matter, striatum and other cortical regions was successfully recovered for the 60 min static image of all 15 human phantoms; the dependence of the solution on accurate anatomical information was demonstrated by the difficulty of the technique to retrieve the subthalamic nuclei due to mismatch between the two atlases used for data simulation and recovery. Structural and functional synergy for resolution recovery (SFS-RR) improved quantification in the caudate and putamen, the main regions of interest, from-30.1% and-26.2% to-17.6% and-15.1%, respectively, for the 60 min static image and from-51.4% and-38.3% to-27.6% and-20.3% for the binding potential (BPND) image, respectively. The proposed methodology proved effective in the RR of small structures from brain [C-11] raclopride PET images. The improvement is consistent across the anatomical variability of a simulated population as long as accurate anatomical segmentations are provided.

Gastrointestinal stromal tumors (GISTs) and malignant lymphomas (MLs) in the abdomen are often observed as tumors of unknown origin on F-18 FDG PET/CT. The purpose of this study was to evaluate the intratumoral metabolic heterogeneity of F-18 FDG uptake on PET to determine if it might be helpful to discriminate between these tumors. The F-18 FDG PET/CT findings of 21 large abdominal tumors were retrospectively evaluated (9 GISTs and 12 MLs). Intratumoral heterogeneity was evaluated by visual scoring (visual score: 0, homogeneous; 1, slightly heterogeneous; 2, moderately heterogeneous; 3, highly heterogeneous) and by the cumulative standardized uptake value (SUV) histograms on transaxial PET images at the maximal cross-sectional tumor diameter. Percent tumor areas above a threshold from 0 to 100% of the maximum SUV were plotted and the area under curve of the cumulative SUV histograms (AUC-CSH) was used as a heterogeneity index, where lower values corresponded with increased heterogeneity. Correlation between the visual score and the AUC-CSH was investigated by the Spearman's rank test. GISTs exhibited heterogeneous uptake of F-18 FDG, whereas MLs showed rather homogeneous uptake on visual analysis (visual score: 2.67 +/- A 0.50 and 0.58 +/- A 0.79, respectively; p &lt; 0.001). The AUC-CSH was significantly lower for the GISTs than for the MLs (0.41 +/- A 0.14 and 0.64 +/- A 0.08, respectively; p &lt; 0.001). Significant correlations were observed between the visual score and the AUC-CSH (rho = -0.866, p &lt; 0.001). GISTs exhibited significantly heterogeneous intratumoral tracer uptake as compared with the MLs. Evaluation of the intratumoral heterogeneity of F-18 FDG uptake may help in the discrimination between these tumors.

Purpose: In small animal imaging using a single photon emitting radionuclide, a high resolution gamma camera is required. Recently, position sensitive photomultiplier tubes (PSPMTs) with high quantum efficiency have been developed. By combining these with nonhygroscopic scintillators with a relatively low light output, a high resolution gamma camera can become useful for low energy gamma photons. Therefore, the authors developed a gamma camera by combining a pixelated Ce-doped Gd2SiO5 (GSO) block with a high quantum efficiency PSPMT. Methods: GSO was selected for the scintillator, because it is not hygroscopic and does not contain any natural radioactivity. An array of 1.9 mm x 1.9 mm x 7 mm individual GSO crystal elements was constructed. These GSOs were combined with a 0.1-mm thick reflector to form a 22 x 22 matrix and optically coupled to a high quantum efficiency PSPMT (H8500C-100 MOD8). The GSO gamma camera was encased in a tungsten gamma-ray shield with tungsten pixelated parallel hole collimator, and the basic performance was measured for Co-57 gamma photons (122 keV). Results: In a two-dimensional position histogram, all pixels were clearly resolved. The energy resolution was similar to 15% FWHM. With the 20-mm thick tungsten pixelated collimator, the spatial resolution was 4.4-mm FWHM 40 mm from the collimator surface, and the sensitivity was similar to 0.05%. Phantom and small animal images were successfully obtained with our developed gamma camera. Conclusions: These results confirmed that the developed pixelated GSO gamma camera has potential as an effective instrument for low energy gamma photon imaging. (C) 2012 American Association of Physicists in Medicine. [DOI: 10.1118/1.3673774]

The purpose of this study was the evaluation of a wavelet-based resolution recovery (RR) method, named structural and functional synergy for RR (SFS-RR), for a variety of simulated human brain [ 11C]raclopride PET images. Simulated datasets of 15 human phantoms were processed by SFS-RR using an anatomical prior. This anatomical information was in the form of a hybrid segmented-atlas, which combines an MRI for anatomical labelling and a PET image for functional labelling of each anatomical structure. First, the relationship between the FWHM of the original the PET image and its resolution recovered version was investigated. Then quantitative evaluation was performed by comparing caudate, putamen and cerebellum regions of the true image simulated PET image and RR image. The spatial resolution of the original PET image effected on how accurately SFS-RR recovers the image counts in striatum regions. The resolution in striatum, and cerebellum regions was successfully recovered for all the 15 human phantoms. The proposed methodology proved effective in the resolution recovery of small structures of brain [ 11C]raclopride PET images. The improvement was consistent across the anatomical variability of a simulated population, provided accurate anatomical segmentations are available. © 2011 IEEE.

We have designed the concept of practical high spatial-resolution SPECT for human brain. This study suggested combination PSPMTs with full-digital circuit can achieve detector intrinsic spatial resolution less than 2 mm. Image reconstruction software will compensate decrease of sensitivity due to collimator for high resolution. This system is expected to have the system resolution of 3-4 mm and the sensitivity higher than that in conventional clinical SPECT system. © 2011 IEEE.

In quantitative measurements of small animal PET studies, blood sampling is limited due to the small amounts of blood such animals can provide. In addition, injection doses are quite limited. In this situation, a high-sensitivity well counter would be useful for reducing the amount of the blood sample needed from small animals. Bismuth germinate (BGO) has a high stopping power for high-energy gamma rays compared to NaI(Tl), which is commonly used for conventional well counters. We have developed a BGO well counter and have tested it for blood-sampling measurements in small animals. The BGO well counter uses a square BGO block (59 × 59 × 50 mm) with a square open space (27 × 27 × 34 mm) in the center of the block. The BGO block was optically coupled to a 59-mm square-shaped photomultiplier tube (PMT). Signals from the PMT were digitally processed for the integration and energy window setting. The results showed that the energy spectrum of the BGO well counter measured with a Na-22 point source provided counts that were about 6 times higher for a 1022-keV (511 keV × 2) gamma peak than the spectrum of a 2-in. NaI(Tl) well counter. The relative sensitivity of the developed BGO well counter was 3.4 times higher than that of a NaI(Tl) well counter. The time activity curve of arterial blood was obtained successfully with the BGO well counter for a F-18-FDG study on rat. The BGO well counter will contribute to reducing the amount of sampled blood and to improving the throughput of quantitative measurements in small animal PET studies.

The silicon photomultiplier (Si-PM) is a promising photo-detector for PET for use in magnetic resonance imaging (MRI) systems because it has high gain and is insensitive to static magnetic fields. Recently we developed a Si-PM-based depth-of-interaction PET system for small animals and performed simultaneous measurements by combining the Si-PM-based PET and the 0.15 T permanent MRI to test the interferences between the Si-PM-based PET and an MRI. When the Si-PM was inside the MRI and installed around the radio frequency (RF) coil of the MRI, significant noise from the RF sequence of the MRI was observed in the analog signals of the PET detectors. However, we did not observe any artifacts in the PET images; fluctuation increased in the count rate of the Si-PM-based PET system. On the MRI side, there was significant degradation of the signal-to-noise ratio (S/N) in the MRI images compared with those without PET. By applying noise reduction procedures, the degradation of the S/N was reduced. With this condition, simultaneous measurements of a rat brain using a Si-PM-based PET and an MRI were made with some degradation in the MRI images. We conclude that simultaneous measurements are possible using Si-PM-based PET and MRI.

A silicon photomultiplier (Si-PM) is a promising photodetector for PET, especially for PET/MRI combined systems, due to its high gain, small size, and lower sensitivity to static magnetic fields. However, these properties are also promising for gamma camera systems for single-photon imaging. We developed an ultra-high-resolution Si-PM-based compact gamma camera system for small animals. Y(2)SiO(5):Ce (YSO) was selected as scintillators because of its high light output and no natural radioactivity. The gamma camera consists of 0.6 mm x 0.6 mm x 6 mm YSO pixels combined with a 0.1 mm thick reflector to form a 17 x 17 matrix that was optically coupled to a Si-PM array (Hamamatsu multi-pixel photon counter S11064-050P) with a 2 mm thick light guide. The YSO block size was 12 mm x 12 mm. The YSO gamma camera was encased in a 5 mm thick gamma shield, and a parallel hole collimator was mounted in front of the camera (0.5 mm hole, 0.7 mm separation, 5 mm thick). The two-dimensional distribution for the Co-57 gamma photons (122 keV) was almost resolved. The energy resolution was 24.4% full-width at half-maximum (FWHM) for the Co-57 gamma photons. The spatial resolution at 1.5 mm from the collimator surface was 1.25 mm FWHM measured using a 1 mm diameter Co-57 point source. Phantom and small animal images were successfully obtained. We conclude that a Si-PM-based gamma camera is promising for molecular imaging research.

Introduction: This study is intended to evaluate the feasibility of using a high-resolution pinhole SPECT system and iodine-123-N-isopropyl-4-iodoamphetamine ( 123I-IMP) for three-dimensional (3D) absolute quantitation of regional cerebral blood flow (rCBF) in mice. Methods: The pinhole SPECT system consists of a rotating stage and a pinhole collimator attached to a clinical gamma camera. The collimator's focal length is 251 mm. Phantom studies were performed to evaluate sensitivity and full-width half-maximum (FWHM) spatial resolution. The aperture-to-object distance was 15 mm. Six mice were studied. Cerebral infarctions were induced by ligating and disconnecting the distal portion of the left middle cerebral artery. Ex vivo SPECT studies were performed using harvested brains and skulls. The CBF volumetric image was computed using the standardized input function. Results: Excellent spatial resolution of 0.9-mm FWHM and uniform sensitivity throughout the 3D volume were demonstrated in the phantom experiments. The CBF images showed a defect in the infarcted areas and a reduction of CBF values in the infarcted region as compared with the control region. Conclusions: This study demonstrated the feasibility of the 3D quantitation of rCBF in mice using a high-resolution pinhole SPECT system and 123I-IMP. © 2011 Elsevier Inc.

The silicon photomultiplier (Si-PM) is a promising photodetector for a high-resolution PET scanner due to its small size, high gain and lower sensitivity to magnetic fields. There are several commercially available Si-PM arrays with different pixel sizes and fill factors, and these parameters can affect the performance of a PET block detector read out by these devices. We compared the performance of block detectors using 4 x 4 Si-PM arrays with 25 mu m(Hamamatsu S11064-025P) and 50 mu m(S11064-050P) pixels combined with the same 15 x 15 matrix LGSO block made of 0.7 x 0.7 x 6 mm(3) scintillator pixels. Evaluated characteristics include photopeak linearity, energy resolution and positioning performance. Although the photopeak linearity and energy resolution are slightly better for the Si-PM with 25 mu m pixels, the position performance measured by the separation of the position histogram is significantly better for the Si-PM with 50 mu m pixels. We conclude that using the Si-PM with 50 mu m pixels will provide a better solution for the development of ultrahigh-resolution PET systems.

脳血管障害など様々な中枢神経変性疾患における活性型ミクログリアの関与が注目されている。18kDa translocator protein(TSPO)は、活性型ミクログリアにおいて高いレベルで発現することが明らかにされ、TSPOを標識した新規PETリガンドの開発が国内外で活発に進んでいる。このような新規PETリガンドを用いたミクログリアのイメージングは、今までの核医学的手法により検出できなかった病変の早期検出を可能にするのみならず、疾患の予後予測や治療効果の判定などにも有用な手段として期待されている。ミクログリアの活性制御に特化したTSPOイメージングに関して、脳血管障害への臨床応用に向けて行われている研究を紹介する。(著者抄録)

Quantitative interpretation of brain [F-18]FDOPA PET data has been made possible by several kinetic modeling approaches, which are based on different assumptions about complex [F-18] FDOPA metabolic pathways in brain tissue. Simple kinetic macro parameters are often utilized to quantitatively evaluate metabolic and physiological processes of interest, which may include DDC activity, vesicular storage, and catabolism from F-18-labeled dopamine to DOPAC and HVA. A macro parameter most sensitive to the changes of these processes would be potentially beneficial to identify impaired processes in a neurodegenerative disorder such as Parkinson&apos;s disease. The purpose of this study is a systematic comparison of several [F-18] FDOPA macro parameters in terms of sensitivities to process-specific changes in simulated time-activity curve (TAC) data of [F-18] FDOPA PET. We introduced a multiple-compartment kinetic model to simulate PET TACs with physiological changes in the dopamine pathway. TACs in the alteration of dopamine synthesis, storage, and metabolism were simulated with a plasma input function obtained by a non-human primate [F-18] FDOPA PET study. Kinetic macro parameters were calculated using three conventional linear approaches (Gjedde-Patlak, Logan, and Kumakura methods). For simulated changes in dopamine storage and metabolism, the slow clearance rate (k(loss)) as calculated by the Kumakura method showed the highest sensitivity to these changes. Although kloss performed well at typical ROI noise levels, there was large bias at high noise level. In contrast, for simulated changes in DDC activity it was found that K-i and V-T, estimated by Gjedde-Patlak and Logan method respectively, have better performance than k(loss). Synapse 65:751-762, 2011. (C) 2010Wiley-Liss, Inc.

The silicon-photomultiplier (Si-PM) is a promising photodetector, especially for integrated PET/MRI systems, due to its small size, high gain, and low sensitivity to static magnetic fields. The major problem using a Si-PM-based PET system within the MRI system is the interference between the PET and MRI units. We measured the interference by combining a Si-PM-based PET system with a permanent-magnet MRI system. When the RF signal-induced pulse height exceeded the lower energy threshold level of the PET system, interference between the Si-PM-based PET system and MRI system was detected. The prompt as well as the delayed coincidence count rates of the Si-PM-based PET system increased significantly. These noise counts produced severe artifacts on the reconstructed images of the Si-PM-based PET system. In terms of the effect of the Si-PM-based PET system on the MRI system, although no susceptibility artifact was observed on the MR images, electronic noise from the PET detector ring was detected by the RF coil and reduced the signal-to-noise ratio (S/N) of the MR images. The S/N degradation of the MR images was reduced when the distance between the RF coil and the Si-PM-based PET system was increased. We conclude that reducing the interference between the PET and MRI systems is essential for achieving the optimum performance of integrated Si-PM PET/MRI systems.

The silicon-photomultiplier (Si-PM) is a promising photodetector for the development of new PET systems due to its small size, high gain and relatively low sensitivity to the static magnetic field. One drawback of the Si-PM is that it has significant temperature-dependent gain that poses a problem for the stability of the Si-PM-based PET system. To reduce this problem, we developed and tested a temperature-dependent gain control system for the Si-PM-based PET system. The system consists of a thermometer, analog-to-digital converter, personal computer, digital-to-analog converter and variable gain amplifiers in the weight summing board of the PET system. Temperature characteristics of the Si-PM array are measured and the calculated correction factor is sent to the variable gain amplifier. Without this correction, the temperature-dependent peak channel shifts of the block detector were -55% from 20 degrees C to 35 degrees C. With the correction, the peak channel variations were corrected within +/- 8%. The coincidence count rate of the Si-PM-based PET system was measured using a Na-22 point source while monitoring the room temperature. Without the correction, the count rate inversely changed with the room temperature by 10% for 1.5 degrees C temperature changes. With the correction, the count rate variation was reduced to within 3.7%. These results indicate that the developed temperature-dependent gain control system can contribute to improving the stability of Si-PM-based PET systems.

Carbon kinetics into the fruit is an agricultural issue on the growth and development of the sink organs to be harvested. Particularly, photoassimilate translocation and distribution are important topics for understanding the mechanism. In the present work, carbon-11 11C labeled photoassimilate translocation into fruits of tomato has been imaged using carbon-11-labeled carbon dioxide and the positron emission tomography (PET). Dynamice PET data of gradual increasing of 11C activity and its distribution is acquired quantitatively in intact plant body. This indicates that the 3-D photoassimilate translocation into the fruits is imaged successfully and carbon kinetics is analyzable to understand the plant physiology and nutrition. © 2011 IEEE.

Positron emission tomography (PET) is an imaging technology used to visualize distribution of particular ligands inside living organisms. The ligand is labeled by a positron-emitting isotope, such as 11C15O13 N and 18F, and injected into subjects. By detecting γ-rays emitted from the ligand, in vivo biodistribution and kinetics of the ligand can be depicted with high sensitivity. By altering the target ligand for PET, one can see different distributions and time courses of the target. PET provides several biological and functional images inside the body, rather than simply an anatomical image. Therefore, PET can potentially detect biological changes that occur long before anatomical changes begin. PET has been widely used for neuroreceptor and neurotransmitter studies by tracing radioligands, which have selective affinity for a particular site. For example, the dopamine and serotonin receptors are highly related to brain disorders. By analyzing the pharmacokinetics of these ligands using PET, it is possible to noninvasively detect abnormalities in the brain. However, signals from PET contain many different types of information, and it is important to interpret the signals appropriately and choose the proper technique to analyze PET data. This chapter discusses several analytical methods for PET data. © 2011, IGI Global.

The purpose of this study was the evaluation of a wavelet-based resolution recovery (RR) method, named structural and functional synergy for RR (SFS-RR), for a variety of simulated human brain [C-11]raclopride PET images. Simulated datasets of 15 human phantoms were processed by SFS-RR using an anatomical prior. This anatomical information was in the form of a hybrid segmented-atlas, which combines an MRI for anatomical labelling and a PET image for functional labelling of each anatomical structure. First, the relationship between the FWHM of the original the PET image and its resolution recovered version was investigated. Then quantitative evaluation was performed by comparing caudate, putamen and cerebellum regions of the true image; simulated PET image; and RR image. The spatial resolution of the original PET image effected on how accurately SFS-RR recovers the image counts in striatum regions. The resolution in striatum, and cerebellum regions was successfully recovered for all the 15 human phantoms. The proposed methodology proved effective in the resolution recovery of small structures of brain [C-11]raclopride PET images. The improvement was consistent across the anatomical variability of a simulated population, provided accurate anatomical segmentations are available.

Positron emission tomography (PET) is a sensitive technique for functional and molecular imaging. In Japan, the incidence of cognitive disorders is increasing at an accelerated pace, partly due to the increasing size of the elderly population. Basic and clinical studies on dementia have become very important. In vivo detection of amyloid beta (Aβ) deposits could be useful for early diagnosis of Alzheimer&#039;s disease (AD). &quot;Aβ imaging&quot; by PET has been recognized as one of the most important methods for the early diagnosis of AD. Clinical PET studies have been conducted using several probes, such as [ 18 F]FDDNP, [ 11 C]SB-13 and [ 11 C]Pittsburgh compound-B ([ 11 C]PIB). [ 11 C]PIB is the most commonly used probe. In this chapter, a novel imaging probe, 2-[2-(2-dimethylaminothiazol-5-yl)-ethenyl] -6- [2-(fluoro)ethoxy] benzoxazole ([ 11 C]BF-227), is reported. To the authors&#039; knowledge, [ 11 C]BF-227 is the first Aβ imaging probe to be used in Japan. The purpose of this chapter is to examine methods for quantitative analysis of Aβ deposition in the human brain using PET and [ 11 C]BF-227. Six AD patients and six healthy control subjects were used in the present study. Dynamic PET images were obtained over 60 min. Blood samples were obtained from the radial arteries. The results were analyzed using Logan graphical analysis and full kinetic analysis. A significantly higher distribution volume ratio (DVR) value was observed in AD patients in cortical regions, e.g., the cingulate, frontal, temporal, parietal and occipital regions, than in control subjects. Satisfactory correlation of these values to the semiquantitative standardized uptake values (SUV) was obtained. These findings suggest that [ 11 C]BF-227 is a promising PET probe for clinical evaluation of early Aβ deposition in AD patients. © 2011, IGI Global.

SPECT can provide valuable diagnostic and treatment response information in large-scale multicenter clinical trials. However, SPECT has been limited in providing consistent quantitative functional parametric values across the centers, largely because of a lack of standardized procedures to correct for attenuation and scatter. Recently, a novel software package has been developed to reconstruct quantitative SPECT images and assess cerebral blood flow (CBF) at rest and after acetazolamide challenge from a single SPECT session. This study was aimed at validating this technique at different institutions with a variety of SPECT devices and imaging protocols. Methods: Twelve participating institutions obtained a series of SPECT scans on physical phantoms and clinical patients. The phantom experiments included the assessment of septal penetration for each collimator used and of the accuracy of the reconstructed images. Clinical studies were divided into 3 protocols, including intrainstitutional reproducibility, a comparison with PET, and rest-rest study consistency. The results from 46 successful studies were analyzed. Results: Activity concentration estimation (Bq/mL) in the reconstructed SPECT images of a uniform cylindric phantom showed an interinstitution variation of +/- 5.1%, with a systematic underestimation of concentration by 12.5%. CBF values were reproducible both at rest and after acetazolamide on the basis of repeated studies in the same patient (mean +/- SD difference, -0.4 +/- 5.2 mL/min/100 g, n = 44). CBF values were also consistent with those determined using PET (-6.1 +/- 5.1 mL/min/100 g, n = 6). Conclusion: This study demonstrates that SPECT can quantitatively provide physiologic functional images of rest and acetazolamide challenge CBF, using a quantitative reconstruction software package.

A Geiger-mode avalanche photodiode (Si-PM) is a promising photodetector for PET, especially for use in a magnetic resonance imaging (MRI) system, because it has high gain and is less sensitive to a static magnetic field. We developed a Si-PM-based depth-of-interaction (DOI) PET system for small animals. Hamamatsu 4 x 4 Si-PM arrays (S11065-025P) were used for its detector blocks. Two types of LGSO scintillator of 0.75 mol% Ce (decay time: similar to 45 ns; 1.1 mm x 1.2 mm x 5 mm) and 0.025 mol% Ce (decay time: similar to 31 ns; 1.1 mm x 1.2 mm x 6 mm) were optically coupled in the DOI direction to form a DOI detector, arranged in a 11 x 9 matrix, and optically coupled to the Si-PM array. Pulse shape analysis was used for the DOI detection of these two types of LGSOs. Sixteen detector blocks were arranged in a 68 mm diameter ring to form the PET system. Spatial resolution was 1.6 mm FWHM and sensitivity was 0.6% at the center of the field of view. High-resolution mouse and rat images were successfully obtained using the PET system. We confirmed that the developed Si-PM-based PET system is promising for molecular imaging research.

Based on their differentiation ability, bone marrow stromal cells (MSCs) are a good source for cell therapy. Using a cynomolgus monkey peripheral nervous system injury model, we examined the safety and efficacy of Schwann cells induced from MSCs as a source for auto-cell transplantation therapy in nerve injury. Serial treatment of monkey MSCs with reducing agents and cytokines induced their differentiation into cells with Schwann cell properties at a very high ratio. Expression of Schwann cell markers was confirmed by both immunocytochemistry and reverse transcription-polymerase chain reaction. Induced Schwann cells were used for auto-cell transplantation into the median nerve and followed-up for 1 year. No abnormalities were observed in general conditions. Ki67-immunostaining revealed no sign of massive proliferation inside the grafted tube. Furthermore, (18)F-fluorodeoxygluocose-positron emission tomography scanning demonstrated no abnormal accumulation of radioactivity except in regions with expected physiologic accumulation. Restoration of the transplanted nerve was corroborated by behavior analysis, electrophysiology and histological evaluation. Our results suggest that auto-cell transplantation therapy using MSC-derived Schwann cells is safe and effective for accelerating the regeneration of transected axons and for functional recovery of injured nerves. The practical advantages of MSCs are expected to make this system applicable for spinal cord injury and other neurotrauma or myelin disorders where the acceleration of regeneration is expected to enhance functional recovery. (C) 2010 Elsevier Inc. All rights reserved.

Purpose Cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of O-2 (CMRO2) can be quantified by PET with the administration of (H2O)-O-15 and O-15(2). Recently, a shortening in the duration of these measurements was achieved by the sequential administration of dual tracers of O-15(2) and (H2O)-O-15 with PET acquisition and integration method (DARG method). A transmission scan is generally required for correcting photon attenuation in advance of PET scan. Although the DARG method can shorten the total study duration to around 30 min, the transmission scan duration has not been optimized and has possibility to shorten its duration. Our aim of this study was to determine the optimal duration for the transmission scan. We introduced &apos;N-index&apos;, which estimates the noise level on an image obtained by subtracting two statistically independent and physiologically equivalent images. The relationship between noise on functional images and duration of the transmission scan was investigated by N-index. Methods We performed phantom studies to test whether the N-index reflects the pixel noise in a PET image. We also estimated the noise level by the N-index on CBF, OEF and CMRO2 images from DARG method in clinical patients, and investigated an optimal true count of the transmission scan. Results We found tight correlation between pixel noise and N-index in the phantom study. By investigating relationship between the transmission scan duration and N-index value for the functional images by DARG method, we revealed that the transmission data with true counts of more than 40 Mcounts results in CBF, OEF, and CMRO2 images of reasonable quantitative accuracy and quality. Conclusion The present study suggests that further shortening of DARG measurement is possible by abridging the transmission scan. The N-index could be used to determine the optimal measurement condition when examining the quality of image.

Positron emission tomography (PET) with [C-11]raclopride has been used to investigate the density (B-max) and affinity (K-d) of dopamine D-2 receptors related to several neurological and psychiatric disorders. However, in assessing the B-max and K-d, multiple PET scans are necessary under variable specific activities of administered [C-11]raclopride, resulting in a long study period and unexpected physiological variations. In this paper, we have developed a method of multiple-injection graphical analysis (MI-GA) that provides the B-max and K-d values from a single PET scan with three sequential injections of [C-11]raclopride, and we validated the proposed method by performing numerous simulations and PET studies on monkeys. In the simulations, the three-injection protocol was designed according to prior knowledge of the receptor kinetics, and the errors of B-max and K-d estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of B-max and K-d, despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the B-max and K-d of diseased or normal striatum in a 150 mins scan with the three-injection protocol of [C-11]raclopride. Estimated B-max and K-d values of D-2 receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 663-673; doi: 10.1038/jcbfm.2009.239; published online 11 November 2009

Patlak analysis, which estimates the net FDOPA influx constant (&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt;) by linear regression of data acquired from [&lt;sup&gt;18&lt;/sup&gt;F] FDOPA PET study, is widely employed in the diagnosis of neurological disorder, such as Parkinson&#039;s disease. In &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; estimation by Patlak analysis, it is assumed that the metabolites of radioligand do not diffuse out of the tissue during PET scan. However, [&lt;sup&gt;18&lt;/sup&gt;F] F-Dopamine, synthesized from [&lt;sup&gt;18&lt;/sup&gt;F] FDOPA, is rapidly metabolized and its metabolites diffuse from the tissue. We aimed at the evaluation of the effect of dopamine metabolism and the clearance of its metabolites on &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; estimated by Patlak analysis. For this purpose, we developed a model describing the detailed pathway of dopamine kinetics in the striatum, and a standard time-activity curve (TAC) was generated based on this model and [&lt;sup&gt;18&lt;/sup&gt;F] FDOPA PET data of a monkey. And TACs in case of altering the dopamine metabolism or the clearance of its metabolites were simulated. Then, we evaluated &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; values estimated by Patlak analysis for these simulated TACs. &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; was increased when the dopamine metabolism to DOPAC (&lt;i&gt;k&lt;/i&gt;&lt;sub&gt;9&lt;/sub&gt;&lt;sup&gt;dopac&lt;/sup&gt;) and the clearance of DOPAC and HVA (&lt;i&gt;k&lt;/i&gt;&lt;sub&gt;11&lt;/sub&gt;&lt;sup&gt;dopac&lt;/sup&gt;, &lt;i&gt;k&lt;/i&gt;&lt;sub&gt;11&lt;/sub&gt;&lt;sup&gt;hva&lt;/sup&gt;) were altered. The results suggest that &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; could be biased by the influence of the metabolism of dopamine and clearance of its metabolites. Therefore, it is important to consider these biases in the interpretation of &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; value estimated Patlak analysis.

ドーパミンの代謝経路、特にDOPACおよびHVAへの代謝について詳細に記述したコンパーメントモデルを新たに構築し、加齢研究およびパーキンソン病等の神経疾患の臨床診断に用いられる取り込み定数Kiにドーパミンの代謝や代謝産物の組織外への流出が及ぼす影響について検討した。シミュレーションモデルに基づいてドーパミンの代謝および代謝産物の組織外への流出が変化した時の放射能時間曲線(TAC)をシミュレーションした。その際にサルに対する[18F]FDOPA PET実験を取得したTACを模してシミュレーションしたTACを基準とし、基準に対してk9 dopac、k9 hva、k11 dopac、k11 hvaを変化させた時のTACを生成した。ドーパミンからDOPACへの代謝(k9 dopac)およびDOPAC(k11 dopac、k11 hva)を基準値に対して減少させた時にKiが大幅に増加した。また、k9 dopacを基準値に対して増加させた時も、Kiの減少がみられた。これらの結果よりKiがドーパミンの代謝やその代謝産物の影響を受けて変化することが示唆された。したがって、Patlak解析で得たKiを脳神経機能の評価や診断に用いる際にはドーパミンの代謝および流出の影響を考慮して結果を解釈すべきと思われた。

Although O-15-O-2 gas inhalation can provide a reliable and accurate myocardial metabolic rate for oxygen by PET, the spillover from gas volume in the lung distorts the images. Recently, we developed an injectable method in which blood takes up O-15-O-2 from an artificial lung, and this made it possible to estimate oxygen metabolism without the inhalation protocol. In the present study, we evaluated the effectiveness of the injectable O-15-O-2 system in porcine hearts. PET scans were performed after bolus injection and continuous infusion of injectable O-15-O-2 via a shunt between the femoral artery and the vein in normal pigs. The injection method was compared to the inhalation method. The oxygen extraction fraction (OEF) in the lateral walls of the heart was calculated by a compartmental model in view of the spillover and partial volume effect. A significant decrease of lung radioactivity in PET images was observed compared to the continuous inhalation of O-15-O-2 gas. Furthermore, the injectable O-15-O-2 system provides a measurement of OEF in lateral walls of the heart that is similar to the continuous-inhalation method (0.71 +/- 0.036 and 0.72 +/- 0.020 for the bolus-injection and continuous-infusion methods, respectively). These results indicate that injectable O-15-O-2 has the potential to evaluate myocardial oxygen metabolism.

近年,我々はコリメータ開口補正による解像度補正,吸収補正,モンテカルロ法に基づいた散乱線補正機構を搭載した画像再構成法を開発してきた.本研究では,^&lt;99m&gt;Tc溶液で満たされた一連のファントム実験を行い,本画像再構成法の定量精度を検証した.東芝製SPECT装置GCA7200Aを用いて,線線源ファントムによる空間解像度の評価,ピラミッドファントム,偏心リングファントムおよび脳ファントムによる定量性の評価を行った.実験の結果,本手法の吸収補正と散乱線補正の妥当性が確認できた.また,コリメータ開口補正は解像度を大きく改善しただけでなく,部分容積効果改善および統計雑音抑制効果もあり,大きな利点と考えられた.本手法は局所機能画像定量SPECTに貢献することが期待される.

Cardiac O-15-water PET studies provide an accurate quantitation of regional myocardial blood flow (rMBF). We developed a motion correction system using an optical motion-tracking device to detect a subject&apos;s global movement for cardiac study. PET studies were carried out on a cardiac phantom and a healthy volunteer at rest. The three-dimensional locations of the markers attached to the subjects during scans were measured using an optical motion-tracking system. In the phantom study, we performed a transmission scan and seven F-18 emission scans of a baseline and with artificial misalignment of shifts and rotations. The correlation coefficients between the baseline and the other images before and after the corrections for the misalignment were calculated. In the human study, we performed a O-15-water dynamic scan with a transmission and axially 30 mm-shifted transmission scans. Motion of the subject was estimated by the information from the system, and was corrected on each sinogram using attenuation maps realigned to dynamic frames. Reconstructed dynamic images were then realigned to the transmission data. We calculated rMBF values for nine segments and myocardial images from the emission images, which were reconstructed with the first attenuation map (reference) and with the misaligned attenuation map before and after our corrections. In the phantom study, the correlation coefficients were improved from 0.929 +/- A 0.022 to 0.987 +/- A 0.010 (mean +/- A SD) after the corrections. In the human study, the global and cyclic movements were detected. The cyclic movement due to respiration was smoothed by frame-averaging, and reasonable information of the global movement was obtained. The rMBF value (mean +/- A SD) was 0.94 +/- A 0.12 mL/min/g for the reference. The rMBF values using the misaligned attenuation map changed from 1.03 +/- A 0.21 to 0.93 +/- A 0.11 mL/min/g after the correction, and spurious defects in myocardial images were also recovered. Our technique provided reasonable information for correcting the global movement of the subject. It was shown that this system was applicable to detect and correct subject movement in cardiac PET studies at rest.

There are several medical imaging scanners and each modality has different aspect for visualizing inside of human body. By combining these images, diagnostic accuracy could be improved, and therefore, several attempts for multimodal image registration have been implemented. One popular approach is to use hybrid image scanners such as PET/CT and SPECT/CT. However, these hybrid scanners are expensive and not fully available. We developed multimodal image registration system with USB cameras, which is inexpensive and applicable to any combinations of existed conventional imaging scanners. The multiple USB cameras will determine the three dimensional positions of a patient while scanning. Using information of these positions and rigid body transformation, the acquired image is registered to the common coordinate which is shared with another scanner. For each scanner, reference marker is attached on gantry of the scanner. For observing the reference marker's position by the USB cameras, the location of the USB cameras can be arbitrary. In order to validate the system, we scanned a cardiac phantom with different positions by PET and MRI scanners. Using this system, images from PET and MRI were visually aligned, and good correlations between PET and MRI images were obtained after the registration. The results suggest this system can be inexpensively used for multimodal image registrations.

Purpose: Regular monitoring of PET scanner performance is mandatory to assure quality of acquired data. While extensive performance measurements include many scanner characteristics such as resolution, count rate, uniformity, sensitivity, and scatter fraction (SF), most daily QC protocols are limited to uniformity and sensitivity measurements. These measurements may be too insensitive to detect more subtle drifts in detector gains that could lead to reduced detection of primary and increased detection of scattered events. Current methods to measure SF, such as those prescribed by the NEMA protocols (SF-NEMA), however, require specially designed phantoms and are too cumbersome to be performed on a daily basis. Methods: In this study, a simple and versatile method to determine SF is described. This method (SF-DAILY) does not require additional measurements, making it suitable for daily QC. The method was validated for four different scanners by comparing results with those obtained with the NEMA 1994 protocol. Results: For all scanner types and acquisition modes, excellent agreement was found between SF-NEMA and SF-DAILY. Conclusions: The proposed method is a very practical and valuable addition to current daily QC protocols. In addition, the method can be used to accurately measure SF in phantoms with other dimensions than the NEMA phantom. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3213096]

For diagnosing patients with ischemic cerebrovascular disease, non-invasive count-based method with (15)O(2) and H (2) (15) O positron-emission tomography (PET) data is widely used to measure asymmetric increases in oxygen extraction fraction (OEF). For shortening study time, we have proposed dual-tracer autoradiographic (DARG) protocol in which (15)O(2) gas and C(15)O(2) gas are sequentially administrated within short period. In this paper, we evaluated feasibility of the non-invasive count-based method with the DARG protocol. Twenty-three patients [67.8 +/- A 9.9 (mean +/- A SD) years] with chronic unilateral brain infarction were examined by the use of measurements of asymmetric OEF elevation. As DARG protocol, (15)O(2) and C(15)O(2) gases were inhaled with 5-min interval and dynamic PET data were acquired for 8 min. Quantitative OEF (qOEF) image was computed with PET data and arterial input function. Ratio image of (15)O(2) and C(15)O(2) phases of PET data was computed as count-based OEF (cbOEF) image. The asymmetric indices (AI) of qOEF (qOEF-AI) and cbOEF (cbOEF-AI) were obtained from regions of interest symmetric placed on left and right sides of cerebral hemisphere. To optimize the summation time of PET data for the cbOEF image, qOEF and cbOEF images with various summation times were compared. Image quality of cbOEF image was better than that of qOEF image. The best correlation coefficient of 0.94 was obtained when the cbOEF image was calculated from 0 to 180 s of (15)O(2) summed image and 340 to 440 s of C(15)O(2) summed image. Using the appropriate summation time, we obtained the cbOEF image with good correlation with qOEF image, which suggests non-invasive cbOEF image can be used for evaluating the degree of misery perfusion in patients with chronic unilateral brain infarction. The count-based method with DARG protocol has a potential to dramatically reduce the examination time of (15)O PET study.

Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) are quantitatively measured with PET with (15)O gases. Kudomi et al. developed a dual tracer autoradiographic (DARG) protocol that enables the duration of a PET study to be shortened by sequentially administrating (15)O(2) and C(15)O(2) gases. In this protocol, before the sequential PET scan with (15)O(2) and C(15)O(2) gases ((15)O(2)-C(15)O(2) PET scan), a PET scan with C(15)O should be preceded to obtain CBV image. C(15)O has a high affinity for red blood cells and a very slow washout rate, and residual radioactivity from C(15)O might exist during a (15)O(2)-C(15)O(2) PET scan. As the current DARG method assumes no residual C(15)O radioactivity before scanning, we performed computer simulations to evaluate the influence of the residual C(15)O radioactivity on the accuracy of measured CBF and OEF values with DARG method and also proposed a subtraction technique to minimize the error due to the residual C(15)O radioactivity. In the simulation, normal and ischemic conditions were considered. The (15)O(2) and C(15)O(2) PET count curves with the residual C(15)O PET counts were generated by the arterial input function with the residual C(15)O radioactivity. The amounts of residual C(15)O radioactivity were varied by changing the interval between the C(15)O PET scan and (15)O(2)-C(15)O(2) PET scan, and the absolute inhaled radioactivity of the C(15)O gas. Using the simulated input functions and the PET counts, the CBF and OEF were computed by the DARG method. Furthermore, we evaluated a subtraction method that subtracts the influence of the C(15)O gas in the input function and PET counts. Our simulations revealed that the CBF and OEF values were underestimated by the residual C(15)O radioactivity. The magnitude of this underestimation depended on the amount of C(15)O radioactivity and the physiological conditions. This underestimation was corrected by the subtraction method. This study showed the influence of C(15)O radioactivity in DARG protocol, and the magnitude of the influence was affected by several factors, such as the radioactivity of C(15)O, and the physiological condition.

Cerebral metabolic rate of oxygen (CMRO2) can be assessed quantitatively using O-15(2) and positron emission tomography. Determining the arterial input function is considered critical with regards to the separation of the metabolic product of O-15(2) (RW) from a measured whole blood. A mathematical formula based on physiologic model has been proposed to predict RW. This study was intended to verify the adequacy of that model and a simplified procedure applying that model for wide range of species and physiologic conditions. The formula consists of four parameters, including of a production rate of RW (k) corresponding to the total body oxidative metabolism (BMRO2). Experiments were performed on 6 monkeys, 3 pigs, 12 rats, and 231 clinical patients, among which the monkeys were studied at varied physiologic conditions. The formula reproduced the observed RW. Greater k values were observed in smaller animals, whereas other parameters did not differ amongst species. The simulation showed CMRO2 sensitive only to k, but not to others, suggesting that validity of determination of only k from a single blood sample. Also, k was correlated with BMRO2, suggesting that k can be determined from BMRO2. The present model and simplified procedure can be used to assess CMRO2 for a wide range of conditions and species.

We developed the high resolution SPECT for the human brain. The SPECT has two kinds of detectors. One middle-size detector views whole a head. The other small detector which has extremely resolution (∼lmm) views localized region. These detectors are rotated simultaneously. The large detector consists of Nal(Tl) scintillator (15cmx20cm), 15 flat panel type multi-anode PMTs (H8500 Hamamatsu). The performance evaluation, spatial and energy resolution, has performed. The obtained spatial resolutions of X-direction and Y-direction are 3.6mm and 3.1mm(FWHM), respectively, and 10%@140keV (FWHM) of the energy resolution was obtained. On the other hand, the small detector for the regional field of view is under the development. We will use the LaBr3(Ce) as the scintillator which has large amount of scintillation lights lather than that of Nal(Tl). The performance of LaBr3(Ce) has estimated by the Monte Carlo simulation of scintillation lights after the comparing the result of the experiments of the middle-size detector with that of the simulation. In this simulation, many optical properties of materials are considered. Using this simulation, the influence of the scintillator thickness on the spatial resolution has investigated. Also, main contribution is given to spatial resolution has been investigated by changing some optical properties such as the amount of emission lights, the refractive index of optical coupling grease and the index of reflector in this simulations. The small detector will be used with a pin-hole collimator, therefore gamma-rays obliquely enter the detector. The spatial resolutions of oblique and parallel incident are also compared. ©2009 IEEE.

We developed the high resolution SPECT for the human brain. The SPECT has two kinds of detectors. One middle-size detector views whole a head. The other small detector which has extremely resolution (-lmm) views localized region. These detectors are rotated simultaneously. The large detector consists of Nal(Tl) scintillator (15cmx20cm), 15 flat panel type multi-anode PMTs (H8500 Hamamatsu). The performance evaluation, spatial and energy resolution, has performed. The obtained spatial resolutions of X-direction and Y-direction are 2.4mm and 2.1mm(FWHM), respectively, and 10%@140keV (FWHM) of the energy resolution was obtained. On the other hand, the small detector for the regional field of view is under the development. We will use the LaBr3(Ce) as the scintillator which has large amount of scintillation lights lather than that of Nal(Tl). The performance of LaBr3(Ce) has estimated by the Monte Carlo simulation of scintillation lights after the comparing the result of the experiments of the middle-size detector with that of the simulation. In this simulation, many optical properties of materials are considered. Using this simulation, the influence of the scintillator thickness on the spatial resolution has investigated. Also, main contribution is given to spatial resolution has been investigated by changing some optical properties such as the amount of emission lights, the refractive index of optical coupling grease and the index of reflector in this simulations. The small detector will be used with a pin-hole collimator, therefore gamma-rays obliquely enter the detector. The spatial resolutions of oblique and parallel incident are also compared. ©2009 IEEE.

We designed a concept of high resolution and quantitative SPECT for imaging a selected small region-ofinterest (ROI) of human brain. This system is aimed at achieving high resolution less than 1 mm and being applied for imaging neurons and evaluating drug delivery system. Pinhole or conebeam collimators are useful for high-resolution imaging of small ROI. However, when the ROI is smaller than the object, the projection data are truncated by radioisotope outside ROI. In the reconstructed image, the truncation causes the artifact and the overestimation of voxel value, which deceases quantitative accuracy of physiological functions. We are introducing the new truncation compensated 3D-OSEM (TC-3DOSEM) reconstruction method. The truncated data can be successfully reconstructed within ROI by fulfilling the condition that ROI contains a priori knowledge. In addition to small field-of-view (FOV) detector, we are introducing the parallel-hole collimator attached large FOV detector covering the entire brain, to acquire the non-truncated data and provide the priori knowledge in small ROI, even if the resolution of the detector is low. For imaging with high resolution, we are using LaBr3(Ce) scintilator with optically coupled to position-sensitive photomultiplier tube (H8500, Hamamatsu, Japan) as the detector. And also, for proof of our concept, we performed preliminary experiment using pinhole SPECT and brain phantom. The reconstruction ROI contained the region outside the brain, that is, zero count as the priori knowledge. The truncated data were reconstructed by TC-3DOSEM. The reconstructed image without artifact and overestimation was obtained with high resolution. This preliminary experiment suggested feasibility of high resolution and quantitative SPECT for imaging a selected small ROI of human brain. ©2009 IEEE.

We developed the high resolution SPECT for the human brain. The SPECT has two kinds of detectors. One middle-size detector views whole a head. The other small detector which has extremely resolution (similar to 1mm) views localized region. These detectors are rotated simultaneously. The large detector consists of NaI(Tl) scintillator (15cmx20cm), 15 flat panel type multi-anode PMTs (H8500 Hamamatsu). The performance evaluation, spatial and energy resolution, has performed. The obtained spatial resolutions of X-direction and Y-direction are 2.4mm and 2.1mm(FWHM), respectively, and 10%@140keV (FWHM) of the energy resolution was obtained. On the other hand, the small detector for the regional field of view is under the development. We will use the LaBr(3)(Ce) as the scintillator which has large amount of scintillation lights lather than that of NaI(Tl). The performance of LaBr(3)(Ce) has estimated by the Monte Carlo simulation of scintillation lights after the comparing the result of the experiments of the middle-size detector with that of the simulation. In this simulation, many optical properties of materials are considered. Using this simulation, the influence of the scintillator thickness on the spatial resolution has investigated. Also, main contribution is given to spatial resolution has been investigated by changing some optical properties such as the amount of emission lights, the refractive index of optical coupling grease and the index of reflector in this simulations. The small detector will be used with a pin-hole collimator, therefore gamma-rays obliquely enter the detector. The spatial resolutions of oblique and parallel incident are also compared.

We developed the high resolution SPECT for the human brain. The SPECT has two kinds of detectors. One middle-size detector views whole a head. The other small detector which has extremely resolution (similar to 1 mm) views localized region. These detectors are rotated simultaneously. The large detector consists of NaI(TI) scintillator (15cmx20cm), 15 flat panel type multi-anode PMTs (H8500 Hamamatsu). The performance evaluation, spatial and energy resolution, has performed. The obtained spatial resolutions of X-direction and Y-direction are 3.6mm and 3.1mm(FWHM), respectively, and 10%@140keV (FWHM) of the energy resolution was obtained. On the other hand, the small detector for the regional field of view is under the development. We will use the LaBr(3)(Ce) as the scintillator which has large amount of scintillation lights lather than that of NaI(TI). The performance of LaBr3(Ce) has estimated by the Monte Carlo simulation of scintillation lights after the comparing the result of the experiments of the middle-size detector with that of the simulation. In this simulation, many optical properties of materials are considered. Using this simulation, the influence of the scintillator thickness on the spatial resolution has investigated. Also, main contribution is given to spatial resolution has been investigated by changing some optical properties such as the amount of emission lights, the refractive index of optical coupling grease and the index of reflector in this simulations. The small detector will be used with a pin-hole collimator, therefore gamma-rays obliquely enter the detector. The spatial resolutions of oblique and parallel incident are also compared.

SPECT using compact high resolution detector or pinhole collimator allows to image physiological functions with high spatial resolution. However, when field-of-view (FOV) is smaller than the object, the projection data are truncated by radioisotope outside FOV. The truncation causes artifact and overestimation, which decreases quantitative accuracy. Recently Defrise et al proposed a new truncation-compensated reconstruction method, that is, the truncated data can be successfully reconstructed by fulfilling following conditions. First, FOV contains zero or background counts outside the object as known value. Second, reconstructed image space is large enough to contain the whole support of the object. They demonstrated their theory by 2D X-ray CT simulation. This study was aimed at evaluating clinical-SPECT usability of a reconstructed image of a selected small region-of-interest (ROI) with the above Defrise's method. This evaluation was performed by computer simulation with a numerical human brain phantom and a detector with 2-mm resolution, 48-mm FOV and a parallel collimator. The projection data were acquired including the area outside the brain. After adding Gaussian noise, the projection data were reconstructed by maximum likelihood expectation maximization (MLEM) method on the reconstruction matrix large enough to contain the whole support of the brain. This simulation showed that the truncation compensated reconstruction method could provide the image with high resolution and the counts almost equivalent to that of original image in the selected small ROI without the effect of truncation for human brain. In conclusion, this result suggests that a compact high resolution detector can be used for quantitatively reconstructing a selected small ROI with clinical SPECT camera. This technique can also use the pinhole collimator instead of the compact high resolution detector.

SPECT using compact high resolution detector or pinhole collimator allows to image physiological functions with high resolution. However, when region-of-interest (ROI) is smaller than the object, the projection data are truncated due to radioisotope outside ROI. The truncation causes artifact and overestimation, which decrease quantitative accuracy. In theory, to eliminate the artifact and the overestimation due to truncation, the untruncated data from another large field-of-view (FOV) detector can be used even if the detector has low resolution. This study was aimed at evaluating feasibility of combination of a small FOV high resolution detector and a large FOV low resolution detector in clinical circumstance. This evaluation was performed by computer simulation with a numerical torso phantom. We tested whether the image in a selected small ROI (in this case, ROI was heart) can be obtained with high resolution and without artifact and overestimation. The small FOV detector with high resolution was with 1.14-mm resolution, 80-mm FOV and parallel collimator. The whole of heart was included in this FOV, but the surrounding area was truncated. The large FOV detector with low resolution has 9-mm resolution, 360-mm FOV and parallel collimator like conventional clinical SPECT. The untruncated projections including the whole of thorax were acquired by this detector. Gaussian noises were added to all projection data. Data from the small detector were reconstructed by maximum likelihood expectation maximization (MLEM) as iterative method, on the reconstruction matrix large enough to contain the whole of thorax. The reconstructed image from the large FOV detector was used as an initial image in iterative reconstruction. The image obtained by our proposed method had high resolution and the counts almost equivalent to that of original image in the small ROI. In conclusion, this result suggests feasibility of the combination of two detectors with small and large FOV to quantitatively obtain high-resolution image of a selected small ROI with clinical SPECT.

This study evaluated the feasibility of imaging rat brains using a human whole-body 3-T magnetic resonance imaging (MRI) scanner with specially developed transmit-and-receive radiofrequency coils. The T1- and T 2-weighted images obtained showed reasonable contrast. Acquired contrast-free time-of-flight magnetic resonance angiography images clearly showed the cortical middle cerebral artery (MCA) branches, and interhemispheric differences could be observed. Dynamic susceptibility contrast MRI at 1.17 mm3 voxel resolution, performed three times following administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, 0.1 mmol/kg), demonstrated that the arterial input function (AIF) can be obtained from the MCA region, yielding cerebral blood flow (CBF), cerebral blood volume, and mean transit time (MTT) maps. The hypothalamus (HT) to parietal cortex (Pt) CBF ratio was 45.11 ± 2.85%, and the MTT was 1.29 ± 0.40 s in the Pt region and 2.32 ± 0.17 s in the HT region. A single dose of Gd-DTPA enabled the assessment of AIF within MCA territory and of quantitative CBF in rats. © 2008 Japanese Society of Radiological Technology and Japan Society of Medical Physics.

We designed a concept of high resolution and quantitative SPECT for imaging a selected small region-of-interest (ROI) of human brain. This system is aimed at achieving high resolution less than 1 mm and being applied for imaging neurons and evaluating drug delivery system. Pinhole or cone-beam collimators are useful for high-resolution imaging of small ROI. However, when the ROI is smaller than the object, the projection data are truncated by radioisotope outside ROI. In the reconstructed image, the truncation causes the artifact and the overestimation of voxel value, which deceases quantitative accuracy of physiological functions. We are introducing the new truncation compensated 3D-OSEM (TC-3DOSEM) reconstruction method. The truncated data can be successfully reconstructed within ROI by fulfilling the condition that ROI contains a priori knowledge. In addition to small field-of-view (FOV) detector, we are introducing the parallel-hole collimator attached large FOV detector covering the entire brain, to acquire the non-truncated data and provide the priori knowledge in small ROI, even if the resolution of the detector is low. For imaging with high resolution, we are using LaBr3(Ce) scintilator with optically coupled to position-sensitive photomultiplier tube (H8500, Hamamatsu, Japan) as the detector. And also, for proof of our concept, we performed preliminary experiment using pinhole SPECT and brain phantom. The reconstruction ROI contained the region outside the brain, that is, zero count as the priori knowledge. The truncated data were reconstructed by TC-3DOSEM. The reconstructed image without artifact and overestimation was obtained with high resolution. This preliminary experiment suggested feasibility of high resolution and quantitative SPECT for imaging a selected small ROI of human brain.

CYRIC Annual Report 2009

CYRIC Annual Report 2009

The aim of this study was to establish kinetic analysis of [5-(11)C-methoxyldonepezil ([(11)C]donepezil), which was developed for the in-vivo visualization of donepezil binding to acetylcholinesterase (AChE) using positron emission tomography (PET). Donepezil is an AChE inhibitor that is widely prescribed to ameliorate the cognitive impairment of patients with dementia. Six healthy subjects took part in a dynamic study involving a 60-min PET scan after intravenous injection of [(11)C]donepezil. The total distribution volume (tDV) of [(11)C]donepezil was quantified by compartmental kinetic analysis and Logan graphical analysis. A one-tissue compartment model (1TCM) and a two-tissue compartment model (2TCM) were applied in the kinetic analysis. Goodness of fit was assessed with chi(2) criterion and Akaike&apos;s Information Criterion (AIC). Compared with a 1TCM, goodness of fit was significantly improved by a 2TCM. The tDVs provided by Logan graphical analysis were slightly lower than those provided by a 2TCM. The rank order of the mean tDVs in 10 regions was in line with the AChE activity reported in a previous post-mortem study. Logan graphical analysis generated voxel-wise images of tDV, revealing the overall distribution pattern of AChE in individual brains. Significant correlation was observed between tDVs calculated with and without metabolite correction for plasma time-activity curves, indicating that metabolite correction could be omitted. In conclusion, this method enables quantitative analysis of AChE and direct investigation of the pharmacokinetics of donepezil in the human brain. (C) 2009 Elsevier Inc. All rights reserved.

Positron emission tomography (PET) with [C-11]raclopride is widely used to investigate temporal changes in the dopamine D-2 receptor system attributed to the dopamine release. The simplified reference tissue model (SRTM) can be used to determine the binding potential (BPND) value using the time-activity curve (TAC) of the reference region as input function. However, in assessing temporal changes in BPND using the SRTM, multiple [C-11]raclopride PET scans are required, and a second scan must be performed after the disappearance of the [C-11]raclopride administered in the first scan. In this study, we have developed an extended multiple-injection SRTM to estimate the BPND change, from a single PET scan with multiple injections of [C-11]raclopride, and we have validated this approach by performing numerous simulations and Studies on monkeys. In the computer simulations, TACs were generated for dual injections of [C-11]raclopride, in which binding conditions changed during the scans, and the BPND values before, and after, the second injection were estimated by the proposed method. As a result, the reduction in BPND was correlated, either with the integral of released dopamine, or with the administered mass of raclopride. This method was applied to studies on monkeys, and was capable of determining two identical BPND values when there were no changes in binding conditions. The BPND after the second injection decreased when binding conditions changed due to an increase in administered raclopride. An advantage of the proposed method is the shortened scan period for the quantitative assessment of the BPND change for neurotransmitter competition studies. (C) 2009 Elsevier Inc. All rights reserved.

Regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) can be estimated from C15O, H-2 15O, and 15O(2) tracers and positron emission tomography (PET) using an autoradiographic (ARG) method. Our objective in this study was to optimize the scan time for 15O(2) gas study for accurate estimation of OEF and CMRO2. We evaluated statistical noise in OEF by varying the scan time and error caused by the tissue heterogeneity in estimated OEF and CMRO2 using computer simulations. The characteristics of statistical noise were investigated by signal-to-noise (S/N) ratio from repeated tissue time activity curves with noise, which were generated using measured averaged arterial input function and assuming CBF = 20, 50, and 80 (ml/100 g per minute). Error caused by tissue heterogeneity was also investigated by estimated OEF and CMRO2 from tissue time activity curve with mixture of gray and white matter varying fraction of mixture. In the simulations, three conditions were assumed (i) CBF in gray and white matter (CBFg and CBFw) was 80 and 20, OEF in gray and white matter (E g and E w) was 0.4 and 0.3, (ii) CBFg and CBFw decreased by 50%, and E g and E w increased by 50% when compared with conditions (i) and (iii). CBFg and CBFw decreased by 80%, and E g and E w increased by 50% when compared with condition (i). The longer scan time produced the better S/N ratio of estimated OEF value from three CBF values (20, 50, and 80). Errors of estimated OEF for three conditions owing to tissue heterogeneity decreased, as scan time took longer. Meanwhile in the case of CMRO2, 3 min of scan time was desirable. The optimal scan time of 15O(2) inhalation study with the ARG method was concluded to be 3 min from taking into account for maintaining the S/N ratio and the quantification of accurate OEF and CMRO2.

Objective The quality of single-photon emission computed tomography (SPECT) imaging is hampered by attenuation, collimator blurring, and scatter. Correction for all of these three factors is required for accurate reconstruction, but unfortunately, reconstruction-based compensation often leads to clinically unacceptable long reconstruction times. Especially, efficient scatter correction has proved to be difficult to achieve. The objective of this article was to extend the well-known transmission-dependent convolution subtraction (TDCS) scatter-correction approach into a rapid reconstruction-based scatter-compensation method and to include it into a fast 3D reconstruction algorithm with attenuation and collimator-blurring corrections. Methods Ordered subsets expectation maximization algorithm with attenuation, collimator blurring, and accelerated transmission-dependent scatter compensation were implemented. The new reconstruction method was compared with TDCS-based scatter correction and with one other transmission-dependent scatter-correction method using Monte Carlo simulated projection data of (99m)Tc-ECD and (123)I-FP-CIT brain studies. Results The new reconstruction-based scatter compensation outperformed the other two scatter-correction methods in terms of quantitative accuracy and contrast measured with normalized mean-squared error, gray-to-white matter and striatum-to-background ratios, and also in visual quality. Highest accuracy was achieved when all the corrections (i.e., attenuation, collimator blurring, and scatter) were applied. Conclusions The developed 3D reconstruction algorithm with transmission-dependent scatter compensation is a promising alternative to accurate and efficient SPECT reconstruction.

Single proton emission computed tomography (SPECT) images are degraded by photon scatter making scatter compensation essential for accurate reconstruction. Reconstruction-based scatter compensation with Monte Carlo (MC) modelling of scatter shows promise for accurate scatter correction, but it is normally hampered by long computation times. The aim of this work was to accelerate the MC-based scatter compensation using coarse grid and intermittent scatter modelling. The acceleration methods were compared to un-accelerated implementation using MC-simulated projection data of the mathematical cardiac torso (MCAT) phantom modelling (99m)Tc uptake and clinical myocardial perfusion studies. The results showed that when combined the acceleration methods reduced the reconstruction time for 10 ordered subset expectation maximization (OS-EM) iterations from 56 to 11 min without a significant reduction in image quality indicating that the coarse grid and intermittent scatter modelling are suitable for MC-based scatter compensation in cardiac SPECT.

Tl-201 has been extensively used for myocardial perfusion and viability assessment. Unlike Tc-99m-labelled agents, such as Tc-99m-sestamibi and Tc-99m-tetrofosmine, the regional concentration of Tl-201 varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of Tl-201 using dynamic SPECT. Method Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of Tl-201 using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K (1)) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments. Results Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBFSPECT) correlated well with the MBF values obtained by the radio-labelled microspheres (MBFMS) (MBFSPECT=-0.067+1.042 MBFMS, p &lt; 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression. Conclusion Absolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using Tl-201 and dynamic SPECT.

SPECT using compact high resolution detector or pinhole collimator allows to image physiological functions with high resolution. However, when region-of-interest (ROI) is smaller than the object, the projection data are truncated due to radioisotope outside ROI. The truncation causes artifact and overestimation, which decrease quantitative accuracy. In theory, to eliminate the artifact and the overestimation due to truncation, the untruncated data from another large field-of-view (FOV) detector can be used even if the detector has low resolution. This study was aimed at evaluating feasibility of combination of a small FOV high resolution detector and a large FOV low resolution detector in clinical circumstance. This evaluation was performed by computer simulation with a numerical torso phantom. We tested whether the image in a selected small ROI (in this case, ROI was heart) can be obtained with high resolution and without artifact and overestimation. The small FOV detector with high resolution was with 1.14-mm resolution, 80-mm FOV and parallel collimator. The whole of heart was included in this FOV, but the surrounding area was truncated. The large FOV detector with low resolution has 9-mm resolution, 360-mm FOV and parallel collimator like conventional clinical SPECT. The untruncated projections including the whole of thorax were acquired by this detector. Gaussian noises were added to allprojection data. Data from the small detector were reconstructedby maximum likelihood expectation maximization (MLEM) as iterative method, on the reconstruction matrix large enough to contain the whole of thorax. The reconstructed image from the large FOV detector was used as an initial image in iterative reconstruction. The image obtained by our proposed method had high resolution and the counts almost equivalent to that of original image in the small ROI. In conclusion, this result suggests feasibility of the combination of two detectors with small and large FOV to quantitatively obtain high-resolution image of a selected small ROI with clinical SPECT. ©2008 IEEE.

SPECT using compact high resolution detector or pinhole collimator allows to image physiological functions with high spatial resolution. However, when field-of-view (FOV) is smaller than the object, the projection data are truncated by radioisotope outside FOV. The truncation causes artifact and overestimation, which decreases quantitative accuracy. Recently Defrise et al proposed a new truncation-compensated reconstruction method, that is, the truncated data can be successfully reconstructed by fulfilling following conditions. First, FOV contains zero or background counts outside the object as known value. Second, reconstructed image space is large enough to contain the whole support of the object. They demonstrated their theory by 2D X-ray CT simulation. This study was aimed at evaluating clinical-SPECT usability of a reconstructed image of a selected small region-of-interest (ROI) with the above Defrise's method. This evaluation was performed by computer simulation with a numerical human brain phantom and a detector with 2-mm resolution, 48-mm FOV and a parallel collimator. The projection data were acquired including the area outside the brain. After adding Gaussian noise, the projection data were reconstructed by maximum likelihood expectation maximization (MLEM) method on the reconstruction matrix large enough to contain the whole support of the brain. This simulation showed that the truncation compensated reconstruction method could provide the image with high resolution and the counts almost equivalent to that of original image in the selected small ROI without the effect of truncation for human brain. In conclusion, this result suggests that a compact high resolution detector can be used for quantitatively reconstructing a selected small ROI with clinical SPECT camera. This technique can also use the pinhole collimator instead of the compact high resolution detector. © 2008 IEEE.

CYRIC Annual Report 2008

Positron emission tomography dynamic studies have been performed to quantify several biomedical functions. In a quantitative analysis of these studies, kinetic parameters were estimated by mathematical methods, such as a nonlinear least-squares algorithm with compartmental model and graphical analysis. In this estimation, the uncertainty in the estimated kinetic parameters depends on the signal-to-noise ratio and quantitative analysis method. This review describes the reliability of parameter estimates for various analysis methods in reversible and irreversible models.

Background The resolution of a gamma camera is depth-dependent and worsens with increasing distance to the camera resulting in a loss of fine details in SPECT images. A common approach to reduce the effects of this resolution loss is to utilize body-contour acquisition orbits. Even though body-contour orbits can improve resolution of reconstructed images their effect on lesion detection is not well known. Objective To investigate whether body-contour orbits offer better defect detection performance than circular orbits in cardiac SPECT. Methods The mathematical cardiac torso (MCAT) phantom was used to model Tc-99m-sestamibi uptake. A total of four phantoms (two male and two female) with eight defects (four locations and two sizes) were generated and projection data were simulated using an analytical projector with attenuation, scatter, collimator response and acquisition orbit modelling. The circular and body-contour projections were reconstructed using the OSEM algorithm with/without collimator response compensation. Defect detection performance was assessed by calculating area under the receiver operating characteristic (ROC) curve for channelized Hotelling observer. Results The defect detection performance of circular and body-contour acquisition was very similar and the difference in the area under the ROC curve between the orbits was not statistically significant with or without collimator response compensation. The collimator response compensation, on the other hand, was noticed to be valuable and it provided significantly better defect detection performance than reconstruction without it regardless of the acquisition orbit type. Conclusions We conclude that by replacing circular orbit with more complex body-contour orbit will not lead to statistically significant increase in defect detection performance in cardiac SPECT.

Objective A conventional pinhole single-photon emission computed tomography (SPECT) with a single circular orbit has limitations associated with non-uniform spatial resolution or axial blurring. Recently, we demonstrated that three-dimensional (3D) images with uniform spatial resolution and no blurring can be obtained by complete data acquired using two-circular orbit, combined with the 3D ordered subsets expectation maximization (OSEM) reconstruction method. However, a long computation time is required to obtain the reconstruction image, because of the fact that 3D-OSEM is an iterative method and two-orbit acquisition doubles the size of the projection data. To reduce the long reconstruction time, we parallelized the two-orbit pinhole 3D-OSEM reconstruction process by using a Beowulf personal computer (PC) cluster. Methods The Beowulf PC cluster consists of seven PCs connected to Gbit Ethernet switches. Message passing interface protocol was utilized for parallelizing the reconstruction process. The projection data in a subset are distributed to each PC. The partial image forward- and back-projected in each PC is transferred to all PCs. The current image estimate on each PC is updated after summing the partial images. The performance of parallelization on the PC cluster was evaluated using two independent projection data sets acquired by a pinhole SPECT system with two different circular orbits. Results Parallelization using the PC cluster improved the reconstruction time with increasing number of PCs. The reconstruction time of 54 min by the single PC was decreased to 10 min when six or seven PCs were used. The speed-up factor was 5.4. The reconstruction image by the PC cluster was virtually identical with that by the single PC. Conclusions Parallelization of 3D-OSEM reconstruction for pinhole SPECT using the PC cluster can significantly reduce the computation time, whereas its implementation is simple and inexpensive.

Physiological functions (e.g., cerebral blood flow, glucose metabolism, and neuroreceptor binding) can be investigated as parameters estimated by kinetic modeling using dynamic positron emission tomography (PET) images. Imaging of these physiological parameters, called parametric imaging, can locate the regional distribution of functionalities. However, the most serious technical issue affecting parametric imaging is noise in dynamic PET data. This review describes wavelet denoising of dynamic PET images for improving image quality in estimated parametric images. Wavelet denoising provides significantly improved quality directly to dynamic PET images and indirectly to estimated parametric images. The application of wavelet denoising to radio-ligand and kinetic analysis is still in the development stage, but even so, it is thought that wavelet techniques will have a substantial impact on nuclear medicine in the near future.

Cerebral metabolic rate of oxygen ( CMRO2), oxygen extraction fraction (OEF) and cerebral blood flow( CBF) images can be quantified using positron emission tomography ( PET) by administrating O-15-labelled water ((H2O)-O-15) and oxygen ( O-15(2)). Conventionally, those images are measured with separate scans for three tracers (CO)-O-15 for CBV, (H2O)-O-15 for CBF and O-15(2) for CMRO2, and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach ( Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO2 rapidly by sequentially administrating (H2O)-O-15 and O-15(2) within a short time. Because quantitative CBF and CMRO2 values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model- based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO2 were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO2 values by the DARG approach did not exceed the acceptable range, i. e., errors in those values were within 5%, when the area under the curve in the input function of the second tracer was larger than half of the first one. Bias and deviation in those values were also compatible to that of the conventional method, when noise was imposed on the arterial TAC. We concluded that the present calculation based methods could be of use for quantitatively calculating CBF and CMRO2 with the DARG approach.

Pinhole SPECT can provide high-resolution image with high sensitivity when a collimator is close to an object. However, truncation causes artifact and decreases quantitative accuracy. Defrise et al proposed new reconstruction theory to prevent overestimation due to truncation. In this paper, we applied Defrise theory to three-dimensional pinhole SPECT reconstruction and validated our implementation by computer simulation. © 2007 IEEE.

Pinhole SPECT can provide high-resolution image with high sensitivity when a collimator is close to an object. However, truncation causes artifact and decreases quantitative accuracy. Defrise et al proposed new reconstruction theory to prevent overestimation due to truncation. In this paper, we applied Defrise theory to three-dimensional pinhole SPECT reconstruction and validated our implementation by computer simulation.

Leukocytapheresis has an achieved well therapeutic efficacy in inflammatory bowel disease such as ulcerative colitis and rheumatoid arthritis in Japan. It has been applied in clinical therapy. CellsorbaE is a column that removes leukocytes of peripheral blood by extracorporeal circulation. It could remove leukocytes from whole blood directly. It is difficult to evaluate and analyze how blood flows in internal adsorption column and how leukocytes are removed. This study was aimed at developing a technique to visualize the flow distribution in the column with X-ray CT scanner. In addition, the flow was quantitatively analyzed on the image basis.

The Logan plot is a widely used algorithm for the quantitative analysis of neuroreceptors using PET because it is easy to use and simple to implement. The Logan plot is also suitable for receptor imaging because its algorithm is fast. However, use of the Logan plot, and interpretation of the formed receptor images should be regarded with caution, because noise in PET data causes bias in the Logan plot estimates. In this paper, we describe the basic concept of the Logan plot in detail and introduce three algorithms for the Logan plot. By comparing these algorithms, we demonstrate the pitfalls of the Logan plot and discuss the solution.

The threshold of cerebral blood flow (CBF) into infarction in rats has been indicated to be similar to that in patients. However, CBF does not reflect metabolic function, and so estimations of oxygen metabolism have been required. Here, we estimated changes in oxygen metabolism after occluding the right middle cerebral artery (MCA) in rats using an injectable O-15-O-2 we developed. A decrease in CBF (left: 0.67 +/- 0.22 mL/min/g, right: 0.44 +/- 0.17 mL/min/g, P &lt; 0.05) and compensatory increase in the oxygen extraction fraction (OEF) (left: 0.42 +/- 0.13, right: 0.50 +/- 0.19, P &lt; 0.05) were observed at 1-h after occlusion. In contrast, a marked decrease in CBF and the cerebral metabolic rate for oxygen and a collapse of the compensatory OEF mechanism were found at 24 h after occlusion. Injectable O-15-O-2 could be used to reliably estimate oxygen metabolism in an infarction rat model with positron emission tomography.

Objective: We compared the diagnostic accuracy achieved by a human observer (nuclear medicine physician) and a channelized Hotelling (CH) observer on the basis of receiver-operating characteristics (ROC) curve for the differential diagnosis of Alzheimer's disease (AD) from SPECT images. Methods: The I-123-IMP brain perfusion SPECT images of 42 subjects (21 AD patients and 21 healthy controls) were used for an interpretation study and those of 10 healthy subjects were for a normal database. SPECT images were processed into four types: original SPECT images, three-dimensional stereotactic surface projection (3DSSP) images derived from them, Z-scores of SPECT images, and Z-scores of 3DSSP images. Five nuclear medicine physicians evaluated the test dataset sequentially as to whether the presented images were those of AD patients, which were rated using five categories of certainty: definitely, possibly, equivocally, possibly not, and definitely not. The test statistics (.) of the dataset generated by the CH observer were rated for ROC analysis. The areas under the ROC curves (Az) for the four image types interpreted by the human and CH observers were estimated and compared. Results: Among the four image types, the best performance based on Az obtained by both the CH and human observers was observed for the Z-score of 3DSSP images, and the lowest was for the original SPECT images. Conclusions: The performance of the CH observer was similar to that of the human observers, and both were dependent on the image type. This indicates that the CH observer may predict human performance in discriminating Alzheimer's dementia and can be useful for comparing and optimizing image processing methods of brain perfusion SPECT without human observers.

PET enables not only visualization of the distribution of radiotracer, but also has ability to quantify several biomedical functions. Compartmental model is a basic idea to analyze dynamic PET data. This review describes the principle of the compartmental model and categorizes the techniques and approaches for the compartmental model according to various aspects: model design, experimental design, invasiveness, and mathematical solution. We also discussed advanced applications of the compartmental analysis with PET.

Background and objectives Statistical reconstruction methods allow resolution recovery in tomographic reconstruction. Even though resolution recovery has the potential to improve overall image quality, pinhole SPECT images are still often reconstructed using simplified models of the acquisition geometry in order to reduce reconstruction time. This paper investigates the benefits of two resolution recovery methods, multi-ray and point-spread function based, in pinhole SPECT by comparing them to uncorrected reconstruction. Methods Resolution recovery was incorporated into ordered subsets expectation maximization reconstruction algorithm. The first of the correction methods used a simple but very fast multiple projection ray approach, whereas the second, much slower, method modelled the acquisition geometry more accurately using the analytical point-spread function of the pinhole collimator. Line source, Jaszczak and contrast phantom studies were performed and used for comparison. Results Resolution recovery improved resolution, contrast and visual quality of the images when compared to reconstructions without it. The method based on the point-spread function performed slightly better, but was almost 50 times slower than the much simpler multi-ray approach. Conclusion The multiple projection ray approach is a promising method for very fast and easy resolution recovery in pinhole SPECT. It has a profound effect on image quality and can markedly improve the resolution-sensitivity trade-off.

Objectives: Pinhole SPECT which permits in vivo high resolution 3D imaging of physiological functions in small animals facilitates objective assessment of pharmaceutical development and regenerative therapy in pre-clinical trials. For handiness and mobility, the miniature size of the SPECT system is useful. We developed a small animal SPECT system based on a compact high-resolution gamma camera fitted to a pinhole collimator and an object-rotating unit. This study was aimed at evaluating the basic performance of the detection system and the feasibility of small animal SPECT imaging. Methods: The gamma camera consists of a 22 x 22 pixellated scintillator array of 1.8 mm x 1.8 mm x 5 mm NaI(Tl) crystals with 0.2-mm gap between the crystals coupled to a 2" flat panel position-sensitive photomultiplier tube (Hamamatsu H8500) with 64 channels. The active imaging region of the camera was 43.8 mm x 43.8 mm. Data acquisition is controlled by a personal computer (Microsoft Windows) through the camera controller. Projection data over 360 degrees for SPECT images are obtained by synchronizing with the rotating unit. The knife-edge pinhole collimators made of tungsten are attached on the camera and have 0.5-mm and 1.0-mm apertures. The basic performance of the detection system was evaluated with Tc-99m and Tl-201 solutions. Energy resolution, system spatial resolution and linearity of count rate were measured. Rat myocardial perfusion SPECT scans were sequentially performed following intravenous injection of 201 TlCl. Projection data were reconstructed using a previously validated pinhole 3D-OSEM method. Results: The energy resolution at 140 keV was 14.8% using a point source. The system spatial resolutions were 2.8-mm FWHM and 2.5-mm FWHM for Tc-99m and Tl-201 line sources, respectively, at 30-mm source distance (magnification factor of 1.3) using a 1.0-mm pinhole. The linearity between the activity and count rate was good up to 10 kcps. In a rat study, the left ventricular walls were clearly visible in all scans. Conclusions: We developed a compact SPECT system using compact gamma camera for small animals and evaluated basic physical performances. The present system may be of use for quantitation of biological functions such as myocardial blood flow in small animals.

Recently, small animal imaging by pinhole SPECT has been widely investigated by several researchers. We developed a pinhole SPECT system specially designed for small animal imaging. The system consists of a rotation unit for a small animal and a SPECT camera attached with a pinhole collimator. In order to acquire complete data of the projections, the system has two orbits with angles of 90 and 45 with respect to the object. In this system, the position of the SPECT camera is kept fixed, and the animal is rotated in order to avoid misalignment of the center of rotation (COR). We implemented a three dimensional OSEM algorithm for the reconstruction of data acquired by the system from both the orbitals. A point source experiment revealed no significant COR misalignment using the proposed system. Experiments with a line phantom clearly indicated that our system succeeded in minimizing the misalignment of the COR. We performed a study with a rat and Tc-99m-HMDP, an agent for bone scan, and demonstrated a dramatic improvement in the spatial resolution and uniformity achieved by our system in comparison with the conventional Feldkamp algorithm with one set of orbital data.

Recently, list mode (event-by-event) data acquisition with positron emission tomography (PET) has been widely noticed because list mode acquisition is superior to conventional frame mode data acquisition in terms of (1) higher efficiency of data storage, (2) higher temporal resolution, and (3) higher flexibility of data manipulation. The aim of this study is to investigate the performance of list mode data acquisition with ECAT EXACT HR and HR+ PET scanners (CTI PET Systems) and its feasibility in clinical applications. A cylindrical phantom (16 cm in diameter and length) filled with a C-11 solution for the HR and a O-15 solution for the HR+ was scanned several times by varying the radioactivity concentration with the list mode and frame mode acquisitions. The scans were also carried out with a septa (2D mode) and without a septa (3D mode) in order to evaluate the effect of the interplane septa on the quality of the list mode data. The acquired list. mode data were sorted into a sinogram and reconstructed using a filtered back-projection algorithm. The count rate performance of the list mode data was comparable to that of the frame mode data. However, the list mode acquisition could not be performed when the radioactivity concentration in the field-of-view was high (exceeding 24 kBq/ml for the 3D mode) due to a lack of sufficient transfer speed for sending data from the memory to hard disk. In order to estimate the pixel noise in a reconstructed image, ten replicated data sets were generated from one list mode data. The reconstructed images with the 3D mode had a signal-to-noise ratio that was more than 60% better than that of the image with the 2D mode. The file size of the generated list mode data was also evaluated. In the case of ECAT EXACT HR+ with the 3D list mode, the list mode data with a generated file size of 2.31 Mbytes/s were generated for 37 MBq injections. Our results suggest that careful attention must be paid to the protocol of the list mode data acquisition in order to obtain the highest performance of the PET scanner.

Two approaches are often applied to reduce the effects of depth-dependent resolution in SPECT. First is to use body-contour acquisition orbits and second is to apply resolution recovery (RR) in reconstruction. Unfortunately it is sometimes difficult to combine these methods, because in body-contour acquisitions especially many older gamma cameras do not record the object-to-detector distances, which are needed to perform RR in reconstruction. The objective of this study was to investigate is it better to use body-contour orbit without RR or circular orbit with RR in cardiac SPECT. The results of simulation and physical phantom studies showed that circular orbit with RR produce images with lower bias, higher contrast and better resolution than the body-contour orbit without RR. Therefore if object-to-detector distances are not available for body-contour orbits circular orbits with RR should be preferred in cardiac SPECT.

Pinhole SPECT allows to image physiological functions in small animals with high spatial resolution. In case of cardiac imaging with higher resolution, the resolution can be improved by positioning a collimator close to an object, but truncation arises from radioisotope in the surrounding organs. This study was intended to evaluate the effect of truncation in quantitative cardiac imaging with small field-of-view pinhole SPECT by a computer simulation. Assuming a rat, a numerical phantom consists of cylinder with 10-mm diameter and 10-mm height, and cylinder with 36-mm diameter and 70-mm height as the cardiac region and the surrounding region (Background). The counts of the cardiac region and the background were 10 and 1, 2, 4 or 8, respectively. In this simulation, the field-of-view of reconstruction was defined as a sphere with 30-mm diameter. The projection data with truncation were reconstructed using pinhole 3D-OSEM algorithm. The counts on the reconstructed images were compared with that on original image. The counts on the cardiac regions in reconstructed images were overestimated 14.5%, 17.6%, 20.5% and 23.2% for the background counts of 1, 2, 4 and 8, respectively. These results suggest that the effect of truncation needs to be considered in quantitative cardiac imaging with pinhole SPECT.

The aim of the present study is to evaluate the validity of the Simplified Reference Tissue Model (SRTM) and of Logan Graphical Analysis with Reference Tissue (LGAR) for quantification of histamine H-1 receptors (H1Rs) by using positron emission tomography (PET) with [C-11]doxepin. These model-based analytic methods (SRTM and LGAR) are compared to Logan Graphical Analysis (LGA) and to the one-tissue model (1TM), using complete datasets obtained from 5 healthy volunteers. Since H1R concentration in the cerebellum can be regarded as negligibly small, the cerebellum was used as a reference tissue in the present study. The comparison of binding potential (BP) values estimated by LGAR and 1TM showed good agreement, on the other hand, SRTM was unstable concerning parameter estimation in several regions of the brain. By including the results of noise analysis, LGAR became a reliable method for parameter estimation of [C-11]doxepin data in the cortical regions.

A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (gamma(ml/100 g/min)= 1.07 x (ml/100 g/min) -1.14, r=0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest-rest study was 1.5 +/- 5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease. (c) 2006 Elsevier Inc. All rights reserved.

Purpose: An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with Tc-99m-labeled tracers, based on comparison with the conventional triple energy window (TEW) method. Methods: The IBSC method corrects scatter on the reconstructed image I-AC(mu b) with Chang's attenuation correction factor. The scatter component image is estimated by convolving I-AC(mu b) with a scatter function followed by multiplication with an image- based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and Tc-99m-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared. Results: Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods. Conclusion: The IBSC method is a simple scatter correction technique feasible for use in clinical routine.

The aim of the present study is to evaluate the validity of the simplified reference tissue model (SRTM) and of Logan graphical analysis with reference tissue (LGAR) for quantification of histamine H-1 receptors (H1Rs) by using positron emission tomography (PET) with [C-11]doxepin. These model-based analytic methods (SRTM and LGAR) are compared to Logan graphical analysis (LGA) and to the one-tissue model (1TM), using complete datasets obtained from 5 healthy volunteers. Since H1R concentration in the cerebellum can be regarded as negligibly small, the cerebellum was selected as the reference tissue in the present study. The comparison of binding potential (BP) values estimated by LGAR and 1TM showed good agreement; on the other hand, SRTM turned out to be unstable concerning parameter estimation in several regions of the brain. By including the results of noise analysis, LGAR became a reliable method for parameter estimation of [C-11]doxepin data in the cortical regions.

Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO2) may be quantified using positron emission tomography (PET) with O-15-tracers, but the conventional three-step technique requires a relatively long study period, attributed to the need for separate acquisition for each of O-15(2), (H2O)-O-15, and (CO)-O-15 tracers, which makes the multiple measurements at different physiologic conditions difficult. In this study, we present a novel, faster technique that provides a pixel-by-pixel calculation I Is of CBF and CMRO2 from a single PET acquisition with a sequential administration of O-15(2) and (H2O)-O-15. Experiments were performed on six anesthetized monkeys to validate this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO2 obtained by the present technique at rest were not significantly different from those obtained with three-step method. The global OEF (gOEF) also agreed with that determined by simultaneous arterio-sinus blood sampling (gOEF(A-V)) for a physiologically wide range when changing the arterial PaCo2 (gOEF=1.03gOEF(A-V) +0.01, P &lt; 0.001). The regional values, as well as the image quality were identical between the present technique and three-step method for CBF, OEF, and CMRO2. In addition, a simulation study showed that error sensitivity of the present technique to delay or dispersion of the input function, and the error in the partition coefficient was equivalent to that observed for three-step method. Error sensitivity to cerebral blood volume (CBV) was also identical to that in the three-step and reasonably small, suggesting that a single CBV assessment is sufficient for repeated measures of CBF/CMRO2. These results show that this fast technique has an ability for accurate assessment of CBF/CMRO2 and also allows multiple assessment at different physiologic conditions.

Recently, lactate has been receiving great attention as an energy substrate in the brain. In this Study, the role of lactate was evaluated by "bioradiography" system with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG), which is a positron emitting radiotracer for glucose uptake quantification. "Bioradiography" is the dynamic living tissue slice imaging system for positron-emitter labeled compounds. We investigated the brain energy metabolism under resting state and neural activated conditions induced by KCl addition. The monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), had no effect on [(18)F]FDG uptake rate in rat brain slices before KCl addition. On the other hand, addition of 4-CIN induced larger [(18) F]FDG uptake rates under the activated condition in comparison with the control condition. Because neurons cannot utilize lactate under the 4-CIN loaded conditions, this indicates that activated neurons consume lactate as an energy substrate. The lactate concentration in the incubation medium was increased with KCl treatment in both groups and the extent was slightly greater in 4-CIN group. These results suggested that: (1) the brain mainly uses glucose, not lactate, as an energy substrate in resting state; (2) when neuron is stimulated, excess amounts of lactate might be produced in astrocytes and the lactate is mobilized as an energy substrate. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Regional myocardial blood flow (MBF) can be measured with O-15-water and PET using the 1-tissue-compartment model with perfusable tissue fraction, which provides an MBF value that is free from the partial-volume effect. Studies with O-15-water have several advantages, such as the ability to repeat a scan. However, because of the short scanning time and the small distribution volume of O-15-water in the myocardium, the image quality of O-15-water is limited, impeding the computation of MBF and perfusable tissue fraction at the voxel level, We implemented the basis function method for generating parametric images of MBF, perfusable tissue fraction, and arterial blood volume V-a with O-15-water and PET. The basis function method linearizes the solution of the 1-tissue-compartment model, which results in a computationally much faster method than the conventional nonlinear least-squares fitting method in estimating the parameters. Methods: To validate the basis function method, we performed a series of PET studies on miniature pigs (n = 7). After acquisition of the transmission scan for attenuation correction and the O-15-CO scan for obtaining the blood-pool image, repeated PET scans with O-15-water were obtained with varying doses of adenosine or CGS-21680 (selective adenosine A(2a) receptor agonist). MBF, perfusable tissue fraction, and V-a values of the myocardial region for each scan were computed using the basis function method and the nonlinear least-squares method, and the parameters estimated by the 2 methods were compared. Results: MBF images generated by the basis function method demonstrated an increase in blood flow after administration of adenosine or CGS-21680. The MBF values estimated by the basis function method and by the nonlinear least-squares method correlated strongly. Conclusion: The basis function method produces parametric images of MBF, perfusable tissue fraction, and Va with O-15-water and PET. These images will be useful in detecting regional myocardial perfusion abnormalities.

Non-uniform spatial resolution or axial blurring is a major limitation in conventional pinhole SPECT, which is largely attributed to incompleteness of the acquired projection data sets. Recently, we have experimentally demonstrated that the non-uniform spatial resolution could be improved by a new design of the pinhole orbit that satisfies the completeness of pinhole SPECT reconstruction (Tuy's condition). This study was intended to evaluate systematically the effect of our two-circular orbit system by a computer simulation and to examine an effective oblique angle about the additional orbit of two orbits. A numerical multiple-disk phantom with seven disks was used. Forwarded projection data without noise and with Gaussian noise were used to evaluate the axial spatial resolution uniformity and the statistical noise property, respectively. The angles of the additional orbit were chosen every 15° in the range from 0° to 75° for object's axis. Single and two-orbit data were reconstructed by 3D-OSEM method for pinhole SPECT. Our simulation showed two-orbit acquisition of any combinations was significantly effective for the improvement of both spatial resolution uniformity (81 - 93% at the edge disk of the phantom) and statistical noise property (69 - 88% at the edge disk of the phantom) compared with single orbit acquisition. Especially, combination of 90° and 60° orbits resulted in the best performance among other orbital combinations. © 2005 IEEE.

Regional myocardial blood flow (MBF) can be measured with ISO-water and PET using the one-tissue compartment model (IT model) with perfusable tissue fraction (PTF), which provides MBF value that is free from the partial volume effect (PVE). Study with ISO-water has several advantages such as the ability of repeated scan. However, the image quality of ISO-water is limited, which impedes the computation of MBF and PTF values at the voxel level. We implemented the basis function method (BFM) for generating parametric images of MBF, PTF and arterial blood volume (Va) with ISO-water and PET. The BFM is to linearize the solution of IT model, which results in a computationally much faster method than the conventional non-linear least squares fitting method (NLM) in estimating the parameters. In order to fully automate the process of the BFM, PET images were realigned to a reference image using Affine transformation. Arterial input function with PVE correction was derived from the realigned PET images using templates of regions of left ventricle and myocardium. In order to validate the BFM, series of PET studies were performed on infarction model pigs (n=4). PET scans with ISO-water were performed with varying doses of adenosine (5-7 scans for each pig). The results by the BFM were well correlated to ones by the NLM.The method automatically generated functional maps computationally fast enough for clinical application. ©2005 IEEE.

Regional myocardial blood flow (MBF) can be measured with 150-water and PET using the one-tissue compartment model (1T model) with perfusable tissue fraction (PTF), which provides MBF value that is free from the partial volume effect (PVE). Study with 150-water has several advantages such as the ability of repeated scan. However, the image quality of 150water is limited, which impedes the computation of MBF and PTF values at the voxel level. We implemented the basis function method (BFM) for generating parametric images of MBF, PTF and arterial blood volume (Va) with 150-water and PET. The BFM is to linearize the solution of 1T model, which results in a computationally much faster method than the conventional non-linear least squares fitting method (NLM) in estimating the parameters. In order to fully automate the process of the BFM, PET images were realigned to a reference image using Affine transformation. Arterial input function with PVE correction was derived from the realigned PET images using templates of regions of left ventricle and myocardium. In order to validate the BFM, series of PET studies were performed on infarction model pigs (n=4). PET scans with 150water were performed with varying doses of adenosine (5-7 scans for each pig). The results by the BFM were well correlated to ones by the NLM. The method automatically generated functional maps computationally fast enough for clinical application.

Non-uniform spatial resolution or axial blurring is a major limitation in conventional pinhole SPECT, which is largely attributed to incompleteness of the acquired projection data sets. Recently, we have experimentally demonstrated that the nonuniform spatial resolution could be improved by a new design of the pinhole orbit that satisfies the completeness of pinhole SPECT reconstruction (Tuy's condition). This study was intended to evaluate systematically the effect of our two-circular orbit system by a computer simulation and to examine an effective oblique angle about the additional orbit of two orbits. A numerical multiple-disk phantom with seven disks was used. Forwarded projection data without noise and with Gaussian noise were used to evaluate the axial spatial resolution uniformity and the statistical noise property, respectively. The angles of the additional orbit were chosen every 15 degrees in the range from 0 degrees to 75 degrees for object's axis. Single and two-orbit data were reconstructed by 3D-OSEM method for pinhole SPECT. Our simulation. showed two-orbit acquisition of any combinations was significantly effective for the improvement of both spatial resolution uniformity (81 - 93% at the edge disk of the phantom) and statistical noise property (69 - 88% at the edge disk of the phantom) compared with single orbit acquisition. Especially, combination of 90 degrees and 60 degrees orbits resulted in the best performance among other orbital combinations.

Central neuropathic pain (CNP) is pain resulting from damage to the central nervous system. Up till now, it has not been possible to identify a common lesion or pharmacological deficit in these patients. This preliminary study in a group of patients with CNP with predominantly post-stroke pain, demonstrates that there is significantly less opioid receptor binding in a number of cortical and sub-cortical structures that are mostly, but not exclusively, within the medial pain system in patients compared to age-matched pain-free controls. The reductions in opioid receptor binding within the medial system were observed mainly in the dorsolateral (Brodman area 10) and anterior cingulate (Brodman area 24 with some extension into area 23) and insula cortices and the thalamus. There were also reductions in the lateral pain system within the inferior parietal cortex (Brodman area 40). These changes in binding could not be accounted for by the cerebral lesions shown by CT or MRI, which were outside the areas of reduced binding and the human pain system. To our knowledge this is the first systematic demonstration of a reduction in opioid receptor-binding capacity in neurotics within the human nociceptive system in patients with CNP. This may be a key common factor resulting in undamped nociceptor activity within some of the structures that are predominantly within the medial nociceptive system. If confirmed, these findings may explain why certain patients with CNP require high doses of synthetic opiates to achieve optimum analgesia. The findings also raise the possibility of new pharmacological approaches to treatment. (C) 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.

Pinhole single-photon emission computed tomography (SPECT) with high spatial-resolution is suitable for small-animal imaging, but has limitations associated with spatial-resolution inhomogeneity or axial blurring. We have hypothesized that this blurring is due to incompleteness of projection data acquired by a single circular pinhole orbit. And we have developed a pinhole SPECT system with two circular orbits which satisfy Tuy's condition so as to provide complete data for 3D pinhole SPECT reconstruction within the whole field-of-view (FOV) a dedicated 3D ordered subsets expectation maximization (3D-OSEM) reconstruction method for two-orbit data. This study is aimed at evaluating accuracy and impact of this system. In this system, not the camera but the object rotates and the two orbits are 90° and 45° relative to object's axis. Experiments using a multiple-disk phantom filled with 99mTc solution and a mouse bone scan using 99mTc-labeled HMDP agent were carried out. The Feldkamp's filtered back-projection (FBP) method and the 3D-OSEM method were applied to these data sets. The axial blurring was apparent on images reconstructed by FBP for single-orbit data, while the 3D-OSEM using two-orbit data dramatically improved the resolution homogeneity and statistical noise property, and also demonstrated considerably better image quality in the mouse scan. © 2004 Elsevier B.V.

Xenon is a promising candidate for an exogenous MRI tracer because of its affinity for lipids and possible polarization. The estimation of net detectability of dissolved phase xenon in vivo is important for a development of diagnostic applications. The purposes of this study were to develop a hyperpolarized 129Xe experiment system on 3-T and to measure dissolved phase signal in a rat lung. The 129Xe gas was polarized using the optical pumping technique, was manually insufflated to male Sprague–Dawley rat under spontaneous respiration anesthetized by intraperitoneal injection of urethane (1 mg/g), and was measured in a rat lung by frequency selective spectroscopy. A full fractional optimum experiment of two-factor (flip angle, TR) and three-level (30°, 60°, 90°, 600, 1000, 1400 ms) was designed for SNR. A flip angle (∼60°) with 1 s TR made maximum signal in dissolved phase dynamic spectroscopy. Two dominant peaks of 212 for RBC and 201 ppm for tissue were observed, and their average signal ratio to that of gas was 5.6% and 4.4%, respectively. We have developed a hyperpolarized 129Xe experiment system, which could yield enough amount and polarization for dynamic analysis in a rat lung using the 3-T MRI system. © 2004 Elsevier B.V.

We proposed a novel PET protocol, which allows shortening of the total PET duration with sequential administration of two tracers. To calculate quantitative OEF, CBF and CMRO2 images, a mathematical formulation was developed. This formulation can be applied both in H2 15O–15O2 and 15O2–H2 15O, and enables estimating the quantitative functions from the PET scan by the residual radioactivity first administrated and built into a model. To test validity and applicability, accuracy and precision of quantitative values of OEF, CBF, and CMRO2 obtained by the present DARG, we compared them with the three-step ARG approach in our experimental study using monkeys. The accuracy of the functional values was confirmed and the enhancement of statistical noise was reasonably small. The global OEF values obtained by the present method also agreed well with those obtained by the arterial-sinus difference measurement. In addition, the simulation study showed that the error sensitivity of the present method was almost of the same degree as the three-step method. These findings suggest that the present protocol could be applicable to human studies. © 2004, Elsevier B.V.

Cerebral blood flow (CBF) obtained by dynamic susceptibility contrast MRI (DSC-MRI) often provides an abnormal contrast between normal and ischemic areas, as compared with those from positron emission tomography (PET) or SPECT. A linear relationship is normally assumed in the transverse relaxation rate change in relation to the regional concentration of the contrast agent. This study was intended to evaluate this assumption. The impact of an alternative, non-linear model based on a realistic capillary structure was also evaluated in the assessment of CBV and CBF by use of DSC-MRI. DSC-MRI and 15O-PET were carried out on 13 patients with chronic cerebrovascular disease. Regions-of-interest (ROI) were selected both in the ischemic and unaffected hemispheres, and the left-to-right (L/R) ratios of CBF and CBV were compared between PET and DSC-MRI. When assuming the linear relationship, the contrast of CBF by DSC-MRI was lower than that by PET (CBFL/R,MRI=0.60CBFL/R,PET+0.40, r=0.63, p&lt 0.0216), and the contrast of CBV by DSC-MRI greater than that by PET (CBVL/R,MRI=1.34CBVL/R,PET−0.33, r=0.84, p=0.0003). Disagreement of CBF was particularly apparent in the area of enhanced CBV. The employment of the non-linear model improved the agreement between DSC-MRI and PET for both CBF and CBV (CBFL/R,MRI=0.89CBFL/R,PET+0.08, r=0.93, p&lt 0.0001 CBVL/R,MRI=1.03CBVL/R,PET−0.04, r=0.79, p=0.0014). These results suggest that the linear model has limited accuracy in the assessment of CBF and CBV in patients with chronic cerebrovascular disease, and that the non-linear correction is essential in order to provide accurate quantitation with DSC-MRI. © 2004, Elsevier Inc. All rights reserved.

Pinhole single-photon emission computed tomography (SPECT) is able to provide information on the biodistribution of several radioligands in small laboratory animals, but has limitations associated with nonuniform spatial resolution or axial blurring. We have hypothesised that this blurring is due to incompleteness of the projection data acquired by a single circular pinhole orbit, and have evaluated a new strategy for accurate image reconstruction with better spatial resolution uniformity. A pinhole SPECT system using two circular orbits and a dedicated three-dimensional ordered subsets expectation maximisation (3D-OSEM) reconstruction method were developed. In this system, not the camera but the object rotates, and the two orbits are at 90degrees and 45degrees relative to the object's axis. This system satisfies Tuy's condition, and is thus able to provide complete data for 3D pinhole SPECT reconstruction within the whole field of view (FOV). To evaluate this system, a series of experiments was carried out using a multiple-disk phantom filled with Tc-99m solution. The feasibility of the proposed method for small animal imaging was tested with a mouse bone study using Tc-99m-hydroxymethylene diphosphonate. Feldkamp's filtered back-projection (FBP) method and the 3D-OSEM method were applied to these data sets, and the visual and statistical properties were examined. Axial blurring, which was still visible at the edge of the FOV even after applying the conventional 3D-OSEM instead of FBP for single-orbit data, was not visible after application of 3D-OSEM using two-orbit data. 3D-OSEM using two-orbit data dramatically reduced the resolution non-uniformity and statistical noise, and also demonstrated considerably better image quality in the mouse scan. This system may be of use in quantitative assessment of biophysiological functions in small animals.

Repetitive transcranial magnetic stimulation (rTMS) recently has been assessed as a noninvasive treatment modality for movement and psychiatric disorders, whereas the mechanism underlying the therapeutic effects is not fully understood. Studies in rodents showed lasting functional changes in some selected regions, such as limbic-associated structures, but unfocused brain stimulation did not clarify the regional effects. To address the topographical and temporal profiles of the effects on glucose metabolism in primate brain, we performed rTMS and repeated F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) before, during, and up to 16 days after rTMS in anesthetized cynomologous monkeys. We delivered a total of 2,000 pulses of 5Hz-rTMS over the right precentral gyrus using a small-sized eight-figured coil that induced a localized electrical field. Voxel-based analysis in a standard space of the macaque brain showed statistically robust changes in FDG uptake: a decrease in the motor/premotor cortices and an increase in the limbic-associated areas involving the anterior/posterior cingulate, and orbitofrontal cortices. Interestingly, these uptake changes continued for at least 8 days and the magnitude of the lasting effects in the limbic-related areas was negatively correlated across subjects with those in the motor/premotor cortices. The results demonstrate that motor rTMS has a long-term lasting effect on motor-related regions and distant limbic-related areas via functional connections.

The rupture of atherosclerotic plaques and the subsequent formation of thrombi are the main factors responsible for myocardial and cerebral infarctions. Thus, the detection of vulnerable plaques in atherosclerotic lesions is a desirable goal, and attempts to image these plaques with (18)F-FDG have been made. In the present study, the relationship between the accumulation of (18)F-FDG and the biologic characteristics of atherosclerotic lesions was investigated. Furthermore, PET imaging of vulnerable plaques was performed with an animal model of atherosclerosis, Watanabe heritable hyperlipidemic (WHHL) rabbits. Methods: WHHL (n = 11) and control (n = 3) rabbits were injected intravenously with (18)F-FDG, and the thoracic and abdominal aortas were removed 4 h after injection. The accumulated radioactivity was measured, and the number of macrophages and the intimal area were investigated by examination of stained sections. PET and CT images were also acquired at 210 min after injection of the radiotracer. Results: (18)F-FDG accumulated to a significantly higher level in the aortas of the WHHL rabbits (mean +/- SD differential uptake ratio [DUR], 1.47 +/- 0.90) than in those of the control rabbits (DUR, 0.44 +/- 0.15); DUR was calculated as (tissue activity/tissue weight)/(injected radiotracer activity/animal body weight), with activities given in becquerels and weights given in kilograms. (113)F-FDG uptake and the number of macrophages were strongly correlated in the atherosclerotic lesions of the WHHL rabbits (R = 0.81). In the PET analysis, intense (18)F-FDG radioactivity was detected in the aortas of the WHHL rabbits, whereas little radioactivity was seen in the control rabbits. Conclusion: The results suggest that macrophages are responsible for the accumulation of (18)F-FDG in atherosclerotic lesions. Because vulnerable plaques are rich in macrophages, (18)F-FDG imaging should be useful for the selective detection of such plaques.

Motion of the head during brain positron emission tomography (PET) acquisitions has been identified as a source of artifact in the reconstructed image. A number of techniques have been proposed to correct for this motion artifact, but they are unable to correct for a motion during an acquisition. The aim of this study was to develop a sinogram-based motion correction (SBMC) technique to correct directly the head motion during a PET scan using a motion tracking system and list-mode data acquisition. This method uses a rebinning procedure whereby the lines of response (LOR) are geometrically transformed according to the current values of six-dimensional motion data. A Michelogram was recomposed using the rebinned LOR, and the motion-corrected sinogram was generated. In the motion corrected image, the blurring artifact due to the motion was reduced by the SBMC technique. This technique was applied to actual PET data acquired in the list-mode, and demonstrated the potential for real-time motion correction of head movements during a PET acquisition.

Transmission-dependent convolution subtraction (TDCS) is a promising technique in quantitative SPECT for subtracting the scatter components from emission images. Usually, a 20% photopeak energy window is used in SPECT acquisitions. To date, no investigation has assessed the effects of energy windows in the subtraction of scatter components from emission images with the TDCS technique. To evaluate the energy dependence of the TDCS technique, we analyzed photopeak energy windows of 5%, 10%, 15%, 20%, 25%, 30%, and 35% using Tc-99m radionuclide. The scatter fractions for a point source placed in a water phantom were estimated using the triple-energy-window (TEW) technique. These estimates were used to establish the parameters of the TDCS equation as a function of transmission. The estimated parameters were applied to the TDCS technique to subtract the scatter components from data of corresponding energy windows using nonuniform and uniform phantoms. All data were reconstructed with the OSEM algorithm. The energy window dependence of the TDCS technique was verified by comparing the coefficients of variance (COV) of the data from the uniform phantom of each energy window. Ten Poisson deviates were generated from each projection's data from the uniform phantom. The nonuniform phantom results showed that the estimated parameters effectively estimated the scatter component from the projection image for each energy window. The COV for the 5%, 10%, 15%, 20%, 25%, 30%, and 35% windows were 2.10%, 1.76%, 1.44%, 1.39%, 1.34%, 1.37%, and 1.61%, respectively. In the TDCS technique, any photopeak energy window from 15% to 30% may work almost as well as judged by the COV measured for a uniform phantom in this study. The best window by that measure was the 25% window.

This chapter describes a brief overview of present advances and challenges in PET methodology from the engineering side. Topics are as follows: (1) advances in hardware design and sophisticated software development for registering PET and anatomical images, (2) higher spatial resolution approaching sub-millimeters, (3) improved temporal resolution, (4) repeat assessment of physiologic functions, (5) corrections for partial volume effect (PVE), and (6) motion correction capability. These features provide potentials of using PET in new application fields. © 2004, Elsevier Inc. All rights reserved.

Background Repetitive transcranial magnetic stimulation (rTMS) has been used as a treatment for neuropsychiatric disorders such as depression and Parkinson's disease (PD). Despite the growing interest in therapeutic application of rTMS, precise mechanisms of its action remain unknown. With respect to PD, activation of the mesostriatal dopaminergic pathway is likely to be a candidate mechanism underlying the therapeutic effects however, modulating effects of rTMS over the primary motor cortex (M1) on the dopaminergic system have not been studied. Methods We used [11C]raclopride positron emission tomography to measure changes of extracellular dopamine concentration after 5Hz rTMS over the M1 in eight anesthetized monkeys. Results rTMS over the right M1 induced a reduction of [11C]raclopride binding potential (BP) in the bilateral ventral striatum, including the nucleus accumbens, and a significant increase of BP in the right putamen no significant BP reduction was found in the dorsal striatum. These data indicate that rTMS over the motor cortex induces a release of endogenous dopamine in the ventral striatum. Conclusions Our results suggest that therapeutic mechanisms of rTMS may be explained in part by an activation of the mesolimbic dopaminergic pathway, which plays critical roles in rewards, reinforcement, and incentive motivation.

Repetitive transcranial magnetic stimulation (rTMS) has recently been assessed as a non-invasive treatment modality for neuropsychiatric disorders. However, the mechanisms underlying the therapeutic effects are still not understood. Studies in rodents revealed lasting effects in limbic-related regions, but species difference in brain structures makes it difficult to infer the regional effect in primate brain. To reveal how rTMS affects primate brain function, we performed positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) and 11C-raclopride (RAC) in anaesthetized macaque monkeys. A total of 2000 pulses of 5Hz-rTMS were delivered on the unilateral primary motor cortex using a small coil. Voxel-based analysis revealed statistically robust changes in FDG activity in the motor, cingulate, and orbitofrontal cortices, as well as in binding potential of RAC in the ventral striatum. Interestingly, the change in FDG activity persisted at least 8 days. These results demonstrate that motor cortical rTMS induces dynamic functional changes in motor and limbic associated structures, suggesting its therapeutic effect on dysfunction of motor and motivation system. © 2004

Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D2 receptors using [123I]epidepride. Eight healthy human subjects [age 30±8 (range 22-46) years] participated in a study with a bolus injection of 373±12 (354-389) MBq [123I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry μ (SC) and without scatter correction using broad-beam μ (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1-1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [18F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies.

Inhomogeneous spatial resolution or axial blurring is a major problem in conventional pinhole SPECT, which is largely attributed to the incompleteness of the acquired projection data sets. In this study we have developed new system that provides 3D images without the axial blurring. The complete projection data sets were acquired using a pinhole collimator fitted to a conventional gamma camera with different two circular orbits (i.e. the 90 degrees and 45 degrees tilted angles to axis of rotation). Data sets from these orbits satisfied the Tuy's condition (Tuy, 1983), to which the 3D-OSEM algorithm was applied. The present system was first evaluated by a cylindrical phantom that had several disk areas of 0.5 mm thickness filled with Tc-99m solution separated by a 10 mm gap. The reconstructed imaged with two orbital data sets demonstrated no axial blurring and better image quality than the image reconstructed with only one orbit. This study suggested that accurate reconstruction without axial blurring could be obtained by acquiring complete data set in pinhole SPECT. This system will be useful for quantitative analysis of bio-physiological functions in small animals.

The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) during physiological and pathological conditions remains a subject of debate. We have developed a physiological model for oxygen delivery and metabolism, which allows the estimation of net oxygen diffusibility at the capillary level, termed "effective oxygen diffusibility (EOD). " The results of PET in monkeys showed dynamic changes in EOD in response to changes in oxygen delivery and consumption. EOD is defined as capillary volume and permeability product, but its change mainly reflects the pericapillary oxygen gradient as long as capillary architecture is preserved. EOD may have sufficient predictability to represent the tissue oxygen demand and application of the model to PET data. In the future, EOD may give us further insight to understand the physiological regulatory system for oxygen demand in the brain. (C) 2004 Published by Elsevier B.V.

Accurate measurement of myocardial blood flow (MBF) can be achieved noninvasively by using dynamic PET with a slow-infusion of O-15 water incorporating O-15 CO gas scan, which is used for identification of myocardium regions to obtain an accurate input function. Although there have been studies using PET with bolus-injection,, the applicability of factor analysis (FA) to slow-infused water data has not been examined yet. In this study, we investigated a method for extracting blood pool activities from dynamic water image with slow-infusion using FA. A dynamic PET scan was performed with slow-infusion of water, after a static CO scan. Both components of blood pool and myocardial tissue were separated from the acquired dynamic water image using FA. Time-activity curve (TAC) of blood pool and myocardium were extracted, and the images of blood volume (VB) and extravascular tissue density (Dev) were generated, respectively. The TAC shape of blood pool was agreed to that of true input function. The effect of spillover from blood pool to myocardium was dramatically eliminated in TAC shape. The both images of VB and myocardium by FA were similar with VB image by CO and washout-phase image of dynamic data, respectively. Both Dev image by CO image and FA were also comparable in terms of spatial distribution and count scale. This approach incorporating factor analysis could be useful for improved quantitation of MBF using simplified acquisition protocol without CO scan.

A method for simultaneous parametric mapping of both cerebral blood flow (CBF) and cerebral blood volume of artery (CBVa) from single dynamic water image is presented. This method incorporates the 2-compartment model including arterial vascular volume (V-a), and cluster analysis for suppressing noise in generating parametric image. A dynamic 015 water PET scan was performed, after a static O-15 CO gas scan. Arterial input function was obtained during the dynamic scan. Using the reconstructed dynamic image, both images of CBF and CBVa were generated by the presented method. Both generated images of CBF and CBVa were compared to those generated by conventional autoradiography (ARG) and CO image. The CBF image by this method showed the elimination of CBV, component and was comparable with that by ARG in terms of quantitative CBF value and noise. The CBVa image showed the spatial distribution of activities of pure arterial blood volume only, quantitative value and suppressed noise, in contrast to the image of total blood volume from CO image including artery and vein together. The new method with cluster analysis could create the images with quantitative values of CBF and V-a, with improved signal-to-noise ratio. The image of CBVa provided the intuitional information of arterial blood volume only. This method could contribute to improved diagnosis of cerebrovascular disease using O-15 water PET.

Head motion during PET scanning produces significant artifact or spatial resolution loss on the reconstructed image. Event-based motion correction (EBMC) technique has been developed to correct head movement during the scan incorporated with list mode acquisition of PET and an optical tracking system. In EBMC technique, each line-of-response (LOR) in the list-mode data was reoriented due to the motion data by the optical tracking system. Although EBMC technique has potential to correct head movement during PET acquisition, large size of list mode data set hampers the capability of on-line processing for the correction. In order to improve in the speed of computing time for EBMC, we implemented EBMC on a Beowulf PC cluster consisting of 7 PCs (2.4 GHz Xeon for a master node and 1.4 GHz PentiumIII for slave nodes) connecting each other through Gbit Ethernet. MPI (Message Passing Interface) protocol was utilized for parallelizing the task of EBMC. The performance of the PC cluster was evaluated using list-mode data and head motion data acquired by ECAT EXACT HR+ (CTI/Siemens) PET scanner and POLARIS (Northern Digital) optical tracking system. The six list-mode data sets (file sizes are from 161 to 253 Mbytes) were corrected for motion by EBMC technique on a single PC and the PC cluster. The PC cluster was 5.2 times faster than the single PC to perform the motion correction. The PC cluster remarkably improves the performance of EBMC with low cost.

Objectives: This study was intended to evaluate the feasibility and applicability of assessing absolute myocardial blood flow (MBF) using 0-15 water and PET 14 times for various doses of vasodilator challenges in miniature pigs. Methods and results: MBFs were quantitated following intravenous injection of 0-15 water during various administration doses of adenosine (25-800 mug/kg/min) and A2A-selective CGS-21680 (0.5-20 mug/kg) in six miniature pigs. A low dose of adenosine increased MBF but reached to a maximum, and gradually decreased MBF with reduced heart rate (HR), reduced systolic blood pressure (SBP), and thus decreased RPP, together with prolonged PR interval. Reduction in HR, SBP and RPP were also observed with CGS-21680, but were significantly less, and the maximum MBF was greater with CGS-21680. These findings were consistent and reproducible among all the six subjects. Discussion and conclusion: The technique of assessing MBF with 0-15 water and PET appeared to be reproducible and useful for quantitative evaluation of the vascular reactivity for various pharmacological/physiological stresses. The ability of accurately correcting for the partial volume effect, and recent advances of generating functional parametric images from the dynamic 0-15 water alone, would be the most important factors in clinical usage of this methodology. (C) 2004 Published by Elsevier B.V.

The rupture of atherosclerotic plaques and the resultant thrombus formation are mainly responsible for myocardial and cerebral infarctions. Thus, the detection of vulnerable plaques in atherosclerotic lesions has been desired, and attempts to image them with [(18)F]FDG are ongoing. Intimal thickening can be observed both in stable and vulnerable plaques; however, in vulnerable plaque, the lesion is inflamed, and the infiltrated macrophages cause the rupture of such plaques. In this study, we investigated whether [(18)F]FDG-PET could specifically detect the vulnerable plaque, other than stable plaque, or not using an animal model of atherosclerosis, the Watanabe heritable hyperlipidemic (WHHL) rabbit. A helical CT angiogram was acquired at 180 min postinjection of [(18)F]FDG, and PET scanning was carried out for 15 min from 210 min postinjection of [(18)F]FDG. At 4 h postinjection of the radiotracer, the aortas were removed, and the radioactivity was measured. Then, each arterial segment was embedded in paraffin, and consecutive 5-mum-thick slices were prepared. They were subjected to Azan-Mallory staining or immunohistochemical staining for measurement of intimal thickness and macrophage number. In the aortas of the WHHL rabbits, intense [(18)F]FDG radioactivity was detected with PET, while little radioactivity was seen in the aortas of control rabbits. Actually, in the removed aortic segments [(18)F]FDG accumulated significantly higher in the aortas of the WHHL rabbits than in those of the control rabbits. Furthermore, in the atherosclerotic lesions of the WHHL rabbits, the [(18)F]FDG uptake was well correlated with macrophage number. On the other hand, the correlation between [(18)F]FDG uptake and the area ratio of the intima to the whole cross-section was poor. These results suggest that the detected radioactivity with [(18)F]FDG-PET in the atherosclerotic lesion is associated with macrophage density. Since macrophages are responsible for plaque vulnerability, [(18)F]FDG imaging should be useful for selective detection of vulnerable plaques. (C) 2004 Elsevier B.V. All rights reserved.

The values of cerebral blood flow (CBF) and vascular volume (V-0) can be estimated using (H2O)-O-15 dynamic PET and the two-compartment model. In this study, we present a method that can generate parametric images of both CBF and V-0, with improvement of image quality, by a single computational procedure. This method is based on the two-compartment model, and employs linear least square algorithm and cluster analysis for parameter estimation and suppressing noise on image data, respectively. The results in computer simulation showed that this method could provide the reduction of error in parameter estimation, as well as noise on parametric images of both CBF and V-0, and the smaller effect of changes of CBF and V-0 on the estimation of both parameters. In the PET study, this method could provide the images of CBF and V-0 with improvement in quality, compared with those without clustering by showing the clear location of arterial vascular components on the V,, image. In the simulation, the error in parameter estimation was sufficiently small for K-1, but not for V-0. These results reveal that the presented method has the potential to make a contribution to the improved diagnosis of cerebral vascular disease and activation. (C) 2004 Published by Elsevier B.V.

Knowledg of the precision in the physiological parameters estimated by positron emission tomography (PET) is helpful for optimizing PET study and accurate diagnosis. Nonparametric bootstrap method proposed by Buvat is resampling techniques that can be used to accurately estimate the statistical properties of PET images in one scan and determine statistics of pixel values. The standard deviation (SD) of time activity curves (TAC) generated by region of interests (ROI) also are estimated by using the bootstrap method and the SD would propagate to estimated parameters such as blood flow. In order to evaluate the present method, a PET study for myocardial blood flow (MBF) measurement with (H2O)-O-15_PET was performed. The statistical properties of MBF were estimated and the effects of scan-duration time and ROI size on the SD of MBF were developed.

Motion of a subject during PET scanning is a significant source of errors in myocardial PET studies. We have developed a motion-correction system based on a rigid body model for thorax PET studies. The present study was intended to evaluate this system in the myocardial blood flow (MBF) study using O-15-labeled water on a normal volunteer. We artificially shifted the bed of the PET scanner horizontally by 30 mm to simulate the subject's repositioning, in addition to a natural movement in the order of 10 mm. The shift was monitored successfully using the system developed. The motion correction provided values of myocardial blood flow with a better reproducibility as compared with those without the motion correction. (C) 2004 Elsevier B.V All rights reserved.

In order to convert scatter uncorrected into corrected SPECT image, an image-based scatter correction (IBSC) method has been developed. The aim of this study was validation of its role as image converter from scatter uncorrected into corrected images equivalent to image corrected by conventional TEW method. IBSC method is executed in the post-reconstruction process and only requires an attenuation corrected main photo-peak image with broad mu value, I-AC(mub). The scatter component image is estimated by convolving I-AC(mub) with a scatter function followed by multiplying with an image-based scatter fraction (SF) function. The IBSC method was evaluated with Monte Carlo simulations and Tc-99m-ECD SPECT human brain perfusion studies obtained from five volunteers. The noise property of the scatter corrected image using IBSC method, I-IBSC was compared with that by TEW method, I-TEW, with simulated brain phantom images. Image contrast between gray with white matter in the human study was also compared between IBSC and TEW method. The global signal-to-noise (S/N) ratio of I-IBSC was decreased to 14% compared to that of I-AC(mub), whereas that of I-TEW was decreased to 21% In human brain imaging, significant difference in image contrast between IIBSC and TEW method was not observed (p&lt;0.05). In conclusion, the IBSC method could be applied to clinical brain perfusion SPECT as conversion I-AC(mub) into a scatter corrected image equivalent to I-TEW. This achieves a better noise property than the TEW method.

Recently, techniques for converting site-specific normal databases to other databases have been required for SPECT image statistical analysis. To implement scatter correction, we developed an image conversion technique named image-based scatter correction (IBSC). Furthermore, we evaluated the applicability of IBSC for SPM analysis. SPECT studies were performed on 28 normal volunteers and 10 patients with Alzheimer's disease (AD) using (123) I-IMP. Two sets of scatter uncorrected images, I-AC(mub), and a corrected image by TEW, I-TEW, were reconstructed with attenuation I-AC(mub) correction using Chang's method. Scatter corrected images by IBSC, I-IBSC, were generated from I-AC(mub). Normal databases of I-AC(mub) I-TEW and I-IBSC were compared by SPM analysis. The Z-score (=(mean - AD)/S.D.) Of I-TEW was compared with that of I-AC(mub) Significant differences (p&lt;0.05) between normal databases of I-AC(mub) and I-TEW observed at the global posterior cingulate and precuneus regions almost disappeared when I-TEW and I-IBSC were compared. The Z-score at the posterior cingulate by I-TEW was increased compared with that of I-AC(mub) We conclude that for SPM analysis of IMP-SPECT, IBSC can convert a normal database of scatter uncorrected images into corrected images, which is equivalent to correction by a conventional TEW method. Scatter correction may improve the ability to detect AD. (C) 2004 Elsevier B.V. All rights reserved.

Head movement during positron emission tomography (PET) studies causes loss of image quality and quantity and is problematic for brain PET study. During the PET scan, the head of the subject is often fixed by a head holder. However, the head holder is not perfect and it is sometimes difficult to use the head holder for a less cooperative patient. Moreover, head fixation might generate unwanted signals in neural activation studies. There are several software packages, such as AIR and SPM, offering software tools to correct head motion between two scans. These tools, however, cannot correct head motions during scanning. We developed a system to correct the head motion during PET scanning using list-mode acquisition and an optical tracking system. To compensate for escaped photon from the FOV of the PET scanner, the concept of a "virtual ring" was introduced. The present system has the potential to do real-time motion correction during PET scanning and makes it possible to scan a subject without any head fixation, which provides a new aspect of brain research using PET. (C) 2004 Elsevier B.V. All rights reserved.

MRI (magnetic resonance imaging) with 129Xe has gained much attention as a diagnostic methodology because of its affinity for lipids and possible polarization. The quantitative estimation of net detectability and stability of hyperpolarized 129Xe in the dissolved phase in vivo is valuable to the development of clinical applications. The goal of this study was to develop a stable hyperpolarized 129Xe experimental 3T system to statistically analyze the dissolved-phase 129Xe signal in the rat lungs. The polarization of 129Xe with buffer gases at the optical pumping cell was measured under adiabatic fast passage against the temperature of an oven and laser absorption at the cell. The gases were insufflated into the lungs of Sprague-Dawley rats (n=15, 400-550 g) through an endotracheal tube under spontaneous respiration. Frequency-selective spectroscopy was performed for the gas phase and dissolved phase. We analyzed the 129Xe signal in the dissolved phase to measure the chemical shift, T2*, delay and its ratio in a rat lungs on 3T. The polarizer was able to produce polarized gas (1.1±0.47%, 120 cm3) hundreds of times with the laser absorption ratio (25%) kept constant at the cell. The optimal buffer gas ratio of 25-50% rendered the maximum signal in the dissolved phase. Two dominant peaks of 211.8±0.9 and 201.1±0.6 ppm were observed with a delay of 0.4±0.9 and 0.9±1.0 s from the gas phase spectra. The ratios of their average signal to that of the gas phase were 5.6±5.2% and 4.4±4.7%, respectively. The T2* of the air space in the lungs was 2.5±0.5 ms, which was 3.8 times shorter than that in a syringe. We developed a hyperpolarized 129Xe experimental system using a 3T MRI scanner that yields sufficient volume and polarization and quantitatively analyzed the dissolved-phase 129Xe signal in the rat lungs. © 2004 by Japanese Society for Magnetic Resonance in Medicine.

The difference in tracer arrival times between the external radiation detector and the brain following administration of radioactivity (delay time) must be estimated correctly in order to quantitatively measure regional cerebral blood flow (rCBF) with positron emission tomography and [ 15O]H 2O by autoradiographic method. Instead of intervenous injection of [ 15O]H 2O, bolus inhalation of [ 15O]CO 2 gas is sometimes used to simplify the measurement of rCBF. In the case of [ 15O]CO 2, radioactive gas in mask and nasal cavity contributes large artifact on the sinogram data and it is difficult to estimate delay time from the sinogram data. In this paper, we proposed a new method to estimate the delay time using the sinogram data and the attenuation map (attenuation weighted sinogram method). In the present method, the attenuation map was used to eliminate the effect of the gas outside the brain region from the sinogram data. For the validation of the present method, PET data with [ 15O]CO 2 (n = 10) were analyzed. Three methods, namely the image method, the sinogram method and the attenuation weighted sinogram method were used to estimate the delay time. The estimated delay times and calculated rCBF images by three methods were compared. Due to the radioactivity outside of the brain, the sinogram method significantly overestimated the delay time and thus underestimated the rCBF value compared with the image base method. On the other hand, there were good agreements between the delay times estimated by the attenuation weighted sinogram method and the image method. The present method can eliminate the effect of the radioactivity outside of the brain on the sinogram data and estimate the delay time accurately and fast enough for clinical use.

The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) during physiologic and pathophysiologic conditions remains the subject of debate. In the present study, we have developed a theoretical model for oxygen delivery and metabolism, which describes the diffusion of oxygen at the capillary-tissue interface and the nonlinear nature of hemoglobin (Hb) affinity to oxygen, allowing a variation in simple-capillary oxygen diffusibility, termed "effective oxygen diffusibility (EOD)." The model was used to simulate the relationship between CBF and CMRO2, as well as oxygen extraction fraction (OEF), when various pathophysiologic conditions were assumed involving functional activation, ischemia, hypoxia, anemia, or hypo- and hyper-capnic CBF variations. The simulations revealed that, to maintain CMRO2 constant, a variation in CBF and Hb required active change in EOD. In contrast, unless the EOD change took place, the brain allowed small but significant nonlinear change in CMRO2 directly dependent upon oxygen delivery. Application of the present model to quantitative neuroimaging of CBF and CMRO2 enables us to evaluate the biologic response at capillary level other than Hb- and flow-dependent properties of oxygen transport and may give us another insight regarding the physiologic control of oxygen delivery in the human brain.

The equivalent mixture of cis-3-hexenol and trans-2-hexenal (hexenol/hexenal), 'green odor', is known to have a healing effect on the psychological damage caused by stress. Behavioral studies in humans and monkeys have revealed that hexenol/hexenal prevents the prolongation of reaction time caused by fatigue. In the present study, we investigated which brain regions are activated by the odor of hexenol/hexenal using positron emission tomography with alert monkeys. Regional cerebral blood flow (rCBF) in the prepyriform area (the primary olfactory cortex) was commonly increased by the passive application of odor: acetic acid, isoamylacetate or hexenol/hexenal. We observed rCBF increases in the orbitofrontal cortex (the secondary olfactory cortex) by these olfactory stimuli in two of three monkeys, and found no predominance of laterality of the activated hemisphere. Furthermore, rCBF increase in the cerebellum was observed in two of three monkeys, and the odor of acetic acid increased rCBF in the substantia innominata in all monkeys. In addition to these olfactory related regions, the anterior cingulate gyrus was activated by the odor of hexenol/hexenal. These findings suggest that the increase of rCBF in the anterior cingulate gyrus by the odor of hexenol/hexenal may contribute the healing effects of this mixture observed in the monkey. © Oxford University Press 2003 all right reserved.

Pinhole collimation can be used to improve spatial resolution in SPET. However, the resolution improvement is achieved at the cost of reduced sensitivity, which leads to projection images with poor statistics. Images reconstructed from these projections using the maximum likelihood expectation maximization (ML-EM) algorithms, which have been used to reduce the artefacts generated by the filtered backprojection (FBP) based reconstruction, suffer from noise/bias trade-off: noise contaminates the images at high iteration numbers, whereas early abortion of the algorithm produces images that are excessively smooth and biased towards the initial estimate of the algorithm. To limit the noise accumulation we propose the use of the pinhole median root prior (PH-MRP) reconstruction algorithm. MRP is a Bayesian reconstruction method that has already been used in PET imaging and shown to possess good noise reduction and edge preservation properties. In this study the PH-MRP algorithm was accelerated with the ordered subsets (OS) procedure and compared to the FBP, OS-EM and conventional Bayesian reconstruction methods in terms of noise reduction, quantitative accuracy, edge preservation and visual quality. The results showed that the accelerated PH-MRP algorithm was very robust. It provided visually pleasing images with lower noise level than the FBP or OS-EM and with smaller bias and sharper edges than the conventional Bayesian methods.

In quantitative pinhole SPECT, photon penetration through the collimator edges (penetration), and photon scattering by the object (object scatter) and collimator (collimator scatter) have not been investigated rigorously. Monte Carlo simulation was used to evaluate these three physical processes for different tungsten knife-edge pinhole collimators using uniform, hotspot and donut phantoms filled with Tl-201, Tc-99m, I-123 and I-131 solutions. For the hotspot phantom, the penetration levels with respect to total counts for a I mm pinhole aperture were 78%, 28% and 23% for I-131, I-123 and Tc-99m, respectively. For a 2 mm aperture, these values were 65% for I-131, 16% for I-123 and 12% for Tc-99m. For all pinholes, Tl-201 penetration was less than 4%. The evaluated scatter (from object and collimator) with a hotspot phantom for the I mm pinhole was 24%, 16%, 18% and 13% for Tl-201, Tc-99m, I-123 and I-131, respectively. Summation of the object and collimator scatter for the uniform phantom was approximately 20% higher than that for the hotspot phantom. Significant counts due to penetration and object and collimator scatter in the reconstructed image were observed inside the core of the donut phantom. The collimator scatter can be neglected for all isotopes used in this study except for I-131. Object scatter correction for all radionuclides used in this study is necessary and correction for the penetration contribution is necessary for all radionuclides but Tl-201.

Correction of scatter and attenuation is essential for quantitative SPECT. In this work, we evaluated the accuracy gained from a method of transmission-dependent convolution subtraction (TDCS) in the quantitation of activity that is highly concentrated in the striatum (STR). Methods: SPECT data were acquired from an I-123-containing phantom with a constant activity in the STR but differing background (BKG) activities, so as to simulate various STR/BKG ratios (19.7:1, 9.7:1, 4.8:1, 1.9:1, and 1:1). In a study of healthy humans (n = 6), a transmission scan followed by an emission scan was performed 24 h after injection of I-123-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane (I-123-beta-CIT). All SPECT data was reconstructed with ordered-subset expectation maximization. TDCS was applied for scatter correction. Values of activity in the STR and occipital lobe (for BKG) were used to calculate binding potential V-3" (= [STR - BKG]/BKG). The effect of SPECT collimator dependency on scatter correction was also evaluated for 6 collimators from 3 different SPECT cameras in the phantom experiment. Results: Scatter correction in the phantom experiment increased the measured values of STR activity (36.2%), resulting in a substantial increase in V-3" (66.1%). Scatter and attenuation corrections with recovery correction showed an overall bias of -7.3% for the STR, -4.0% for BKG activity, and -7.8% for V-3". TDCS corrections of phantom activities were relatively uniform for the 6 different collimators, with variabilities of &lt;5.5% for the STR and &lt;3.0% for BKG activities. TDCS correction of human I-123-beta-CIT images was of a similar, although slightly larger, magnitude than for the phantom data, with increased V-3" values of 9.4 +/- 2.3 and 4.9 +/- 0.6, with and without scatter correction, respectively. Conclusion: The TDSC method significantly improved the accuracy of SPECT images with a nonuniform distribution of activity highly concentrated in central regions. The value of V-3" was significantly increased in phantom and human data, with most of the improvement derived from an increase in STR activity. This scatter correction method was approximately equally useful with data from the 6 different collimators and is recommended for more accurate quantitation of nonuniformly distributed brain activities.

Objectives: Accurate p maps are important for quantitative image reconstruction in SPECT. The Compton scatter energy window (CSW) technique has been proposed to define the outline of objects. In this technique, a lower energy window image is acquired in addition to the main photopeak energy window. The image of the lower energy window is used to estimate the edge of the scanned object to produce a constant attenuation map. The aim of this study was to investigate the dependency of CSW on the spatial and energy distribution of radioisotope to predict the edges of objects. Methods: Two particular cases of brain study were considered, namely uniform distribution and non-uniform distribution using Monte Carlo simulation and experiments with uniform cylindrical phantom and hotspot phantom. The phantoms were filled with water and a radioactive solution of Tc-99m. For each phantom, 20%, 30%,40% and 50% thresholds of the mean profile were applied to estimate E-wt, the energy window for minimum difference between the estimated and true edge of objects. Results: The E-wt's were 100-120 keV with a 40% threshold and 92-114 keV with a 30% threshold for uniform and hotspot phantoms, respectively. Conclusions: Edge of the objects with CSW technique varies with energy window and thresholds. Careful setting of the energy window is required to use the CSW technique.

A new input function monitoring system has been developed and evaluated using a GSO detector assembly for both PET and SPECT quantitative studies. Energy resolutions were 11% for 511 keV photons, 20% for 140 keV(Tc-99m) photons and 28% for 70 keV(Tl-201) photons, enabling the use of this system in SPECT studies. The paired assembly of crystals provided an absolute sensitivity of approximately 7% for PET tracers and 70% for Tc-99m and Tl-201 (SPECT tracers). Multiple arrangement of paired detectors would make it possible to correct for the transit time of radioactivity through the catheter tube. This study demonstrates that the present system can be of use in both clinical and small animal studies using SPECT and PET tracers.

Since recent Positron Emission Tomography (PET) scanner has a high spatial resolution, head motion during brain PET study could cause motion artifact on the image, which might make serious problem in terms of image quality as well as image quantity. Several techniques have been proposed to correct head movement in PET images, for example SPM and AIR software packages. However these techniques are only applicable for correcting the motion between two scans and assume no head movement during scanning. The aim of this study is to develop a technique to correction head motion in event-by-event base during a PET scan using a list-mode data acquisition and optical motion tracking system (POLARIS). This system uses a rebinning procedure whereby the lines of response (LOR) are geometrically transformed according to six-dimensional motion data detected by the POLARIS. A motion-corrected Michelogram was directly composed using the reoriented LOR. In the motion corrected image, the blurring artifact due to the motion was reduced by the present technique. Since the list-mode acquisition stores data as event-by-event base, the present technique makes it possible to correct head movement during PET scanning and has a potential for real-time motion correction of head movement.

A method has been developed for repeat quantitation of physiological parameters from multiple administrations of radiotracers. The background activity distribution due to the previous tracer administration was formulated according to a compartment model, so as to allow initiation of the next scan while residual radioactivity exists, minimizing the intervals between scans, with the minimum enhancement of the statistical noise. Theoretical simulation for repeat administration of (H2O)-O-15 demonstrated that the transient tracer distribution was highly weighted on transient rCBF immediately after the previous tracer administration, and that the change of rCBF after a certain period has only small contribution to the estimated tracer distributions. Another set Of Simulation showed that estimated rCBF was sensitive to the transient rCBF only immediately after the tracer administration, and that the change after a certain period does not contribute to the rCBF estimated by the present approach. This technique was then applied to a clinical study of serial administration of (H2O)-O-15 and O-15(2), and demonstrated that the yielded CBF and CMRO2 are well agreed with those determined based on the classical 3-step measurements. We thus conclude that quantitation of physiological parameters can be determined by PET with much shorter examination interval as compared with the previous study protocol.

Transmission-dependent convolution subtraction (TDCS) technique is a promising technique in quantitative SPECT to subtract the scatter components from emission images. Usually a 20% photo-peak energy window is used in SPECT acquisitions. So far no investigation has been done to investigate the effect of energy windows to subtract the scatter components from emission images with the TDCS technique. To evaluate the energy dependency of the TDCS technique, SPECT acquisitions were performed for the photo-peak energy windows of 5% 10%, 15%, 20%, 25%, 30% and 35% by, acquiring the data of non-uniform and uniform phantom with Tc-99m radionuclide. The parameters of scatter fraction to be used in the TDCS technique were. estimated with the point sources placed in the water phantom. The estimated parameters were used in the TDCS technique to subtract scatter components from the data of corresponding energy windows of non-uniform and uniform phantom. Poisson noises were added to each projection's data of uniform phantom before scatter corrections. All data were reconstructed with OSEM algorithm. Energy window dependency of the TDCS technique was verified by comparing the coefficients of variance (COV) of the data of uniform phantom of each energy window. The non-uniform phantom results showed that the estimated parameters effectively estimated the scatter component from the projection images for each energy window. The COV for 5%, 10%, 15%, 20%, 25%, 30% and 35% energy window were 2.10%, 1.76%, 1.44 %, 1.39%, 1.34%, 1.37% and 1.61%, respectively. The COV in 25% window was lower than the COV of other energy windows. In the TDCS technique the photo-peak energy window 25% or 30% may be more effective to obtain emission images for higher statistics of counts, which may make scan time shorter.

PET and SPECT have been widely used to investigate the physiological function of animals in vivo. However, little efforts have been done to estimate absolute physiological parameters i.e. blood flow. of small animals. The present study was aimed at the absolute quantitation of myocardial blood flow of rats by means of the dynamic SPECT fitted with a pinhole collimator with a careful determination of the arterial input function (IF). The center-of-rotation was carefully aligned to the center of the field-of-view of a fixed gamma camera with the accuracy &lt; 0.05 mm. A rat was placed on a rotating device that fixes the rat in a stand position. The arterial blood samples were frequently collected and their radioactivity concentration was measured using a well counter cross-calibrated to the SPECT images. Dynamic SPECT (the step-and-shoot mode) was initiated at 5 min after the injection of 201TICl into the tail vein. Acquisition period was 10 sec at each rotation angle, and 120 view projection data were obtained. The 360-degree complete data sets were obtained at approximately 20 min interval for 5 time frames. Images were reconstructed by filtered-back projection technique with Feldkamp algorithm. The cross-calibration factor was determined using a cylindrical phantom of 5 cm diameter filled with the 201TICl solution. Regions-of-Interest were placed on the left ventricular wall to generate the tissue time activity curve (TTAC). TTAC and IF were fitted to the previously validated single-tissue compartment model to estimate the regional myocardial blood flow (rMBF) and volume of distribution (Vd) of thallium. The present system provided clear images of myocardial uptake of 201TICl, and the time-dependent change of the tissue radioactivity concentration in regional basis, which was statistically sufficient for applying the compartment model analysis. The kinetic analysis yielded the rMBF of approximately 0.77 ml/min/g, which appeared to be an acceptable value with a consideration of contribution of partial volume effect and other error sources. Vd of approximately 91.9 ml/ml was also consistent with the know value of potassium potential across the cell membrane. These results strongly suggested the potential of the dynamic pinhole SPECT as a tool for absolute quantitation of physiological parameters in small animals.

Measurements of the oxygen consumption in brain have been studied by PET. Autoradiographic method(ARG) was suggested (Mintum et al.) to yield CMRO2. This method required separately obtained information about CBF, CBV, thus time of 30-60 min. is required for three separate scans. To decrease the scan time, a new protocol was suggested as a rapid dual table method(ARG-D), in which [O-15]water injection scan and [O-15]O-2 inhalation scan are continuously carried out. Another method of weighted integration(WI) method with single 3 min. O-15(2) inhalation scan was suggested (Ohta et al.). We modified this method by taking into account the water re-circulation(WI-WR). In this study, the statistical noise properties and effects of error propagated from dispersion, delay, and volume of distribution on CMRO2 image, derived by these methods were evaluated. Tissue time activity curves was generated from typical blood time activity curves. A 80 % of noise at a peak in [O-15]water tissue time acticity curve was added to study the noise propagation and accuracy in CMRO2 image. Also dispersion, delay, and volume of distribution was varied and evaluated the error propagation. Methods of ARG, WI-WR and ARG-D, reproduce the given CMRO2 within 2% accuracy, while method WI gives CMRO2 5-15 The effect of noise in unit of %SD was 12 % for ARG, 25 % for WI and WI-WR, and 17 % for ARG-D method. On the basis of simulation study suggests that the ARG-D method developed could be used to estimate the CMRO2 values in clinic.

A new input function monitoring system has been developed using a GSO detector for both PET and SPECT quantitative studies. The paired assembly of crystals provided an absolute sensitivity of approximately 7 % for PET tracers and 70 % for Tc-99m and Tl-201 (SPECT tracers). This system was applied to clinical use and animal study such as monkey and rat. This study demonstrates that the present system can be of use in both clinical and small animal studies using SPECT and PET tracers.

For the application of a kinetic model to PET data, it is necessary to obtain the arterial input function. Since arterial blood sampling is invasive and labor intensive, a method to evaluate the input function without arterial blood sampling is important. In case of the [O-15]water injection study, because of the noise in the time activity curve obtained from PET reconstructed image round carotid artery region, a model based evaluation method might be promised. In this study, a model function is composed of combination of blood time activity curve function and tissue time activity curve function which is generated from blood activity curve function. Present method was applied to IS of dynamic PET scans of O-15 water (10 normal subjects, 10 : Rest, and 5 : Diamox) for normal volunteers. The time activity curve obtained was fitted with the above model function. The shapes of input function obtained was in agreement with that by arterial blood sampling. The accuracy of height of the peak was 14 % and the accuracy of area under the curve was 10 %. This study supposed that present method could be used for direct extraction of carotid artery input function from dynamic PET image, and could be used in the quantitative CBF study using O-15 water PET.

A head motion during brain imaging has been recognized as a source of image degradation and introduces distortion in Positron Emission Tomography (PET) image. There are several techniques to correct the motion artifact, but these techniques cannot correct the motion during scanning. The aim of this study is to develop a sinogram-based motion correction (SBMC) method to correct directly the head motion during PET scanning using a motion tracking system and list-mode data acquisition. This method is a rebinning procedure by which the lines of response (LOR) are geometrically transformed according to the current values of the six-dimensional motion data. Michelogram was recomposed using rebinned LOR and motion corrected sinogram was generated. In the motion corrected image, the blurring artifact due to motion was reduced by SBMC method. This method was applicable to real PET data acquired with list-mode and shows a potential for real-time motion correction of head motion during PET scanning.

Measurements of the oxygen consumption in brain have been studied by PET. Autoradiographic method(ARG) was suggested (Mintum et at.) to yield CMRO2. This method required separately obtained information about CBF, CBV, thus time of 30-60 min. is required for three separate scans. We developed a rapid dual table method, in which water and oxygen are continuously administrated with the 90-180 sec of water and 180 sec of oxygen scan. In order to derive the quantitative CNMO2 in PET scan, it is necessary to obtain the arterial blood time activity curve. In this study, a method to estimate the input functions corresponds to [O-15]water injection and [O-15]oxygen inhalation, in a continuously administration study, was developed. A method developed was model-based, employing a fitting method. In order to estimate the reliability of developed method, input functions of [O-15]water injection and [O-15]oxygen inhalation obtained separately in a clinical study was combined with time lag of 90 seconds and 180 seconds. The reproducibility was examined by comparing the blood input functions obtained from present method and from original input functions obtained in clinical study. After fitting the combined input function with model function, each input function of [O-15]water injection and [O-15]oxygen inhalation was derived. The whole shapes were in agreement with each other. This method could be used for estimation of each input function in continuously water and oxygen administrated study.

Recently list mode (event-by-event) data acquisition with Positron Emission Tomography (PET) has been widely noticed because the list mode acquisition is superior to the conventional frame mode data acquisition in terms of (1) higher efficiency of data storage, (2) higher temporal resolution and (3) higher flexibility of data manipulation. The aim of this study is to investigate the performance of list mode data acquisition with ECAT HR and HR+ PET scanners(CTI PET Systems). The cylindrical phantom (16 cm diameter and 16 cm long) filled with C-11 solution for HR and O-15 solution for HR+ was scanned several times varying the radioactivity with list mode and frame mode acquisitions. The scans with the septa (2D mode) and without the septa (3D mode) were also carried out in order to evaluate the effect of interplane septa on quality of the list mode data. The acquired list mode data were sorted to sinogram and reconstructed using filtered back-projection algorithm. The count rate performance of the list mode data was comparable to the frame mode data. However list mode acquisition could not be performed if radioactivity in the field-of-view was high (more than 3 mCi for 3D mode) due to lack of transfer speed for sending data from memory to hard disk. 10 replicated data set from one list mode data were generated to estimate the noise in the reconstructed image. The reconstructed images with 3D mode has more than 60 % better signal-to-noise ratio compared to the image with 2D mode. Generated Me size of fist mode was also evaluated. In the case of HR+ with 3D list mode, list mode data with 2.31 MBytes/s for 1mCi injection were generated. Out results suggest that careful attention must be paid for protocol of the list mode data acquisition in order to obtain the highest performance of the PET scanner.

The purpose of this study was to develop a reliable and practical strategy that generates quantitative CBF and OEF maps accurately from PET data sets obtained with O-15-tracers. Sequential sinogram data sets were acquired after the administration of O-15-tracers, and combined single-frame images were obtained. The de lay time between sampled input function and the brain was estimated from the (H2O)-O-15 study with the whole brain and the arterial time-activity curves (TACs). The whole-brain TACs were obtained from the reconstructed images (image-base method) and the sinogram data (sinogram-base method). Six methods were also evaluated for the dead-time and decay correction procedures in the process of generating a single-frame image from the dynamic sinogram. The estimated delay values were similar with both the sinogram-based and image-based methods. A lumped correction factor to a previously added single-frame sinogram caused an underestimation of CBF, OEF and CMRO2 by 16% at maximum, as compared with the correction procedure for a short sinogram. This suggested the need for a dynamic acquisition of a sinogram with a short interval. The proposed strategy provided an accurate quantification of CBF and OEF by PET with O-15-tracers.

Attenuation and scatter of photons are the main causes that hinder the quantification of regional cerebral blood flow (rCBF) value by single photon emission computed tomography (SPECT), using 99mTc-Ethyl cysteinate dimer (ECD). We investigated the effects of attenuation correction and scatter correction on rCBF values with 99mTc-ECD SPECT. In particular, the applicability of uniform attenuation maps (μ maps) was evaluated in terms of errors on the estimated CBF values and the optimal threshold levels for extracting brain contours. SPECT scans were performed on seven subjects, in the presence of 99mTc-ECD. Quantitative K 1 images were computed using the reconstructed images and the input function obtained with the frequent arterial blood sampling method. The images were reconstructed by the ordered subset expectation maximization (OSEM) reconstruction in which uniform and segmented μ maps were used for attenuation correction with and without scatter correction. The transmission-dependent convolution subtraction technique was utilized for scatter correction. Segmented and uniform μ maps were generated from magnetic resonance (MR) images. We also produced uniform μ maps using ECD images obtained at various threshold levels and μ values (0.11, 0.15, and 0.172 cm -1). Scatter correction improved the image contrast dramatically. There were no significant differences between K 1 images with attenuation and scatter corrections assuming a uniform μ map (not 0.15 but 0.172 cm -1) and those corrected with segmented μ maps for most regions. However, in the former images, values were overestimated for deep structures (e.g., overestimation of 9.5% in the striatum and 7.3% in the central semi oval). This small but significant error was also observed in phantom studies and Monte Carlo simulations. We show that the overestimation using uniform μ maps is due to the weight of the path length in the bone. Absolute K 1 values were sensitive to the threshold level when the edge of the brain was determined from the ECD images, but the variation of the estimated K 1 was ±9.0% when the optimal threshold level was selected. This study suggests that the use of uniform attenuation μ maps provides reasonable accuracy, despite a small but significant error in deep structure regions, and that uniform μ maps may be provided from the emission data alone in this patient population.

A rapid multi-phase 3D tagging method based on TrueFISP sequence and its postprocessing algorithm are proposed for 3D regional myocardial motion analysis. SPAMM (SPAtial Modulation of Magnetization) plane tags perpendicular to the read-out direction were imposed for easy tagged-image analysis. To acquire images covering a whole heart within a single breath hold (25 heartbeats), an ellipsoidal cylinder region in the 3D k-space was filled in a 3D centric reordering manner. The post-processing algorithm was based on a Hessian matrix. Since the eigenvalues of the Hessian matrix defined at each voxel represent the curvature of the 3D image along the corresponding eigenvectors, a group of voxels, at which the largest eigenvalue was positive, much greater than the others and for when the corresponding eigenvector pointed almost along the read-out direction, were selected as a tag-plane. On the resulting images, clear tag contrast can be observed in spite of the small number of k-space lines. Almost all tag planes can be extracted with the algorithm. Those results show our methods are potentially clinically useful. © 2002 SPIE · 1605-7422/02/$15.00.

Japanese insurers had suffered catastrophic typhoon wind losses infrequently, and the losses made insurance operation unstable. The prediction of future loss scenarios associated with various return periods will be useful for insurers to make a future decision for insurance operation. Therefore we have developed a stochastic typhoon loss estimation model. In the model, huge numbers of typhoon events were stochastically generated on Japanese coastline from statistical distributions using Monte-Carlo method. After that gust wind speed are estimated for each events at various insured's locations. On the other hand, historical typhoon insurance claim data were analyzed to develop the damage function that is the relation between gust wind speed and degree of damaged buildings. By these functions to applying to the gust wind speed, various loss scenarios are obtained for each generated typhoon events. By extending the simulation area from Japan, the model also will be applied to other typhoon prone Asian countries.

Scatter correction (SC) has been shown to be essential for the quantification of brain perfusion in SPECT. However, in the case using the tracer showing a high activity accumulation in a small region with only a small activity in other areas of brain, the contribution of SC has yet to be studied. In this work, the impact of SC on the quantitative kinetic parameters derived from SPECT studies using a dopamine D2 receptor ligand was investigated. SPECT data were acquired dynamically with serial arterial blood sampling following intravenous injection of I-123 iodobezofuran (IBF). SC was performed with the previously validated transmission dependent convolution subtraction (TDCS) technique. Images were reconstructed by OSEM including the attenuation correction (AC), and FBP with post AC by Chang's method. Time activity curves (TACs) were generated from the striatum (STR) and occipital lobe (OCC) regions, with and without SC. Quantitative values of binding potential (BP) were then compared for four kinetic models, including the 3 compartment model (3COM), linear graphic plot (GRP), reference tissue method (RTM), and multi-regression method (MLR). SC changed both TACs of STR and OCC, and introduced significant changes in kinetic parameters, which induced the significantly increased BP in 4 kinetic models, compared to those without SC. The change in BP by SC was greater with 3COM model, than the other models. SC caused significant change in the shape of TACs in both STR and OCC, resulting in increased BP with all four kinetic methods. Likewise for the brain perfusion study, SC is required for the dopamine D2 receptor ligand studies in SPECT.

For the quantitation of cerebral blood flow (CBF) using (H2O)-O-15 PET, the measurement of arterial input function (AIF) is essential. In this study, for the simplified quantitation, we present a method for the blind and noninvasive extraction of carotid input function (CIF) from dynamic PET images. On 8 healthy volunteers, the PET scans of (CO)-O-15 and (H2O)-O-15 were sequentially performed with arterial blood sampling using beta-detector. With the inhalation of (CO)-O-15 gas, dynamic PET data was acquired. And then after the injection of (H2O)-O-15, dynamic PET scans of (H2O)-O-15 was perform. For 4 subjects, PET data for both rest and Acetazolamide (ACZ)-induced stress states were acquired, respectively. In the transverse dynamic images of (CO)-O-15 and (H2O)-O-15, the regions of dynamic images including carotid artery were selected by masking. Non-negative matrix factorization (NMF) algorithm was used to extract the CIF from the selected dynamic images. The partial volume correction estimated from dynamic (CO)-O-15 image, was applied to the extracted CIF. Whole brain CBF was estimated by kinetic analysis based on single compartment model. The error was analyzed using the area under the curve (AUC) and estimated CBF. NMF provided the good separation of the component of CIF from others in both images of (CO)-O-15 and (H2O)-O-15. The shape of estimated CIF by NNIF was similar with AIF measured by blood sampling. The AUC between the measured AIF and the estimated CIF was not so different at both rest and ACZ states. The difference of CBF before and after the injection of ACZ was also same between the measured AIF and the estimated CIF. These results show that NMF technique may be a tool for the noninvasive extraction of carotid input function, and this carotid input function might be used in the noninvasive quantitation of CBF using (H2O)-O-15 PET.

Attentiation correction (AC) is essential in order to get quantitative data with Positron Emission Tomography (PET). AC is normally carried out using transmission scan, which is obtained by scanning a subject with external radiation source before the administration of radiopharmaceuticals. The transmission scan makes longer time of PET study and additional radiation exposure to the subject. To avoid these inconveniences, we have aimed to develop a technique to generate attenuation map without the transmission scan for brain PET study. In the procedure, a special cap was designed to put on the head of the subject to be scanned for brain PET study. The surface of the cap has 22 points of markers. An optical tracking system was utilized to determine positions of these 22 markers. In order to obtain the reference attenuation map and positions of 22 markers, the cap was put on the head of a reference subject and the transmission scan was performed. In order to generate a subject's attenuation map, the subject put on the cap and the positions of 22 markers were determined by the optical tracking system. The thin plate spline (TPS) technique was employed to transform from the reference attenuation map to a target subject's attenuation map using 22 markers as control points. Preliminary experiment showed good agreement between the attenuation map computed by the present method and the actual attenuation map by the transmission scan. The present method has potential to shorten brain PET study and reduce the exposure of radiation to the subject. The method might provide an accurate attenuation map for single-photon emission computed tomography (SPECT) study.

A new input function monitoring system has been developed using the GSO detector assembly for both PET and SPECT quantitative studies. Due to the rapid rise time of the pulse (about 10nsec), the coincidence time window can he reduced &lt; 1nsec, reducing contribution of randoms associated with the high background activity surrounding the detector. Large light output improved the energy resolution of approximately 11% for 511keV photons, and 20% at 140 keV, as compared with the BGO detector, enabling the use of this system also in SPECT studies. The paired assembly of crystals provided the absolute sensitivity of approximately 7% for PET and 75% for PET tracers. Multiple arrangement of the paired detectors provided possibility of correcting for the transit time of radioactivity through the catheter tube. This study demonstrated that the present system can be of use in both clinical and small animal studies using SPECT and PET tracers.

We have developed a phoswich detector composed of a plastic scintillator and a BGO scintillator for a continuous blood-sampling system. The beta particle (positron) from the tube is detected by the plastic scintillator and emits 511-keV gamma photons. The BGO scintillator that is optically coupled to the plastic scintillator detects one of the gamma photons. Since the decay time of the plastic scintillator and the BGO are very different, it is possible to discriminate true (beta + gamma) events from background gamma events. First, the pulse height and pulse shape of plastic scintillator for beta particles and BGO scintillator for 511-keV gamma photons were measured and compared to estimate the possibility of the proposed method. Second, the proposed phoswich detector was fabricated and tested. Absolute sensitivity for Ga-68 (maximum energy of 1.90 MeV) and F-18 (maximum energy of 633 keV) positrons was measured and compared with conventional beta detector of similar size. The absolute sensitivity of the developed detector was 0.15 counts/Bq for Ga-68 positrons at the center of the detector. This was approximately five times higher in sensitivity than the conventional beta detector. The absolute sensitivity of the developed detector for F-18 positrons was 0.017 counts/Bq. The count rate of the developed detector was linear up to 10 kcps. The background count rate was small. These results indicate that the developed detector is useful not only for higher energy positrons such as O-15 but also for lower energy positrons such as F-18 or C-11.

Scatter correction is important for absolute quantification in SPECT. Among the approaches taken to achieve scatter correction, some methods using transmission information for scatter estimation require the scatter models based on the physical characteristics of the scattered photons. The influence of the SPECT collimator on the characteristics of the scattered photon, however, has not been well studied yet. In this paper, we investigate the relationship between scatter and collimator design for the use of the transmission.dependent convolution subtraction (TDCS) method. Monte Carlo simulations with various collimator acceptance angles and experiments with four collimators of two SPECT cameras were performed to obtain the scatter fraction (SF) and the line-spread function (LSF) of Tc-99m. The experiments with I-123 also used six collimators of three SPECT systems to obtain the SF and the LSF. In the simulations, the SF of Tc-99m did not change with the collimator acceptance angles. The LSFs measured for Tc-99m showed an excellent agreement between collimators. In the experiments for I-123, the SF was practically the same for the six collimators, although a small difference could be observed due to the septal penetration. Also, the shape of the LSF was very similar between the collimators, and the counts in the background region of reconstructed images did not differ when using different sets of TDCS parameters. These results reveal that scatter is independent of SPECT collimator design for Tc-99m even I-123, and that the TDCS could be applicable to scatter correction of I-123 using a unique collimator-independent set of parameters.

We synthesized [F-18]FCWAY, an analog of [carbonyl-C-11]WAY-100635 ([C-11]N-(2-(1-(4(2-methoxyphenyl)-piperazinyl)ethyl))-N-(2-(pyridinyl))cyclohexanecarboxamide}, by replacing the cyclohexanecarbonyl group acid with a trans-4-fluorocyclohexanecarbonyl group (FC). Control and preblocking studies were performed in anesthetized monkeys. Plasma radioactive metabolite analysis showed the presence of [F-18]FC and [F-18]fluoride. Tissue time-radioactivity curves were corrected for metabolite contamination based on separate positron-emission tomography studies of these two labeled metabolites. Analysis using a two-tissue compartment model gave distribution volume (V) estimates (mL/mL) ranging from 33 in frontal cortex to 4 in cerebellum. Preblocking data showed uniform V of 2-3 mL/mL. These studies demonstrate that [F-18]FCWAY has very similar kinetic characteristics to [C-11]WAY-100635. NUCL MED BIOL 27;5:493-497, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.

The goal of this study was to develop a suitable kinetic analysis method for quantification of 5-HT(2A) receptor parameters with [(11)C]MDL 100,907. Twelve control studies and foul preblocking studies (400 nmol/kg unlabeled MDL 100,907) were performed in isoflurane-anesthetized rhesus monkeys. The plasma input function was determined from arterial blood samples with metabolite measurements by extraction in ethyl acetate. The preblocking studies showed that a two-tissue compartment model was necessary to fit the time activity curves of all brain regions including the cerebellum-in other words, the need fur two compartments is not proof of specific binding. Therefore, a three-tissue compartment model was used to analyze the control studies, with three parameters fixed based on the preblocking data. Reliable fits of control data could be obtained only if no more than three parameters were allowed to vary. For routine use of [(11)C]MDL 100,907, several simplified methods were evaluated. A two-tissue (2T&apos;) compartment with one fixed parameter was the most reliable compartmental approach: a one-compartment model failed to fit the data adequately. The Logan graphical approach was also tested and produced comparable results to the 2T&apos; model. However, a simulation study showed that Logan analysis produced a larger bias at higher noise levels. Thus, the 2T&apos; model is the best choice for analysis of [(11)C]MDL 100,907 studies.

PET studies with [C-11]raclopride provide an indirect measure of changes in synaptic dopamine. Previously, we used the bolus-plus-infusion (B/I) method to assess dopamine response from the percentage change in binding potential (Delta BP) before and after administration of amphetamine. The goal of this work is to optimize the measurement of changes in neurotransmitter with the B/I method by choosing the optimal timing for pre- and poststimulus scanning. Methods: Two sources of variability in Delta BP were considered: within-subject and between-subject noise. A noise model based on a phantom study and human data was used to evaluate the within-subject noise. For between-subject noise, simulated time-activity curves were generated from measured [C-11]raclopride input functions. Optimal timing to measure bBP was determined and applied to human data. Results: According to the simulation study, the optimal scan times for pre- and poststimulus scans were 39-50 and 58-100 min, respectively. The optimal timing resulted in a 28% noise reduction compared with the original timing. By applying the optimal timing to human studies, the statistical significance of the difference in Delta BP between patients with schizophrenia and healthy volunteers increased from P = 0.038 to 0.012. Conclusion: careful assessment of the sources of noise in receptor imaging studies can increase the sensitivity of the B/I method for the detection of biologic signals.

The purpose of this study was to measure the cumulated activity and absorbed dose in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18-FDG) using whole-body positron emission tomography (PET) and magnetic resonance imaging (MRI). Whole-body dynamic emission scans for F-18-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method using S-values adjusted to the individuals. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the "Japanese reference man'' to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1x10(-1), 3.7x10(-2) and 2.8x10(-2) mGy/MBq. respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9x10(-2) mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1x10(-2) mSv/MBq, The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered F-18-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals.

We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient&apos;s body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals C-11-labelled Doxepin, C-11-labelled YM09151-2 and C-11-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6+/-6.2 and 32.1 +/- 12.0 kBq h MBq(-1) respectively, which are compared with the respective values of 33.3 +/- 9.9 and 23.9 +/- 6.2 kBq h MBq(-1) with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92 x 10(-3), 7.08 x 10(-3) and 7.65 x 10(-3) mSv MBq(-1) respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements.

In the steady stale method, O-15-labeled gases ((CO2)-O-15, O-15(2) and (CO)-O-15) are administered to the body by continuous inhalation in various clinical PET studies, During inhalation, the nasal cavity and major airway may obtain a substantial amount of dose, being the source organs as well as the target organs, The internal absorbed dose to those organs and their contribution to the other target organs have not been calculated by the MIRD method, To calculate the internal dose in the MIRD method, the S values, the absorbed doses per unit of cumulated activities from nasal cavity and major airway to the other organs and vice versa, are needed, and these values are not available. Methods: In this study, we introduced a mathematical model of the nasal cavity and major airway to calculate their S values to 23 target organs and from 11 source organs to them, Individual experiments were performed to measure the total uptake percentage and body surface doses of O-15-labeled gases from continuous inhalation. Results: Using the body surface doses measured by thermoluminescent dosimeters, the cumulated activities of 11 source organs were estimated with the mathematical transformation method, acid then the internal absorbed doses in 23 target organs were calculated by the MIRD method, Our experimental results were compared with the other results, and good agreements were observed, Conclusion: Among the target organs, the critical organ is the airway, and the absorbed dose is 2.57 x 10(-2) mGy . MBq(-1).

We have developed a miniature γ-ray endoscopic probe consisting of dual BGO detector probes for tumor detection inside the body cavities. The dual detector system was coupled with random coincidence to decrease the distant background radiation and to improve its spatial resolution for tumor localization. Method: The performance of the probe was investigated with a point source and a water phantom. A solution of positron emitting 18F isotope was used as the source. Clinical trials of the probe were done to localize tumors on the skin surface of four subjects carrying tumors close to the body surfaces, into whom 67Ga-citrate and 18F-FDG radiopharmaceuticals were injected. Results: Measurements indicated that the spatial resolution of the dual detector probes is around 1.5 times better than the single detector probe, and both single and dual detector endoscopic probe systems are capable of localizing a tumor on a large photon background. Conclusion: The endoscopic probe may be easier to insert inside body cavities due to the small crystal size and the flexible light guides. A single detector probe with higher sensitivity may be useful in searching for tumors over a wide intracavity area but a dual detector probe can be used for precise tumor localization. The detector probe may also be suitable for intraoperative observation.

This study proposes a new method for the pixel-by-pixel quantification of regional CBF (rCBF) with positron emission tomography and (H2O)-O-15 by using a reference tissue region. No arterial blood is required. Simulation studies revealed that the calculation of rCBF was fairly stable provided that the frame time was relatively short compared with total scan time. In practice, calculated CBF images correlated significantly with those obtained with the dynamic/integral method. Because the method accurately detects changes in CBF, it is particularly suitable for brain activation studies.

This study proposes a new solution for the quantification of rCBF pixel-by-pixel using PET and15O-H2O. The method represents an application of weighted integration that uses PET image only, requiring no input function of arterial blood. It generates the rCBF image quickly and automatically. Simulation studies revealed that the calculation of rCBF was fairly stable as long as a relatively shorter scan frame time and longer scan time were selected. Calculated images of actual PET study by this method correlated significantly with those identified by the dynamic/integral method. Because this procedure could detect whole brain CBF change between different studies as accurately as by the dynamic/integral method, this procedure may be the most suitable for brain activation studies. © 1995 Springer-Verlag.

A noninvasive blood radioactivity monitor system for Positron Emission Tomography (PET) study has been developed. This system has dual plastic scintillators to detect positrons from the wrist artery. One is for monitoring the blood radioactivity in artery and tissue, and another is for monitoring only in tissue, in order to subtract background radiation from tissue. We carried out phantom experiments for evaluating basic characteristics of this monitor system. Clinical experiments using O-15-labeled water were also done to compare this system with a conventional invasive monitor.

We proposed a new method ('Linearized method') to analyze neuroleptic ligand-receptor specific binding in a human brain using positron emission tomography (PET). We derived the linear equation to solve four rate constants, k(3). k(4). k(5). k(6) from PET data. This method does not demand radioactivity curve in plasma as an input function to brain, and can do fast calculations in order to determine rate constants. We also tested Nonlinearized method including nonlinear equations which is conventional analysis using plasma radioactivity corrected for ligand metabolites as an input function. We applied these methods to evaluate dopamine D-2 receptor specific binding of [C-11] YM-09151-2. The value of B-max/K-d = k(3)/k(4) obtained by Linearized method was 5.72 +/- 3.1 which aas consistent with the value of 5.78 +/- 3.4 obtained by Nonlinearized method.

A noninvasive method, the double-integration method, was developed to estimate regional cerebral blood flow (rCBF) by using O-15-water and PET, It relies on the acquisition of images with a correction of nonlinearity of brain tissue counts and can produce rCBF images on a pixel-by-pixel basis. Methods: Oxygen-15-water PET studies were performed on five normal human volunteers, and continuous sampling from the radial artery was conducted to generate functional CBF images according to the invasive catheterization method. The method centers on a computer-based program elaborated to calculate an arterial input function with an assumption of the whole brain blood rate of 50 ml/dl/min and consequently does not require arterial catheterization or arterial input function sampled from other studies. Results: The results indicate a good correlation between this method and the invasive method (r &gt; 0.966, p &lt; 0.001). Conclusion: This noninvasive method was demonstrated to provide an accurate estimation of rCBF and may simplify the activation studies.

We developed two types of miniature gamma-ray endoscopic probes to be inserted into a body cavity to detect invisibly small or deeply located tumors. One is a single detector system using a small BGO (Bi4Ge3O12) Crystal connected with a fiber optic light guide and the other is a dual detector system using a pair of single detector probes of the same size combined with a random coincidence technique. The performance of these detectors was tested by using a point source and a hollow cylindrical water phantom that simulated a body cavity. Measured and calculated results indicated that a dual detector system can be used for realistic tumor localization in a body cavity and a single detector system may be applied only for the detection of tumors in which radiopharmaceuticals that emit gamma rays of energy below about 200 keV are accumulated.

Absorbed doses were estimated after intravenous administration of F-18-labeled radiopharmaceuticals in Positron Emission Tomography (PET) studies. These radiopharmaceuticals, [F-18]-2-Fluoro-2-Deoxy-D-Glucose (FDG), 6-[F-18]Fluoro-L-Dopa (FDOPA) and F-18-5-Fluorodeoxyuridine (FdUR), are used in clinical research at the Cyclotron and Radioisotope Center of Tohoku University. Radiopharmaceutical biokinetic values were measured in humans or extrapolated from animal experiments. Selective organ uptake and rapid clearance of activity from the blood were observed. High activity in the bladder contents of humans was found. Calculations were made by the MIRD method, modified to account for the differences in physique and organ mass between in Caucasian Reference Man and the Japanese one. The bladder wall receives the highest dose (more than 1.23 x 10(-1) mGy/MBq) when any of these compounds are administered. Other organs receiving high doses are the heart, brain and kidneys from FDG; the kidneys and pancreas from FDOPA, and the kidneys and small intestine from FdUR. These organs received absorbed doses of more than 2.7 x 10(-2) mGy/MBq. Effective dose equivalents of 2.4 x 10(-2), 2.6 x 10(-2) and 3.3 x 10(-2) mSv/MBq were estimated in the intravenous administration of F-18-FDG, F-18-FDOPA and F-18-FdUR respectively.