Abstract For early diagnosis of atherosclerosis, we have developed a method to measure the initial minute surface roughness utilizing the natural longitudinal displacement of the intima-media-complex (IMC) on the carotid artery caused by pulsation. However, the IMC displaces not only in the longitudinal direction but also in the axial direction due to the pulsation. In the present paper, we proposed a novel method to remove the pulsation component by spatially convolving a high-pass filter with the measured depths of IMC in the longitudinal direction. The proposed method was validated by a phantom experiment, and the surface roughness with ten saw teeth was correctly measured. Next, the surface roughness of the carotid artery wall was measured for two healthy volunteers. The proposed method reduced the variation of measured surface roughness among beams compared to the previous method.

Abstract Improving the accuracy of heart wall motion measurement is essential to realise better cardiac function evaluation. This paper proposed a two-dimensional (2D) displacement estimation method with a high temporal resolution using the 2D complex cross-correlation of element RF signals of an ultrasonic probe between frames returned from the target scatterers. The application of the proposed method to the phantom displacement confirmed its principle. The estimated 2D displacement of the phantom was consistent with the set displacement. Subsequently, the method was applied to two healthy subjects to measure the 2D displacement of the interventricular septum during one cardiac cycle. Consequently, during systole and diastole, the movement of the myocardium was measured, and the results were validated.

Abstract Previously, we proposed an ultrasonic measurement method of arterial wall elasticity for the early detection of arteriosclerosis. Since vascular wall elasticity depends on blood pressure, in this study, the elasticity and viscosity were estimated using the hysteresis loop determined between the incremental strain in the wall and internal pressure by altering the internal pressure in the phantom and in vivo experiments. Consequently, both the estimated elasticity and viscosity increased with the internal pressure. Moreover, the slope of each hysteresis loop was larger than that of the approximated curve for the lowest blood pressures of the hysteresis loops with different internal pressures, as the blood pressure changed in the order of several hertz within a single heartbeat. Hence, we conclude that measuring both the blood pressure and the elastic and viscous moduli would be beneficial in comprehensively investigating more vessel wall properties that change with the progression of arteriosclerosis.

Abstract The thickness of the carotid arterial wall obtained from B-mode imaging using ultrasonic diagnostic devices is widely used for the diagnosis of atherosclerosis. However, the measurement interval in the lateral direction of the B-mode image depended on the beam interval (>100 μm). Therefore, the B-mode image is discrete in the lateral direction and cannot reflect changes in local and minute thicknesses. A method for measuring the roughness of the luminal surface of the wall was proposed using the displacement of the carotid arterial wall in the lateral direction during one heartbeat. In this method, the lateral measurement interval is much shorter than the beam interval, enabling a smooth measurement of the luminal surface. By simultaneously applying the method to the lumen-intima and medial-adventitia boundaries of the wall, we propose a novel method to measure the local and minute thicknesses of the carotid arterial wall.

Right ventricular failure (RVF) is a leading cause of death in patients with pulmonary hypertension; however, effective treatment remains to be developed. We have developed low-intensity pulsed ultrasound therapy for cardiovascular diseases. In this study, we demonstrated that the expression of endothelial nitric oxide synthase (eNOS) in RVF patients was downregulated and that eNOS expression and its downstream pathway were ameliorated through eNOS activation in 2 animal models of RVF. These results indicate that eNOS is an important therapeutic target of RVF, for which low-intensity pulsed ultrasound therapy is a promising therapy for patients with RVF.

Quantification of the dynamics of the carotid artery wall is useful in evaluating arteriosclerosis and atherosclerosis. As the carotid artery wall moves not only in the radial direction but also in the longitudinal direction, longitudinal movement should be considered in the analysis of the dynamic properties of the carotid artery wall. In this study, we propose a "lateral M-mode" method for visualizing the longitudinal movement of the intima-media complex (IMC). For the lateral M-mode, we set the target line in the longitudinal direction along the IMC and visualize the signals on the target line frame-by-frame by correcting the position of the target line along the radial displacement estimated by the phased tracking method. Differentiating the envelope signals between consecutive ultrasound beams was effective in visualizing the lateral movement of the IMC. The precision of the longitudinal displacement of the IMC estimated using the conventional block-matching method was validated by comparing it with the lateral M-mode. Because the conventional M-mode sequence plays an important role in evaluation of the dynamics of various tissues, the proposed "lateral M-mode" contributes to a detailed understanding of vascular dynamics and the development of diagnostic methods for vascular diseases.

In this study, the attenuation coefficient of blood was measured in vivo in the frequency range of 10–45 MHz. A procedure to correct the distribution of sound pressure in the measurements was discussed. Further, in vivo measurements were applied on the dorsal hand vein of four healthy subjects at rest and during avascularization. As a preliminary result, less variation of the measured attenuation coefficients was achieved by the proposed method. The comparable results of the inclination of the attenuation coefficients were obtained at rest and during avascularization. Furthermore, the attenuation coefficients during avascularization were markedly higher than those at rest, reflecting the degree of red blood cell aggregation promoted by avascularization. This method may aid in the non-invasive evaluation of blood properties reflecting the degree of red blood cell aggregation.

Abstract Differential bone marrow (BM) cell counting is an important test for the diagnosis of various hematological diseases. However, it is difficult to accurately classify BM cells due to non-uniformity and the lack of reproducibility of differential counting. Therefore, automatic classification systems have been developed in which deep learning is used. These systems requires large and accurately labeled datasets for training. To overcome this, we used semi-supervised learning (SSL), in which learning proceeds while labeling. We used three methods: self-training (ST), active learning (AL), and a combination of these methods, and attempted to automatically classify 16 types of BM cell images. ST involves data verification, as in AL, before adding them to the training dataset (confirmed self-training: CST). After 25 rounds of CST, AL, and CST + AL, the initial number of training data increased from 425 to 40,518; 3682; and 47,843, respectively. Accuracies for the test data of 50 images for each cell type were 0.944, 0.941, and 0.976, respectively. Data added with CST or AL showed some imbalances between classes, while CST + AL exhibited fewer imbalances. We suggest that CST + AL, when combined with two SSL methods, is efficient in increasing training data for the development of automatic BM cells classification systems.

For the early diagnosis of atherosclerosis, our group developed an ultrasound probe that can simultaneously measure blood pressure and vessel diameter at the same position. However, because the developed probe requires the blood vessel to be deformed by pushing to measure the blood pressure, it affects the estimation of the vessel's elastic modulus. In the present study, we derived a series of equations to estimate the elastic modulus of a blood vessel considering the pushing pressure applied by the ultrasound probe and the resultant deformation of the blood vessel. The validity of the proposed method was verified by numerical calculations, and then the method was applied to in vivo measurements. The proposed method resulted in fewer variations in the elastic modulus estimates with different pushing pressures compared with the conventional method.

In epidural anesthesia, it is difficult to specify the puncture position of the anesthesia needle. We have proposed an ultrasonic method to depict the thoracic spine using the different characteristics of reflection from bone and scattering from muscle tissue. In the present paper, we investigated the transmission aperture's width of the ultrasound probe to emphasize the differences in the reflection and scattering characteristics. First, we determined the optimum transmission aperture's width using a simulation experiment. Next, we measured reflection and scattering signals by changing the transmission aperture's width in a water tank experiment and confirmed that the results corresponded to the simulations. However, as the transmission aperture's width increased, the lateral resolution at the focal point improved. Therefore, better imaging of the human thoracic vertebrae can be achieved by selecting the transmission aperture's width, which considers the effect on lateral resolution.

Improving spatial resolution is a crucial issue in medical ultrasound. One of the improving methods is the post-processing of the received ultrasound RF signal. In the present paper, we proposed a design method for a noise-robust broadband filter based on the singular value decomposition of the received RF signal. To design a noise-robust filter, we proposed a logical method to determine the optimal truncated order of singular values, which was validated by applying the filter to noise-contaminated signals. Furthermore, the proposed filter applied to the wire phantom resulted in a better axial resolution than that obtained without the filter and with our previously designed Wiener filter.

Noninvasive measurement of the degree of red blood cell (RBC) aggregation is useful for evaluating blood properties. In the present paper, we proposed a method to estimate the size of RBC aggregates without using the power spectrum of the posterior wall by introducing a reference scattering spectrum. The reference power spectra were calculated using the power spectrum measured for an ultrafine wire with a hemispherical tip. They were applied to the size estimation of microparticles simulating RBC aggregates. The estimated sizes were close to the true values, which shows that the calculated reference power spectra were suitable for accurate size estimation. The proposed method was also applied to in vivo measurements, and the estimated sizes between at rest and in RBCs aggregated by avascularization were successfully differentiated. This demonstrates that the proposed method will be useful for estimating the size of RBC aggregates.

The heart wall has a multilayered structure and moves rapidly during ejection and rapid filling periods. Local strain rate (SR) measurements of each myocardial layer can contribute to accurate and sensitive evaluations of myocardial function. However, ultrasound-based velocity estimators using a single-frequency phase difference cannot realize these measurements owing to insufficient maximum detectable velocity, which is limited by a quadrature frequency. We previously proposed a velocity estimator using multifrequency phase differences to improve the maximum detectable velocity. However, the improvement is affected by a spatial discrete Fourier transform (DFT) window length that represents the locality of the velocity estimation. In this article, we theoretically describe that shortening the window increases the interference between different frequency components and decreases the maximum detectable velocity. The tradeoff between the maximum detectable velocity and the window length was confirmed through simulations and a water-tank experiment. Under the tradeoff, the Hanning window, which was used in previous studies, is not always appropriate for the local measurement of the velocity, which sometimes exceeds 100 mm [Formula: see text] depending on the subject, direction of the ultrasound beam to the heart wall, and cardiac periods. In the in vivo measurement with the short window, the Tukey window with a large flat part that has a high-frequency resolution and ameliorates the discontinuity at both edges of the windowed signal was appropriate to measure the maximum velocity. This study offers the potential for local measurements of each myocardial layer using the multifrequency velocity estimator with the appropriate window function and window length.

目的:医用超音波は,硬膜外麻酔時の穿刺位置の特定に用いられている.しかし,胸椎の構造は複雑であり,胸椎と筋組織の描出の区別は難しい.本研究では,超音波の反射・散乱特性の差異に基づき,骨と筋組織の描出を区別することを目的とする.方法:骨と筋組織からの受信信号の差を実験的に調べた.骨を強調するための新しいパラメータとして,理想的な遅延線上のみの受信信号の振幅と,その周囲の広い範囲における受信信号の平均振幅との比を提案した.結果:はじめに,基礎実験により,骨と筋組織からの受信信号の差を確認した.また,トリもも肉を用いたin vitro実験,ヒトにおけるin vivo実験により,その差を確認した.両実験において,提案法は,通常のBモード像と比較して,骨の描出を強調し,筋組織の描出を抑制することに成功した.結論:骨からの反射特性と筋組織からの散乱特性の差を用いて,提案法により,骨と筋組織を区別することができた.(著者抄録)

Since the treatment window of thrombolytic therapy for stroke is limited, new therapy remains to be developed. We have recently developed low-intensity pulsed ultrasound (LIPUS) therapy to improve cognitive dysfunction in mouse models of vascular dementia and Alzheimer’s disease. Here, we further aimed to examine whether our LIPUS therapy improves neurological recovery from ischemic stroke, and if so, to elucidate the mechanisms involved. In a mouse model of middle cerebral artery occlusion (MCAO), we applied LIPUS (32 cycles, 193 mW/cm2) to the whole brain 3 times in the first week (days 1, 3, and 5) after MCAO. We evaluated neurological functions using behavioral tests and performed histological analyses. Furthermore, to elucidate how LIPUS works within the injured brain, we also tested the effects of LIPUS in endothelial nitric oxide synthase (eNOS)-deficient (eNOS−/−) mice. In wild-type mice, the LIPUS therapy markedly improved neurological functions in the tightrope and rotarod tests at 28 days after MCAO. Histological analyses showed that the LIPUS therapy significantly increased the numbers of CD31-positive blood vessels in the perifocal lesion and doublecortin (DCX)-positive neurons in the ischemic striatum, indicating the angio-neurogenesis effects of the therapy. Importantly, these beneficial effects of the LIPUS therapy were totally absent in eNOS−/− mice. No adverse effects of the LIPUS therapy were noted. These results indicate that the LIPUS therapy improves neurological functions after stroke through enhanced neuro-angiogenesis in mice in vivo in an eNOS-dependent manner, suggesting that it could a novel and non-invasive therapeutic option for stroke.

Measurement of the myocardial strain rate (SR), with high spatial resolution, is useful in evaluation of the transmurality of myocardial infarction. As the SR distribution is calculated using velocities observed at multiple positions in the heart wall, it is necessary to estimate the local velocity to measure SR distribution. In the present study, our previously proposed local velocity estimator, with multifrequency phase differences, was used to measure SR distribution in the heart wall. The SR distribution measured with the proposed local velocity estimator revealed alternate layers of contraction and relaxation, which were not measured with the conventional velocity estimator with spatial averaging. The reproducibility of the SR distributions was confirmed in three consecutive heartbeats with three subjects. High-spatial-resolution SR measurement with the proposed local velocity estimator will allow myocardial layer-specific analysis in the transmural direction.

A measurement by transmitting ultrasonic non-focusing beams increases the temporal resolution but causes an error in the velocity measurements because of the lower signal-to-noise ratio (SNR) caused by the lower transmitted power and the lower spatial resolution. In the present study, we evaluated the relationship between the SNR and the transmitted beamwidth by the phantom experiment. The SNR decreased as the beamwidth became wider, and the measurement error increased when SNR was lower than 10 dB. Furthermore, the error factor due to the low spatial resolution more affected the measurement error than that due to the low transmitted power.

The in vivo measurement of the contractile response caused by electrical excitation has been studied to detect myocardial ischemia in its early stages. In the present study, we used our previously proposed local velocity estimator to measure the two-dimensional distribution of the strain rate using high-density beam scanning to obtain propagation of the local and minute contractile response in the heart walls of healthy humans. Alternate layers of contraction and relaxation were observed around the time phase representing the onset of the conduction of electrical excitation. The contraction propagated along the direction of the myocardial fiber in the myocardial layer. These results indicated that the electrical excitation conducted in each myocardial layer and the transmural shearing deformation occurred at the boundary between alternate layers of contraction and relaxation. The measurement of the propagation of the local and minute contractile response can reveal the effective contraction with the transmural shearing deformation.

We developed a single ultrasound probe to simultaneously measure blood pressure and changes in the diameter of the radial artery to estimate the wall viscoelasticity during flow-mediated dilatation (FMD). This probe can be used for the early diagnosis of arteriosclerosis. This paper introduces the pulse transit time method to accurately measure changes in blood pressure during FMD. Using the single ultrasound probe and the proposed method, in vivo experiments involving three subjects were conducted, and reasonable results on blood pressure were obtained. Thus, the usefulness of the pulse transit time method was experimentally confirmed.

Studies to investigate the ultrasound elasticity measurement of the carotid artery, for early detection of arteriosclerosis, are ongoing. In the long-axis cross-sectional measurement in vivo, the position where the intima-media complex (IMC) is visible on the B-mode image was assumed to be the central axis of the short-axis view of the carotid artery. However, the IMC is also visible near the central axis of the short-axis view of the carotid artery. In the present study, accuracy in elasticity measurement within the IMC visible range was evaluated through a phantom experiment. The elasticities of the posterior wall measured at plural points within the IMC visible range differed by up to 6%. From the experimental results, we concluded that for the highest accuracy, it is important to measure along the central axis of the short-axis view of the carotid artery.

Purpose: In coherence-based beamforming (CBB) using a generalized coherence factor (GCF), unnecessary signals caused by sidelobes are reduced, and an excellent contrast-to-noise ratio (CNR) is achieved in ultrasound imaging. However, the GCF computation is complex compared to the standard delay-and-sum (DAS) beamforming. In the present study, we propose a method that significantly reduces the number of GCF computations. Methods: In the previously proposed GCFreal, generation of the analytic signal for each element in the conventional GCF could be omitted. Furthermore, in GCF estimated from binarized signals (GCFB) proposed in the present study, the GCF value is calculated after the received signal of each element is binarized to reduce the computational complexity of the GCF. Results: The values of GCFB and GCFreal estimated from simulation and experimental data were compared. We also evaluated the image quality of B-mode images weighted by GCFB and GCFreal. Compared with GCFreal, GCFB was superior in reducing unnecessary signals but tended to reduce the brightness of the diffused scattering media. The CNR improvement was comparable for both methods. Conclusion: Generalized coherence factor estimated from binarized signals exhibits excellent CNR improvement compared to DAS. CNR improvements yielded by GCFB and GCFreal may depend on the observation target; however, under the conditions of the present study, comparable performances were obtained. Because GCFB can significantly reduce the computational complexity, it is potentially applicable in clinical diagnostic equipment.

A sharp depiction of the puncture point of the needle by differentiating muscle and bone is required for ultrasound-guided epidural anesthesia in the thoracic spine. In the present paper, we proposed a method for depicting the thoracic vertebral surface by utilizing the difference between scattering and reflection characteristics. This method estimates whether an object is a scatterer or a reflector referring to the scattering and reflection characteristics acquired in the water tank experiment. The proposed method was applied to basic experiments and in vivo experiments. In the basic experiments, the matching using root mean squared error allowed us to differentiate the depiction between scattering and reflection. In the in vivo experiment, we were able to estimate the position of the bone as a reflector and the slope was generally correct.

The quality of ultrasonic images can be improved by estimating the sound velocity accurately. Our previous study proposed a method to estimate the sound velocity based on the difference between the reception times of radiofrequency signals received by elements in an ultrasonic probe. Because the method assumed an ideal point scatterer as the target, the estimation error in the sound velocity increased with an increase in the target scatterer size. In the present study, the effect of the target scatterer size on the estimation method was examined, and the relationship between the size of the target scatterer and the estimation error in the sound velocity was quantified. Through simulations and basic experiments, it was confirmed that the estimation error was caused by the change in the reception time from the target surface and that the estimation error depended on the depth and size of the target scatterer.

AIMS: Heart failure with preserved left ventricular ejection fraction (HFpEF) is a serious health problem worldwide, as no effective therapy is yet available. We have previously demonstrated that our low-intensity pulsed ultrasound (LIPUS) therapy is effective and safe for angina and dementia. In this study, we aimed to examine whether the LIPUS therapy also ameliorates cardiac diastolic dysfunction in mice. METHODS AND RESULTS: Twelve-week-old obese diabetic mice (db/db) and their control littermates (db/+) were treated with either the LIPUS therapy [1.875 MHz, 32 cycles, Ispta (spatial peak temporal average intensity) 117-162 mW/cm2, 0.25 W/cm2] or placebo procedure two times a week for 4 weeks. At 20-week-old, transthoracic echocardiography and invasive haemodynamic analysis showed that cardiac diastolic function parameters, such as e', E/e', end-diastolic pressure-volume relationship, Tau, and dP/dt min, were all deteriorated in placebo-treated db/db mice compared with db/+ mice, while systolic function was preserved. Importantly, these cardiac diastolic function parameters were significantly ameliorated in the LIPUS-treated db/db mice. We also measured the force (F) and intracellular Ca2+ ([Ca2+]i) in trabeculae dissected from ventricles. We found that relaxation time and [Ca2+]i decay (Tau) were prolonged during electrically stimulated twitch contractions in db/db mice, both of which were significantly ameliorated in the LIPUS-treated db/db mice, indicating that the LIPUS therapy also improves relaxation properties at tissue level. Functionally, exercise capacity was also improved in the LIPUS-treated db/db mice. Histologically, db/db mice displayed progressed cardiomyocyte hypertrophy and myocardial interstitial fibrosis, while those changes were significantly suppressed in the LIPUS-treated db/db mice. Mechanistically, western blot showed that the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cGMP-protein kinase G (PKG) pathway and Ca2+-handling molecules were up-regulated in the LIPUS-treated heart. CONCLUSIONS: These results indicate that the LIPUS therapy ameliorates cardiac diastolic dysfunction in db/db mice through improvement of eNOS-NO-cGMP-PKG pathway and cardiomyocyte Ca2+-handling system, suggesting its potential usefulness for the treatment of HFpEF patients.

Local high-accuracy velocity estimation is important for the ultrasound-based evaluation of regional myocardial function. The ultrasound phase difference at the center frequency of the transmitted signal has been conventionally used for velocity estimation. In the conventional method, spatial averaging is necessary owing to the frequency-dependent attenuation and interference of backscattered waves. Here, we propose a method for suppressing these effects using multifrequency phase differences. The resulting improvement in velocity estimation in the heart wall was validated by in vivo experiments. In the conventional method, the velocity waveform exhibits spike-like changes. The velocity waveform estimated using the proposed method did not exhibit such changes. Because the proposed method estimates myocardium velocity without spatial averaging, it can be used for measuring heart wall dynamics involving thickness changes.

Purpose: Red blood cell (RBC) aggregation is one of the main factors that determines blood viscosity and an important indicator for evaluating blood properties. As a noninvasive and quantitative method for diagnosing blood properties, our research group estimated the size of RBC aggregates by fitting the scattered power spectrum from the blood vessel lumen with the theoretical scattering characteristics to evaluate the degree of RBC aggregation. However, it was assumed that the propagation attenuation of ultrasound in the vascular lumen was the same regardless of whether RBCs were aggregated or not, which caused systematic errors in the estimated size. Methods: To improve the size estimation accuracy, we calculated and corrected the attenuation of the blood vessel lumen during RBC aggregation and non-aggregation. The attenuation in the blood vessel lumen was calculated with the spectra acquired from two different depths. Results: In the basic experiments using microparticles, the estimation accuracy decreased as the concentration increased in the case of the conventional method, but the estimated size tended to approach the true size irrespective of the concentration, removing the propagation attenuation component with the proposed method. In the in vivo experiment on the human hand dorsal vein, the size was estimated to be larger during RBC aggregation and smaller during non-aggregation using the proposed method. Conclusion: These results suggest that the proposed method can provide precise size estimation by considering the propagation attenuation component regardless of differences in blood conditions such as RBC concentration and degree of aggregation.

Phased tracking (PT) is a high-precision ultrasonic technology that enables measurements of pulse pressure (PP). The aim of this study was to verify the accuracy of estimated PP using PT. Estimated PPs were compared with measured PPs in three sheep fetuses that were connected to an artificial placenta system. Similarly, estimated and measured PPs of 30 human neonates were compared. PP was calculated using the Water–Hammer equation (PP = ρ × PWV (pulse wave velocity) × ΔU). PWV was estimated by measuring the transit times of pulse waves at two sites along the aorta using the PT method, and ΔU was obtained by subtracting end-diastolic velocity from peak systolic velocity. The correlation between the estimated and measured PPs of the sheep fetuses was strong (r = 0.95, p ˂ 0.01), as was the case with the human neonates (r = 0.88, p ˂ 0.05). It can be concluded from the results of this study that PT may be a non-invasive alternative method used to predict PP.

Aim: This study aimed to compare the accuracy of fetal pulse pressure estimated with a vascular simulator with that obtained by a manometer (reference) and evaluate the pulse pressure in normal human fetuses and fetuses whose mothers received corticosteroids. Methods: Fetal pulse pressure was estimated as the product of blood flow velocity and pulse wave velocity, based on the water hammer equation. Ultrasonic raw radiofrequency signals for blood flow velocity were captured from the fetal descending aortas at the diaphragm level, and pulse wave velocity was simultaneously measured from different directions using the phased-tracking method. First, the precision and accuracy of pulse pressure in the estimated method were verified by a circulatory phantom simulator, which reproduced fetal blood flow using a pulsating pump. Then, the pulse pressure of 98 normal human fetuses after 17 weeks of gestation and the fetal pulse pressure in 21 mothers who received antenatal corticosteroids for fetal maturation were measured. Results: A significant correlation between the estimated pulse pressure values and the actual values was found in the phantom simulation (r = 0.99, P < 0.01). The estimated pulse pressure was significantly correlated with gestational age in normal fetuses (r = 0.74, P < 0.01). In steroid-treated pregnant women, fetal pulse pressure was observed to increase significantly on the second day of administration (P < 0.01). Conclusion: A noninvasive and accurate estimation model of fetal pulse pressure could be established using phased-tracking method, and this method has the potential to improve the assessment of human fetal hemodynamics.

Measurement of roughness in tens of microns on the luminal surface of the arterial wall is expected to provide the basis for an extremely early diagnosis of atherosclerosis. We have previously proposed a method for measuring the surface profile with micron-order precision by exploiting the longitudinal displacement due to pulsation and measuring the radial displacement due to surface roughness. This method allows estimation of the surface profile without influence by the region of heterogeneous sound velocity between the carotid artery and the skin. However, since the radial displacement of the carotid artery wall measured by ultrasound is not only due to the surface roughness but also the artery expansion due to pulsation, the latter has to be removed. In the present study, a novel method for locally removing radial displacements due to pulsation is proposed by using the spatial distribution of the pulsation component. The proposed method was verified by using a target consisting of urethane resin with a 10-µm-high sawtooth shape on the surface. The agreement with the actual profile was significantly improved by the proposed method. This result indicates that locally removing the pulsation component by the proposed method is useful for accurately estimating the micron-order surface profile of the arterial wall.

To establish an evaluation index for vascular endothelial function, we estimated the change of viscoelasticity of the radial artery during flow-mediated dilatation (FMD) using a developed ultrasonic probe that can simultaneously measure the blood pressure and the diameter at the same position. The elasticity after the recirculation from avascularization was larger than that at rest. Moreover, the elasticity increased 100 seconds after the recirculation. The absolute value of the elasticity was different from that before the avascularization. However, the tendency of the change was consistent with our previous study. These results show the possibility to measure the change of viscoelastic characteristics during FMD using a single ultrasonic probe.

We have developed a non-invasive and quantitative method to estimate the size of RBC aggregates by analyzing ultrasonic backscattering properties from blood vessel lumen and comparing those with the theoretical scattering characteristics. In the present study, we aimed to improve accuracy by calculating and correcting the attenuation in the blood vessel lumen. The attenuation in the blood vessel lumen was calculated with the spectra acquired from two different depths. In the basic experiments using microparticles, the estimated size tended to approach the true size irrespective of the concentration removing the propagation attenuation component by the proposed method.

To establish an evaluation index for vascular endothelial function, we developed an ultrasonic probe that can measure changes in blood pressure and blood vessel diameter at the same position in the radial artery. Based on phantom experiments, the pressure waveforms measured using the piezoelectric effect of the ultrasonic probe element and those using a pressure sensor exhibited a high correlation (correlation coefficient: r = 0.979 - 0.999). We confirmed the continuous measurement of the relationship between changes in blood pressure and the diameter from the in vivo experiments. We could then estimate the changes in viscoelasticity by calibrating the output from the probe element to the absolute blood pressure values in advance. The average coefficients of variations were 0.02 and 0.24 for elasticity and viscosity, respectively. This study demonstrated the possibility of measuring changes in the viscoelastic moduli of the radial arterial wall due to flow-mediated dilation using the developed ultrasonic probe.

An estimation of anisotropic viscoelasticity is important for evaluating muscle lesions. In the previous study, we proposed a method for estimating viscoelasticity in a local region by exciting a phantom specimen from both directions. In the present study, we observed the acoustic field having the locality and directivity generated by dual ultrasound excitation. In addition, the displacement distributions for the isotropic and anisotropic viscoelastic phantoms were measured, and the local generation of large displacement and its directionality was confirmed around the excitation focal point. Furthermore, we applied our viscoelasticity estimation method to the anisotropic viscoelastic phantom. The estimated shear modulus differed depending on the angle between the opposite direction of the ultrasound transducer projected on the phantom surface and longitudinal direction of the cylindrical urethane rubber bundle in the anisotropic viscoelastic phantom. Therefore, the viscoelasticity estimation method in the present study could estimate anisotropic viscoelasticity locally.

Purpose: The generalized coherence factor (GCF), an adaptive beamforming technique, can reduce unnecessary signals from an unfocused position without reducing the contrast-to-noise ratio. However, the computational complexity of this method is large compared to the conventional delay-and-sum (DAS) beamformer. In the present paper, we propose a novel method to achieve the same reduction effect of unnecessary signals with a smaller computational load than that of the conventional GCF approach. Methods: One of the factors increasing the computational complexity of the GCF-based beamformer compared with DAS is the generation of analytic signals at receiving elements. We clarified the mechanism of generating unnecessary signal components to enable the calculation of the GCF value directly from real signals without generating analytic signals. Furthermore, we proposed a method to filter out these components without generating analytic signals. Results: The GCF values obtained using the proposed and conventional methods were compared and verified using the actual data acquired from a phantom with an ultrasound diagnostic system. We also compared the B-mode images. As a result, equivalent GCF values and similar B-mode image quality were achieved with the proposed method with reduced computational complexity. Conclusion: With the proposed method, generation of analytic signals at receiving elements can be omitted, and as a result, the computational load of the GCF method can be greatly reduced, while preserving the effect of reducing unnecessary signals like with the conventional method.

Purpose: Medical ultrasound is often used to specify the puncture position during epidural anesthesia. However, visualization of the thoracic spine is difficult because of the complex structure, i.e., it is difficult to determine whether the thoracic spine or muscle is depicted. Therefore, this study aims to distinguish bone from muscle tissue using the differences in reflection and scattering characteristics of ultrasound. Methods: We experimentally investigated the difference in signals received from bone and muscle. We proposed a new parameter utilizing the ratio of the amplitude of the received signals averaged in a wide range around the ideal delay line and that only along the ideal delay line, to emphasize the bone. Results: First, we confirmed the difference in signals received from bone and muscle tissue by basic experiments. We also investigated the difference by in vitro experiments using chicken thigh and in vivo experiments in humans. In both experiments, the proposed method succeeded to clearly depict bone, suppressing the depiction of muscle, compared with conventional B-mode imaging. Conclusion: Using the difference in the characteristics of reflection from bone and scattering from muscle tissue, we could distinguish bone from muscle tissue with the proposed method.

Purpose: From the correlation between the blood flow dynamics and wall dynamics in the left ventriocle (LV) analyzed using echo-dynamography, the ejection mechanisms and role of the intra-ventricular vortex in the LV were elucidated in detail during the pre-ejection transitional period (pre-ETP), the very short period preceding LV ejection. Methods: The study included 10 healthy volunteers. Flow structure was analyzed using echo-dynamography, and LV wall dynamics were measured using both high-frame-rate two-dimensional echocardiography and a phase difference tracking method we developed. Results: A large accelerated vortex occurred at the central basal area of the LV during this period. The main flow axis velocity line of the LV showed a linearly increasing pattern. The slope of the velocity pattern reflected the deformity of the flow route induced by LV contraction during the pre-ETP. The centrifugal force of the vortex at its junction with the main outflow created a stepwise increase of about 50% of the ejection velocity. Conclusion: Ejection of blood from the LV was accomplished by the extruding action of the ventricular wall and the centrifugal force of the accelerated vortex during this period. During ejection, acceralated outflow was considered to create a spiral flow in the aorta with help from the spherical structure of the Valsalva sinus.

We have evaluated the viscoelastic properties of arterial walls by measuring the relationship from radial arterial pressure to the change in arterial diameter to evaluate vascular endothelial functions. In our previous study, these parameters were measured at different positions, which caused timing errors. In the present study, a novel probe was developed to measure both radial arterial pressure and the change in arterial diameter at the same position. The central piezoelectric element of the linear array probe was disconnected from the ultrasonic diagnostic equipment and used to measure the arterial pressure. To obtain the blood pressure waveform, the output was integrated and calibrated using the systolic and diastolic pressures measured by a conventional sphygmomanometer. The arterial diameter was measured using the other 191 elements of the ultrasonic diagnostic apparatus via the phased-tracking method. The hysteresis loop, which is the relationship between the change in diameter and instantaneous pressure during a heartbeat, and thus reflects the viscoelasticity of the arterial wall, was measured successfully. The reproducibility for successive two heartbeats was confirmed for two subjects.

For early diagnosis of arteriosclerosis, we have developed methods of measuring arterial wall characteristics such as local elastic modulus and luminal surface roughness by measuring the arterial wall movement. Since the carotid artery moves not only in the radial direction but also in the longitudinal direction due to the contraction of the heart, the movement in the longitudinal direction has to be estimated and introduced into measurement methods of arterial wall characteristics. However, the estimation of the longitudinal movement of the intima-media complex (IMC) is difficult because the acoustic property of IMC is homogeneous in the longitudinal direction, especially in the very early-stage of arteriosclerosis. Therefore, the objective of the present study is to examine an accurate estimation method of the arterial wall movement in the longitudinal direction. The longitudinal displacement of IMC was measured by the block matching method. As the conventional method, the block matching method was applied to the envelope of radio-frequency (RF) signals in IMC. In the present paper, it was also applied to the difference signals of the envelope of RF signals between the neighboring beams to amplify the change of subjects in the longitudinal direction. The block matching methods were applied to the signals in IMC acquired in the right common carotid artery of healthy subjects in the twenties, and the estimated results were compared with the trajectory of the longitudinal movement of IMC which was the change of maximum amplitudes of echo envelope in IMC. In the conventional method, several estimated displacements did not correspond with the trajectory of the longitudinal movement of IMC. By subtracting echo envelope signals in the longitudinal direction, the change of signals was amplified; therefore, the estimated displacements well corresponded with the trajectory of the longitudinal movement of IMC.

Measuring myocardial contractile movement caused by electrical excitation leads to early detection of abnormalities of cardiomyocytes due to disease. However, the detailed mechanism of the transition process in the myocardium from dilation to contraction at the pre-ejection period is still unclear. In the present study, we acquired ultrasonic RF signals with a high frame rate of 1.16 ms using the parallel beamforming [1] by transmitting a plane wave with a sector probe. Velocity waveform in the 2D direction, the beam direction (the radial direction in the heart wall), and the direction orthogonal to the beam (the longitudinal direction in the heart) were simultaneously estimated by applying the speckle tracking along the heart wall. The cross-correlation coefficient was interpolated so that the spatial resolutions in displacement estimation along the radial and longitudinal directions were increased to 1.0 and 2.2 μm, respectively. We then detected the propagation speeds of contraction response due to electrical excitation along the radial and longitudinal directions at the pre-ejection period. The radial component of 2D velocity waveforms was measured at 112 points along the septum around the R wave of ECG. The velocity component to RV (LV expansion) and that of LV (contraction) were obtained. In the period around R wave, two components propagated along the septum from the basal to apical sides with speeds of 3 m/s and 6 m/s. On the other hand, for the longitudinal component, three components propagated with speeds of 1 m/s, 3 m/s and 12 m/s. Though these all velocity components were simultaneously measured for the same points in the septum, the situations of 2D velocity waveforms were quite different, which would be useful for understanding what occurs at the pre-ejection period.

High blood glucose level (BGL) is related to the high viscosity of blood. Red blood cells (RBCs) tend to gather each other in the condition of high viscosity. Backscattered echoes become high as RBCs aggregate. Therefore, the intensity of backscattered echo is anticipated to be high as the BGL increases. In the present study, we investigated the relationship between RBC aggregations by ultrasound and the BGL for the development of non-invasive BGL measurement methods. Ultrasonic backscattering echoes for dorsal hand vein and BGLs were repeatedly measured from fasting to 190 min after injecting 40-g glucose for a healthy subject. The brightness of the B-mode image increased as the BGL increased. The brightnesses of B-mode image and the BGLs after 160-190 min were less than those at fasting. The relationship between the brightness of the B-mode image and BGL was almost linear, although the hysteresis characteristic was observed. This is because multiple factors other than BGL are closely related to the RBC aggregations.

An ultrasonic method to measure the changes in radial arterial diameter and blood pressure in a noninvasive manner was proposed to estimate viscoelastic characteristics of the arterial wall to diagnose vascular endothelial dysfunction at an extremely early stage. In the present study, a measurement method of blood pressure using the piezoelectric effect of the ultrasonic probe was investigated. At first, blood pressure waveform measured by the piezoelectric element was discussed using piezoelectric constitutive equations. We confirmed that the blood pressure waveform can be obtained by integrating the waveform measured by the piezoelectric element. Then, a conventional ultrasonic probe was modified to measure a blood pressure waveform and the measurement is demonstrated. Changes in the radial diameter was also measured using an ultrasonic diagnosis equipment with a conventional linear ultrasonic probe. The measured voltage by the piezoelectric element was of the same order as the result estimated from the theoretical consideration with typical material constants of the piezoelectric element. The diameter expanded with an increase in blood pressure and then gradually returned due to the decrease in blood pressure with viscosity. From the relationship between the arterial diameter and blood pressure, the hysteresis characteristic of the artery wall during one heartbeat was confirmed.

Purpose: To develop methods for noninvasively and quantitatively measuring blood glucose levels. Methods: In the present study, we evaluated the degree of red blood cell (RBC) aggregation at a low shear rate robustly by introducing two new parameters determined from changes in the scattering power spectrum of the echoes from the intravascular lumen before and after cessation of blood flow. We also considered the clinical significance of these parameters and the change in sizes estimated by the conventional method by comparing them with the blood glucose level obtained just before the ultrasonic measurements. We performed the measurements in one healthy subject and 11 diabetic patients. Results: A correlation was found between one of the proposed parameters and the blood glucose level. However, the p value was not very high, and one of the reasons for the decline of the correlation will be that some factors other than blood glucose also affect RBC aggregation. Conclusion: The proposed method has potential for clinical application after elucidation of the various factors affecting RBC aggregation.

Purpose: With commercial ultrasonic equipment, the sound velocity is fixed to a constant value of 1530 or 1540 m/s, which is used for beam formation. However, the assumption of a constant sound velocity is not optimal, as the sound velocity in a living body is heterogeneous. In this study, a novel method was proposed to estimate the distribution of the sound velocity in a region of interest. Methods: The sound velocity distribution was estimated by fitting the theoretical propagation time of the ultrasonic wave from the scatterer to each of the probe elements with measured values. Results: In a phantom experiment, the sound velocity distribution was estimated by the proposed method with a maximum estimation error of 0.6%, and the resultant local sound velocity values successfully improved the quality of the ultrasonic image. Conclusion: The proposed method has the potential to improve ultrasonic image quality in in vivo experiments by estimating the sound velocity distribution.

It has been revealed that the ultrasound measurement with high temporal resolution is useful for diagnosis of myocardial tissue properties. However, it is considered that the dynamic measurement of the target tissue is affected by the motion of neighbor tissues because of the wide width of the transmitted wave. For this reason, the measurement error is affected by spatial and temporal factors. In the present study, we constructed an experimental system for measuring these effects quantitatively and investigated the accuracy of the velocity measurement using some transmitted waves such as focused, plane, and diverging waves. In the conditions of the present study, the measurement error is minimized at 9° of the angular width of the transmitted wave. This method is useful for evaluating the conditions of transmitted waves for measurements of other targets which need a high temporal resolution such as shear wave, cardiac blood flow, and so on.

The propagation of myocardial contraction caused by the conduction of electrical excitation in the heart has been visualized in our previous study. However, it was assumed that the contraction propagated parallel to the heart wall and the propagation speed was constant within the measurement area. In the present study, we estimated the two-dimensional propagation speed of contraction at each local area by ultrasonic measurement, and examined the mechanism of the contraction propagation in the heart by calculating the spatial distribution of the propagation speed vectors. By applying the proposed method to the interventricular septum of the human heart, the propagation speed in the lateral direction was approximately 1.6 times faster than that in the beam direction. The significant difference in propagation speeds between the specialized and ordinary myocardia was detected successfully. This study suggests that the proposed method can detect the myocardial ischemic and arrhythmia regions non-invasively.

Ischemia causes abnormality in excitation propagation of the local myocardium. Therefore, measuring myocardial contractile movement caused by electrical excitation leads to early detection of abnormalities of cardiomyocytes due to disease. However, the detail mechanism of the transition process in the myocardium from dilation to contraction is still unclear. In the present study, we acquired ultrasonic RF signals with a high frame rate of 1.2 ms using the parallel beam forming by transmitting a plane wave from a sector probe. Furthermore, velocity and displacement in the 2D direction, the ultrasonic beam direction, and the direction orthogonal to the ultrasonic beam (lateral direction), were simultaneously estimated by applying the speckle tracking method, where the cross-correlation coefficient was interpolated so that the spatial resolutions in displacement estimation along the axial and lateral directions were increased to 1.0 and 2.2 um, respectively. We then detected the propagation of contraction response due to electrical excitation along the ultrasound beam and lateral directions around the R-wave of ECG. By showing the instantaneous velocity vector mapping of the ventricular septal wall, just after the Q-wave, the myocardium moved toward the base of the heart and the right ventricle (RV), which corresponds to the expansion. After this, the myocardium began to move to the side of the left ventricle (LV), it began to move towards the apical side a few ms later, and contraction of the LV started. From the S-wave, the myocardium moved so that the LV expanded in the direction of the RV and the base of the heart. The motion then became smaller and contraction of the LV temporarily stopped. Finally, from the end of the first sound, the myocardium moved again to the LV sides and the apex, and substantial contraction of the LV started. The contraction response propagates spirally with 1-4 m/s from Q-wave to the first sound. These results suggest that the proposed method would be useful for evaluating the cardiac contractile function.

Fatal necrosis of the myocardium can be avoided by prompt re-perfusion at the onset of myocardial ischemia. Therefore, rapid identification of the ischemic region is essential for diagnosis and subsequent correct treatment in the early stage of ischemic heart disease. In the present study, in order to establish an ultrasonic-based method of identification of the ischemic region, the change of the myocardial contraction response from a normal to ischemic state was elucidated by ultrasonic measurement. Ultrasonic measurement was applied to the interventricular septum (IVS)of open-chest hearts of 5 swine under normal conditions. Ischemia in the IVS was then induced by avascularizing the left anterior descending (LAD)coronary artery, and ultrasonic measurement of the ischemic IVS was applied within several seconds. The number of the scanning ultrasonic beams was restricted to 13 in order to keep the high pulse repetition interval. By applying the phased-tracking method to the signals acquired under each condition, velocity waveforms with minute vibration were simultaneously obtained at about 3,000 points in the IVS. The propagation of the myocardial contraction was evaluated as spatial transition of the delay time by a cross-correlation method. In the IVS, the myocardial contraction response propagated from the basal to apical sides. The propagation velocity was almost constant at 2.7 ± 0.5 m/s under normal conditions. On the other hand, an approximately 31% decrease in the propagation velocity to 1.9 ± 0.5 m/s was observed about 5 s after LAD avascularization. Furthermore, about 7 s after LAD avascularization, an approximately 49% decrease in the propagation velocity to 1.4 ± 0.3 m/s was observed. These results suggest that the myocardial ischemic regions can be identified noninvasively by ultrasonic measurement.

We have proposed an evaluation method of the viscoelastic parameters of blood walls by measuring a relationship between radial arterial pressure and diameter to evaluate vascular endothelial functions. In our previous study, those were measured at different position, which caused timing errors because of the difference of pulse wave velocity during a heartbeat. In the present study, a novel probe was developed to measure both radial arterial pressure and diameter at identical position. One cord connecting the central piezoelectric element of the linear array probe and the ultrasonic diagnosis equipment was cut off to measure the arterial pressure. The output from the element was amplified 100 times, filtered with a low pass filter, and acquired with an oscilloscope. The output was obtained as the differential form of the blood pressure waveform. To obtain the blood pressure waveform, the output was integrated and calibrated with the systolic and diastolic blood pressures measured by the tonometry. The arterial diameter was measured using the other 127 elements with the ultrasonic diagnosis apparatus by the phased-tracking method. The hysteresis loop between the diameter and pressure during a heartbeat, which reflect the viscoelasticity of the blood wall, was successfully confirmed.

To develop methods for noninvasively and quantitatively measuring blood glucose levels (BGL)., the degree of red blood cell (RBC) aggregation at a low shear rate were robustly evaluated by introducing two new parameters determined from changes in the scattering power spectrum of the echoes from the intravascular lumen before and after cessation of blood flow. The clinical significance of these parameters was discussed by comparing them with BGL obtained just before the ultrasonic measurements in one healthy subject. A correlation was found between one of the proposed parameters and BGL. However, the p value was not very high. One of the reasons for the decline of the correlation will be that some factors other than blood glucose also affect RBC aggregation. The proposed method has the potential for clinical application after elucidation of the various factors affecting RBC aggregation.

Background: Therapeutic focused-ultrasound to the hippocampus has been reported to exert neuroprotective effects on dementia. In the present study, we examined whether the whole-brain LIPUS (low-intensity pulsed ultrasound) therapy is effective and safe in 2 mouse models of dementia (vascular dementia, VaD and Alzheimer's disease, AD), and if so, to elucidate the common underlying mechanism(s) involved. Methods: We used bilateral carotid artery stenosis (BCAS) model with micro-coils in male C57BL/6 mice as a VaD model and 5XFAD transgenic mice as an AD model. We applied the LIPUS therapy (1.875 MHz, 6.0 kHz, 32cycles) to the whole brain. Results: In both models, the LIPUS therapy markedly ameliorated cognitive impairments (Y-maze test and/or passive avoidance test) associated with improved cerebral blood flow (CBF). Mechanistically, the LIPUS therapy significantly increased CD31-positive endothelial cells and Olig2-positive oligodendrocyte precursor cells (OPCs) in the VaD model, while it reduced Iba-1-positive microglias and amyloid-β (Aβ) plaque in the AD model. In both models, endothelium-related genes were significantly upregulated in RNA-sequencing, and expressions of endothelial nitric oxide synthase (eNOS) and neurotrophins were upregulated in Western blotting. Interestingly, the increases in glia cells and neurotrophin expressions showed significant correlations with eNOS expression. Importantly, these beneficial effects of LIPUS were absent in eNOS-knockout mice. Conclusions: These results indicate that the whole-brain LIPUS is an effective and non-invasive therapy for dementia by activating specific cells corresponding to each pathology, for which eNOS activation plays an important role as a common mechanism.

Pulse wave velocity (PWV) is used as a diagnostic criterion for arteriosclerosis, a major cause of heart disease and cerebrovascular disease. However, there are several problems with conventional PWV measurement techniques. One is that a pulse wave is assumed to only have an incident component propagating at a constant speed from the heart to the femoral artery, and another is that PWV is only determined from a characteristic time such as the rise time of the blood pressure waveform. In this study, we noninvasively measured the velocity waveform of small vibrations at multiple points on the carotid arterial wall using ultrasound. Local PWV was determined by analyzing the phase component of the velocity waveform by the least squares method. This method allowed measurement of the time change of the PWV at approximately the arrival time of the pulse wave, which discriminates the period when the reflected component is not contaminated.

We proposed a new method for estimating the viscoelastic property of the local region of a sample. The viscoelastic parameters of the phantoms simulating the biological tissues were quantitatively estimated by analyzing the frequency characteristics of displacement generated by acoustic excitation. The samples were locally strained by irradiating them with the ultrasound simultaneously generated from two point-focusing transducers by applying the sum of two signals with slightly different frequencies of approximately 1 MHz. The surface of a phantom was excited in the frequency range of 20–2,000 Hz, and its displacement was measured. The frequency dependence of the acceleration provided by the acoustic radiation force was also measured. From these results, we determined the frequency characteristics of the transfer function from the stress to the strain and estimated the ratio of the elastic modulus to the viscosity modulus (K/η) by fitting the data to the Maxwell model. Moreover, the elastic modulus K was separately estimated from the measured sound velocity and density of the phantom, and the viscosity modulus η was evaluated by substituting the estimated elastic modulus into the obtained K/η ratio.

In our studies on ultrasonic elasticity assessment, minute change in the thickness of the arterial wall was measured by the phased-tracking method. However, most images in carotid artery examinations contain multiple-reflection noise, making it difficult to evaluate arterial wall elasticity precisely. In the present study, a modified phased-tracking method using the pulse inversion method was examined to reduce the influence of the multiple-reflection noise. Moreover, aliasing in the harmonic components was corrected by the fundamental components. The conventional and proposed methods were applied to a pulsated tube phantom mimicking the arterial wall. For the conventional method, the elasticity was 298 kPa without multiple-reflection noise and 353 kPa with multiple-reflection noise on the posterior wall. That of the proposed method was 302 kPa without multiple-reflection noise and 297 kPa with multiple-reflection noise on the posterior wall. Therefore, the proposed method was very robust against multiple-reflection noise.

We proposed a robust analysis method for the acoustic properties of biological specimens measured by acoustic microscopy. Reflected pulse signals from the substrate and specimen were converted into frequency domains to obtain sound speed and thickness. To obtain the average acoustic properties of the specimen, parabolic approximation was performed to determine the frequency at which the amplitude of the normalized spectrum became maximum or minimum, considering the sound speed and thickness of the specimens and the operating frequency of the ultrasonic device used. The proposed method was demonstrated for a specimen of malignant melanoma of the skin by using acoustic microscopy attaching a concave transducer with a center frequency of 80 MHz. The variations in sound speed and thickness analyzed by the proposed method were markedly smaller than those analyzed by the method based on an autoregressive model. The proposed method is useful for the analysis of the acoustic properties of bilogical tissues or cells.

Aims: Detection of early-stage atherosclerosis in type 2 diabetes mellitus (T2DM) patients is important for preventing cardiovascular disease. A phased tracking method for evaluating arterial wall elasticity sensitively detects early-stage atherosclerosis. However, biochemical markers for early-stage atherosclerosis have yet to be established. Methods: This cross-sectional study enrolled 180 T2DM patients, who were classified as not having atherosclerosis according to the carotid intima-media thickness (IMT) criteria. We measured serum cystatin C, the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR), and analyzed the associations between these markers and arterial wall elasticity (Eθ), IMT and the cardio-ankle velocity index. Results: Multiple linear regression analyses revealed that cystatin C was significantly associated with Eθ, while neither eGFR nor ACR showed an association. Furthermore, among the examined atherosclerotic markers, Eθ was most reliably associated with cystatin C. Additionally, the association between cystatin C and Eθ disappeared in the low elasticity subgroup, which included subjects in whom no atherosclerotic changes had yet been initiated. Conclusions: In T2DM patients without apparent arterial wall thickening, cystatin C is strongly and independently associated with arterial wall elasticity, which reflects the degree of subclinical atherosclerosis. Thus, cystatin C is a potentially useful marker of early-stage atherosclerosis.

Scanning acoustic microscopy (SAM) using impulsive signals is useful for characterization of biological tissues and cells. The operating center frequency of an ultrasonic device strongly depends on the performance characteristics of the device if the measurement is conducted by using impulsive signals. In this paper, a method for the design of ultrasonic devices for SAM using impulsive signals was developed. A new plane-wave model was introduced to calculate frequency characteristics of loss of ultrasonic devices by taking into account the conversion loss at the ultrasonic transducer, the transmission loss at the acoustic anti-reflection coating, and the propagation loss in the couplant. Ultrasonic devices were fabricated with a ZnO ultrasonic transducer using two acoustic lenses with aperture radii of 1.0 mm and 0.5 mm, respectively. The frequencies at which measured losses became minima corresponded to the calculation results by the plane-wave model. This numerical calculation method is useful for designing ultrasonic devices for acoustic microscopy using impulsive signals.

In the original version of the article, the third author name was incorrectly published. The correct name is Kosei Yoh.

Ultrasound signals that pass through cancellous bone may be considered to consist of two longitudinal waves, which are called fast and slow waves. Accurate decomposition of these fast and slow waves is considered to be highly beneficial in determination of the characteristics of cancellous bone. In the present study, a fast decomposition method using a wave transfer function with a phase rotation parameter was applied to received signals that have passed through bovine bone specimens with various bone volume to total volume (BV/TV) ratios in a simulation study, where the elastic finite-difference time-domain method is used and the ultrasound wave propagated parallel to the bone axes. The proposed method succeeded to decompose both fast and slow waves accurately; the normalized residual intensity was less than -19.5 dB when the specimen thickness ranged from 4 to 7 mm and the BV/TV value ranged from 0.144 to 0.226. There was a strong relationship between the phase rotation value and the BV/TV value. The ratio of the peak envelope amplitude of the decomposed fast wave to that of the slow wave increased monotonically with increasing BV/TV ratio, indicating the high performance of the proposed method in estimation of the BV/TV value in cancellous bone. (C) 2017 Acoustical Society of America.

Introduction Chronic left ventricular (LV) pressure overload causes relative ischemia with resultant LV dysfunction. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we thus examined whether LIPUS also ameliorates contractile dysfunction in LV pressure-overloaded hearts. Methods and results Chronic LV pressure overload was induced with transverse aortic constriction (TAC) in mice. LIPUS was applied to the whole heart three times in the first week after TAC and was repeated once a week for 7 weeks thereafter (n = 22). Animals in the control groups received the sham treatment without LIPUS (n = 23). At 8 weeks after TAC, LV fractional shortening was depressed in the TAC-Control group, which was significantly ameliorated in the TAC-LIPUS group (30.4±0.5 vs. 36.2±3.8%, P<0.05). Capillary density was higher and perivascular fibrosis was less in the LV in the TAC-LIPUS group than in the TAC-Control group. Myocardial relative ischemia evaluated with hypoxyprobe was noted in the TAC-Control group, which was significantly attenuated in the TAC-LIPUS group. In the TAC-LIPUS group, as compared with the control group, mRNA expressions of BNP and collagen III were significantly lower (both P<0.05) and protein expressions of VEGF and eNOS were significantly up-regulated associated with Akt activation (all P<0.05). No adverse effect related to the LIPUS therapy was noted. Conclusions These results indicate that the LIPUS therapy ameliorates contractile dysfunction in chronically pressure-overloaded hearts through enhanced myocardial angiogenesis and attenuated perivascular fibrosis. Thus, the LIPUS therapy may be a promising, non-invasive treatment for cardiac dysfunction due to chronic pressure overload.

Non-invasive identification of ischemic regions is important for diagnosis and treatment of myocardial infarction. In the present study, ultrasound measurement was applied to the interventricular septum of three open-chest swine hearts. The properties of the myocardial contraction response of the septum were compared between normal and acute ischemic conditions, where the acute ischemic condition of the septum originated from direct avascularization of the left anterior descending (LAD) coronary artery. The result showed that the contraction response propagated from the basal side to the apical side along the septum. The estimated propagation velocities in the normal and acute ischemic conditions were 3.6 and 1.9m/s, respectively. This finding indicates that acute ischemia which occurred 5 s after the avascularization of the LAD promptly suppressed the propagation velocity through the ventricular septum to about half the normal velocity. It was suggested that the myocardial ischemic region could be identified using the difference in the propagation velocity of the myocardial response to contraction. (C) 2017 The Japan Society of Applied Physics

Ultrasonic integrated backscatter (IB) from the heart wall, which has been employed for quantitative tissue characterization of the myocardium, is known to have cyclic variation-a decrease in systole and an increase in diastole. In the present study, by tracking the measurement position of the myocardium and compensating for the movement due to the heartbeat, IB and its temporal variation were obtained from the same site with a high temporal resolution of 1.73 ms. In an in vivo study on a healthy subject, the temporal variation of IB values homogeneously changed across the heart wall, especially during the slow filling and the atrial systole phases. This new finding shows that the IB value reflects a small movement of the myocardium of about 5mm/s. Thus, the proposed measurement has a potential for quantitative and accurate evaluation of the contraction and relaxation of the myocardium. (C) 2017 The Japan Society of Applied Physics

Epidural anesthesia is a common technique for perioperative analgesia and chronic pain treatment. Since ultrasonography is insufficient for depicting the human vertebral surface, most examiners apply epidural puncture by body surface landmarks on the back such as the spinous process and scapulae without any imaging, including ultrasonography. The puncture route to the epidural space at thoracic vertebrae is much narrower than that at lumber vertebrae, and therefore, epidural anesthesia at thoracic vertebrae is difficult, especially for a beginner. Herein, a novel imaging method is proposed based on a bi-static imaging technique by making use of the transmit beam width and direction. In an in vivo experimental study on human thoracic vertebrae, the proposed method succeeded in depicting the vertebral surface clearly as compared with conventional B-mode imaging and the conventional envelope method. This indicates the potential of the proposed method in visualizing the vertebral surface for the proper and safe execution of epidural anesthesia. (C) 2017 The Japan Society of Applied Physics.

In most current methods for evaluating the cardiac function by ultrasound, the heart wall area is identified manually by an examiner. To eliminate examiner dependence and to improve usability, an automatic heart wall identification method is desirable. Identification based on only echogenicity often fails because of low echogenicity of some areas of the heart wall. In the present study, to determine more essential features, we focused on the relative temporal change of ultrasonic scatterer distribution and proposed three features for identification of the heart wall and the chamber: cross-correlation of RF signals, that of envelopes, and spatial dispersion of movement vectors in small regions. In an in vivo experiment, using echogenicity and the three features, we identified the heart wall and the chamber in the left ventricular long-axis view, resulting in criteria of separability J of 1.69, 1.40, and 3.02 using these features compared with the result of 0.979 using echogenicity. (C) 2017 The Japan Society of Applied Physics

<p>When the lesion progresses in living tissue, the hardness of the tissue changes. Therefore, quantitative measurement of tissue hardness is required. In this study, the object is vibrated by dual acoustic radiation pressure. We aim to estimate viscoelastic properties by examining the frequency response of the tissue. In this report, we observed the change in the displacement amplitude of the object by changing the oscillating frequency. As a result, it was found that the displacement amplitude becomes smaller as the frequency is set higher. It was confirmed that it decreases with a slope of -40dB/decade between 10 Hz and 200 Hz. This phenomenon is thought to be due to stress relaxation. We will clarify frequency characteristics from stress relaxation function.</p>

For early detection of disorder in the vascular endothelial function, a technique to evaluate the viscoelastic characteristic of the vascular wall was developed by measuring the blood pressure of the radial artery and measuring the change of the vessel diameter at a different close position. By it measurement, however, an accurate evaluation of the viscoelastic characteristic is difficult due to the small time lag between the waveforms. Therefore, for measuring both the blood pressure and the change of the vessel diameter at the same position, the present study presents a new method to acquire the blood pressure by the same ultrasonic probe as that for the ultrasonic measurement of the change of the vessel diameter. From the resultant waveforms, the hysteresis characteristic of the vessel diameter was obtained in in vivo experiments.

When the lesion progresses in living tissue, the hardness of the tissue changes. Therefore, quantitative measurement of tissue hardness is required. In this study, the object is vibrated by dual acoustic radiation pressure. We aim to estimate viscoelastic properties by examining the frequency response of the tissue. In this report, we observed the change in the displacement amplitude of the object by changing the oscillating frequency. As a result, it was found that the displacement amplitude becomes smaller as the frequency is set higher. It was confirmed that it decreases with a slope of -40dB/decade between 10 Hz and 200 Hz. This phenomenon is thought to be due to stress relaxation. We will clarify frequency characteristics from stress relaxation function.

Background: Although the deformability of the left ventricular (LV) wall appears to be important in maintaining effective cardiac performance, this has not been debated by anyone, probably owing to the difficulties of the investigation. Objectives: This study applies a new technology to demonstrate how the LV wall deforms so as to adjust for optimum cardiac performance. Subjects and methods: Ten healthy volunteers were the subjects. Using echo-dynamography, an analysis at the "microscopic" (muscle fiber) level was done by measuring the myocardial axial strain rate (aSR), while the "macroscopic" (muscle layer) level contraction-relaxation/extension (C-R/E) properties of the LV wall were analyzed using high frame rate 2D echocardiography. Results: Deformability of the LV was classified into three types depending on the non-uniformity of both the C-R/E properties and the aSR distribution. "Basic" deformation (macroscopic): The apical posterior wall (PW) thickness change was concentric and monophasic, whereas it was eccentric and biphasic in the basal part. This deformation was large in the PW, but small in the interventricular septum (IVS). The elongation of the mitral ring diameter and the downward movement of its posterior part were shown to be concomitant with the anterior extrusion of the PW. "Combined" deformation (macroscopic and microscopic): This was observed when the basic deformation was coupled with the spatial aSR distribution. Three patterns were observed: (a) peristaltic; (b) bellows-like; and (c) pouch-like. "Integrated" deformation: This was the time serial aSR distribution coupled with the combined deformation, illustrating the rotary pump-like function. The deformability of the LV assigned to the apical part the control of pressure and to the basal part, flow volume. The IVS and the PW exhibited independent behavior. Conclusions: The non-uniformity of both the aSR distribution and the macroscopic C-R/E property were the basic determinants of LV deformation. The apical and basal deformability was shared in LV mechanical function. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Several speckle tracking methods have been proposed for noninvasive and quantitative evaluation of tissue motion. Since the low temporal resolution causes a large myocardial motion in the elevational direction and a large deformation, two-dimensional (2D) speckle tracking at a high frame rate is desirable for accurate estimation of myocardial contraction and relaxation. 2D speckle tracking at a high frame rate requires a high computational load, and the large suppression of calculation time is, therefore, essential for clinical use. In the present study, we investigate the minimum frame rate required for the estimation of myocardial contraction and relaxation. Furthermore, we employ a parallel computing principle using a graphical processing unit (GPU) system with 2,496 streaming processors to decrease the calculation time effectively. The employment of a parallel computing principle with a GPU system successfully decreased the calculation time to 1/50 of that using a desktop PC with a CPU. When the number of tracking points is 64, the calculation time was decreased to 28.7 s for the estimation during 1 s at a frame rate of 287 Hz, indicating that the proposed method with a GPU system has a potential to realize a near real-time estimation of myocardial contraction and relaxation.

Cardiovascular diseases are risk factors for depression in humans. We recently proposed that sigma(1) receptor (sigma R-1) stimulation rescued cardiac hypertrophy and heart failure induced by transverse aortic constriction (TAC) in mice. Importantly, sigma R-1 stimulation reportedly ameliorates depression-like behaviors in rodents. Thus, we hypothesized that impaired sigma R-1 activity in brain triggers depression-like behaviors in animals with cardiovascular disease. Indeed, here we found that cardiac hypertrophy and heart failure induced by TAC were associated with depression-like behaviors concomitant with downregulation of sigma R-1 expression in brain 6 weeks after surgery. sigma R-1 levels significantly decreased in astrocytes in both the hippocampal CA1 region and dentate gyrus. Oral administration of the specific sigma R-1 agonist SA4503 (0.3-1.0mg/kg) significantly improved TAC-induced depression-like behaviors concomitant with rescued astrocytic sigma R-1 expression in CA1 and the dentate gyrus. Plasma corticosterone levels significantly increased 6 weeks after TAC, and chronic treatment of mice with corticosterone for 3 weeks elicited depression-like behaviors concomitant with reduced astrocytic sigma R-1 expression in hippocampus. Furthermore, the glucocorticoid receptor antagonist mifepristone antagonized depressive-like behaviors and ameliorated decreased hippocampal sigma R-1 expression in TAC mice. We conclude that elevated corticosterone levels trigger hippocampal sigma R-1 downregulation and that sigma R-1 stimulation with SA4503 is an attractive therapy to improve not only cardiac dysfunction but depression-like behaviors associated with heart failure.

Anthracyclines are among the most effective and widely used anticancer drugs; however, their use is limited by serious cardiotoxicity. Early detection is necessary to prevent the high mortality rate associated with heart failure (HF). We evaluated cardiac function in 142 patients using conventional echocardiography and the phased tracking method (PTM), which was measured using the minute vibration and the rapid motion components, neither of which is recognized in standard M-mode nor in tissue Doppler imaging. For systolic function comparison, we compared left ventricular ejection fraction (LVEF) in conventional echocardiography with the average velocity of ventricular septum myocytes (V-ave) in the PTM. The V-ave of 12 healthy volunteers was 1.5 (m/s)/m or more. At baseline of 99 patients, there was a positive correlation between LVEF and V-ave in all patients. There were no significant differences in baseline cardiac function between patients with and without HF. There was a negative correlation between the cumulative anthracycline dose and LVEF or V-ave among all patients. We determined that V-ave 1.5 (m/s)/m was equivalent to LVEF 60%, 1.25 (m/s)/m to 55%, and 1.0 (m/s)/m to 50%. During the follow-up period, there was a pathological decrease in LVEF (&lt;55%) and V-ave (&lt;1.25m/s/m) in patients with HF; decreases in V-ave were detected significantly earlier than those in LVEF (P&lt;0.001). When V-ave declined to 1.5 (m/s)/m or less, careful continuous observation and cardiac examination was required. When V-ave further declined to 1.0 (m/s)/m or lower, chemotherapy was postponed or discontinued; thus, serious drug-induced cardiomyopathy was avoided in patients who did not relapse. The PTM was superior to echocardiography for early, noninvasive detection and intermediate-term monitoring of left ventricle systolic function associated with anthracycline chemotherapy, among patients with hematologic malignancies. The PTM was an effective laboratory procedure to avoid the progression to serious cardiomyopathy.

An acute shortage of cardiologists and many rural clinics were run by nurses in Indonesia. We proposed to develop of a screening technique based on artificial intelligence that classifies of normal and pathological heart sound signals of human subjects due to signs important and symptoms for heart diagnosis based on knowledge of auscultation experts. Heart sound signal analysis system consisted of three stages. Firstly, preprocessing. Secondly, feature extraction with respect to the cardiac cycle based on wavelet analysis to differentiate normal and pathological heart sounds. Feature reduction using PCA was also carried out to reduce the dimension of the heart sound feature vectors for classification. Thirdly, three classifiers: ANN MLP-BP, FCM clustering and HCM clustering to classify normal, systolic murmur, diastolic murmur, and continuous murmur, respectively. The performance of each classifier was evaluated with statistical validation method. From our experimental results, the three classifiers that showed significant potential in their use as an alternative diagnostic tool were compared. The ANN achieved the best performance as an automated classifier rather than FCM and HCM methods. Its performance was 100% for sensitivity, specificity, and accuracy, respectively, of input 20,000 features. Furthermore, for input 300 features, the performance was 98.90%, 99.37%, and 99.03% for sensitivity, specificity, and accuracy, respectively. The heart sound signal analysis system was suitable to classify of normal and pathological cases. The proposed method was considered very important for objective screening and very useful as an alternative diagnostic tool that complies with the requirements for rural clinics. We hoped that the method would be beneficial in study of auscultatory technique for medical students. Surrogate data modeling of pathological heart sounds signals as an alternative tool of the heart sound simulator and for classification purpose was further study.

Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (sigma R-1) and inhibits it irreversibly. A serious outcome of haloperidol treatment of schizophrenia patients is death due to sudden cardiac failure. Although the cause remains unclear, we hypothesized that these effects were mediated by chronic haloperidol inhibition of cardiac sigma R-1. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them to angiotensin II and assessed hypertrophy, sigma R-1 expression, mitochondrial Ca2+ transport and ATP levels. In this context, haloperidol treatment altered mitochondrial Ca2+ transport resulting in decreased ATP content by inactivating cardiac sigma R-1 and/or reducing its expression. We also performed transverse aortic constriction (TAC) and then treated mice with haloperidol. After two weeks, haloperidol-treated mice showed enhanced heart failure marked by deteriorated cardiac function, reduced ATP production and increasing mortality relative to TAC only mice. ATP supplementation via sodium pyruvate rescued phenotypes seen in haloperidol-treated TAC mice. We conclude that sigma R-1 inactivation or downregulation in response to haloperidol treatment impairs mitochondrial Ca2+ mobilization, depleting ATP depletion from cardiomyocytes. These findings suggest a novel approach to mitigate haloperidol-related adverse effects in schizophrenia patients by ATP supplementation. (C) 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

In our previous study, the viscoelasticity of the radial artery wall was estimated to diagnose endothelial dysfunction using a high-frequency (22MHz) ultrasound device. In the present study, we employed a commercial ultrasound device (7.5 MHz) and estimated the viscoelasticity using arterial pressure and diameter, both of which were measured at the same position. In a phantom experiment, the proposed method successfully estimated the elasticity and viscosity of the phantom with errors of 1.8 and 30.3%, respectively. In an in vivo measurement, the transient change in the viscoelasticity was measured for three healthy subjects during flow-mediated dilation (FMD). The proposed method revealed the softening of the arterial wall originating from the FMD reaction within 100 s after avascularization. These results indicate the high performance of the proposed method in evaluating vascular endothelial function just after avascularization, where the function is difficult to be estimated by a conventional FMD measurement. (C) 2016 The Japan Society of Applied Physics

We propose a method for assessment of the degree of red blood cell (RBC) aggregation using the backscattering property of high-frequency ultrasound. In this method, the scattering property of RBCs is extracted from the power spectrum of RBC echoes normalized by that from the posterior wall of a vein. In an experimental study using a phantom, employing the proposed method, the sizes of microspheres 5 and 20 mu m in diameter were estimated to have mean values of 4.7 and 17.3 mu m and standard deviations of 1.9 and 1.4 mu m, respectively. In an in vivo experimental study, we compared the results between three healthy subjects and four diabetic patients. The average estimated scatterer diameters in healthy subjects at rest and during avascularization were 7 and 28 mu m, respectively. In contrast, those in diabetic patients receiving both antithrombotic therapy and insulin therapy were 11 and 46 mu m, respectively. These results show that the proposed method has high potential for clinical application to assess RBC aggregation, which may be related to the progress of diabetes. (C) 2016 The Japan Society of Applied Physics

An elastic property of biological soft tissue is an important indicator of the tissue status. Therefore, quantitative and noninvasive methods for elasticity evaluation have been proposed. Our group previously proposed a method using acoustic radiation pressure irradiated from two directions for elastic property evaluation, in which by measuring the propagation velocity of the shear wave generated by the acoustic radiation pressure inside the object, the elastic properties of the object were successfully evaluated. In the present study, we visualized the propagation of the shear wave in a three-dimensional space by the synchronization of signals received at various probe positions. The proposed method succeeded in visualizing the shear wave propagation clearly in the three-dimensional space of 35 x 41 x 4 mm(3). These results show the high potential of the proposed method to estimate the elastic properties of the object in the three-dimensional space. (C) 2016 The Japan Society of Applied Physics

OBJECTIVE: Left ventricular (LV) remodeling after acute myocardial infarction still remains an important issue in cardiovascular medicine. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we aimed to demonstrate whether LIPUS also ameliorates LV remodeling after acute myocardial infarction and if so, to elucidate the underlying molecular mechanisms involved in the beneficial effects of LIPUS. APPROACH AND RESULTS: We examined the effects of LIPUS on LV remodeling in a mouse model of acute myocardial infarction, where the heart was treated with either LIPUS or no-LIPUS 3 times in the first week (days 1, 3, and 5). The LIPUS improved mortality and ameliorated post-myocardial infarction LV remodeling in mice. The LIPUS upregulated the expression of vascular endothelial growth factor, endothelial nitric oxide synthase, phosphorylated ERK, and phosphorylated Akt in the infarcted area early after acute myocardial infarction, leading to enhanced angiogenesis. Microarray analysis in cultured human endothelial cells showed that a total of 1050 genes, including those of the vascular endothelial growth factor signaling and focal adhesion pathways, were significantly altered by the LIPUS. Knockdown with small interfering RNA of either β1-integrin or caveolin-1, both of which are known to play key roles in mechanotransduction, suppressed the LIPUS-induced upregulation of vascular endothelial growth factor. Finally, in caveolin-1-deficient mice, the beneficial effects of LIPUS on mortality and post-myocardial infarction LV remodeling were absent. CONCLUSIONS: These results indicate that the LIPUS therapy ameliorates post-myocardial infarction LV remodeling in mice in vivo, for which mechanotransduction and its downstream pathways may be involved.

The ultrasonic &lsquo;phased tracking method&rsquo; (PTM) is a newly developed technique in which we can observe the phase difference of adjoining received RF signals. We aim to apply PTM&mdash;which enables precise measurement of the target&rsquo;s velocity with 0.1 mm/s accuracy without restriction of transmitting wave length&mdash;for noninvasive measurements of fetal arterial diameter change, pulse wave velocity (PWV), and estimated fetal pulse pressure. We analyzed normal and growth-restricted fetuses using PTM. The fetal descending aorta was identified in the long axis direction using conventional B-mode with a convex array probe. Raw radiofrequency signals were recorded from the vessel wall of the descending aorta. Offline analysis was attempted for wall motion velocity waves. We employed PTM for measurement of pulsatile fine movement of the fetal descending aorta. Changes in internal diameter and PWV were analyzed. Pulse pressure was estimated from the transformed formula of Moens-Korteweg. PWVs were revealed to be significantly higher in growth-restricted fetuses. We could also demonstrate elevated estimated fetal pulse pressure in growth restriction. Measurement of fetal aortic diameter changes and fetal PWV using PTM is a feasible, noninvasive approach to evaluate fetal hemodynamics. Elevated PWV and estimated pulse pressure in growth-restricted fetuses suggest altered arterial wall compliance by histological remodeling that has already originated in the fetal period. Fetal PWV and estimated pulse pressure possibly distinguish cases at high risk for hypertensive complications later in life, which substantiates Developmental Origins of Health and Disease (DOHaD) theory.

We observe traveling waves, measured by the ultrasonic noninvasive imaging method, in a longitudinal beam direction from the apex to the base side on the interventricular septum (IVS) during the period from the end-diastole to the beginning of systole for a healthy human heart wall. We present a possible phenomenological model to explain part of one-dimensional cardiac behaviors for the observed traveling waves around the time of R-wave of echocardiography (ECG) in the human heart. Although the observed two-dimensional patterns of traveling waves are extremely complex and no one knows yet the exact solutions for the traveling homoclinic plane wave in the one-dimensional complex Ginzburg-Landau equation (CGLE), we numerically find that part of the one-dimensional homoclinic dynamics of the phase and amplitude patterns in the observed traveling waves is similar to that of the numerical homoclinic plane-wave solutions in the CGLE with periodic boundary condition in a certain parameter space. It is suggested that part of the cardiac dynamics of the traveling waves on the IVS can be qualitatively described by the CGLE model as a paradigm for understanding biophysical nonlinear phenomena.

<p>For the assessment of cardiac functions using ultrasonography, several researchers have reported the efficiency of the two-dimensional myocardial displacement measurement. However, it requires the identification of heart wall areas. It is important to identify heart wall areas automatically for the convenience and the elimination of the examiner dependence. Previously, the heart wall areas are estimated from the echo intensity of B-mode images, and it is difficult to identify the heart wall areas with low echo intensity. In the present study, we propose a novel feature, magnitude squared coherence function (MSC), which is effective for automatic heart wall identification. This feature represents the time changes of the ultrasonic RF signals. We have identified heart wall areas using a linear discriminant analysis with MSC. Most of the identified areas agreed with those with high echo intensity, showing a great potential of the proposed feature for heart wall identification.</p>

Minimum variance beamformer has high potential in improving image quality through an adaptive apodization weight optimization approach, but its impact is conventionally limited to lateral resolution enhancements. Recently, we reported a high range resolution technique that applies minimum variance beamformer to the frequency components of the RF signal after a delay-and-sum process. The technique has high performance in the improvement of the range resolution when a target has flat interfaces, such as a longitudinal section of an artery. In the present study, we report further advance of this technique to enhance image quality of a normal swine eye whose anatomy is marked by multiple layers of curved interfaces. The reference signal is acquired by the coherent integration of the echoes from isolated interfaces to take account of the attenuation and the interface shape. The proposed technique succeeded to offer a sharp rendering of the cornea boundaries of the swine eye, where the center frequency of the transmit ultrasound pulse was 12 MHz. Computationally, it required 5 seconds using a laptop PC with a single CPU for the depiction of an image in the ROI that consists of 422,528 pixels. We reckon that, if the proposed technique is implemented using GPUs, high-quality images of the eye (with both lateral and range resolution enhancements) can be readily achieved in real time.

One of the valuable methods of cardiac valve diagnosis can be performed by auscultation. We proposed a signal processing and extensive characterization method based on wavelet analysis to investigate important characteristics of heart sounds of normal and pathologic systolic murmur human subjects. Time-scale maps yielded by wavelet transform calculation were solved using magnitude thresholding operation and centre of gravity to restrict temporal and frequency-related of valvular activities. From our experimental results, temporal and frequencyrelated parameters of S1, S2, and their components could be characterized precisely. Application of our method was adequate to characterize the heart sounds objectively, clearly, systematically, and comprehensively. The method was considered valuable to explain mechanisms of cardiac valves functions. We expected that the method would be helpful for clinical diagnosis as well as developing of heart sound modelling and educational purpose. Next topic of our study was addressed for classification of the heart sounds.

High frame rate ultrasound is an emerging technique for medical ultrasound imaging. However, spatial resolution and contrast are degraded compared to conventional beamforming using focused transmit beams. In the present study, a kind of minimum variance beamformer, namely, amplitude and phase estimation (APES) beamformer, was examined for improvement of the spatial resolution. The APES beamformer estimates the desired signal, i.e., echo from the focal point, using delay-and-sum beamforming without considering the element directivity and removes it from the spatial covariance matrix. By omitting the element directivity, the error in estimation of the desired signal increases and, as a result, more part of the desired signal remains in the spatial covariance matrix. Consequently, sub-array averaging is necessary for further suppressing the desired signal contained in the spatial covariance matrix. In the present study, the APES beamformer was modified so as to consider the element directivity in estimation of the desired signal. Also, the proposed APES beamforming was further modified to be applied to outputs of sub-aperture beamforming to reduce dimension of the spatial covariance matrix. In the present study, the effect of the element directivity on APES beamforming was evaluated by a basic experiment using a phantom. In parallel beamforming with the conventional DAS, lateral spatial resolution, which was evaluated from the lateral full width at half maximum of the amplitude profile of an echo from a fine wire, was 0.50 mm. Using conventional APES, the lateral spatial resolution was improved to 0.26 mm. Lateral spatial resolution was further improved to 0.25 mm using the modified APES. In both APES beamforming, sub-array averaging was not used, and outputs from 6 sub-apertures were processed. Also in B-mode imaging of a carotid artery, undesired echoes are suppressed significantly by the modified APES.

In our series of studies on the ultrasonic assessment of the regional elasticity of the arterial wall, the change in the thickness of the arterial wall caused by the heartbeat was measured by the ultrasonic phased-tracking method. In the measurement of elasticity, the boundaries of the anterior and posterior walls must be assigned in advance. Currently the boundaries are manually determined by the operator, which is time-consuming and results in observer variability. In this paper, we propose an automated method for the detection of arterial wall boundaries using multiscale dynamic programming, in which the cost function includes the correlation term between ultrasonic echoes in adjacent receive scan lines. The correlation term enables boundary detection that is more robust than conventional methods against noises. The effectiveness of the proposed method was validated using a phantom and applied to the in vivo measurements of carotid arteries. The root mean square error between the results obtained by the proposed method and the manual assignment of the boundaries was significantly improved. (C) 2015 The Japan Society of Applied Physics

Visualization of the vortex blood flow in the cardiac chamber is a potential diagnostic tool for the evaluation of cardiac function. In the present study, a method for automatic selection of the desirable cutoff frequency of a moving target indicator filter, namely, a clutter filter, was proposed in order to visualize complex blood flows by the ultrahigh-frame-rate imaging of echoes from blood particles while suppressing clutter echoes. In this method, the cutoff frequency was adaptively changed as a function of the velocity of the heart wall (clutter source) in each frame. The feasibility of the proposed method was examined through the measurement of a healthy volunteer using parallel receive beamforming with a single transmission of a non-steered diverging beam. Using the moving target indicator filter as above with the cutoff frequency determined by the proposed method, the vortex-like blood flow in the cardiac chamber was visualized as movements of echoes from blood particles at a very high frame rate of 6024 Hz while suppressing clutter echoes. (C) 2015 The Japan Society of Applied Physics

Ultrasonic imaging of blood flow in the cardiac lumen is a very useful tool to evaluate the pumping function of the human heart. The speckle tracking technique makes it possible to estimate the blood velocity vector. However, a stable estimation of the velocity vector of blood flow is difficult because signal-to-noise ratios of echoes from tiny blood particles are low. In this study, the speckle tracking technique with averaging of multiple two-dimensional correlation functions was employed for stable estimation of the blood velocity vector. Multiple two-dimensional correlation functions can be averaged during a very short period by using the echo data acquired by high-frame-rate echocardiography with diverging beam transmission. A steady flow experiment using blood-mimicking fluid (mean fluid velocity 0.2 m/s, flow angle 56A degrees from the transducer surface) was implemented to investigate the effect of the averaging of two-dimensional correlation functions at a frame rate of 6024 Hz. First, to examine the averaging duration required for stable estimation of the flow velocity vector, the accuracies of vector estimates were evaluated at different durations for averaging of two-dimensional correlation functions in the steady flow measurement. It was found that the proposed averaging process with an averaging duration of over 8 frames could reduce the directional error in vector estimation to almost half that of the conventional speckle tracking technique. In subsequent experiments, the averaging duration was set at 12 frames corresponding to 2 ms. Measurements of steady flow at higher velocities were further implemented. The steady flow measurements with higher flow velocities of 0.4 and 0.6 m/s were simulated by changing the frame interval of the echo data at a flow velocity of 0.2 m/s. Although the averaging duration was a mere 2 ms, directional errors at mean flow velocities of 0.2, 0.4, and 0.6 m/s were reduced significantly. In an in vivo experiment of the healthy human heart, to produce a fine B-mode image, the diverging wave transmissions with different steered angles for compounding were interleaved in the transmission sequence. From the in vivo experimental result, the blood velocity vector of the left ventricular cavity showed the flow getting into/out of the cavity in ejection and early diastolic phases. Furthermore, estimated flow directions revealed rotating flow in the cavity in mid-diastole. Our proposed method has the feasibility to visualize the vortex flow by velocity vector mapping without a contrast agent.

Phased tracking (PT) is an ultrasound-based technique that enables precise measurement of a target velocity. The aims of this study were to use PT to evaluate arterial pulse waveform, pulse wave velocity and fetal pulse pressure in normal and growth-restricted fetuses. One hundred fetuses with normal development and 15 fetuses with growth restriction were analyzed. Ultrasonic raw radiofrequency signals were captured from a direction perpendicular to the vascular axis at the fetal diaphragmatic level for the difference in internal dimensions (DID), or simultaneously from different directions for the pulse wave velocity. Pulsatile movement of the proximal and distal intima of the vessels was analyzed using PT. The fetal DID exhibited no significant changes in growth-restricted fetuses. Pulse wave velocity (3.8 +/- 0.32 m/s vs. 2.2 +/- 0.069 m/s, p &lt; 0.001) and estimated pulse pressure (6.9 +/- 0.90 kPa vs. 2.5 +/- 0.18 kPa, p &lt; 0.001) were significantly elevated in growth-restricted fetuses. Assessment of DID and pulse wave velocity of the descending aorta using PT is a feasible, non-invasive approach to evaluation of fetal hemodynamics. (C) 2015 World Federation for Ultrasound in Medicine & Biology.

High-frame-rate ultrasound is a promising technique for measurement and imaging of cardiovascular dynamics. In high-frame-rate ultrasonic imaging, unfocused ultrasonic beams are used in transmit and multiple focused receiving beams are created by parallel beamforming using the delay and sum (DAS) method. However, the spatial resolution and contrast are degraded compared with conventional beamforming using focused transmit beams. In the present study, the minimum variance beamformer was examined for improvement of the spatial resolution in high-frame-rate ultrasound. In conventional minimum variance beamforming, the spatial covariance matrix of ultrasonic echo signals received by individual transducer elements is obtained without considering the directivity of the transducer element. By omitting the element directivity, the error in estimation of the desired signal (i.e., the echo from the focal point) increases, and as a result, the improvement of the spatial resolution is degraded. In the present study, the element directivity was taken into account in estimation of the spatial covariance matrix used in minimum variance beamforming. The effect of the element directivity on adaptive beamforming was evaluated by computer simulation and basic experiments using a phantom. In parallel beamforming with the conventional DAS beamformer, the lateral spatial resolution, which was evaluated from the lateral full width at half maximum of the echo amplitude profile in the basic experiment, was 0.50 mm. Using conventional amplitude and phase estimation (APES) beamforming, the lateral spatial resolution was improved to 0.37 mm. The lateral spatial resolution was further improved to 0.30 mm using the modified APES beamforming by considering the element directivity. Image contrast and contrast-to-noise ratios, respectively, were -12.3 and 6.5 dB (DAS), -32.8 and -11.3 dB (APES), and -7.0 and 3.1 dB (modified APES).

Measurement of cardiovascular dynamics is valuable for diagnosis of the cardiovascular system. High frame rate ultrasound, which was introduced in the 1980s [1], is a promising technique for such purposes. This technique uses unfocused transmit beams and creates multiple focused receiving beams in each transmission. High frame rate ultrasound was first applied to the measurement of the displacement distribution in tissue induced by acoustic radiation force for assessment of viscoelasticity [2]. Recently, we have shown that high frame rate ultrasound is also useful for B-mode, tissue strain, and blood flow imaging [3]. Currently, various methods based on high frame rate ultrasound have been developed for measurement of cardiovascular dynamics [4-8]. In this presentation, recent development in high frame rate ultrasound and its application to measurement of cardiovascular dynamics are shown.

Objective: This study aimed to assess the cardiac function of healthy and pathological fetuses by measuring radial velocity using phased tracking (PT). Based on phase differences, PT allows the displacement of a specified point to be detected with improved spatial and temporal resolution. Methods: PT was used to assess cardiac radial velocity in the basal free wall of the left and right ventricles in 134 healthy fetuses, 10 second-trimester intrauterine growth-restricted (IUGR) fetuses, and 10 recipient twins with twin-to-twin transfusion syndrome (TTTS). Maximum velocities were measured in systole and early diastole. Results: Maximum radial velocity was successfully measured in 126 healthy fetuses (94%) at gestational ages of 16-40 weeks. Systolic and early diastolic maximum velocities increased with gestational age in both ventricles. As compared with controls, IUGR fetuses had significantly lower early diastolic maximum velocities in the right ventricle, and recipient twins with TTTS had significantly lower systolic and early diastolic maximum velocities in both ventricles. Conclusions: PT demonstrated right ventricular diastolic dysfunction in second-trimester IUGR fetuses as well as systolic and diastolic dysfunctions in both ventricles in recipient twins with TTTS. PT could be useful for evaluating fetal cardiac radial function. (C) 2015 S. Karger AG, Basel

Objective: We attempted to disclose the microscopic characteristics of the non-uniform distribution of the contraction and extension (C-E) of the left ventricular (LV) myocardium using a new methodology (echo-dynamography). Methods: The distributions of the "axial strain rate" (aSR) and the intra-mural velocity in the local areas of the free wall including the posterior wall (PW) and interventricular septum (IVS) were microscopically obtained using echo-dynamography with a high accuracy of 821 mu m in the spatial resolution. The results were shown by the color M-mode echocardiogram or curvilinear graph. Subjects were 10 presumably normal volunteers. Results: (1) Both the C-E in the pulsating LV wall showed non-uniformity spatially and time-sequentially. (2) The C-E property was better evaluated by the aSR distribution method rather than the intra-mural velocity distribution method. (3) Two types of non-uniformity of the aSR distribution were observed: i.e. (i) the difference of its (+)SR (contraction: C) or (-)SR (extension: E) was solely the "magnitude"; (ii) the coexistence of both the (+) SR and (-)SR at the same time. (4) The aSR distribution during systole was either "spotted," or "multi-layered," or "toned" distribution, whereas "stratified," "toned," or "alternating" distributions were observed during diastole. (5) The aSR distribution in the longitudinal section plane was varied in the individual areas of the wall even during the same timing. (6) To the mechanical function of the LV, there was a different behavior between the IVS and PW. Conclusions: The aSR and its distribution were the major determinants of the C-E property of the LV myocardium. Spatial as well as time-sequential uniformity of either contraction or extension did not exist. The myocardial function changed depending on the assemblage of the aSR distribution, and by the synergistic effect of (+)SR and (-)SR, the non-uniformity itself potentially served to hold the smooth LV mechanical function. (C) 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

High-frame-rate echocardiography using unfocused transmit beams and parallel receive beamforming is a promising method for evaluation of cardiac function, such as imaging of rapid propagation of vibration of the heart wall resulting from electrical stimulation of the myocardium. In this technique, high temporal resolution is realized at the expense of spatial resolution and contrast. The phase coherence factor has been developed to improve spatial resolution and contrast in ultrasonography. It evaluates the variance in phases of echo signals received by individual transducer elements after delay compensation, as in the conventional delay-and-sum beamforming process. However, the phase coherence factor suppresses speckle echoes because phases of speckle echoes fluctuate as a result of interference of echoes. In the present study, the receiving aperture was divided into several subapertures, and conventional delay-and-sum beamforming was performed with respect to each subaperture to suppress echoes from scatterers except for that at a focal point. After subaperture beamforming, the phase coherence factor was obtained from beamformed RF signals from respective subapertures. By means of this procedure, undesirable echoes, which can interfere with the echo from a focal point, can be suppressed by subaperture beamforming, and the suppression of the phase coherence factor resulting from phase fluctuation caused by such interference can be avoided. In the present study, the effect of subaperture beamforming in high-frame-rate echocardiography with the phase coherence factor was evaluated using a phantom. By applying subaperture beamforming, the average intensity of speckle echoes from a diffuse scattering medium was significantly higher (-39.9 dB) than that obtained without subaperture beamforming (-48.7 dB). As for spatial resolution, the width at half-maximum of the lateral echo amplitude profile obtained without the phase coherence factor was 1.06 mm. By using the phase coherence factor, spatial resolution was improved significantly, and subaperture beamforming achieved a better spatial resolution of 0.75 mm than that of 0.78 mm obtained without subaperture beamforming.

Introduction In early-stage atherosclerosis, the luminal surface of the arterial wall becomes rough because of detachment of endothelial cells and degeneration of the internal elastic layer. Therefore, it would be useful if minute luminal surface roughness of the carotid arterial wall, which occurs in the early stage of atherosclerosis, could be measured noninvasively with ultrasound. The injured luminal surface is believed to have roughness of a few hundred micrometers. However, in conventional ultrasonography, the axial resolution of a B-mode image depends on the ultrasonic wavelength (150 mu m at ultrasonic center frequency of 10 MHz) because a B-mode image is constructed using the amplitude of the RF echo signal. Therefore, such surface roughness cannot be measured accurately from a conventional B-mode image. Recently, we successfully measured such minute surface profile transcutaneously using the phase shift of an ultrasonic echo from the carotid arterial wall. In our previous validation experiment, a silicone phantom with minute surface roughness of 10-20 mu m was measured. However, the feasibility of our proposed method has never been validated using biological tissues. Materials and methods In the present study, luminal surface roughness of a porcine artery was measured and the result was evaluated by comparing it with the result measured using a stylus profilometer. Results and conclusion The root mean squared difference between the surface roughness measured by ultrasound and the stylus profilometer was 10.5 mu m. This result proves that our proposed method can be used to measure minute surface roughness of biological tissue.

High temporal resolution, such unique property is a big advantage of ultrasonography for measurement of tissue dynamics. High frame rate ultrasound can increase the imaging frame rate from several tensof Hertz of conventional ultrasonography up to several thousand Hertz and, thus, significantly enhances the advantage of ultrasonography. We investigated appropriate transmit-receive conditions for B-mode and blood flow imaging of the carotid artery at a very high frame rate of over 3 kHz using a linear-array probe. Also, we have also realized high frame rate echocardiography using spherically diverging beams (frame rate: 316 Hz), whose image quality is very similar to conventional beamforming (frame rate: 39 Hz). Such methods would be useful for measurement of tissue dynamics.

Background: Although a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD. Methods and Results: We first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P &lt; 0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32-cycle with 193 mW/cm(2) for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46 +/- 4 to 57 +/- 5%, P &lt; 0.05) without any adverse effects, whereas it remained unchanged in the sham group (46 +/- 5 to 47 +/- 6%, P = 0.33). Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084 +/- 175 vs. 858 +/- 151/mm(2), P &lt; 0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78 +/- 0.2 to 1.39 +/- 0.4 ml/min/g, P &lt; 0.05), but not in the control group (0.84 +/- 0.3 to 0.97 +/- 0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group. Conclusions: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD.

For the realization of noninvasive and regional myocardial tissue characterization, in the present study, we attempted to elucidate the characteristics of the myocardial response to electrical excitation and its propagation by an ex vivo experiment using a rat left ventricular wall. To visualize such a propagation phenomenon, whose speed is up to several m/s, high-frame-rate ultrasound was used to measure the myocardial vibrations driven by electrical excitation at 72 points along the heart wall with 200 mu m intervals at a frame rate of 3472 Hz. The propagation of myocardial vibration was visualized by estimating the delay time between vibration waveforms measured in the reference ultrasonic beam and each ultrasonic beam using the cross-correlation function between the vibration waveforms. From the estimated delay time, we visualized the propagation of myocardial vibration caused by electrical excitation. The propagation speed was estimated to be 2.5m/s in the entire excised myocardium. It was also estimated to be 1.8m/s in the middle of the heart wall and 2.2m/s at the internal and external surfaces of the left-ventricular wall. The results showed that the myocardial vibration driven by electrical excitation could be measured with high-frame-rate ultrasound. (C) 2014 The Japan Society of Applied Physics

Echocardiography is a predominant modality for diagnosis of the heart by noninvasive and real-time observation of its cross-sectional images. In addition, it has been recently shown that measurement of the rapid transition of myocardial contraction/relaxation and propagation of heart-wall vibration would be useful for assessment of myocardial function and viscoelasticity. However, such measurements require a higher frame rate of several hundred hertz. Therefore, we realized high-frame-rate echocardiography using parallel beamforming with unfocused transmit beams. On the other hand, there is another imaging method, namely, diffraction tomography. It has been reported that diffraction tomography realizes high spatial resolution. One of the problems of parallel beamforming with unfocused transmit beams is the degradation of spatial resolution; diffraction tomography may alleviate this problem. In the present study, diffraction tomography was applied to high-frame-rate echocardiography with unfocused transmit beams, and spatial resolutions realized by diffraction tomography and parallel beamforming were compared. Diffraction tomography showed a spatial resolution (1.16mm) similar to that (1.18 mm) of parallel beamforming in a relatively near region (44mm in range distance). In a deeper region (84mm), diffraction tomography realized better spatial resolution (1.90 mm) than that (2.27 mm) of parallel beamforming. However, still better spatial resolution (1.57mm) was realized by parallel beamforming when it was used with a phase coherence factor. The use of the phase coherence factor is not computationally intensive, and parallel beamforming with a phase coherence factor was shown to be feasible in high-frame-rate echocardiography for the improvement of spatial resolution. (C) 2014 The Japan Society of Applied Physics

The diagnosis of early-stage atherosclerosis is important for preventing cardiovascular diseases such as a stroke or a heart attack. The main cause of such diseases is atherosclerosis. In early-stage atherosclerosis, the luminal surface of the arterial wall becomes rough because of the detachment of endothelial cells and the degeneration of the internal elastic layer. Therefore, it would be useful if the minute luminal surface roughness of the carotid arterial wall observed in the early stage of atherosclerosis can be measured noninvasively by ultrasonography. In conventional ultrasonography, the axial resolution of a B-mode image depends on the ultrasonic pulse length of 150 mu m (at 10 MHz) because a B-mode image is constructed using the amplitude of the RF echo. However, the thickness of an endothelial cell covering the luminal surface is 10-20 mu m. Therefore, a minute surface roughness cannot be measured from a conventional B-mode image. We have realized the transcutaneous measurement of such a minute surface roughness of about 10 mu m using the phased-tracking method. However, the lateral spatial resolution degrades owing to the point spread function (PSF) because the diameter of an ultrasonic beam is finite. In the present study, we proposed a method of improving the lateral spatial resolution in the estimation of surface roughness using a Wiener filter to suppress the effect of the PSF of the ultrasound system employed. The proposed method was validated using a phantom and then applied to the in vivo measurement of carotid arteries. (C) 2014 The Japan Society of Applied Physics

In most current methods of evaluating the cardiac function based on echocardiography, the heart wall in an ultrasonic image is currently identified manually by an operator. However, this task is very time-consuming and leads to inter- and intraobserver variability. To facilitate the analysis and eliminate operator dependence, automated identification of heart wall regions is essential. We previously proposed a method of automatic identification of heart wall regions using multiple features based on information of the amplitude and phase of the ultrasonic RF echo signal by pattern recognition. In the present study, we investigate a new method of segmenting an ultrasonic image into the heart wall, lumen, and external tissues (includes pericardium) by two-step pattern recognition. Also, parameters in the proposed classification method were examined for application to different cross sections, i.e., long-axis and short-axis views, by considering differences in the motion and echogenicity of the heart walls. Furthermore, moving target indicator (MTI) filtering to suppress echoes from clutters was improved to enhance the separability in the short-axis view. (C) 2014 The Japan Society of Applied Physics

It is considered that the endothelial dysfunction occurs in the initial step of atherosclerosis. Although assessments of the endothelial function and viscoelastic properties of the intima-media region are important for the diagnosis of early-stage atherosclerosis, regional viscoelasticity has not yet been measured in vivo. Our group has developed an ultrasonic method for measuring the transient change in viscoelasticity during flow-mediated dilation (FMD). However, in this method, the stress (blood pressure) and strain of the intima-media region of the radial artery are measured in different arms, and the change in pulse wave velocity (PWV) due to FMD has not yet been considered. In the present study, we measured blood pressure waveforms using two pressure sensors, which were placed along the same radial artery for the ultrasonic measurement, to obtain blood pressure waveforms and estimate the PWV between the two sensors. Using the measured PWV, the pulse wave propagation time from the pressure sensor to the position of the ultrasound probe was corrected, and viscoelasticity was estimated from the corrected stress-strain relationship. In the basic experiment, we applied the proposed method to a silicone tube phantom and evaluated the accuracy of the estimation of viscoelasticity by comparing the ultrasonic measurement to the results of the tensile test. In the in vivo measurements, the change in the propagation time delay of the pulse wave was also corrected using the two pressure sensors and the stress-strain relationship of the radial arterial wall was then obtained to estimate viscoelasticity. Furthermore, a decrease in elasticity owing to FMD after recirculation was clearly observed, and the unstable temporal variation in viscosity was significantly reduced. These results demonstrated the improvement in the accuracy of the measurement of viscoelasticity by the proposed method. (C) 2014 The Japan Society of Applied Physics

It is important to evaluate the viscoelasticity of muscle for assessment of its condition. However, quantitative and noninvasive diagnostic methods have not yet been established. In our previous study, we developed a method, which used ultrasonic acoustic radiation forces irradiated from two opposite horizontal directions, for measurement of the viscoelasticity. Using two continuous wave ultrasounds, an object can be actuated with an ultrasonic intensity, which is far lower (0.9W/cm(2)) than that in the case of the conventional acoustic radiation force impulse (ARFI) method. In the present study, in vitro experiments using phantoms made of polyurethane rubber and porcine muscle tissue embedded in a gelatin block were conducted. We actuated phantoms by ultrasonic radiation force and measured the propagation velocity of the generated shear wave inside the phantoms using a diagnostic ultrasound system. The viscoelasticities of phantoms were estimated by fitting a viscoelastic model, i.e., the Voigt model, to the frequency characteristic of the measured shear wave propagation speed. In the mechanical tensile test, a softer polyurethane phantom exhibited a lower elasticity and a higher viscosity than a polyurethane phantom with a higher elasticity and a lower viscosity. The viscoelasticity measured by ultrasound showed the same tendency as that in the tensile test. Furthermore, the viscoelasticity of the phantom with porcine muscular tissue was measured in vitro, and the estimated viscoelasticity agreed well with that reported in the literature. These results show the possibility of the proposed method for noninvasive and quantitative assessment of the viscoelasticity of biological soft tissue. (C) 2014 The Japan Society of Applied Physics

Cardiac blood flow patterns such as the vortex flow pattern inside the left ventricle have been studied to provide new information for the diagnosis of the pumping function of the human heart. Complex blood flow is visualized by imaging echo speckles of blood particles because the speckle-like texture translates to the motion of blood particles. We proposed an imaging method for echo speckles of blood particles using high-frame-rate ultrasound for the visualization of the intracardiac blood flow direction. High-frame-rate ultrasound is useful for continuously observing the fast motion of echoes from blood particles in the heart. In the present study, weighting by coherence and compounding the magnitudes of echo signals in different transmissions were introduced to visualize weak echoes from blood particles. The feasibility of the visualization of cardiac blood flow using high-frame-rate ultrasound was demonstrated by basic and in vivo experiments. (C) 2014 The Japan Society of Applied Physics

Speckle tracking is a useful diagnostic method for assessing the cardiac function from ultrasonic echoes. Some factors influence the performance of the conventional speckle tracking method. Deformation due to myocardial contraction and relaxation decreases the correlation between RF echoes. Also, if a strong echo, such as echoes from the epicardium, is included in a correlation kernel, the displacement estimated from the kernel becomes close to the displacement of the epicardium even when the myocardium in the middle of the heart wall is the target to be tracked. To overcome such a problem, in the present study, we proposed a two- step tracking method. In the first step, the displacement is coarsely estimated using a correlation kernel of size similar to that in conventional speckle tracking of (13.8 degrees, 9.1 mm) in the lateral and axial directions. The kernel is divided into small subkernels (2.8 degrees, 1.9 mm). By estimating the correlation coefficient with respect to each subkernel and averaging correlation coefficients obtained from all subkernels, the contribution of a peculiar strong echo included in one of the subkernels can be suppressed. In the second step, the residual displacement is finely estimated using a smaller kernel (13.8 degrees, 3.6 mm). Using a smaller kernel, the influence of myocardial deformation can be suppressed, but there might be multiple regions that have echo patterns similar to that in the kernel, leading to tracking errors. Therefore, the search region in the second step is narrowed because the coarse displacement has already been estimated and compensated in the first step. In the present study, the proposed method was validated using a phantom made of urethane rubber, which was deformed by an actuator. The displacement of the phantom could be estimated with a lower error of 0.059 mm by the proposed method compared to the error in the conventional method of 0.097 mm. Furthermore, the proposed method was applied to in vivo measurement of the human heart. The myocardial displacement could be estimated successfully even when the epicardium was included in a correlation kernel. These results show that the proposed method provides a more accurate and robust estimation of the myocardial displacement. (C) 2014 The Japan Society of Applied Physics

Autocorrelation using in-phase and quadrature (IQ) signals suffers from aliasing when the velocity of rapidly moving tissue, such as the heart wall, is measured. In the present study, a simple method was proposed to expand the aliasing limit. In the proposed method, the velocity difference between two successive frames (corresponding to acceleration) of tissue was also estimated directly from IQ signals. When aliasing occurs in the velocity in the current frame, which was estimated from IQ signals, the velocity in the current frame was corrected by adding the velocity difference to the velocity in the previous frame. Using this procedure, the velocity can be estimated if the difference between velocities in the current and previous frames is less than the aliasing limit. The velocity of the posterior heart wall in the longitudinal-axis view of about 0.08 m/s could be estimated under the aliasing limit of the conventional autocorrelation method of 0.047 m/s. Myocardial velocity over the conventional aliasing limit could be measured by the proposed method.

Objectives: Using newly developed ultrasonic technology, we attempted to disclose the characteristics of the left ventricular (LV) contraction-extension (C-E) property, which has an important relationship to LV function. Methods: Strain rate (SR) distribution within the posterior wall and interventricular septum was microscopically measured with a high accuracy of 821 mu m in spatial resolution by using the phase difference tracking method. The subjects were 10 healthy men (aged 30-50 years). Results: The time course of the SR distribution disclosed the characteristic C-E property, i.e. the contraction started from the apex and propagated toward the base on one hand, and from the epicardial side toward the endocardial side on the other hand. Therefore, the contraction of one area and the extension of another area simultaneously appeared through nearly the whole cardiac cycle, with the contracting part positively extending the latter part and vice versa. The time course of these propagations gave rise to the peristalsis and the bellows action of the LV wall, and both contributed to effective LV function. The LV contraction started coinciding in time with the P wave of the electrocardiogram, and the cardiac cycle was composed of 4 phases, including 2 types of transitional phase, as well as the ejection phase and slow filling phase. The sum of the measurement time duration of either the contraction or the extension process occupied nearly equal duration in normal conditions. Conclusion: The newly developed ultrasonic technology revealed that the SR distribution was important in evaluating the C-E property of the LV myocardium. The harmonious succession of the 4 cardiac phases newly identified seemed to be helpful in understanding the mechanism to keep long-lasting pump function of the LV. (C) 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Purpose: Echocardiography is a widely used modality for diagnosis of the heart. It enables observation of the shape of the heart and estimation of global heart function based on B-mode and M-mode imaging. Subsequently, methods for estimating myocardial strain and strain rate have been developed to evaluate regional heart function. Furthermore, it has recently been shown that measurements of transmural transition of myocardial contraction/relaxation and propagation of vibration caused by closure of a heart valve would be useful for evaluation of myocardial function and viscoelasticity. However, such measurements require a frame rate much higher than that achieved by conventional ultrasonic diagnostic equipment. In the present study, a method based on parallel receive beamforming was developed to achieve high-frame-rate (over 300 Hz) echocardiography. Methods: To increase the frame rate, the number of transmits was reduced to 15 with angular intervals of 6 degrees, and 16 receiving beams were created for each transmission to obtain the same number and density of scan lines as realized by conventional sector scanning. In addition, several transmits were compounded to obtain each scan line to reduce the differences in transmit-receive sensitivities among scan lines. The number of transmits for compounding was determined by considering the width of the transmit beam. For transmission, plane waves and diverging waves were investigated. Diverging waves showed better performance than plane waves because the widths of plane waves did not increase with the range distance from the ultrasonic probe, whereas lateral intervals of scan lines increased with range distance. Results: The spatial resolution of the proposed method was validated using fine nylon wires. Although the widths at half-maxima of the point spread functions obtained by diverging waves were slightly larger than those obtained by conventional beamforming and parallel beamforming with plane waves, point spread functions very similar to those obtained by conventional beamforming could be realized by parallel beamforming with diverging beams and compounding. However, there was an increase in the lateral sidelobe level in the case of parallel beamforming with plane and diverging waves. Furthermore, the heart of a 23-year-old healthy male was measured. Conclusion: Although the contrast of the B-mode image obtained by the proposed method was degraded due to the increased sidelobe level, a frame rate of 316 Hz, much higher than that realized by conventional sector scanning of several tens of Hertz, was realized with a full lateral field of view of 90 degrees. © 2014, The Japan Society of Ultrasonics in Medicine. All rights reserved.

Novel diagnostic method named "sonocytometry", in which streaming blood cell is diagnosed by the reflection of high frequency ultrasound from the cell, is proposed. In the present study, the differentiation of the particle size is performed as a basic study on sonocytometry. Ultrasonic backscatter signal from either 80 or 100 mu m diameter polystyrene particles was measured by an ultrasonic transducer with the central frequency of 30 MHz. The spectrum of the reflected signal showed different characteristics according to the particle diameter. Theoretical value of backscatter was calculated by Faran-Hickling model and the correlation coefficient of measured and theoretical value by varying the spherical diameter showed the local maximum value at either 80 or 100 mu m diameter. The principle was also validated on the streaming particles in a flow channel. The method successfully classified the particle size. Sonocytometry would be clinically applied for diagnosis of malaria or leukemia.

Flow cytometry is widely used to classify individual cells optically but blood sampling is required for cell measurement in blood. If the principle of the cytometry is applicable directly in vivo, diagnosis of malaria would become easier. However, optical observation of the cell in blood flow is difficult because absorption and scattering of the light is large in vivo. In this study, novel ultrasonic method called "Sono-cytometry" for differentiating cells is proposed. The backscatter signal from the sphere with the diameter of 8 and 10-micron were detected by a transducer with the central frequency of 75 MHz. When the theoretical value is calculated from Faran-Hickling Model, linear approximate slope matched with theoretical slope. When calculating the slope of theoretical value by changing the spherical diameter, the slope value was very different between 8 and 10 micron. The result shows that it is possible that this method can classify spheres.

The assessment of the intima-media thickness (IMT) of the carotid arterial wall, which is the most frequently used indicator to diagnose atherosclerosis by ultrasound, involves the measurement of the lumen-intima boundary (LIB) and media-adventitia boundary (MAB). In this study, using the mean squared error (MSE) method and by applying the template matching technique, an adaptive model of an ultrasonic echo, which is obtained from an ultrasonic pulse measured with a hydrophone, was fitted with the measured in vivo RF echo to estimate the boundaries of the carotid arterial wall. In the present study, the frequency and phase of the adaptive model were considered to improve the accuracy in the determination of the LIB and MAB. For a 7.5-mm-long short segment of the carotid artery in the longitudinal direction, the average IMTs estimated by the improved technique and the previous method were 502 +/- 61 and 558 +/- 120 mu m, respectively, showing a decrease in the standard deviation by the proposed method. Moreover, the result obtained by the improved technique presented only 0.4% difference between the automatically detected boundary and the manually detected boundary, which is smaller than that obtained by the previous method (10.7% difference). These results verified that the boundary detected by the improved technique was more accurate than that detected by the previous method. (c) 2013 The Japan Society of Applied Physics

It is very important to make early diagnoses of atherosclerosis for the prevention of lifestyle-related diseases. The intima-media thickness (IMT) is used as a diagnostic index of cerebrovascular diseases and atherosclerosis throughout the body including the coronary artery. In the field of the medical diagnostics, ultrasonic equipment using a pulse-echo method is widely used. In conventional ultrasonic diagnostic equipment, ultrasonic images are obtained by receiving ultrasonic echoes and converting their amplitudes into brightness. In general, ultrasonic B-mode images are degraded by the narrow-band characteristics of the ultrasonic transducer. In the present study, a method was proposed for shortening the lengths of the received ultrasonic pulses from an object of interest using a Wiener filter. As a result, the lengths of ultrasonic pulses were shortened and the visibility of interfaces of the intima-media complex of the carotid arterial wall was improved by the proposed method, which realizes accurate measurement of the IMT. © 2013 The Japan Society of Applied Physics.

For the facilitation of analysis and elimination of the operator dependence in estimating the myocardial function in echocardiography, we have previously developed a method for automated identification of the heart wall. However, there are misclassified regions because the magnitude-squared coherence (MSC) function of echo signals, which is one of the features in the previous method, is sensitively affected by the clutter components such as multiple reflection and off-axis echo from external tissue or the nearby myocardium. The objective of the present study is to improve the performance of automated identification of the heart wall. For this purpose, we proposed a method to suppress the effect of the clutter components on the MSC of echo signals by applying an adaptive moving target indicator (MTI) filter to echo signals. In vivo experimental results showed that the misclassified regions were significantly reduced using our proposed method in the longitudinal axis view of the heart. (C) 2013 The Japan Society of Applied Physics

Background We previously reported that the σ1-receptor (σ1R) is down-regulated following cardiac hypertrophy and dysfunction in transverse aortic constriction (TAC) mice. Here we address how σ1R stimulation with the selective σ1R agonist SA4503 restores hypertrophy-induced cardiac dysfunction through σ1R localized in the sarcoplasmic reticulum (SR). Methods We first confirmed anti-hypertrophic effects of SA4503 (0.1-1 μM) in cultured cardiomyocytes exposed to angiotensin II (Ang II). Then, to confirm the ameliorative effects of σ1R stimulation in vivo, we administered SA4503 (1.0 mg/kg) and the σ1R antagonist NE-100 (1.0 mg/kg) orally to TAC mice for 4 weeks (once daily). Results σ1R stimulation with SA4503 significantly inhibited Ang II-induced cardiomyocyte hypertrophy. Ang II exposure for 72 h impaired phenylephrine (PE)-induced Ca2 + mobilization from the SR into both the cytosol and mitochondria. Treatment of cardiomyocytes with SA4503 largely restored PE-induced Ca2 + mobilization into mitochondria. Exposure of cardiomyocytes to Ang II for 72 h decreased basal ATP content and PE-induced ATP production concomitant with reduced mitochondrial size, while SA4503 treatment completely restored ATP production and mitochondrial size. Pretreatment with NE-100 or siRNA abolished these effects. Chronic SA4503 administration also significantly attenuated myocardial hypertrophy and restored ATP production in TAC mice. SA4503 administration also decreased hypertrophy-induced impairments in LV contractile function. Conclusions σ1R stimulation with the specific agonist SA4503 ameliorates cardiac hypertrophy and dysfunction by restoring both mitochondrial Ca 2 + mobilization and ATP production via σ1R stimulation. General significance Our observations suggest that σ1R stimulation represents a new therapeutic strategy to rescue the heart from hypertrophic dysfunction. © 2012 Elsevier B.V.

Purpose: Pulse wave velocity (PWV) is the propagation velocity of the pressure wave along the artery due to the heartbeat. The PWV becomes faster with progression of arteriosclerosis and, thus, can be used as a diagnostic index of arteriosclerosis. Measurement of PWV is known as a noninvasive approach for diagnosis of arteriosclerosis and is widely used in clinical situations. In the traditional PWV method, the average PWV is calculated between two points, the carotid and femoral arteries, at an interval of several tens of centimeters. However, PWV depends on part of the arterial tree, i.e., PWVs in the distal arteries are faster than those in the proximal arteries. Therefore, measurement of regional PWV is preferable. Methods: To evaluate regional PWV in the present study, the minute vibration velocity of the human carotid arterial wall was measured at intervals of 0.2 mm at 72 points in the arterial longitudinal direction by the phased-tracking method at a high temporal resolution of 3472 Hz, and PWV was estimated by applying the Hilbert transform to those waveforms. Results: In the present study, carotid arteries of three healthy subjects were measured in vivo. The PWVs in short segments of 14.4 mm in the arterial longitudinal direction were estimated to be 5.6, 6.4, and 6.7 m/s, which were in good agreement with those reported in the literature. Furthermore, for one of the subjects, a component was clearly found propagating from the periphery to the direction of the heart, i.e., a well known component reflected by the peripheral arteries. By using the proposed method, the propagation speed of the reflection component was also separately estimated to be -8.4 m/s. The higher magnitude of PWV for the reflection component was considered to be the difference in blood pressure at the arrivals of the forward and reflection components. Conclusion: Such a method would be useful for more sensitive evaluation of the change in elasticity due to progression of arteriosclerosis by measuring the regional PWV in a specific artery of interest (not the average PWV including other arteries). © 2012 The Japan Society of Ultrasonics in Medicine.

Aim: The aim of this study was to investigate the relationship between atherosclerotic manifestations and brachial and radial arterial wall elasticity (AWE) measured using the phased tracking method in patients with type 2 diabetes mellitus (T2DM). Methods: This study included T2DM patients (n=220, mean age 59 years) without a history of stroke or coronary artery disease. The brachial AWE, radial AWE, carotid mean intima-media thickness (IMT), max-IMT and flow-mediated vasodilation (FMD) were measured. The patients were classified according to the number of atherosclerotic risk factors, including obesity, dyslipidemia and hypertension. Group 1 included T2DM patients only, group 2 included patients with two risk factors, group 3 included patients with three risk factors and group 4 included patients with four risk factors. The patients were also divided into two groups according to microangiopathic complications, including retinopathy and nephropathy. The between-group differences were analyzed. Results: The brachial AWE (548, 697, 755 and 771 kPa for groups 1, 2, 3 and 4, respectively) and radial AWE (532, 637, 717 and 782 kPa for groups 1, 2, 3 and 4, respectively) significantly increased in association with an increasing number of risk factors. The brachial AWE and radial AWE were significantly higher in the patients with microangiopathic complications than in those without microangiopathic complications (brachial AWE 797 and 694 kPa and radial AWE 780 and 660 kPa, respectively). Receiver operating characteristic curve analyses revealed that, for brachial AWE and radial AWE, the area under the curve was equal to the max-IMT and higher than the mean-IMT and FMD. Conclusions: Upper limb AWE measurement can reflect the degree of atherosclerosis risk overload and may be useful for evaluating vascular complications in T2DM patients.

In linear array transducers, owing to regular spacing of the array elements, grating lobes exist in transmission and reception. In ultrasonic imaging involving the use of diverging (unfocused) transmitting beams and steered receiving beams by linear transducer arrays, aperture apodization and spatial combination of steered receiving beams from multiple transmissions are not sufficient to suppress receive-grating lobe artifacts. To further suppress receive-grating lobe artifacts in reconstructed B-mode images, we propose a technique of modulating the receiving beams by a factor that is governed by the envelope of a corresponding signal, which is formed by filtering the receiving beam with a zero-phase low-pass filter with a cut-off frequency that is determined by the receiving beam steering angle. This technique suppressed receive-grating lobe artifacts without significant loss in spatial resolution in offline reconstructed B-mode images from simulation, phantom and in vivo imaging of the carotid artery. In a simulation of point scatterers, a relative reduction in grating lobe artifacts of 40 dB was realized in images from diverging beam scanning. © 2013 World Federation for Ultrasound in Medicine &amp Biology.

Echocardiography has become an indispensable modality for diagnosis of the heart. It enables observation of the shape of the heart and estimation of global heart function based on B-mode and M-mode imaging. Methods for echocardiographic estimation of myocardial strain and strain rate have also been developed to evaluate regional heart function. Furthermore, it has been recently shown that echocardiographic measurements of transmural transition of myocardial contraction/relaxation and propagation of vibration caused by closure of the heart valve would be useful for evaluation of myocardial function and viscoelasticity. However, such measurements require a frame rate (typically &gt; 200 Hz) much higher than that achieved by conventional ultrasonic diagnostic equipment. We have recently realized a high frame rate of about 300 Hz with a full field of view of 90 using diverging transmit beams and parallel receive beamforming. Although high-frame-rate imaging was made possible by this method, the side lobe level was slightly larger than that of the conventional method. To reduce the side lobe level, phase coherence imaging has recently been developed. Using this method, the spatial resolution is improved and the side lobe level is also reduced. However, speckle-like echoes, for example, echoes from the inside of the heart wall, are also suppressed. In the present study, a method for reducing the side lobe level while preserving speckle-like echoes was developed. The side lobe level was evaluated using a wire phantom. The side lobe level of the high-frame-rate imaging using unfocused diverging beams was improved by 13.3 dB by the proposed method. In in vivo measurements, a B-mode image of the heart of a 23-year-old healthy male could be obtained while preserving the speckle pattern in the heart wall at a frame rate of 316 Hz with a full field of view of 90 degrees.

We observe some phase singularities in traveling excited waves noninvasively measured by a novel ultrasonic method, on a human cardiac interventricular septum (IVS) for a healthy young male. We present a possible physical model explaining a part of one-dimensional cardiac dynamics of the observed phase defects on the IVS. We show that at least one of the observed phase singularities in the excited waves on the IVS can be explained by the Bekki-Nozaki hole solution in the complex Ginzburg-Landau equation, although the creation and annihilation of phase singularities on the IVS give birth to a variety of complex patterns.

Integrated backscatter (IB) from the heart wall is gaining attention as a quantitative tissue characterization method and the cyclic variation (CV) in IB during a cardiac cycle offers potential for the evaluation of myocardial contractility. Since there is large motion in the heart wall owing to the heartbeat, in the conventional method, the position of the region of interest (ROI) for calculating the IB is manually assigned in each frame during one cardiac cycle. Moreover, the change in the size of the ROI during contraction and relaxation of the myocardium is not considered. In this study, the phased tracking method was applied to multiple points in the heart wall for automatic tracking of the position and size of the ROI and, then, IB in the same site of the heart wall was measured in each frame by improving temporal resolution and spatial resolution in the axial direction. As a result, cyclic variations, which differed site by site, were found. Furthermore, the rate of change in thickness was estimated by using the interference cycle obtained by applying the discrete Fourier transform (DFT) to IB signals. According to the results, the rate of change in thickness estimated using the interference cycle of IB was in good agreement with that estimated by the phased tracking method. These results indicate the possibility of estimating the rate of change in thickness using the IB signal. (C) 2012 The Japan Society of Applied Physics

For noninvasive and quantitative measurements of global two-dimensional (2D) heart wall motion, speckle tracking methods have been developed and applied. In these conventional methods, the frame rate is limited to about 200 Hz, corresponding to the sampling period of 5 ms. However, myocardial function during short periods, as obtained by these conventional speckle tracking methods, remains unclear owing to low temporal and spatial resolutions of these methods. Moreover, an important parameter, the optimal kernel size, has not been thoroughly investigated. In our previous study, the optimal kernel size was determined in a phantom experiment under a high signal-to-noise ratio (SNR), and the determined optimal kernel size was applied to the in vivo measurement of 2D displacements of the heart wall by block matching using normalized cross-correlation between RF echoes at a high frame rate of 860Hz, corresponding to a temporal resolution of 1.1 ms. However, estimations under low SNRs and the effects of the difference in echo characteristics, i.e., specular reflection and speckle-like echoes, have not been considered, and the evaluation of accuracy in the estimation of the strain rate is still insufficient. In this study, the optimal kernel sizes were determined in a phantom experiment under several SNRs and, then, the myocardial strain rate was estimated such that the myocardial function can be measured at a high frame rate. In a basic experiment, the optimal kernel sizes at depths of 20, 40, 60, and 80mm yielded similar results: in particular, SNR was more than 15 dB. Moreover, it was found that the kernel size at the boundary must be set larger than that at the inside. The optimal sizes of the correlation kernel were seven times and four times the size of the point spread function around the boundary and inside the silicone rubber, respectively. To compare the optimal kernel sizes, which was determined in a phantom experiment, with other sizes, the radial strain rates estimated using different kernel sizes were examined using the normalized mean-squared error of the estimated strain rate from the actual one obtained by the 1D phase-sensitive method. Compared with conventional kernel sizes, this result shows the possibility of the proposed correlation kernel to enable more accurate measurement of the strain rate. In in vivo measurement, the regional instantaneous velocities and strain rates in the radial direction of the heart wall were analyzed in detail at an extremely high temporal resolution (frame rate of 860 Hz). In this study, transition in contraction and relaxation was able to be detected by 2D tracking. These results indicate the potential of this method in the high-accuracy estimation of the strain rates and detailed analyses of the physiological function of the myocardium. (C) 2012 The Japan Society of Applied Physics

In line with the fact that the intima-media thickness (IMT) of the carotid arterial wall is the most frequently used indicator to diagnose atherosclerosis by ultrasound, it is essential to accurately estimate the thickness of the intima-media complex (IMC) boundaries, i.e., the lumenintima boundary (LIB) and media-adventitia boundary (MAB). In this study, an improved adaptive model of an ultrasonic echo was developed for the model to realize better fitting to the reference RF echo, which is measured from a glass plate, using a Gaussian window for the envelope function of the adaptive model. Using the mean squared error (MSE) method, the envelope of the improved adaptive model (multiply the sinusoidal wave with the Gaussian window) was fitted with the envelope of an RF echo measured in vivo to estimate the boundaries of the carotid arterial wall. Firstly, a computer simulation of the carotid arterial wall was conducted to evaluate the accuracy of boundary detection using the envelope of the improved adaptive model. In the simulation, IMT was set at 0.50mm in a 7.2-mm-long short segment in the longitudinal direction. The IMT estimated by the proposed method was 0.54 mm. The 8% error between the true and detected IMTs showed the high accuracy of the envelope of the improved adaptive model in boundary detection. In the in vivo measurement, for the 4.8-mm-long short segment in the longitudinal direction, the average IMT automatically estimated by the proposed method was 0.57 mm. The result was compared with those obtained by the previous method and manually. The IMT estimated by the previous method, which uses an RF adaptive model, was 0.59mm and the manually determined IMT was 0.56 mm. The smaller difference between the results obtained by the proposed method and manually verified that boundary detection by the proposed method was better than that by the previous method. (C) 2012 The Japan Society of Applied Physics

It would be useful to measure the minute surface roughness of the carotid arterial wall to detect the early stage of atherosclerosis. In conventional ultrasonography, the axial resolution of a B-mode image depends on the ultrasonic wavelength of 150 mu m at 10MHz because a B-mode image is constructed using the amplitude of the radio-frequency (RF) echo. Therefore, the surface roughness caused by atherosclerosis in an early stage cannot be measured using a conventional B-mode image obtained by ultrasonography because the roughness is 10-20 mu m. We have realized accurate transcutaneous estimation of such a minute surface profile using the lateral motion of the carotid arterial wall, which is estimated by block matching of received ultrasonic signals. However, the width of the region where the surface profile is estimated depends on the magnitude of the lateral displacement of the carotid arterial wall (i.e., if the lateral displacement of the arterial wall is 1mm, the surface profile is estimated in a region of 1mm in width). In this study, the width was increased by combining surface profiles estimated using several ultrasonic beams. In the present study, we first measured a fine wire, whose diameter was 13 mu m, using ultrasonic equipment to obtain an ultrasonic beam profile for determination of the optimal kernel size for block matching based on the correlation between RF echoes. Second, we estimated the lateral displacement and surface profile of a phantom, which had a saw tooth profile on its surface, and compared the surface profile measured by ultrasound with that measured by a laser profilometer. Finally, we estimated the lateral displacement and surface roughness of the carotid arterial wall of three healthy subjects (24-, 23-, and 23-year-old males) using the proposed method. (C) 2012 The Japan Society of Applied Physics

In our previous study, the stress-strain relationship of the radial arterial wall was measured and the viscoelasticity of the intima-media region was estimated from the stress-strain relationship. Furthermore, the transient change in viscoelasticity due to flow-mediated dilation (FMD) was estimated by the automated detection of wall boundaries. In the present study, the strain rate was adaptively filtered to improve the accuracy of viscoelasticity estimation by decreasing the high-frequency noise. Additionally, in a basic experiment, this method was validated using a silicone tube (simulating artery). In the basic experiment, the elasticity was estimated with a mean error of 1.2%. The elasticity measured at each beam position was highly reproducible among measurements, whereas there was a slight variation in measured elasticity among beams. Consequently, in in vivo measurements, the normalized mean square error (MSE) was clearly decreased. Additionally, the stress-strain relationship of the radial arterial wall was obtained and the viscoelasticity was estimated accurately. The inner small loop, which corresponds to the negative pressure wave caused by the closure of the aortic valve, can be observed using the adaptive low-pass filtering (LPF). Moreover, the transient changes in these parameters were similar to those in the previous study. These results show the potential of the proposed method for the thorough analysis of the transient change in viscoelasticity due to FMD. (C) 2012 The Japan Society of Applied Physics

In most of the methods for evaluation of cardiac function based on echocardiography, the heart wall, which is the object to be analyzed, is currently identified manually by an operator. However, this task is very time-consuming and suffers from inter-and intraobserver variability. In the present study, a method was proposed for automated identification of the heart wall region in ultrasonic data throughout an entire cardiac cycle. The heart wall region at the optimal frame of interest in the cardiac phase was identified by applying the expectation-maximization (EM) algorithm to extracted features, and heart wall regions in the following frames were identified by tracking each point, which was classified in the optimal (initial) frame as the heart wall region, using the phased tracking method. The results showed that the proposed method was feasible in automated identification of the heart wall in the longitudinal axis view.

To assess mechanical properties of tissues, strain must be generated in an object. However, a single radiation force is not effective because it mainly generates translational motion when the object is much harder than the surrounding medium. In the present study, two cyclic radiation forces are simultaneously applied to a muscle phantom from two opposite horizontal directions so that the object is cyclically compressed in the horizontal direction. By the horizontal compression, the object is expanded vertically based on its incompressibility. The resultant vertical displacement is measured using another ultrasound pulse. The displacement of several micrometers in amplitude was measured by the ultrasonic phased-tracking method. Increase in thickness inside the object in the vertical direction was observed at the time of increasing acoustic radiation forces. Such changes in thickness corresponded to vertical expansion due to horizontal compression and show that the proposed method successfully generated strains inside the object.

Background: The existence as well as the exact genesis of left ventricular suction during rapid filling phase have been controversial. In the present study, we aimed at resolution of this problem using noninvasive and sophisticated ultrasonic methods. The clinical meaning was also documented. Methods: Ten healthy male volunteers were examined by 20 echocardiography and echo-dynamography which enables us to obtain detailed instantaneous data of blood flow and wall motion simultaneously from the wide range of the left ventricle. The correlation of blood flow and wall motion was also studied. Results: Rapid ventricular filling was divided into 2 phases which had different physiology. The early half (early rapid filling: ERF) showed the effect which was alike drawing a piston. This was proved by the shape of the velocity of inflow and the basal muscle contraction which actively assisted extension of the relaxed apical and central parts of the left ventricle, giving the negative pressure which causes the ventricular suction. The later half (late rapid filling: LRF) showed the turning of the fundamental flow and the squeezed basal part just like the sphincter in addition to the expansion of the apical and central portions of the left ventricle, and all of these cooperatively augmented the suction effect. Conclusion: Ventricular suction does exist to help ventricular filling. Simultaneous appearance of the contraction in the basal part and the relaxation or extension in the apical part during the post-ejection transitional period was made to occur the suction in the LV. And it can be said that the suction appeared in the late stage of systole as the one of the serial systolic phenomena. (C) 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

August 26-29, 2011, Vienna, Autsria

A prototype of wireless surface electrical stimulation system combined with the fuzzy FES controller was developed for rehabilitation training with functional electrical stimulation (FES). The developed FES system has three features for rehabilitation training: small-sized electrical stimulator for surface FES, wireless connection between controller and stimulators, and between controller and sensors, and the fuzzy FES controller based on the cycle-to-cycle control for repetitive training. The developed stimulator could generate monophasic or biphasic high voltage stimulus pulse and could output stimulation pulses continuously more than 20 hours with 4 AAA batteries. The developed system was examined with neurologically intact subjects and hemiplegic subjects in knee joint control. The maximum knee joint angle was controlled by regulating burst duration of stimulation pulses by the fuzzy controller. In the results of two experiments of knee extension angle control and knee flexion and extension angle control, the maximum angles reached their targets within small number of cycles and were controlled stably in the stimulation cycles after reaching the target. The fuzzy FES controller based on the cycle-to-cycle control worked effectively to reach the target angle and to compensate difference in muscle properties between subjects. The developed wireless surface FES system would be practical in clinical applications of repetitive execution of similar movements of the limbs for motor rehabilitation with FES. © 2011 Informa UK, Ltd.

Red blood cell (RBC) aggregation, as one of the determinants of blood viscosity, plays an important role in blood rheology, including the condition of blood. RBC aggregation is induced by the adhesion of RBCs when the electrostatic repulsion between RBCs weakens owing to increases in protein and saturated fatty acid levels in blood, excessive RBC aggregation leads to various circulatory diseases. This study was conducted to establish a noninvasive quantitative method for assessment of RBC aggregation. The power spectrum of ultrasonic RF echoes from nonaggregating RBCs, which shows the frequency property of scattering, exhibits Rayleigh behavior. On the other hand, ultrasonic RF echoes from aggregating RBCs contain the components of reflection, which have no frequency dependence. By dividing the measured power spectrum of echoes from RBCs in the lumen by that of echoes from a posterior wall of the vein in the dorsum manus, the attenuation property of the propagating medium and the frequency responses of transmitting and receiving transducers are removed from the former spectrum. RBC aggregation was assessed by the diameter of a scatterer, which was estimated by minimizing the square difference between the measured normalized power spectrum and the theoretical power spectrum. In this study, spherical scatterers with diameters of 5, 11, 15, and 30 mu m were measured in basic experiments. The estimated scatterer diameters were close to the actual diameters. Furthermore, the transient change of the scatterer diameters were measured in an in vivo experiment with respect to a 24-year-old healthy male during the avascularization using a cuff. The estimated diameters (12-22 mu m) of RBCs during avascularization were larger than the diameters (4-8 mu m) at rest and after recirculation. These results show the possibility of the use of the proposed method for noninvasive assessment of RBC aggregation. (C) 2011 The Japan Society of Applied Physics

Purpose Echocardiography is a widely used modality for diagnosis of the heart. It enables observation of the shape of the heart and estimation of global heart function based on B-mode and M-mode imaging. Subsequently, methods for estimating myocardial strain and strain rate have been developed to evaluate regional heart function. Furthermore, it has recently been shown that measurements of transmural transition of myocardial contraction/relaxation and propagation of vibration caused by closure of a heart valve would be useful for evaluation of myocardial function and viscoelasticity. However, such measurements require a frame rate much higher than that achieved by conventional ultrasonic diagnostic equipment. In the present study, a method based on parallel receive beamforming was developed to achieve high-frame-rate (over 300 Hz) echocardiography. Methods To increase the frame rate, the number of transmits was reduced to 15 with angular intervals of 6A degrees, and 16 receiving beams were created for each transmission to obtain the same number and density of scan lines as realized by conventional sector scanning. In addition, several transmits were compounded to obtain each scan line to reduce the differences in transmit-receive sensitivities among scan lines. The number of transmits for compounding was determined by considering the width of the transmit beam. For transmission, plane waves and diverging waves were investigated. Diverging waves showed better performance than plane waves because the widths of plane waves did not increase with the range distance from the ultrasonic probe, whereas lateral intervals of scan lines increased with range distance. Results The spatial resolution of the proposed method was validated using fine nylon wires. Although the widths at half-maxima of the point spread functions obtained by diverging waves were slightly larger than those obtained by conventional beamforming and parallel beamforming with plane waves, point spread functions very similar to those obtained by conventional beamforming could be realized by parallel beamforming with diverging beams and compounding. However, there was an increase in the lateral sidelobe level in the case of parallel beamforming with plane and diverging waves. Furthermore, the heart of a 23-year-old healthy male was measured. Conclusion Although the contrast of the B-mode image obtained by the proposed method was degraded due to the increased sidelobe level, a frame rate of 316 Hz, much higher than that realized by conventional sector scanning of several tens of Hertz, was realized with a full lateral field of view of 90A degrees.

Red blood cell (RBC) aggregation, as one of the determinants of blood viscosity, plays an important role in blood rheology, including the condition of blood. RBC aggregation is induced by the adhesion of RBCs when the electrostatic repulsion between RBCs weakens owing to increases in protein and saturated fatty acid levels in blood, excessive RBC aggregation leads to various circulatory diseases. This study was conducted to establish a noninvasive quantitative method for assessment of RBC aggregation. The power spectrum of ultrasonic RF echoes from nonaggregating RBCs, which shows the frequency property of scattering, exhibits Rayleigh behavior. On the other hand, ultrasonic RF echoes from aggregating RBCs contain the components of reflection, which have no frequency dependence. By dividing the measured power spectrum of echoes from RBCs in the lumen by that of echoes from a posterior wall of the vein in the dorsum manus, the attenuation property of the propagating medium and the frequency responses of transmitting and receiving transducers are removed from the former spectrum. RBC aggregation was assessed by the diameter of a scatterer, which was estimated by minimizing the square difference between the measured normalized power spectrum and the theoretical power spectrum. In this study, spherical scatterers with diameters of 5, 11, 15, and 30 mu m were measured in basic experiments. The estimated scatterer diameters were close to the actual diameters. Furthermore, the transient change of the scatterer diameters were measured in an in vivo experiment with respect to a 24-year-old healthy male during the avascularization using a cuff. The estimated diameters (12-22 mu m) of RBCs during avascularization were larger than the diameters (4-8 mu m) at rest and after recirculation. These results show the possibility of the use of the proposed method for noninvasive assessment of RBC aggregation. (C) 2011 The Japan Society of Applied Physics

Transverse cross sectional imaging of the intima-media complex of the carotid arterial wall is difficult to obtain by conventional linear scanning. The angular widths of imaged regions of the anterior and posterior walls are limited. In this study, multi element diverging beam from a linear array transducer was investigated by simulations and experiments. B-mode image was reconstructed, using combinations of multi angle receiving beams from multiple transmissions per frame. The images obtained by the proposed method from simulations and silicone-rubber tube phantom showed an increase in the angular width over that in the case of conventional linear scanning. Also, images were investigated for sub aperture sizes of 36, 56, and 96 elements with different beam-spread angles. On the basis of the results of the present study, the sub aperture size of 36 elements and beam-spread angle of 90 degrees are recommended for achieving the optimum results for this application in in-vivo imaging. (C) 2011 The Japan Society of Applied Physics

We measured the stress-strain relationship of the radial arterial wall during a heartbeat noninvasively. In our previous study, the viscoelasticity of the intima-media region was estimated from the stress-strain relationship, and the transient change in viscoelasticity due to flow-mediated dilation (FMD) was estimated. In this estimation, it is necessary to detect the lumen-intima boundary (LIB) and the media-adventitia boundary (MAB). To decrease the operator dependence, in the present study, a method is proposed for automatic and objective boundary detection based on template matching between the measured and adaptive model ultrasonic signals. Using this method, arterial wall boundaries were appropriately detected in in vivo experiments. Furthermore, the transient change in viscoelasticity estimated from the stress-strain relationship was similar to that obtained manually. These results show the feasibility of the proposed method for automatic boundary detection enabling an objective and appropriate analysis of the transient change in viscoelasticity due to FMD. (C) 2011 The Japan Society of Applied Physics

There are two approaches to three-dimensional (3D) image reconstruction using a 1D array ultrasonic transducer: mechanical linear scanning and free-hand scanning. Mechanical scanning employs a motorized mechanism to translate the transducer linearly. However, the large size and weight of the scanning system sometimes make it inconvenient to use. In free-hand scanning, a sensor (e. g., electromagnetic or optical) is attached to the ultrasonic transducer to measure the position and orientation of the transducer. These techniques are sensitive to the usage environment. Recently, sensorless free-hand scanning techniques have been developed. Seabra et al. reported sensorless free-hand techniques for the carotid artery by monitoring the velocity of the ultrasound probe [J. C. R. Seabra, L. M. Pedro, and J. F. Ferandes: IEEE Trans. Biomed. Eng. 56 (2009) 1442]. This system achieved an accuracy of 2.5mm [root mean square (RMS) error] of the location. To develop accurate sensorless measurement, we propose a novel method using the phase shift between ultrasonic RF echoes. In this study, we measured the transmit-receive directivity of a linear-array transducer using a silicone phantom and estimated the elevational distance between two 2D US images using the phase shift. An accuracy of 49.9 mu m in RMS, which is less than that of the previous sensorless free-hand method, could be achieved by the proposed method. (C) 2011 The Japan Society of Applied Physics

In most methods for evaluation of cardiac function based on echocardiography, the heart wall is currently identified manually by an operator. However, this task is very time-consuming and suffers from inter- and intraobserver variability. The present paper proposes a method that uses multiple features of ultrasonic echo signals for automated identification of the heart wall region throughout an entire cardiac cycle. In addition, the optimal cardiac phase to select a frame of interest, i.e., the frame for the initiation of tracking, was determined. The heart wall region at the frame of interest in this cardiac phase was identified by the expectation-maximization (EM) algorithm, and heart wall regions in the following frames were identified by tracking each point classified in the initial frame as the heart wall region using the phased tracking method. The results for two subjects indicate the feasibility of the proposed method in the longitudinal axis view of the heart. (C) 2011 The Japan Society of Applied Physics

Complexity of the cardiac contraction sequence is still not fully understood because the dynamic mechanical excitation process, which directly correlates with contraction, cannot be accurately measured based on the electro-magnetic phenomena. By developing a noninvasive novel imaging modality with high temporal and spatial resolutions, the present study shows that the propagation of the mechanical wave-front occurs at the beginning of cardiac contraction sequence for the first time (about 60 ms prior to the ordinarily accepted onset time of the contraction). From the apical side of the interventricular septum, a minute velocity component with an amplitude of several tenth micrometers is generated and it propagates from the apex to the base of the posterior wall, and then from the base to the apex of the septum, with a propagation speed of 3-9 m/s. This dynamic measurement modality is also applicable to various tissues in biology. (C) 2011 The Japan Society of Applied Physics

June 26-29, 2011, Artimino, Italy

June 5-9, 2011, Beijing, China

To detect minute roughness, we utilized the phase change that occurs in a radio frequency echo from the rough surface of an object during its lateral motion. The new method was optimized and validated using saw-tooth-shaped silicone phantoms sized from 13 to 33 mu m; results were compared to those obtained using a confocal laser scanning microscope.

March 22-23, 2011, Sendai

March 22-23, 2011, Sendai

March 22-23, 2011, Sendai

December 15-16, 2010, Singapore, Singapore

Tagashira H, Bhuiyan S, Shioda N, Hasegawa H, Kanai H, Fukunaga K. sigma(1)-Receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice. Am J Physiol Heart Circ Physiol 299: H1535-H1545, 2010. First published August 27, 2010; doi:10.1152/ajpheart.00198.2010.-Selective serotonin reuptake inhibitors (SSRIs) are known to reduce post-myocardial infarction-induced morbidity and mortality. However, the molecular mechanism underlying SSRI-induced cardioprotection remains unclear. Here, we investigated the role of sigma(1)-receptor (sigma R-1) stimulation with fluvoxamine on myocardial hypertrophy and cardiac functional recovery. Male ICR mice were subjected to transverse aortic constriction (TAC) in the cardiac aortic arch. To confirm the cardioprotective role of fluvoxamine by sigma R-1 stimulation, we treated mice with fluvoxamine (0.5 or 1 mg/kg) orally once per day for 4 wk after the onset of aortic banding. Interestingly, in untreated mice, sigma R-1 expression in the left ventricle (LV) decreased significantly over the 4 wk as TAC-induced hypertrophy increased. In contrast, fluvoxamine administration significantly attenuated TAC-induced myocardial hypertrophy concomitant with recovery of sigma R-1 expression in the LV. Fluvoxamine also attenuated hypertrophy-induced impaired LV fractional shortening. The fluvoxamine cardioprotective effect was nullified by treatment with a sigma R-1 antagonist [NE-100 (1 mg/kg)]. Importantly, another SSRI with very low affinity for sigma(1)Rs, paroxetine, did not elicit antihypertrophic effects in TAC mice and cultured cardiomyocytes. Fluvoxamine treatment significantly restored TAC-induced impaired Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in the LV. Our findings suggest that fluvoxamine protects against TAC-induced cardiac dysfunction via upregulated sigma R-1 expression and stimulation of sigma R-1-mediated Akt-eNOS signaling in mice. This is the first report of a potential role for sigma R-1 stimulation by fluvoxamine in attenuating cardiac hypertrophy and restoring contractility in TAC mice.

September 13-16, 2010, Matsushima

September 13-16, 2010, Matsushima

September 13-16, 2010, Matsushima

Using echo-dynamography, systolic blood flow structure in the ascending aorta and aortic arch was investigated in 10 healthy volunteers. The blood flow structure was analyzed based on the two-dimensional (2D) and 1D velocity vector distributions, changing acceleration of flow direction (CAFD), vorticity distribution, and Doppler pressure distribution. To justify the results obtained in humans, in vitro experiments were done using straight and curved tube models of 20 mm diameter. The distribution of the CAFD showed a spiral staircase pattern along the flow axis line. In addition, the changes in the velocity profile in the short-axis direction, 20 distribution of the vorticity, and velocity vector distribution on the aortic cross-section plane, all confirmed the presence of systolic twisted spiral flow rotating clockwise toward the peripheral part of the ascending aorta. The rotation cycle of this spiral flow correlated inversely with the maximum velocity of the aortic flow, so that this cycle was shorter in early systole and longer in late systole. The model experiments showed similar results. The spiral flow seemed to be produced by several factors: (i) anterior shift of the direction of ejected blood flow due to the anterior displacement of the projection of the aorta; (ii) accelerated high pressure flow ejected antero-upward; (iii) inertia resistance at the peripheral boundary of the sinus of Valsalva; and (iv) reflection caused by the concave spherical structure of the inner surface of the basal part of the aorta. Because the main spiral flow axis line nearly coincided with the center line of the aorta, it is concluded that the occurrence of the spiral flow plays an important role in maintaining the blood flow direction passing through the cylindrical curved aortic arch and thus in keeping the most effective ejection as well as in dispersing the shear stress in the aortic wall. (c) 2010 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.

March 26-27, 2010, Sendai

February 24-25, 2010, Sendai

February 24-25, 2010, Sendai

February 24-25, 2010, Sendai

February 24-25, 2010, Sendai

February 24-25, 2010, Sendai

February 23, 2010, Sendai

February 23, 2010, Sendai

Using a heart ischemia/reperfusion model in rats, we recently demonstrated that 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a calmodulin inhibitor, is a cardioprotective drug. Here, we examined cardioprotective mechanisms of DY-9760e in hypertrophy and heart failure using a mouse transverse aortic constriction (TAC) model. Mice were subjected to TAC and 2 weeks later they were administered DY-9760e for another 6 weeks (at 10 or 20 mg/kg/day p.o.). Chronic administration inhibited TAC-induced increased heart-to-body weight ratio dose-dependently. Consistent with inhibition of hypertrophy, fraction shortening, an indicator of heart contractile function, assessed by echocardiography was completely restored by DY-9760e (20 mg/kg/day) administration. Inhibition of TAC-induced atrial natriuretic peptide (ANP) up-regulation further confirmed an antihypertrophic effect of DY-9760e. It is note-worthy that we found that breakdown of dystrophin and spectrin by calpain was associated with heart failure in TAC mice. Caveolin-3 breakdown was closely associated with endothelial nitric-oxide synthase (eNOS) dissociation from the plasma membrane and its subsequent uncoupling. Uncoupled monomeric eNOS formation was associated with increased protein tyrosine nitration, suggesting peroxynitrite production and NO and superoxide formation. It is important to note that 6 weeks of DY-9760e treatment significantly blocked hypertrophic responses, such as increased heart weight and ANP induction. Overall, we show that inhibition of both dystrophin/spectrin breakdown and uncoupling of eNOS probably underlies the cardio-protective mechanisms of DY-9760e. The observed protection of sarcolemmal proteins and eNOS by DY-9760e during pressure overload suggests a novel therapeutic strategy to rescue the heart from hypertrophy-induced failure.

Acoustic radiation forces induced by ultrasound can be used to apply external forces to an object, and the viscoelastic property of the object can be evaluated by measuring the resultant regional displacement of the object using a different ultrasonic probe for measurement. However, according to safety guidelines for the use of ultrasound, the recommended intensity is below 1W/cm(2) for continuous waves. Therefore, to generate a measurable displacement or strain by acoustic actuation, a method of effectively applying acoustic radiation forces needs to be devised. A potential way to improve the efficiency of acoustic actuation is to use line-focus transducers. However, there are undesired fluctuations in the emitted sound field due to the finite aperture size with uniform apodization when a single-element line-focus transducer (SELFT) is used to emit plane waves, which are focused only in the elevational direction. To suppress such undesired fluctuations, in the present study, a pair of line-focus array transducers (LFATs) was constructed to realize spatially smoother radiation forces by applying an appropriate apodization. As a result, the three dominant undesired peaks in the sound field emitted from a SELFT were suppressed using the LFATs with the examined appropriate apodization, and the displacement distribution induced in a phantom, which was measured by the phased tracking method using the different ultrasonic probe, became spatially smooth. (C) 2010 The Japan Society of Applied Physics

The present paper introduces in vivo measurements of viscoelasticity of arterial wall developed in our laboratory. The endothelial dysfunction is considered to be an earliest stage of atherosclerosis. Moreover, it was reported that the smooth muscle, which constructs the media of the artery, changes its characteristics due to atherosclerosis. Therefore, it is essential to develop an in vivo measurement method to assess the regional endothelial function and mechanical property (viscoelasticity) of the arterial wall. To evaluate the endothelial function, there is a conventional technique for measuring the transient change in the diameter of the brachial artery caused by flow mediated dilation (FMD) after the release of avascularization. However, this method does not directly evaluate the viscoelasticity of the intima-media region of the arterial wall. In the present paper, therefore, we proposed a method for simultaneous measurement of waveforms of the radial strain and blood pressure at the radial artery, and we developed its measurement system. From in vivo experiments, the viscoelasticity parameters of the arterial wall were estimated from the measured stress-strain relationship (hysteresis loop) using the least-square method and their transient changes after the release of avascularization were revealed. For healthy young persons, the slope of the hysteresis loop decreased due to the FMD, which corresponds to decrease in the elastic modulus. At the same time, the area of the loop increased after recirculation, which corresponds to the increase of the ratio of the loss modulus (viscosity) to the elastic modulus when the Voigt model is assumed. These results show a potential of the proposed method for thorough analysis of the transient change in viscoelasticity due to FMD. Copyright © 2010 by ASME.

Acoustic radiation forces induced by ultrasound can be used to apply external forces to an object, and the viscoelastic property of the object can be evaluated by measuring the resultant regional displacement of the object using a different ultrasonic probe for measurement. However, according to safety guidelines for the use of ultrasound, the recommended intensity is below 1W/cm(2) for continuous waves. Therefore, to generate a measurable displacement or strain by acoustic actuation, a method of effectively applying acoustic radiation forces needs to be devised. A potential way to improve the efficiency of acoustic actuation is to use line-focus transducers. However, there are undesired fluctuations in the emitted sound field due to the finite aperture size with uniform apodization when a single-element line-focus transducer (SELFT) is used to emit plane waves, which are focused only in the elevational direction. To suppress such undesired fluctuations, in the present study, a pair of line-focus array transducers (LFATs) was constructed to realize spatially smoother radiation forces by applying an appropriate apodization. As a result, the three dominant undesired peaks in the sound field emitted from a SELFT were suppressed using the LFATs with the examined appropriate apodization, and the displacement distribution induced in a phantom, which was measured by the phased tracking method using the different ultrasonic probe, became spatially smooth. (C) 2010 The Japan Society of Applied Physics

For noninvasive and quantitative measurements of global two-dimensional (2D) heart wall motion, speckle tracking methods have been developed and applied. These methods overcome the limitation of tissue Doppler imaging (TDI), which is susceptible to aliasing, by directly tracking backscattered echoes by pattern matching techniques, i.e., the cross-correlation or the sum of absolute differences, in real time. In these conventional methods, the frame rate (FR) is limited to about 200 Hz, corresponding to the sampling period of 5 ms. However, myocardial function during the isovolumic contraction period obtained by these conventional speckle tracking methods remains unclear owing to low temporal and spatial resolutions of these methods. Moreover, the accuracy of the speckle tracking method depends on an important parameter, i.e., the size of the correlation kernel. To track backscattered echoes accurately, it is necessary to determine the optimal kernel size. However, the optimal kernel size has not been thoroughly investigated. In this study, correlation kernel size, which determines the tracking accurately, was optimized by evaluating root mean squared (RMS) errors in the lateral and axial displacements of a phantom estimated by speckle tracking methods at high spatial and temporal resolutions. For this purpose, the RF data from the longitudinal-axis cross-sectional view for the interventricular septum (IVS) were acquired on the basis of parallel beam forming (PBF) to improve temporal and spatial resolutions. A wide transmit beam scanned in 7 different directions sparsely and 16 receiving beams were generated for each transmission. The RF data of the phantom and the heart wall were obtained at high spatial (angle intervals of scan lines: 0.375 degrees) and temporal [frame rate (FR): 1020 Hz] resolutions. The determined optimal size of the correlation kernel was 7.9 degrees x 4.8mm. Estimated displacements of the phantom were in good agreement with the actual displacement at an RMS error of 0.34 mm. Furthermore, the IVS motion during the isovolumic contraction (IC) was analyzed in detail. The speckle tracking method using the optimal kernel size 7.9 degrees x 4.8mm was applied to multiple points in IVS to estimate 2D displacements during the IC period. In this period, a rapid displacement of IVS at a small amplitude of 1.5 mm, which suggests the expansion of the left ventricle and has not been measured by conventional tracking methods at a low temporal resolution, was detected by 2D tracking. Furthermore, the displacement on the apical side was found to be delayed by 10 ms compared with that on the basal side. These results indicate the potential of this method in the high-accuracy estimation of 2D displacements and detailed analyses of physiological function of the myocardium. (C) 2010 The Japan Society of Applied Physics

Ultrasonic blood flow imaging is useful for diagnosis of the cardiovascularsystem. Doppler-based blood flow measurements are widely used in clinicalsituations to estimate blood flow velocity. However, Doppler-based method doesnot show the direction of blood flow. Recently, a new method called B-Flow,which shows echoes from blood particles, was introduced to directly observe thedirection of blood flow. In this study, we further investigated ultrasonic bloodflow imaging to visualize stream lines of blood flow. In conventional bloodflow imaging, ultrasonic pulses emitted at each beam position for several times,typically 8 times, to increase signal-to-noise ratios (SNRs) of weak echoesfrom blood particles. In this case, 0.8 ms is required to create one scan linewhen the pulse repetition frequency is 10 kHz, and the frame rate would be 17 Hzwhen the number of scan lines is 75. Under such condition, blood particles moveby 60 mm during one frame interval at a typical blood flow velocity in thecarotid artery of 1 m/s. Therefore, blood particles observed in a certain framemove out from the imaging region in the next frame, and echoes from the sameblood particles cannot be observed continuously between frames. In this study,parallel receive beamforming with plane wave transmission was used to increasethe frame rate over 3 kHz. Blood particles moves by only 0.3 mm at a frame rateof 3 kHz, and echoes from the same blood particles can be observed continuously.In this study, receiving beams were created at three different steering angle(5, 0, 5 degrees) to avoid the beam-to-flow angle being 90 degrees. Eachexcitation was coded with the 5-bit Barker code to increase SNRs of received RFsignals. In the measurement of a carotid artery of a 33-year-old male, envelopesof RF echoes were averaged for 20 ms in the direction of frame. This averagingprocedure corresponded to lithographic exposure in photography, and trajectoriesof echoes during 20 ms were visualized. In this study, we developed a novelmethod to visualize blood flow stream lines by imaging trajectories of echoesfrom blood particles based on very high frame rate imaging. © 2010 IEEE.

Conventional echocardiography visualizes cross-sectional images, motion, and torsional deformation during contraction of the heart. However, it is restricted to static configurations or large and slow motion. We have previously found that minute pulsive vibration occurs just after electrical stimulation of the extracted papillary muscle of a rat [Acoust Sci &amp Tech 2003 24:17]. By applying a novel ultrasound-based method [IEEE UFFC 1997 44:752] to human hearts, we were able to successfully measure the spontaneous response of the myocardium to electrical excitation [UMB 2009 35:936]. In the present study, we visualize the propagation of the myocardial response of the electric excitation in human hearts during systole. In the parasternal short-axis view of the left ventricle (LV), the RF reflective wave along each ultrasonic beam was acquired. The number of directions of the ultrasonic transmission was restricted to 16 to maintain a high frame rate (500 Hz), and then at all of about 25,000 points set in the heart wall, the velocity components toward the ultrasonic probe were simultaneously obtained as waveforms, and their instantaneous phases of 40-Hz components were color-coded (red: come close to). The instantaneous distribution of the phase was rearranged along the circumferential direction and set in an array consecutively at every 2 ms from the time of P-wave of the ECG, precisely revealing the propagation of the velocity components in the LV circumferential direction. This novel method was applied to healthy subjects. A velocity component corresponding to the contraction was generated at the septum at a time of R-wave of ECG, and propagated slowly (0.4 m/s) in clockwise direction along the LV circumferential direction. On the other hand, just from each radiation time of the first and second heart sounds, mechanical shear was generated at the septum and propagated in counterclockwise direction. These phenomena were observed for other subjects. The propagation of the contraction will correspond to one of the layers consisting of the LV. The subtle dynamic response of the myocardium to the arrival of the electrical stimulation accurately measured in the present study will show a potential for noninvasive assessment of myocardial damage due to heart failure. © 2010 IEEE.

December 6-8, 2009, Edinburgh, UK

Artery-wall motion due to the pulsation of the heart is often measured to evaluate mechanical properties of the arterial wall. Such motion is thought to occur only in the arterial radial direction because the main source of the motion is an increase of blood pressure. However, it has recently been reported that the artery also moves in the longitudinal direction. Therefore, a 2-D motion estimator is required even when the artery is scanned in the longitudinal direction because the arterial wall moves both in the radial (axial) and longitudinal (lateral) directions. Methods based on 2-D correlation of RF echoes are often used to estimate the lateral displacement together with axial displacement. However, these methods require much interpolation of the RF echo or correlation function to achieve a sufficient resolution in the estimation of displacement. To overcome this problem, Jensen et al. modulated the ultrasonic field in the lateral direction at a designed spatial frequency to use the lateral phase for the estimation of lateral motion. This method, namely, the lateral modulation method, generates complex signals whose phases change depending on the lateral motion. Therefore, the lateral displacement can be estimated with a good resolution without interpolation, although special beamformers are required. The present paper describes a method that can be applied to ultrasonic echoes obtained by a conventional beamformer to estimate lateral displacements using the phases of lateral fluctuations of ultrasonic echoes. In the proposed method, complex signals were generated by the Hilbert transform, and the phase shift was estimated by correlation-based estimators. The proposed method was validated using a cylindrical phantom mimicking an artery. The error in the lateral displacement estimated by the proposed method was 13.5% of the true displacement of 0.5 mm with a kernel size used for calculating the correlation function of 0.6 mm in the lateral direction, which was slightly smaller than the width at -20 dB of the maximum lateral ultrasonic field (about 0.8 mm).

September 20-23, 2009, Rome, Italy

A new method has been developed for evaluating arterial stiffness using transcutaneous and high-frequency ultrasound. There may be a difference in the clinical significance of peripheral arteries, such as the radial artery (a muscular property), and other medium/large-sized arteries (an elastic property). The aim of this study was to determine the relationship between upper limb peripheral arterial stiffness (ULPAS) using the new method for the radial artery and atherosclerotic parameters in comparison with carotid intima-media thickness (IMT) and cardio-ankle vascular index (CAVI) in a healthy population and a diseased population with hypertension (HT) and diabetes mellitus (DM). Forty-four apparently healthy individuals (mean age = 26.3 years, men/women = 14/30), 45 patients with drug-treated HT (mean age = 55.3 years, men/women = 17/28), and 37 patients with drug-treated DM (mean age = 55.2 years, men/women = 21/16) were investigated. Body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), CAVI, IMT, ultrasonographically measured ULPAS, blood lipid/glucose-related parameters, and C-reactive protein (CRP) were all determined. Among the healthy subjects, ULPAS showed a significantly positive correlation with SBP and CRP. ULPAS showed a different correlation pattern with atherosclerotic parameters from that of IMT and CAVI. The HT subjects had significantly higher ULPAS levels than those with DM. In this diseased population, ULPAS showed a significant positive correlation with SBP and DBP, as well as a significant negative correlation with glucose. These results suggest that ULPAS may provide new information in association with some atherosclerotic conditions as a unique index different from IMT and CAVI.

Background: We previously reported the arterial elasticity value we measured to reflect the characteristic features of vessel walls, and to possibly be useful for detecting early stage atherosclerosis in type 2 diabetes. Obesity, especially visceral adiposity, is well known to play a crucial role in the development of metabolic disorders and atherosclerosis. To assess whether arterial elasticity value reflects the effect of obesity on atherosclerosis, we examined the associations of obesity characteristics with atherosclerosis values including arterial elasticity, carotid intima-media thickness (IMT) and pulse wave velocity (PM). Methods: Three atherosclerosis values were measured in 78 obese subjects (body mass index &gt;= 30). We investigated the associations of atherosclerosis values with obesity-related parameters including abdominal fat accumulation determined by computed tomography. Results: Arterial elasticity values were positively related to established atherosclerosis values, carotid IMT and PWV, in obese subjects. Age, systolic blood pressure and hypertension also correlated with these atherosclerosis values. Single regression analysis showed all three atherosclerosis values to correlate significantly with visceral fat area. Intriguingly, visceral fat area is an independent variable affecting arterial elasticity, but not IMT or PWV. Furthermore, multiple regression analysis revealed that arterial elasticity correlates strongly with visceral fat area. Conclusions: Arterial elasticity value we measure is a new parameter for evaluating atherosclerosis in subjects with visceral adiposity and more sensitive than the currently established atherosclerosis values, carotid IMT and PWV. Measuring arterial elasticity has the potential to reveal minute vascular changes, and may have broad clinical applications for evaluating early stage atherosclerosis. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Red blood cell (RBC) aggregation, a determinant of blood viscosity, plays an important role in blood flow rheology. RBC aggregation is induced by the adhesion of RBCs when the electrostatic repulsion between RBCs weakens owing to increases in protein and saturated fatty acid levels in blood, and excessive RBC aggregation may lead to various circulatory diseases. This study was conducted to establish a noninvasive quantitative method for the assessment of RBC aggregation. The spectrum of nonaggregating RBCs presents Rayleigh behavior, indicating that the power of a scattered wave is proportional to the fourth power of frequency. By dividing the measured power spectrum of echoes from scatterers by that from a silicone plate reflector, the frequency responses of transmitting and receiving transducers are removed from the former spectrum. This normalized power spectrum changes linearly with respect to logarithmic frequency. In non-Rayleigh scattering, on the other hand, the spectral slope decreases because a larger scatterer behaves as a reflector and echoes from a reflector do not show frequency dependence. Therefore, it is possible to assess RBC aggregation using the spectral slope value. In this study, spherical scatterers with diameters of 5, 11, 15, and 30 mu m were measured in basic experiments. The spectral slope of the normalized power spectrum of echoes from the lumen of the vein in the dorsum manus of a 24-year-old healthy male was close to that from microspheres with a diameter of 15 mu m, and the typical RBC diameter was smaller than this value. The frequency-dependent attenuation of ultrasound during propagation in a biomedical tissue was considered to be one reason for this. Furthermore, during avascularization, the slope gradually decreased owing to the aggregation of RBCs. These results show the possibility of using the proposed method for the noninvasive assessment of RBC aggregation. (C) 2009 The Japan Society of Applied Physics

The endothelial dysfunction is considered to be an initial step in atherosclerosis. Additionally, it was reported that the smooth muscle, which constructs the media of the artery, changes its characteristics owing to atherosclerosis. Therefore, it is essential to develop a method of assessing the regional endothelial function and mechanical properties of the arterial wall. To evaluate the endothelial function, a conventional technique of measuring the transient change in the diameter of the brachial artery caused by flow-mediated dilation (FMD) after the release of avascularization is used. However, this method can not evaluate the mechanical properties of the wall. We previously developed a method for the simultaneous measurements of waveforms of radial strain and blood pressure in the radial artery. In this study, the viscoelasticity of the arterial wall was estimated from the measured stress-strain relationship using the least-squares method and the transient changes in the mechanical properties of the arterial wall ware revealed. From in vivo experimental results, the stress-strain relationship showed a hysteresis loop and viscoelasticity was estimated by the proposed method. The slope of the loop decreased owing to FMD, which resulted in the decrease in estimated elastic modulus. The increase in the area of the loop occurred after recirculation, which corresponds to the increase in the ratio of the loss modulus (depends on viscosity) to the elastic modulus when the Voigt model is assumed. In this study, the variance in estimates was evaluated by in vivo measurement for 10 min. The temporal decrease in static elasticity after recirculation due to FMD was much larger than the evaluated variance. These results show a potential of the proposed method for the thorough analysis of the transient change in viscoelasticity due to FMD. (C) 2009 The Japan Society of Applied Physics

The ability to noninvasively detect regional dynamic myocardial damage related to action potentials and mechanical properties affected by heart disease is of great clinical importance. Though there are invaluable clinical tools for diagnosis of a broad range of cardiac conditions, such myocardial properties cannot be evaluated. We have previously shown that pulsive vibration occurs on the myocardium after electrical stimulation of an isolated heart. In this study, using a novel technique for ultrasonic measurement of the myocardial motion, we detected pulsive vibrations spontaneously caused by electrical excitation and by valve closure. Using a sparse sector scan, the vibrations were measured almost simultaneously at about 10,000 points set in the heart wall at a high temporal resolution. The consecutive spatial distributions of the phase of the vibrations revealed wave propagation along the wall in healthy subjects for the first time in vivo. At around the time of the Q-wave of the electrocardiogram, the propagation started from the interventricular septum and extended to both the base and apical sides of the heart with a speed of 1 m/s, which corresponds to the propagation of electrical excitation from the Purkinje fiber-myocyte junction in the interventricular septum. Other vibrations then propagated from the base at several m/s, although some of them had dispersion properties. These are shear waves caused by the mitral-valve closure, corresponding to the first heart sound. These phenomena have potential for detection of regional myocardial tissue damage related to propagation of the action potentials and regional myocardial viscoelasticity. (E-mail: hkanai@ecei.tohoku.ac.jp) (C) 2009 World Federation for Ultrasound in Medicine & Biology.

April 16-17, 2009, Christchurch, New<br /> Zealand

April 16-17, 2009, Christchurch, New<br /> Zealand

March 27-28, 2009, Sendai

March 5-6, 2009, Sendai

March 5-6, 2009, Sendai

March 5-6, 2009, Sendai

March 5-6, 2009, Sendai

March 5-6, 2009, Sendai

March 5-6, 2009, Sendai

In orthodontic dentistry for young subjects, it is important to assess the degree of growth of the jaw bones to determine the optimum time for treatment. The structure of the digital joint changes with age, with such changes correlating to the degree of bone growth (including jaw bones). There are two gaps in the digital joint of a young subject, one of which disappears with aging. In the present study, a method for noninvasive assessment of such change in the structure of a digital joint was examined, in which continuous-wave ultrasound is radiated to a digital joint by a single-element ultrasonic transducer. This continuous ultrasound, which passes through the digital joint, is received by a linear array ultrasonic probe situated opposite the transducer. The probe simultaneously realizes pulse-echo imaging and imaging of transmission ultrasound, which passes through the joint. Using this experimental apparatus, the existence and position of a gap can be detected clearly by imaging the transmission ultrasound on a pulse-echo image. In basic experiments, continuous-wave ultrasound generated by a planar or focused transducer was radiated to a gap between two acrylic bars, which simulated that in a digital joint; transmission ultrasound, which passed through the gap, was measured with a linear array probe. The basic experimental results showed that a gap with a width &gt;0.4 mm is detectable and that the width at half maximum of the amplitude profile of the received transmission ultrasound that passed through the gap correlated with the width of the gap. Furthermore, in the preliminary in vivo experiments, transmission ultrasound that passed through two gaps in the case of a child was clearly imaged by the proposed method, and that which passed through only one gap in the case of an adult was also imaged. These results show the possibility for the use of the proposed method to noninvasively assess the change in the structure of a joint as a result of aging. (E-mail: hasegawa@ecei.tohoku.ac.jp) (C) 2009 World Federation for Ultrasound in Medicine & Biology.

Atherosclerotic change of the arterial wall leads to a significant change in its elasticity. For assessment of elasticity, measurement of arterial wall deformation is required. For motion estimation, correlation techniques are widely used, and we developed a phase-sensitive correlation method, namely, the phased-tracking method, to measure the regional strain of the arterial wall due to the heartbeat. Although phase-sensitive methods using demodulated complex signals require less computation in comparison with methods using the correlation between RF signals or iterative methods, the displacement estimated by such phase-sensitive methods are biased when the center frequency of the RF echo apparently varies. One of the reasons for the apparent change in the center frequency would be the interference of echoes from scatterers within the wall. In the present study, a method was introduced to reduce the influence of variation in the center frequencies of RF echoes on the estimation of the artery-wall strain when using the phase-sensitive correlation technique. The improvement in the strain estimation by the proposed method was validated using a phantom. The error from the theoretical strain profile and the standard deviation in strain estimated by the proposed method were 12.0% and 14.1%, respectively, significantly smaller than those (23.7% and 46.2%) obtained by the conventional phase-sensitive correlation method. Furthermore, in the preliminary in vitro experimental results, the strain distribution of the arterial wall well corresponded with pathology, i.e., the region with calcified tissue showed very small strain, and the region almost homogeneously composed of smooth muscle and collagen showed relatively larger strain and clear strain decay with respect to the radial distance from the lumen.

Aim: As an approach to tissue characterization, we attempted to classify in vivo carotid plaque tissues in terms of arterial wall elasticity instead of echogenicity on B-mode scanning and investigated whether the effect of fluvastatin on carotid elasticity can be detected in hypercholesterolemic patients. Methods: In 170 subjects, simultaneous measurements of intima-media thickness (IMT) and elastic modulus in the circumferential direction (E θ) were performed using a new transcutaneous high-resolution Doppler technique. Results: From the observation of various tissues, an elasticity library was obtained as follows: lipid core, 22 ± 15 kPa calcification, 674 ± 384 kPa lipid core- and calcification-free plaques, 173 ± 69 kPa smooth muscle, 104 ± 32 kPa blood clot, 85 ± 68 kPa fibrosis, 273 ± 173 kPa. The effect of fluvastatin (30 mg/day, n = 62) was assessed over 12 months using the elasticity distribution and serum markers. The statin reduced low-density lipoprotein cholesterol, high-sensitivity CRP, mean IMT and mean Eθ, and increased nitrite/nitrate. In the max IMT ≥ 1.1 mm group, both Eθ and IMT decreased significantly. On the other hand, in the max IMT &lt 1.1 mm group, Eθ but not IMT decreased significantly. The histogram of the subgroups showing increased Eθ with max IMT ≥ 1.1 mm revealed a decrease in areas corresponding to Eθ of 20-200 kPa (lipid/smooth muscle-rich tissue) and an increase in relatively hardened areas of &lt 250 kPa (collagen fibers). Conclusion: Non-invasive echographic carotid arterial elasticity measurement is useful for the classification of atherosclerotic plaques and evaluation of chronological and histopathological changes.

Artery-wall motion due to the pulsation of the heart is often measured to evaluate mechanical properties of the arterial wall. Such motion is thought to occur only in the arterial radial direction because the main source of the motion is an increase of blood pressure. However, it has recently been reported that the artery also moves in the longitudinal direction. Therefore, a 2D motion estimator is required even when the artery is scanned in the longitudinal direction because the arterial wall moves both in the radial (axial) and longitudinal (lateral) directions. Methods based on 2D correlation of RF echoes are often used to estimate the lateral displacement together with axial displacement. However, these methods require much interpolation of the RF echo or correlation function to achieve a sufficient resolution in the estimation of displacement. To overcome this problem, Jensen et al. modulated the ultrasonic field in the lateral direction at a designed spatial frequency to utilize the lateral phase for the estimation of lateral motion. This method, namely, the lateral modulation method, generates complex signals whose phases change depending on the lateral motion. Therefore, the lateral displacement can be estimated with a good resolution without interpolation, although special beamformers are required. The present paper describes a method, which can be applied to ultrasonic echoes obtained by a conventional beamformer, to estimate lateral displacements using the phases of lateral fluctuations of ultrasonic echoes. In the proposed method, complex signals were generated by the Hilbert transform, and the phase shift was estimated by correlation-based estimators. The proposed method was validated using a cylindrical phantom mimicking an artery. The error in the lateral displacement estimated by the proposed method was 13.5% of the true displacement of 0.5 mm with a kernel size used for calculating the correlation function of 0.6 mm in the lateral direction, which was slightly smaller than the width at -20 dB of the maximum lateral ultrasonic field (about 0.8 mm).

December 5 - 6, 2008, Suntec, Singapore

Mechanical properties of the arterial walls are significantly altered by atherosclerosis, and various studies have been recently conducted to measure the regional elastic properties (radial strain) of the arterial wall. We have developed a phase-sensitive correlation-based method, namely, the phased-tracking method, to measure the regional radial strain. On the other hand, the measurement of blood flow is an important practical routine in the diagnosis of atherosclerosis. It would be useful if the regional strain of the arterial wall as well as blood flow could be assessed simultaneously. Such measurement would require a high frame rate of several kilohertz. In this study, acquisition of ultrasonic RF echoes at a high frame rate (about 3500 Hz) was achieved using parallel beamforming in which plane waves were transmitted only 3 times and receive beamforming created 24 beams for each transmit beam. The accuracy in measurement of the minute radial strain was evaluated by a basic experiment using a cylindrical phantom. The error of the measured strain from the theoretical strain profile and its standard deviation were 4.8% and 9.5%, respectively. Furthermore, the radial strain of a carotid arterial wall and blood flow were simultaneously imaged in vivo.

November 2-5, 2008, Beijing, China

October 16 - 17, 2008, Tainan, Taiwan

Using our "echo-dynamography", blood flow structure and flow dynamics during ventricular systole were investigated in 10 normal volunteers. The velocity vector distribution demonstrated blood flow during ejection was laminar along the ventricular septum. The characteristic flow structure was observed in each cardiac phases, early, mid- and late systole and was generated depending on the wall dynamic events such as peristaltic squeezing, hinge-like movement of the mitral ring plane, bellows action of the ventricle and dimensional changes in the funnel shape of the basal part of the ventricle, which were disclosed macroscopically by using the new technology of high speed scanning echo-tomography and microscopically by the strain rate distribution measured by phase tracking method. The pump function was reflected on the changes in the flow structure represented by the flow axis tine distribution and the acceleration along the flow axis line. The acceleration of the ejection had three modes, "A", "B" and "C", and generated by the watt dynamic events. "A" appeared from the apical to the outflow area along the main flow axis line, "B'' along the anterior mitral leaflet and the branched flow axis tine, and "C'' generated by the high speed vortex behind the mitral valve. The magnitude of the acceleration was estimated quantitatively from the velocity gradient along the flow axis tine. Macroscopic and microscopic asynchrony in the myocardial contraction and extension appeared systematically in the local part of the ventricular watt, which was helpful for making the flow structure and for performing the smooth pump function. (C) 2008 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.

Atherosclerotic change of the arterial wall leads to a significant change in its elasticity. For assessment of elasticity, measurement of arterial wall deformation is required. For motion estimation, correlation techniques are widely used, and we have developed a phase-sensitive correlation method, namely, the phased-tracking method, to measure the regional strain of the arterial wall due to the heartbeat. Although phase-sensitive methods using demodulated complex signals require less computation in comparison with methods using the correlation between RF signals or iterative methods, the displacement estimated by such phase-sensitive methods are biased when the center frequency of the RF echo apparently varies. One of the reasons for the apparent change in the center frequency would be the interference of echoes from scatterers within the wall. In the present study, a method was introduced to reduce the influence of variation in the center frequencies of RF echoes on the estimation of the artery-wall strain when using the phase-sensitive correlation technique. The improvement in the strain estimation by the proposed method was validated using a phantom. The error from the theoretical strain profile and the standard deviation in strain estimated by the proposed method were 12.0% and 14.1%, respectively, significantly smaller than those (23.7% and 46.2%) obtained by the conventional phase-sensitive correlation method. Furthermore, in the preliminary in vitro experimental results, the strain distribution of the arterial wall well corresponded with pathology, i.e., the region with calcified tissue showed very small strain, and the region almost homogeneously composed of smooth muscle and collagen showed relatively larger strain and clear strain decay with respect to the radial distance from the lumen.

June 29 - July 4, 2008, Paris, France

June 29 - July 4, 2008, Paris, France

June 29 - July 4, 2008, Paris, France

In conventional ultrasonic tomographic images, the heart wall cannot be distinguished from the cardiac lumen automatically on the basis of only the echogenicity. One of the biggest problems is that echogenicity, which corresponds to the amplitude of an RF echo, in the heart wall is as low as that in the lumen. In this study, ultrasonic RF echoes from the heart wall and lumen were analyzed in the frequency domain in order to distinguish the heart wall from the lumen automatically. Temporal changes in complex frequency spectra were evaluated using the magnitude-squared coherence function. The coherence function of RF signals scattered from the interventricular septum (IVS) was high. In contrast, the coherence function in the right ventricle (RV) and left ventricle (LV) was low because the scatterers (blood cells) slipped off front the focal area of the ultrasonic beam by blood flow. For automated identification of the heart wall using the coherence function, the optimal threshold T(0)(f) for the coherence function should be determined. In this study, on the basis of the Bayes decision rule, the optimal value of T(0)(f) was determined. The coherence function of the region near the anterior wall in the RV was as high as that in the IVS because there are artifacts in the region near the anterior wall owing to echoes from the external tissue resulting from the sidelobe. However, the artifacts can be reduced by removing the stationary component from RF echoes before evaluting the coherence function. In vivo experimental results show that the differentiation of the heart wall from the lumen was improved significantly using the proposed method. [DOI: 10.1143/JJAP.47.4155]

The endothelial dysfunction is considered to be an initial step of atherosclerosis. Additionally, it was reported that the smooth muscle, which constructs the media of the artery, changes its characteristics owing to atherosclerosis. Therefore, it is essential to develop a method for assessing the regional endothelial function and mechanical property of the arterial wall. There is a conventional technique of measuring the transient change in the diameter of the brachial artery caused by flow-mediated dilation (FMD) after the release of a vascularization. For more sensitive and regional evaluation, we developed a method of measuring the change in the elasticity of the radial artery due to FMD. In this study, the transient change in the mechanical property of the arterial wall was further revealed by measuring the stress-strain relationship during each heartbeat. The minute change in the thickness (strain) of the radial arterial wall during a cardiac cycle was measured by the phased tracking method. together with the waveform of blood pressure which was continuously measured with a sphygmometer at the radial artery. The transient change in stress-strain relationship during a cardiac cycle was obtained from the measured changes in wall thickness and blood pressure to show the transient change in instantaneous viscoelasticity. From the in vivo experimental results, the stress-strain relationship shows the hysteresis loop. The slope of the loop decreased owing to FMD, which shows that the elastic modulus decreased, and the increasing area of the loop depends on the ratio of the loss modulus (depends on viscosity) to the elastic modulus when the Voigt model is assumed. These results show a potential of the proposed method for the thorough analysis of the transient change in viscoelasticity, due to FMD. [DOI: 10.1143/JJAP.47.4165]

Pathologic changes in arterial walls significantly influence their mechanical properties. We have developed a correlation-based method, the phased tracking method [H. Kanai et al.: IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43 (1996) 791], for measurement of the regional elasticity of the arterial wall. Using this method, elasticity distributions of lipids, blood clots. fibrous tissue, and calcified tissue were measured in vitro by experiments on excised arteries (mean +/- SD; lipids 89 +/- 47 kPa, blood clots 131 +/- 56 kPa, fibrous tissue 1022 +/- 1040 kPa, calcified tissue 2267 +/- 1228 kPa) [H. Kanai et al.: Circulation 107 (2003) 3018; J. Inagaki et al.: Jpn. J. Appl. Phys. 44 (2005) 4593]. It was found that arterial tissues can be classified into soft tissues (lipids and blood clots) and hard tissues (fibrous tissue and calcified tissue) on the basis of their elasticity. However, there are large overlaps between elasticity distributions of lipids and blood clots and those of fibrous tissue and calcified tissue. Thus, it was difficult to differentiate lipids from blood clots and fibrous tissue from calcified tissue by simply thresholding elasticity value. Therefore, we previously proposed a method by classifying the elasticity distribution in each region of interest (ROI) (not a single pixel) in an elasticity image into lipids, blood clots. fibrous tissue, or calcified tissue based on a likelihood function for each tissue [J. Inagaki et al.: Jpn. J. Appl, Phys. 44 (2006) 4732]. In our previous study, the optimum size of an ROI was determined to be 1,500 mu m in the arterial radial direction and 1,500 mu m in the arterial longitudinal direction [K. Tsuzuki et al.: Ultrasound Med. Biol. 34 (2008) 573]. In this study, the threshold for the likelihood function used in the tissue classification was set by evaluating the variance in the ultrasonic measurement of radial strain. The recognition rate was improved from 50 to 54% by the proposed thresholding. [DOI: 10.1143/JJAP.47.4180]

One possible way, to evaluate acupuncture therapy quantitatively is to measure the change in the elastic property of muscle after application of the therapy. Many studies have been conducted to measure mechanical properties of tissues using ultrasound-induced acoustic radiation force. To assess mechanical properties, strain must be generated in an object. However a single radiation force is not effective because it mainly generates translational motion when the object is much harder than the surrounding medium. In this study, two cyclic radiation forces are simultaneously applied to a muscle phantom from two opposite horizontal directions so that the object is cyclically compressed in the horizontal direction. By the horizontal compression. the object is expanded vertically based on its incompressibility. The resultant vertical displacement is measured using another ultrasound pulse. Two ultrasonic transducers for actuation were both driven by the sum of two continuous sinusoidal signals at two slightly different frequencies [1 MHz and (1M + 5) Hz]. The displacement of several micrometers in amplitude, which fluctuated at 5 Hz, was measured by the ultrasonic phased tracking method. Increase in thickness inside the object was observed just when acoustic radiation forces increased. Such changes in thickness correspond to vertical expansion due to horizontal compression. [DOI: 10.1143/JJAP.47.4193]

Pathologic changes in arterial walls significantly influence their mechanical properties. We have developed a correlation-based method, the phased tracking method, for measurement of the regional elasticity of the arterial wall. Using this method, elasticity distributions of lipids, blood clots, fibrous tissue and calcified tissue were measured by in-vitro experiments of excised arteries (mean +/- SD: lipids, 89 +/- 47 kPa; blood clots, 131 +/- 56 kPa; fibrous tissue, 1022 +/- 1040 kPa; calcified tissue, 2267 +/- 1228 kPa). It was found that arterial tissues can be classified into soft tissues (lipids and blood clots) and hard tissues (fibrous tissue and calcified tissue) on the basis of their elasticity. However, there are large overlaps between elasticity distributions of lipids and blood clots and those of fibrous tissue and calcified tissue. Thus, it was difficult to differentiate lipids from blood clots and fibrous tissue from calcified tissue by setting a threshold for a single elasticity value. Therefore, we previously proposed a tissue classification method using the elasticity distribution in each small region. In this method, the elasticity distribution of each small region of interest (ROI) (not a single pixel) in an elasticity image is used to classify lipids, blood clots, fibrous tissue and calcified tissue by calculating the likelihood function for each tissue. In the present study, the optimum size of the ROI and threshold T-o for the likelihood function were investigated to improve the tissue classification. The ratio of correctly classified pixels to the total number of classified pixels was 29.8% when the size of a small region was 75 mu m x 300 mu m (a single pixel). The ratio of correctly classified pixels became 35.1% when the size of a small region was 1,500 mu m x 1,500 mu m (100 pixels). Moreover, a region with an extremely low likelihood with respect to all tissue components was defined as an unclassified region by setting threshold T-o for the likelihood function to 0.21. The tissue classification of the arterial wall was improved using the elasticity distribution of a small region whose size was larger than the spatial resolution (800 mu m x 600 mu m) of ultrasound. In this study, the arteries used in construction of the elasticity databases were classified into each tissue using the constructed elasticity databases. Other arteries, which are not used for constructing the elasticity databases, should be classified in future work to thoroughly show the effectiveness of the proposed method.

March 27-28, 2008, Matsushima

March 7, 2008, Sendai

March 7, 2008, Sendai

March 7, 2008, Sendai

March 7, 2008, Sendai

March 7, 2008, Sendai

March 5-6, 2008, Sendai

March 5-6, 2008, Sendai

March 5-6, 2008, Sendai

March 5-6, 2008, Sendai

March 5-6, 2008, Sendai

March 5-6, 2008, Sendai

Atherosclerotic change of the arterial wall leads to a significant change in its elasticity. For assessment of elasticity, measurement of arterial wall deformation is required. For motion estimation, correlation techniques are widely used, and we have developed a phase-sensitive correlation-based method, namely, the phased-tracking method, to measure the regional strain of the arterial wall due to the heartbeat. Although phase-sensitive methods require less computation in comparison with the correlation between RF signals, the displacements estimated by such phase-sensitive methods are biased when the center frequency of RF echo varies. One of reasons for the change in the center frequency is the interference of echoes from scatterers within the wall. The artery-wall displacement includes both the component due to the radial translation of the arterial wall and that contributing to strain. In the case of the arterial wall, the displacement due to radial translation is larger than that contributing to strain by a factor of 10, and, thus, the error resulting from the translational motion often becomes larger than the small displacement contributing to strain. To reduce this error, in this study, a method is proposed in which the global translational motion is compensated before correlating echoes in two different frames to estimate the displacement distribution contributing to strain. Using this procedure, the significant error due to the large translational motion can be suppressed in comparison with the simultaneous estimation of the displacements due to translational motion and strain in the conventional methods. In this study, the accuracy improvement by the proposed method was validated using phantoms. The error from the theoretical strain profile and standard deviation in strain estimated by the proposed method was 12.0% and 14.1%, respectively, significantly smaller than that (23.7% and 46.2%) obtained by the conventional method.

We recently developed a novel method for evaluating the elasticity of arterial walls, the phased tracking method. Herein, we evaluated atherosclerosis of the carotid artery with this method in 242 individuals with type 2 diabetes. In multiple regression analysis of subject status, age, systolic blood pressure and hyperlipidemia were found to be independently associated with carotid artery elasticity values. We also measured currently established values for atherosclerosis, carotid artery IMT and baPWV, in these subjects. Carotid artery elasticity correlated with max IMT (r = 0.291, p &lt; 0.01), plaque score (PS) (r = 0.220, p &lt; 0.01) and baPWV (r = 0.345, p &lt; 0.01). Elasticity, max IMT and plaque score, all correlated with the number of risk factors for atherosclerosis, i.e. hypertension, hyperlipidemia and smoking, in addition to diabetes, consistent with the view that these values reflect atherosclerosis. Importantly, however, in subjects with IMT &lt; 1.1 mm, who are classified as not having atherosclerosis as defined by IMT criteria, only carotid artery elasticity correlated with the number of risk factors (p &lt; 0.05). These results suggest that (1) the measured carotid artery elasticity values reflect atherosclerosis and (2) our novel method has potential for detecting atherosclerosis in its early stage. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

Mechanical properties of the arterial walls are significantly altered by atherosclerosis, and various studies have been recently conducted to measure the regional elastic properties (radial strain) of the arterial wall. We have developed a phase-sensitive correlation-based method, namely, the phased-tracking method, to measure the regional radial strain. On the other hand, the measurement of blood flow is an important practical routine in the diagnosis of atherosclerosis. It would be useful if the regional strain of the arterial wall as well as blood flow could be assessed simultaneously. Such measurement would require a high frame rate of several kilohertz. In this study, acquisition of ultrasonic RF echoes at a high frame rate (about 3500 Hz) was achieved using parallel beamforming, in which plane waves were transmitted only three times and receive beamforming created 24 beams for each transmit beam. The accuracy in measurement of the minute radial strain was evaluated by a basic experiment using a cylindrical phantom. The error of the measured strain from the theoretical strain profile and its standard deviation were 4.8% and 9.5%, respectively. Furthermore, the radial strain of a carotid arterial wall and blood How were simultaneously imaged in vivo.

Red blood cell (RBC) aggregation, which is one of the induces showing blood viscosity, plays an important role in blood rheology. RBC aggregation is formed by adhension of RBCs because electrostatic repulsion between RBCs weakens as protein and saturated fatty acid in blood increase. Excessive RBC aggregation promotes various circulatory diseases in the clinical situation. The purpose of this study is to establish a noninvasive and quantitative method for assessment of RBC aggregation. The spectrum of nonaggregating RBCs presents Rayleigh behavior, which means that the power of scattered wave is in proportion to the fourth power of frequency. By dividing the measured power spectrum by that of echo from a silicone plate, the frequency responses of transmitting and receiving transducer are removed from the measured power spectrum. The normalized power spectrum changes linearly with respect to logarithmic frequency. In non-Rayleigh scattering, on the other hand, the spectral slope decreases. This is derived that a larger scatterer also behaves as a reflector and on echo from a reflector does not show frequency dependence. As a result, the influence of Rayleigh scattering is getting weak. Therefore, it is possible to assess the RBC aggregation from the spectral slope value. The spectral slope of the normalized power spectrum of echoes from the lumen of the vein in dorsum manus of 24-year-old healthy male was close to that from microspheres with diameter of 11 Am, and the standard RBC diameter is similar to this value. These results show the possibility of the proposed method for the noninvasive assessment of RBC aggregation.

Methods for imaging of strain rate in the heart wall are useful techniques for the quantitative evaluation of regional myocardial function. However, a mechanism of the transitions between myocardial contraction and relaxation is unclear. Except for a method based on ECG triggering, a required high temporal resolution was realized by scanning the heart wall sparsely at the expense of the lateral spatial resolution. Therefore, the spatial resolution in measurement of the transition of myocardial contraction / relaxation in the lateral direction have been limited. In this study, the RF data was acquired in a typical cross-sectional view (interventricular septum (IVS) longitudinal-axis view) based on parallel beam forming (PBF). A wide transmitted beam scanned 7 different directions sparsely and 16 receiving beams were created in each transmit. The typical cross-sectional image was realized to obtain with high spatial (the angle between neighbor beams was 0375 degree) and temporal (the frame rate (FIR) was 1020 Hz) resolution. In addition, the strain rate was obtained by spatial differentiation of the velocity distribution along the ultrasonic beam using the phased tracking method applied to multiple points in the heart wall. Slight spatial transition of contraction / relaxation in the axial and lateral directions during a very short period less than 10 ins was able to visualized by PBF. On the other hand, the transition in only the axial direction was visualized by sparse scan. Measurement of myocardial strain rate at high temporal and spatial resolutions was achieved using PBF. In vivo experimental results show a possibility of this method for elucidation of the transition of myocardial contraction and relaxation in two dimensions. It is supposed that such transition corresponds to the propagation of myocardial excitation along the conduction system of the heart (from sinoatrial node to Purkinje fibers).

The endothelial dysfunction is considered to be an initial step of atherosclerosis. Additionally, it was reported that the smooth muscle, which constructs the media of the artery, changes its characteristics due to early-stage atherosclerosis. Therefore, it is essential to develop a method for assessing endothelial function and mechanical property of arterial wall. There is a technique to measure the transient change in diameter of the brachial artery caused by flow-mediated dilation (FMD) after release of avascularization. For more sensitive and regional evaluation, we developed a method to measure the change in elasticity of the radial artery due to FMD. In this study, the transient change in the mechanical property of the arterial wall was further revealed by measuring the stress-strain relationship during each heartbeat. The minute change in thickness (strain) of the radial arterial wall during a cardiac cycle was measured using the phased tracking method. At the same time, the waveform of blood pressure at the radial artery was continuously measured with a sphygmometer. Transient change due to FMD in the stress-strain relationship during a cardiac cycle was obtained from the measured strain and blood pressure to show instantaneous viscoelasticity. From the stress-strain relationship, we estimated the viscoelasticity by using least-squire method. In this study, the repeated in vivo measurement for 10 minutes shows the deviation of this method. The temporal decrease of static elasticity after recirculation due to FMD is much larger than maximum difference from the mean. These results show a potential of the proposed method for thorough analysis of the transient change of viscoelasticity due to FMD.

October 2-3, 2007, Orebro, Sweden

September 1-5, 2007, Vienna, Austria

September 1-5, 2007, Vienna, Austria

July 25-28, 2007, Vietnum, Hanoi

Recently, ultrasonic surgical knives have been applied in a variety of surgical operations. In this paper, the operation frequency of a surgical knife is focused on . Prototype ultrasonic knives operated at 24.3, 44.3, and 71.9 kHz were constructed. Differences in the effects on soft tissue depending on the operation frequency were investigated using these knives. Frequency characteristics were measured using two parameters: coagulation ratio and coagulated depth. For the same vibration velocity, at a lower frequency, the distribution of the coagulated tissue was deep and in a narrower region around the center of the tip. For the same vibration amplitude, the coagulated depth at each frequency was similar for all these frequencies. Furthermore, the dependences of tissue coagulation on the vibration velocity, pressure load, contact of the tip with tissue, and direction of vibration were investigated. From these investigations, it was found that the mechanical effect, rather than ultrasound absorption, is the dominant factor in tissue coagulation.

Recently, there have been several studies on ultrasonic cross-sectional imaging based on simultaneous reception of echo signals with an array transducer without scanning ultrasonic beams during transmission. In those studies, parallel processing was applied to create an image from a data set simultaneously received by the array. However, the lateral resolution of the parallel processing is not high. In this study, in order to improve the spatial resolution of parallel processing, the least-squares estimation and the truncated singular value decomposition (tSVD) are applied to the echo signals from two wire targets simultaneously received with a multichannel transducer array. We introduced a weighting for correcting the effect of the directivity of the elements of the array. The experimental results show a higher lateral resolution of the tSVD method with weighting than that of conventional parallel processing. The axial resolution is also improved by considering the finite duration of the transmitted. ultrasonic pulse. A typical application of this method is nondestructive evaluation, that is, the detection of cavities and cracks in welded metal structures.

Atherosclerosis is the main cause of circulatory diseases, and it is very important to diagnose atherosclerosis in its early stage. In an early stage of atherosclerosis, the luminal surface of an arterial wall becomes rough due to injury of the endothelium. Conventional ultrasonic diagnostic equipments cannot detect such micron-order surface roughness because their spatial resolution is, at most, 100 mu m. In this study, for the accurate detection of surface roughness, ultrasonic beams were insonified from various angles relative to the surface of an object that has a micron-order asperity. Then, we focused on the angular dependence of echo amplitude and frequency characteristics in both temporal and spatial domains. Using this method, it is shown that the angular dependence and frequency characteristics vary when an object has a surface roughness that cannot be detected by conventional B-mode imaging using linear scanning.

Ross hypothesized that an endothelial dysfunction is considered to be an initial step in atherosclerosis. Endothelial cells, which release nitric oxide (NO) in response to shear stress from blood flow, have a function of relaxing smooth muscle in the media of the arterial wall. For the assessment of the endothelial function, there is a conventional method in which the change in the diameter of the brachial artery caused by flow-mediated dilation (FMD) is measured with ultrasound. However, despite the fact that the collagen-rich hard adventitia does not respond to NO, the conventional method measures the change in diameter depending on the mechanical property of the entire wall including the adventitia. Therefore, we developed a method of measuring the change in the thickness and the elasticity of the brachial artery during a cardiac cycle using the phased tracking method for the evaluation of the mechanical property of only the intima-media region. In this study, the initial positions of echoes from the lumen-intima and media-adventitia boundaries are determined using complex template matching to accurately estimate the minute change in the thickness and the elasticity of the brachial and radial arteries. The ambiguity in the determination of such boundaries was eliminated using complex template matching, and the change in elasticity measured by the proposed method was larger than the change in inner diameter obtained by the conventional method.

Strain and strain rate imaging have been shown to be useful for the assessment of regional myocardial function. However, some of the mechanisms of transition in myocardial contraction/relaxation remain unclear. In this study, the RF echoes from the left ventricular (LV) wall were acquired in both the longitudinal-axis view and the apical view by scanning ultrasonic beams sparsely to improve the temporal resolution, and a frame rate of about 600Hz was realized. The phased tracking method was applied to multiple points in the heart wall to estimate the strain rate. The spatial distribution of the strain rate measured about every 2 ms showed the continuous transition in the myocardium. In the apical view, the propagation speed of contraction from the apex to the base side in the interventricular septum was found to be about 0.8 m/s. These results indicate the potential of this method in the estimation of the physiological function of the myocardium.

The longitudinal motion of the arterial wall can be observed in a B-mode image obtained by recent ultrasonic diagnostic equipment. In this study, the longitudinal displacement was quantitatively estimated by the block matching of RF echoes using cross correlation. However, the estimated longitudinal displacement is discrete depending on the spacing between two ultrasound beams of about 0.1 mm. Such an accuracy is not sufficient for tracking the region of interest (ROI) in the arterial wall. Therefore, the spacing of 0.1 mm is reduced using the interpolation of measured RF echoes to improve the tracking of the ROI in the displacement estimation. In this study, the optimum parameter in the interpolation was investigated. The spatial distribution of longitudinal displacements along the arterial radial direction was estimated using the optimum parameter. There were significant differences between the longitudinal displacements in the arterial wall and those in the region considered to be tissue outside the arterial wall. These results show the possibility of using this method to identify the outer boundary of the adventitia, which has not been achieved by conventional ultrasonic imaging.

The difference between a normal and a hypertrophic heart is whether the direction of regional myocardial fibers are homogeneously aligned along one direction. In order to investigate the angle dependence of ultrasonic scattering in relation to the fiber direction, we measured the ultrasonic echoes from a metal wire phantom, which mimics a bundle of myocardium fibers, as a function of the insonification angle. In this study, we focused on ultrasonic scattering properties in relation to the azimuth and elevation angles of insonification and reception. Experimental results showed that the amplitude of the reflected echo from the metal wire became maximum when the ultrasonic beam was insonified parallel to the fiber direction. In the case of such parallel insonification, echoes from the wire showed directivity like those from an interface. Such directivity was considered to contribute to the dependence of echoes on the azimuth angle.

June 4-6, 2007, Sendai

June 4-6, 2007, Sendai

June 4-6, 2007, Sendai

June 4-6, 2007, Sendai

June 4-6, 2007, Sendai

January 8-9, 2007, Sendai

January 8-9, 2007, Sendai

January 8-9, 2007, Sendai

To image the intima-media complex of the carotid artery in a wider region, a method for measuring cross-sectional images in the arterial short-axis plane is presented. Using the proposed mechanical scanning system for an ultrasonic probe, cross-sectional images of a silicon rubber tube and a human carotid artery are measured in basic experiments and in in vivo experiments, respectively. These experiments show that this method successfully images the short-axis cross sections. Using the method proposed in this article, B-mode images in the short-axis plane can be accurately measured in a wider region than is possible with conventional methods.

Purpose: Strain and strain rate imaging have been shownto be useful for assessment of regional myocardial function. However, the mechanism of transition in myocardial contraction and relaxation remains unclear. In this study, we investigated the mechanismby measuring myocardial strain rate at high temporal resolution. Method: The RF data of two young males were acquired in a typical cross-sectional image(the transthoracic parasternal longitudinal-axis view)by scanning ultrasonic beams sparsely to improve temporal resolution. In the periods around the R-wave in electrocardiogram(ECG)and the second heart sound in phonocardiogram (PCG), the phased tracking method was applied to multiple points in the heart wall for estimation of the strain rate. Result: In the case of transition from contraction to relaxation around the second heart sound, the right ventricle(RV)side preceded theleft ventricle(LV)side by 15-30 ms in the interventricular septum(IVS), and the epicardium preceded the endocardium by 100-130 ms in the posterior wall. Furthermore, the spatial distribution of strain rate showed that there was a time lag between the apex side andbase side in contraction and relaxation. In particular, transition from the apex side to base side was found in the posterior wall. Conclusion: Myocardial strain rate was measured at high temporal resolution. In vivo experimental results showedthe possibility of using this method for elucidation of the mechanismin myocardial contraction and relaxation. © 2007, The Japan Society of Ultrasonics in Medicine. All rights reserved.

To assess elastic properties, correlation techniques are widely used to measure the displacement and strain of the arterial wall caused by the heartbeat. However, the displacements estimated by the phase-sensitive correlation methods are biased when the frequency used for the displacement estimation is different from the center frequency of RF echo. One of reasons for the frequency variation is the interference of echoes. In the case of the arterial wall, the displacement due to radial translation is larger than that contributing to strain by a factor of 10 and, thus, the error resulting from the translational motion due to the mismatch between the frequency used for displacement estimation and the actual center frequency is not negligible compared with the minute displacement contributing to strain. In this study, a method is proposed in which the radial translation is removed prior to the calculation of complex correlation between echoes in two different frames to estimate the phase change between the echoes. The radial translation is removed by tracking the echo from the luminal interface of the wall because it is dominant compared with echoes from scatterers in the wall and is less affected by the interference. Using this procedure, the significant error resulting from the large translation can be greatly suppressed. After the removal of translation, an error correcting function based on complex correlation is introduced to further reduce the error due to the frequency mismatch. Accuracy improvement by the proposed method was validated using phantoms. As shown in the figure, the error in strain estimated by the proposed method was 12.0% from the theoretical strain profile, significantly smaller than that (23.7%) by the conventional method. Furthermore, in the in vitro experiments using extracted femoral arteries, the arterial wall containing calcified tissue showed very small strain in comparison with that almost homogeneously composed of fibrous tissue (mixture of smooth muscle and collagen). The means and the standard deviations of distensibility (calculated from strain and internal pressure) of fibrous and calcified tissues obtained for 7 sections of 5 femoral arteries were 2.42 +/- 2.1 and 0.35 +/- 0.50 MPa-1, respectively.

Atherosclerosis is the main cause of circulatory diseases, and it is very important to diagnose atherosclerosis in its early stage. In an early stage of atherosclerosis, the luminal surface of an arterial wall becomes rough due to injury of the endothelium. Conventional ultrasonic diagnostic equipments cannot detect such micron-order surface roughness because their spatial resolution is, at most, 100 mu m. In this study, for the accurate detection of surface roughness, ultrasonic beams were insonified from various angles relative to the surface of an object that has a micron-order asperity. Then, we focused on the angular dependence of echo amplitude and frequency characteristics. Using this method, it is shown that the angular dependence and frequency characteristics vary when an object has a surface roughness that cannot be detected by conventional B-mode imaging using linear scanning.

Early diagnosis of atherosclerosis is essential as many of the risk factors are life-style dependent. We suggest a new method to measure minute roughness of the size of micrometers of the arterial wall. The method was evaluated using three silicone phantoms sized 13 fun, 23 itm and 33 pm, respectively. The mean of the measured heights of the phantoms were 8.1 mu m (SD 0.0), 23.3 mu m (SD 0.2) and 29.6 mu m (SD 0.1) in the forward direction, and 7.7 mu m (SI) 0.0), 21.9 mu m (SI) 0.2) and 27.3 mu m (SI) 3.6) In the backward direction, respectively. The phantom study shows very promising result and encourages to further evaluation and in vivo Investigations.

We have already shown that the pulsive vibration Is excited on the myocardium 15 ms after the electrical stimulation to an isolated heart [1]. If the heart wall vibration caused by spontaneous electric excitation Is visualized using ultrasound, the regional cell damage regarding electric potential due to diseases can be noninvasively detected. In this study, the spatial distribution of the minute vibration caused just around R-wave of ECG is visualized In In vivo experiments as follows: By the ultrasonic measurement of the myocardial motion [2], we detect pulsive waves spontaneously caused by electrical excitation or valve closure. Using a sparse sector scan [3], the waves are measured almost simultaneously at about 1,000 points set In the heart wall at a high frame rate (400 Hz). The consecutive spatial distributions of the Interpolated phase of the waves reveal wave propagation along the wall. The propagation time Is several ins, which is too short to be detected by conventional methods. The method was applied to 5 healthy subjects. The spontaneously driven pulsive waves and their propagations were clearly visible in all subjects in the longitudinal-axis, short-axis, and apical views. Just after the Q-wave of ECG, the propagation started from the apex, which Is close to the papillary muscle (terminal of Purkinje fiber), to the base side of the heart. Its propagation speed was slow (1-2 m/s for 20-100 Hz), which shows the propagation of electrical excitation. Then, after R-wave of ECG, another pulsive wave started to propagate reversely from base to apex. Since Its speed was several m/s for about 50 Hz but there was dispersion, this is the shear wave caused by the mitral-valve closure. The method noninvasively reveals the propagation of electrical conduction wave by measuring regional myocardial response to it in human heart, which will be a novel tissue characterization of the heart.

The endothelial dysfunction is considered to be an initial step of atherosclerosis. Additionally, it was reported that the smooth muscle, which constructs the media of the artery, changes its characteristics due to atherosclerosis. Therefore, it is essential to develop a method for assessing regional endothelial function and mechanical property of arterial wall. There is a technique to measure the transient change in diameter of the brachial artery caused by flow-mediated dilation (FMD) after release of avascularization. For more sensitive and regional evaluation, we developed a method to measure the change in elasticity of the radial artery due to FMD. In this study, the transient change in the mechanical property of the arterial wall was further revealed by measuring the stress-strain relationship during each heartbeat. The minute change in thickness (strain) of the radial arterial wall during a cardiac cycle was measured using the phased tracking method. At the same time, the waveform of blood pressure at the radial artery was continuously measured with a sphygmometer. Transient change due to FMD in the stress-strain relationship during a cardiac cycle was obtained from the measured strain and blood pressure to show instantaneous viscoelasticity. From the results, the stress-strain relationship shows the hysteresis loop. The slope of the loop decreased due to FMD, which shows that the elastic modulus became lower, and the increasing area of the loop depends on the ratio of the loss modulus (depends on viscosity) to the elastic modulus when the Voigt model is assumed. These results show a potential of the proposed method for thorough analysis of the transient change of viscoelasticity due to FMD.

In the ultrasonic tomographic images, the heart wall cannot be distinguished from the cardiac lumen automatically using only the echogenicity, which corresponds to the amplitude of the RF echo, because the echogenicity inside the heart wall is as low as that in the lumen. In this paper ultrasonic RF echoes from the heart wall and lumen were analyzed in frequency domain in order to distinguish the heart wall from the lumen automatically. Temporal change in complex frequency spectra was evaluated using magnitude-squared coherence function. The coherence function of the RF signal scattered from the interventricular septum (IVS) is high. In contrast, the coherence function in the right ventricle (RV) and left ventricle (LV) is low because the scatterers (blood cells) slipped off from the focal area of the ultrasonic beam by blood flow. For automated identification of the heart wall using the coherence function, the optimal threshold To for the coherence function should be determined. In this study, based on the Bayes decision rule, the optimum value of To is determined. Although the coherence function of the region near the anterior wall in the RV is as high as that in the IVS due to echoes from the external tissue resulting from the sidelobe, the artifact can be reduced by removing the static component from RF echoes before evaluation of the coherence function. In vivo experimental results show the differentiation of the heart wall from the lumen was improved using the proposed method.

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

December 9-10, 2006, Sendai

(December 6-9, 2006, Prague, Czech Republic

Purpose. The aim of this study was to evaluate early-stage changes in the arterial wall caused by smoking. Methods. A newly developed real-time ultrasonic measurement system was used to measure the elasticity distribution of the carotid arterial intima-media complex in 53 healthy male volunteers (mean age: 37.6 years), including 27 smokers. Simultaneous measurement of the elasticity distribution and intima-media thickness (IMT) was performed at six locations in the bilateral carotid arteries. Results. The mean elastic modulus in the radial direction (Er) of the carotid arterial area where the IMT was less than 1.1 mm in smokers was larger than that in age-matched nonsmokers. There were no significant correlations between IMT and Er at the same location. However, a significant positive correlation was observed between the maximum IMT (maxIMT) and that of Er (maxEr) in six locations. In smokers, maxEr had a better correlation with the smoking index, and areas of IMT less than 1.1 mm containing harder lesions of Er ≥ 160 kPa were significantly more frequent than in nonsmokers. Conclusion. Measurement of carotid arterial wall elasticity is useful for detecting distortion in the intramural elasticity distribution that occurs prior to IMT thickening caused by smoking as an early-stage atherosclerotic sign. © 2006 The Japan Society of Ultrasonics in Medicine.

(December 6-9, 2006, Prague, Czech Republic

Noninvasive measurement of mechanical properties, such as elasticity, of the arterial wall, is useful for diagnosis of atherosclerosis. For assessment of mechanical properties, it is necessary to measure the deformation of the arterial wall. In this study, a modification of the previously proposed phased-tracking method was conducted to improve measurement of the small change in thickness (deformation) of the arterial wall due to the heartbeat. In our previous method, a set of two points along an ultrasonic beam was initially assigned, and the change in thickness of the layer between these two points during an entire cardiac cycle was estimated. In motion estimation with ultrasound, the motion of an interface or a scatterer, which generates an echo, can be obtained by estimating the change in time delay of the echo. For example, in the case of a carotid artery of a healthy subject, there are only two dominant echoes from the lumen-intima and media-adventitia interfaces. Thus, only the displacements of the lumen-intima and media-adventitia interfaces can be estimated, which means that ultrasound can estimate only the change in distance (thickness) between these two interfaces. However, even in this case, our previous method gives different estimates of the change in thickness, depending on the depths (positions in the arterial radial direction) of the two initially assigned points. In this study, modifications of the previous method in terms of the strategy for assignment of layers and the required thickness of an assigned layer were made to reduce such an artificial spatial variation in the estimated changes in thickness. Using the proposed method, errors in estimated changes in thickness were reduced from 21.2 +/- 24.1% to 0.19 +/- 0.04% (mean +/- standard deviation) in simulation experiments. As in the case of the simulation experiments, the spatial variation in estimated changes in thickness also was reduced in in vivo experiments in a carotid artery of a healthy subject and in vitro experiments using two excised, diseased arteries.

November 12-15, 2006, Chicago, USA)

November 27, 2007, Honolulu, USA

November 27, 2007, Honolulu, USA

November 27, 2007, Honolulu, USA

November 28-December 2, 2006, Honolulu, USA

November 28-December 2, 2006, Honolulu, USA

November 28-December 2, 2006, Honolulu, USA

November 28-December 2, 2006, Honolulu, USA

October 8-11, 2006, Snowbird, USA

October 8-11, 2006, Snowbird, USA

October 15-19, 2006, Fukuoka)

Purpose. For tissue characterization of the arterial wall, we developed a "phased tracking" method to measure the strain (change in wall thickness) and elasticity of the arterial wall. To improve the accuracy of tissue characterization, we are now attempting to measure other mechanical properties in addition to elasticity. Methods. In this study, the change in elasticity during the cardiac diastole was measured with ultrasound by generating a change in internal pressure using remote cyclic actuation. Results. From the measured change in elasticity during cardiac diastole, the nonlinear property in the stress-strain relationship of the artery wall was estimated. In basic experiments using a silicone rubber tube and in vivo experiments in human carotid arteries. Conclusion. The proposal method enables the noninvasive measurement of the nonlinear mechanical property in addition to the elasticity of the arterial wall. © 2006 The Japan Society of Ultrasonics in Medicine.

Many studies have been carried out on the measurement of mechanical properties of tissues by applying an acoustic. radiation force induced by ultrasound to an object. However, one acoustic radiation force in a given direction (e.g., vertical direction) does not generate strain in an object effectively because it also causes changes in the object's position, which has zero spatial gradient in displacement ( = no strain). Especially when the elastic modulus of the object is much higher than that of the surrounding tissue (such as a tumor in breast tissue), one acoustic radiation force might generate only a change in the position of the object unlike a strain in the object is hardly generated. In such cases, mechanical properties of the object cannot be evaluated. In this study, two cyclic acoustic radiation forces are simultaneously applied to an object in two different directions (e.g., two opposite horizontal directions) to effectively generate strain inside the object, even when the object is much harder than the surrounding tissue.

Recently, cardiovascular disease has become the second most common cause of death in Japan following malignant neoplasm formation. Therefore, it is necessary to diagnose atherosclerosis during its early stages because atherosclerosis is one of the main causes of cardiovascular diseases. The carotid sinus is a site that is easily affected by atherosclerosis [C. K. Zarins et al.: Circ. Res. 53 (1983) 502]; therefore, the diagnosis of this disease at this site is important [S. C. Nicholls et al.: Stroke 20 (1989) 175]. However, it is difficult to accurately diagnose atherosclerosis in the carotid sinus in the long-axis plane, which is parallel to the axis of the vessel, using conventional linear scanning because the carotid sinus is not flat along the axis, of the vessel, and the ultrasonic beams used in linear scanning are perpendicular to the arterial wall in a limited region. Echoes from regions that are not perpendicular to the ultrasonic beams are very weak and the arterial wall in such regions is hardly recognized in a B-mode image. In this study, the position of the arterial wall was predetermined on the basis of the B-mode image obtained by conventional linear scanning, then ultrasonic beams were transmitted again so that all beams were almost perpendicular to the arterial wall. In basic experiments, a nonflat object made of silicone rubber was measured and it was shown that it is possible to image a nonflat object over the entire scanned area using the proposed beam steering method. Furthermore, in in vivo experiments, the intima-media complex was imaged over the entire scanned area at the carotid sinus.

It is essential for the diagnosis of heart diseases to noninvasively measure instantaneous myocardial movability and transition properties during one cardiac cycle. This study proposes a novel method of noninvasively perturbing left ventricle (LV) internal pressure by remotely actuating the brachium artery with sinusoidal vibration for the diagnosis of myocardial movability. By attaching an actuator to the brachium artery and driving it with a sinusoidal wave of f(0) Hz, the internal pressure of the artery is perturbed. The perturbation propagates along the artery to the LV of the heart and the sinusoidal perturbation of the LV internal pressure is induced. Using an ultrasound-based phased tracking method, the resultant minute motion of the heart wall can be noninvasively measured. Because the vibration mode of the heart wall depends on actuation frequency, by phantom experiments using a spherical shell made of silicone rubber,. to which a silicone rubber tube is connected, the vibration mode was identified from the measurement of the spatial distribution of the motions by scanning with an ultrasonic beam. From an in vivo experiment, the principle of remote actuation was confirmed.

Atherosclerosis is the main cause of circulatory diseases such as myocardial infarction and cerebral infarction, and it is very important to diagnose atherosclerosis in its early stage. In the early stage of atherosclerosis, the luminal surface of an arterial wall becomes rough because of the injury of the endothelium [R. Ross: New Engl. J. Med. 340 (2004) 115]. Conventional ultrasonic diagnostic equipments cannot detect such roughness on the order of micrometer because of their low resolution of approximately 0.1 mm. In this study, for the accurate detection of surface roughness, an ultrasonic beam was scanned in the direction that is parallel to the surface of an object. When there is a gap on the surface, the phase of the echo from the surface changes because the distance between the probe and the surface changes during the scanning. Therefore, surface roughness can be assessed by estimating the phase shift of echoes obtained during the beam scanning. Furthermore, lateral resolution, which is deteriorated by a finite diameter,of the ultrasound beam, was improved by an inverse filter. By using the proposed method, the surface profile of a phantom, which had surface roughness on the micrometer order, was detected, and the estimated surface profiles became more precise by applying the inverse filter.

The phased tracking method was developed for measuring the minute change in thickness during one cardiac cycle and the elasticity of the arterial wall. By comparing elasticity images measured by the phased tracking method with the corresponding pathological images, the elasticity distribution for each tissue in the arterial wall was determined. We have already measured the elasticity distributions for lipids, fibrous tissues (mixture of smooth-muscle and collagen fiber), blood clots and calcified tissues. From these previous studies, it was found that arterial tissues can be classified into soft tissues (lipids and blood clots) and hard tissues (fibrous tissue and calcified tissue) on the basis of their elasticity. However, it was difficult to differentiate lipids from blood clots and also fibrous tissue from calcified tissue. In this study, we investigated how to improve the tissue classification of the arterial wall using statistical properties of the elasticity distribution of each tissue.

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

International Symposium on Bio- and Nano-Electronics in Sendai, March 2-3, 2006, Sendai

Purpose: The aim of this study was to find an array of frequencycomponents, ranging from 0 Hz (direct current) to several tens of hertz that comprise the small vibrations on the arterial wallusing noninvasive in vivo experiments. These vibrations are caused mainly by blood flow. The viscoelasticity of the arterial wallwas estimated from the frequency characteristics of these vibrations propagating from the intima to the adventitia. Methods: Propagation of these frequencies in human tissue displays certain frequency characteristics. Based on the Voigt model, shear viscoelasticity can be estimated from the frequency characteristics of the propagating vibrations. Moreover, we estimated shear viscoelasticity from the measured frequency characteristics of shearwave attenuation. Results: Shear wave propagation from the intima to the adventitia resulting from blood flow was explained theoretically based on the obtained measurements. Shear viscoelasticity was also estimated from the measured frequency characteristics of shear wave attenuation. Conclusions: Based on the proposedmethod, shear viscoelasticity can be estimated from ultrasonographic measurements. These results have a novel potential for characterizing tissue noninvasively. © 2006, The Japan Society of Ultrasonics in Medicine. All rights reserved.

Ultrasound can be used for mechanical property measurements of the arterial wall in addition to imaging of its morphology. This paper describes (1) accurate imaging of the carotid sinus which cannot be assumed to be a straight cylindrical shell, (2) measurement of elasticity and tissue characterization of the arterial wall based on the axial motion estimation, and (3) lateral motion estimation in the carotid artery.

This paper describes a noninvasive method for evaluating regional elasticity of atheroma by measuring the minute change in thickness of the arterial wall during one heartbeat. By comparing the pathological findings with the elasticity images, elasticity distributions for lipid and fibrous tissue (mixture of smooth muscle and collagen fiber) were determined in vitro. Furthermore, to characterize the fibrous cap of plaque, which almost consists of smooth muscle and collagen fiber, the correlation between the collagen content and elasticity was investigated for fibrous tissue. Based on these elasticity reference data, fibrous tissue surrounding the soft inclusion of lipids was noninvasively clarified in a carotid plaque and the collagen content in the fibrous cap was also estimated. This method offers potential for detection of plaque vulnerability in a clinical setting.

Noninvasive measurement of mechanical properties, such as elasticity, of the arterial wall, is useful for diagnosis of atherosclerosis. The elasticity of the arterial wall can be estimated by combining measurement of displacement of the arterial wall with that of blood pressure. In general, the displacement of the arterial wall is estimated from the phase shift of radio frequency (RF) echoes between two consecutive frames using a correlation estimator with quadrature demodulated complex signals. Recently, digitized data of broadband RIP echoes are available in modern diagnostic equipment. The Fourier transform can be used to estimate the phase of the RF echo at each frequency within the RF frequency bandwidth. Therefore, the phase shifts between RF echoes of two consecutive frames can be estimated at multiple frequencies. In this estimation, due to object displacement, the RF echo is time shifted in comparison with that of the previous frame. However, the position of the time window for the Fourier transform is not changed between two consecutive frames. This change in relative position between the RIP echo and the time window has a strong influence on the estimation of the artery-wall displacement, resulting in error. To suppress this error, the phase shift should be estimated at the actual RIP center frequency. In this paper, this error suppression was investigated through simulation experiments and in vivo experiments on the human carotid artery.

Though myocardial viscoelasticity is essential in the evaluation of heart diastolic properties. it has never been noninvasively measured in vivo. By the ultrasonic measurement of the myocardial motion, we have already found that some pulsive waves are spontaneously excited bv aortic-valve closure (AVC) at end-systole (T(0)) (IEEE UFF643(1996)791-810). Using a sparse sector scan, in which the beam directions are restricted to about 16, the pulsive waves were measured almost simultaneously at about 160 points set along the heart wall at a sufficiently high frame rate (UMB 27(2001)752-768). The consecutive spatial phase distributions clearly revealed wave propagation along the heart wall for the first time (IEEE UFFC-51(2005)1931-1942). The propagation time of the wave along the heart wall is very small and cannot be measured by conventional equipment. Based on this phenomenon, we developed a means to measure the myocardial viscoelasticity in vivo. The phase velocity of the wave is determined for each frequency component. By comparing (he dispersion of the phase velocity with the theorctical one of the Lamb wave, which propagates along the viscoelastic plate (heart wall) immersed in blood, the instantaneous viscoelasticitv is determined noninvasively (IEEE UFFC-51(2005)1931-1942). In this study. the phase distribution obtained by the sparse scan is interpolated and extrapolated, and then iiie spatial distribution of the instantaneous phase velocity of the wave components propagating from the base side to the apical side of the heart wall is obtained for the longitudinal cross-sectional image.

Objective: To evaluate fetal myocardial movement by using newly developed ultrasonic technique. Methods: We analyzed 50 normal fetuses between 25 and 41 weeks' gestation for changes in thickness of fetal myocardium using the phased-tracking method, a technique with high vertical distance resolution and the potential to evaluate fine ventricular wall movements. We analyzed differences in the rate of change in ventricular wall thickness and in changes in the inner and outerwall layers with advancing gestation. We also analyzed myocardial thickening period and evaluated the ratio of increasing thickness period to stroke interval. Results: Mean thickness changing rate was significantly higher in the right (1.18 0.34m/s/m) than in the left ventricular wall (0.86 0.31 m/s/m) (p &lt; 0.001). Mean ratio of increasing thickness period to stroke interval was significantly higher in the right (0.57 +/- 0.064) than in the left ventricle (0.46 +/- 0.075) (p &lt; 0.001), indicating that myocardial contraction in the fetal right ventricle predominates. The thickness- changing rate of the bilateral ventricular walls was positively and linearly correlated with gestational age. The myocardial-wall thickness-changing rate was higher in the outer layer than in the inner layer in late gestation. Conclusions: We conclude that measurement of the thickness-changing rate of fetal ventricular walls using the phased-tracking method might be useful for evaluation of fetal cardiac function. Copyright (c) 2006 S. Karger AG, Basel.

Though myocardial viscoelasticity is essential in the evaluation of heart diastolic properties, it has never been noninvasively measured in vivo. By the ultrasonic measurement of the myocardial motion, we have already found that some pulsive waves are spontaneously excited by aortic-valve closure (AVC) time (T-0) (IEEE UFFC-43(1996)791-810). Using a sparse sector scan, in which the beam directions are restricted to about 16, the pulsive waves were measured almost simultaneously at about 160 points set along the heart wall at a sufficiently high frame rate (UMB 27(2001)752-768). The consecutive spatial phase distributions clearly revealed wave propagation along the heart wall for the first time (IEEE UFFC-51(2005)1931-1942). The propagation time of the wave along the heart wall is very small and cannot be measured by conventional equipment. Based on this phenomenon, we developed a means to measure the myocardial viscoelasticity in vivo. The phase velocity of the wave is determined for each frequency component. By comparing the dispersion of the phase velocity with the theoretical one of the Lamb wave, which propagates along the viscoelastic plate (heart wall) immersed in blood, the instantaneous viscoelasticity is determined noninvasively (IEEE UFFC-51(2005)1931-1942). In this study, the phase distribution obtained by the sparse scan was interpolated, and then the spatial distribution of the propagation speed (phase velocity) of the wave components propagating from the base side to the apical side of the heart wall was obtained. After confirming the principle with phantom study, the method was applied to healthy subjects. The spatial distribution of the propagation speed varies from 3 to 6 m/s for 60 Hz component. The results show inhomogeneity and the region with high speed corresponds to the high intensity region (fibrous region) in the conventional B-mode image.

Pathological changes in arterial walls significantly influence their mechanical properties. We have developed a correlation-based method, the phased tracking method, for measuring the regional elasticity of the arterial wall. Using this method, elasticity distributions of lipids, blood clots, fibrous tissue, and calcified tissue have already been measured in vitro. However, these elasticity distributions were found to overlap each other, and this overlap worsens the tissue classification based on elasticity images. In this study, spatial compounding of the correlation estimator for estimating strain was introduced to reduce undesirable variances in elasticity distributions. To determine radial strain (change in thickness) of the arterial wall caused by heartbeat, a combination of two points are assigned along an ultrasonic beam, and the rate of the change in thickness between these two points (=layer) are estimated. Then, the combination of two points is slid along the ultrasonic beam with an interval of sampled points to obtain the spatial distribution. In this process, the initial distance between two points is set to be larger than the duration of ultrasonic pulse (eight times of the interval of sampled points), and the combination of two points is slid with an interval of sampled points. Therefore, layers, which are defined by the region between each combination of two points, overlap each other. In this study, complex correlation functions of overlapping layers are compounded to reduce the variance in estimated rates of changes in thickness. Temporal integration is applied to the estimated rate of change in thickness to obtain the radial strain and elastic modulus. Eighteen arteries (femoral and iliac) were measured in vitro. The change in internal pressure was applied using a flow pump. By comparing measured elasticity images with corresponding pathological images, elasticity distributions of lipids, blood clots, fibrous tissue, and calcified tissue (mean +/- SD) were determined to be 67 +/- 37, 105 +/- 76, 989 +/- 1359, and 1292 +/- 839 kPa, respectively, by the previous phased tracking method. By the proposed method with spatial compounding, they were determined to be 89 +/- 47, 131 +/- 56, 1022 +/- 1040, and 2267 +/- 1228 kPa, respectively. The proposed spatial compounding suppressed variances and increased the difference among their mean elasticity. This result shows that the proposed method improves the tissue classification based on elasticity.

To provide useful information for diagnosis of atherosclerosis in addition to the imaging of morphology using the B-mode ultrasonography, we have developed a method in which an elasticity image is classified into tissue components using the reference data obtained by in vitro experiments. We have already measured the elasticity distributions for lipids, blood clots, fibrous tissue, and calcified tissue [H. Kanai, et al.: Circulation, 107, (2003) 3018, J. Inagaki, et al.: Jpn. J. Appl. Phys., 44, (2005) 4593]. From these previous studies, it was found that arterial tissues can be classified into soft tissues (lipids, blood clots) and hard tissues (fibrous tissue, calcified tissue) on the basis of their elasticity. However, it was difficult to differentiate lipids from blood clots and fibrous tissue from calcified tissue. Therefore, we proposed a tissue classification method using the likelihood function [J. Inagaki, et al.: Jpn. J. Appl. Phys., 45, (2006) 4732]. In this method, the elasticity distribution of each small region of interest (not a single pixel) in an elasticity image was used in classification of lipids, blood clots, fibrous tissue, and calcified tissue. In this paper, the optimum size of the region of interest was investigated to improve the tissue classification.

Recently, cardiovascular disease has become the second most common cause of death in Japan following malignant neoplasm formation. Therefore, it is necessary to diagnose atherosclerosis during its early stages because atherosclerosis is one of the main causes of cardiovascular diseases. The carotid sinus is a site that is easily affected by atherosclerosis [C. K. Zarins et al.: Circ. Res. 53 (1983) 502]; therefore, the diagnosis of this disease at this site is important [S. C. Nicholls et A: Stroke 20 (1989) 175]. However, it is difficult to accurately diagnose atherosclerosis in the carotid sinus in the long-axis plane, which is parallel to the axis of the vessel, using conventional linear scanning because the carotid sinus is not flat along the axis of the vessel, and the ultrasonic beams used in linear scanning are perpendicular to the arterial wall in a limited region. Echoes from regions that are not perpendicular to the ultrasonic beams are very weak and the arterial wall in such regions is hardly recognized in a B-mode image. In this study, the position of the arterial wall was predetermined on the basis of the B-mode image obtained by conventional linear scanning, then ultrasonic beams were transmitted again so that all beams were almost perpendicular to the arterial wall. In basic experiments, a nonflat object made of silicone rubber was measured and it was shown that it is possible to image a nonflat object over the entire scanned area using the proposed beam steering method. Furthermore, in in vivo experiments, the intima-media complex was imaged over the entire scanned area at the carotid sinus.

The 7th International Symposium of Future Medical Engineering Based on Bio-nanotechnology,<br /> pp. 28-31 (December 7-10, 2005, Singapole)

The 7th International Symposium of Future Medical Engineering Based on Bio-nanotechnology,<br /> pp. 28-31 (December 7-10, 2005, Singapole)

8th Sendai Symposium on Ultrasonic Tissue Characterization, (November<br /> 11, 2005, Sendai)

8th Sendai Symposium on Ultrasonic Tissue Characterization, (November<br /> 11, 2005, Sendai)

8th Sendai Symposium on Ultrasonic Tissue Characterization, (November<br /> 11, 2005, Sendai)

8th Sendai Symposium on Ultrasonic Tissue Characterization, (November<br /> 11, 2005, Sendai)

Though myocardial viscoelasticity is essential in the evaluation of heart diastolic properties, it has never been noninvasively measured in vivo. By the ultrasonic measurement of the myocardial motion, we have already found that some pulsive waves are spontaneously excited by aortic-valve closure (AVC) at end-systole (T-o). These waves may serve as an ideal source of the intrinsic heart sound caused by AVC. In this study, using a sparse sector scan, in which the beam directions are restricted to about 16, the pulsive waves were measured almost simultaneously at about 160 points set along the heart wall at a sufficiently high frame rate. The consecutive spatial phase distributions, obtained by the Fourier transform of the measured waves, clearly revealed wave propagation along the heart wall for the first time. The propagation time of the wave along the heart wall is very small (namely, several milliseconds) and cannot be measured by conventional equipment. Based on this phenomenon, we developed a means to measure the myocardial viscoelasticity in vivo. In this measurement, the phase velocity of the wave is determined for each frequency component. By comparing the dispersion of the phase velocity with the theoretical one of the Lamb wave (the plate flexural wave), which propagates along the viscoelastic plate (heart wall) immersed in blood, the instantaneous viscoelasticity, is determined noninvasively. This is the first report of such noninvasive determination. In in vivo experiments applied to five healthy subjects, propagation of the pulsive wave was clearly visible in all subjects. For the 60-Hz component, the typical propagation speed rapidly decreased from 5 m/s just before the time of AVC (t = T-o - 8 ms) to 3 m/s at t = T-0 + 10 ms. In the experiments, it was possible to determine the viscosity more precisely than the elasticity. The typical value of elasticity was about 24-30 kPa and did not change around the time of AVC. The typical transient values of viscosity decreased rapidly from 400 Pa(.)s at t = T-0 - 8 ms to 70 Pa(.)s at t = T-o + 10 ms. The measured shear elasticity and viscosity in this study are comparable to those obtained for the human tissues using audio frequency in in vitro experiments reported in the literature.

Fourth International Conference on the Ultrasonic Measurement and Imaging of Tissue Elasticity<br /> (October 16-19, 2005, Austin, Texas, USA)

WCU/UI’05 (August 28-31, 2005, Beijing, China)

Endothelial dysfunction is considered to be an initial step of arteriosclerosis [R. Ross: N. Engl. J. Med. 340 (2004) 115]. For the assessment of the endothelium function, brachial artery flow-mediated dilation (FMD) caused by increased blood flow has been evaluated with ultrasonic diagnostic equipment. In the case of conventional methods, the change in artery diameter caused by FMD is measured [M. Hashimoto et al.: Circulation 92 (1995) 3431]. Although the arterial wall has a layered structure (intima, media, and adventitia), such a structure is not taken into account in conventional methods because the change in diameter depends on the characteristic of the entire wall. However, smooth muscle present only in the media contributes to FMD, whereas the collagen-rich hard adventitia does not contribute. In this study, we measure the change in elasticity of only the intima-media region including smooth muscle using, the phased tracking method [H. Kanai et al.: IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43 (1996) 791]. From the change in elasticity, FMD measured only for the intima-media region by our proposed method was found to be more sensitive than that measured for the entire wall by the conventional method.

For the assessment of the elasticity of the arterial wall, we have developed the phased tracking method [H. Kanai et al.: IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43 (1996) 79 1] for measuring the minute change in thickness due to heartbeats and the elasticity of the arterial wall with transcutaneous ultrasound. For various reasons, for example, an extremely small deformation of the wall, the minute change in wall thickness during one heartbeat is largely influenced by noise in these cases and the reliability of the elasticity distribution obtained from the maximum change in thickness deteriorates because the maximum value estimation is largely influenced by noise. To obtain a more reliable cross-sectional image of the elasticity of the arterial wall, in this paper, a matching method is proposed to evaluate the waveform of the measured change in wall thickness by comparing the measured waveform with a template waveform. The maximum deformation, which is used in the calculation of elasticity, was determined from the amplitude of the matched model waveform to reduce the influence of noise. The matched model waveform was obtained by minimizing the difference between the measured and template waveforms. Furthermore, a random error, which was obtained from the reproducibility among the heartbeats of the measured waveform, was considered useful for the evaluation of the reliability of the measured waveform.

Previously, we developed the phased tracking method [H. Kanai et al.: IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43 (1996) 791] for measuring the minute change in thickness during one heartbeat and the elasticity of the arterial wall. By comparing pathological images with elasticity images measured with ultrasound, elasticity distributions for respective tissues in the arterial wall were determined. We have already measured the elasticity distributions for lipids and fibrous tissues (mixtures of smooth-muscle and collagen fiber) [H. Kanai et al.: Circulation 107 (2003) 3018]. In this study, elasticity distributions were measured for blood clots and calcified tissues. We discuss whether these elasticity distributions, which were measuerd in vitro, can be used as reference data for classifying cross-sectional elasticity images measured in vivo into respective tissues. In addition to the measurement of elasticity distributions, correlations between collagen content and elasticity were investigated with respect to fibrous tissue to estimate the collagen and smooth-muscle content based on elasticity. Collagen and smooth-muscle content may be important factors in determining the stability of the fibrous cap of atherosclerotic plaque. Therefore, correlations between elasticity and elements of the tissue in the arterial wall may provide useful information for the noninvasive diagnosis of plaque vulnerability.

For tissue characterization of atherosclerotic plaque, we have developed a method, namely, the phased tracking method, [H. Kanai et al.: IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43 (1996) 791] to measure the regional strain (change in wall thickness) and elasticity of the arterial wall. In addition to the regional elasticity, we are attempting to measure the regional viscosity for a more precise tissue characterization. Previously, we showed that the viscosity can be obtained by measuring the frequency dependence of the elastic modulus using remote actuation [H. Hasegawa et al.: Jim. J. Appl. Phys. 43 (2004) 3197]. However, in this method, we need to apply external actuation to the subject. To simplify the measurement, we instead to obtain the frequency dependence of the elastic modulus from the change in arterial wall thickness spontaneously caused by the heartbeat because this change in thickness consists of frequency components up to 20-30 Hz. In this paper, the frequency dependence of the elastic modulus of a silicone rubber tube was investigated by applying frequency analysis to the change in wall thickness caused by the change in internal pressure simulating the actual arterial blood pressure.

Purpose. The aim of this study was to find an array of frequency components, ranging from 0∈Hz (direct current) to several tens of hertz that comprise the small vibrations on the arterial wall using noninvasive in vivo experiments. These vibrations are caused mainly by blood flow. The viscoelasticity of the arterial wall was estimated from the frequency characteristics of these vibrations propagating from the intima to the adventitia. Methods. Propagation of these frequencies in human tissue displays certain frequency characteristics. Based on the Voigt model, shear viscoelasticity can be estimated from the frequency characteristics of the propagating vibrations. Moreover, we estimated shear viscoelasticity from the measured frequency characteristics of shear wave attenuation. Results. Shear wave propagation from the intima to the adventitia resulting from blood flow was explained theoretically based on the obtained measurements. Shear viscoelasticity was also estimated from the measured frequency characteristics of shear wave attenuation. Conclusions. Based on the proposed method, shear viscoelasticity can be estimated from ultrasonographic measurements. These results have a novel potential for characterizing tissue noninvasively. © The Japan Society of Ultrasonics in Medicine 2005.

The 30th International Symposium on Ultrasonic Imaging and Tissue Characterization (May 25-27, 2005)

6th Asian-Pacific Conference on Medical and Biological Engineering (APCMBE2005) (April 24-27, 2005, Tsukuba, Japan)

The 5th International Symposium on Future Medical Engineering based on Bionanotechnology 21st Century Center of Excellence (COE) Program, Nano Science and Technology for Medical Applications (February 15, 2005, Sendai)

Though myocardial viscoelasticity is essential in the evaluation of heart diastolic properties, it has never been noninvasively measured in vivo. By the ultrasonic measurement of the myocardial motion, we have already found that some pulsive waves are spontaneously excited by aortic-valve closure (AVC) at end-systole (T-0). In this study, a sparse sector scan at a sufficiently high frame rate clearly reveals wave propagation along the heart wall. The propagation time of the wave along the heart wall is very small, namely, several milliseconds, and cannot be measured by conventional equipment. From the measured phase velocity, we estimate the myocardial viscoelasticity in vivo. In in vivo experiments applied to 6 healthy subjects, 3 patients with hypertrophic cardiomyopathy (HCM), and 3 patients with aortic stenosis (AS), the propagation of the pulsive wave was clearly visible in all subjects. For the frequency component up to 90 Hz, the typical propagation speed is about several m/s and rapidly decreased around the time of AVC. For the healthy subject, the typical value of elasticity was about 24-30 kPa and did not change around the time of AVC. The typical transient values of viscosity decreased rapidly from 400 Pa-s to 70 Pa-s around the time of AVC. The measured shear elasticity and viscosity in this study are comparable to those obtained for the human tissues using audio frequency in in vitro experiments reported in the literature. The method cannot be easily applied to these patients because there were inhomogeneities in the phase velocities due to the diseased myocardium. By applying the measurement of the phase velocity to each of 5 layers set in the heart wall, the phase velocity in the middle layer was lower than those in the LV- and RV-sides of the heart wall, which will corresponds to the change in myocardial fiber orientations. This method offers potential for in vivo imaging of the spatial distribution of the passive mechanical properties of the myocardium, which cannot be obtained by conventional echocardiography, CT, or MRI.

This study proposes a novel method to noninvasively perturb the left ventricular (LV) internal pressure by remotely actuating the brachium artery with the sinusoidal vibration for diagnosis of the myocardial movability. By attaching an actuator to the brachium artery and driving it by sinusoidal wave of f(0) Hz, the inner pressure of the artery is perturbed. The perturbation propagates along the artery to the LV of the heart and the perturbation of the LV inner pressure is generated. Using ultrasound-based method, the resultant minute motion on the heart wall can be measured. Since the vibration mode of the heart wall depend on the actuated frequency, the vibration mode and the positions of the nodes can be identified from the measurement of the spatial distribution of the heart wall motions by scanning the ultrasonic beam. Finally, from the resultant strain and the delay of the strain to the applied pressure, the instantaneous myocardial movability and its transition property during one cardiac cycle are noninvasively estimated. By the phantom experiments using a spherical shell made of silicone rubber was set in a water tank with a silicone rubber tube and in vivo experiment, the principle was confirmed. By measuring the spatial distribution of the heart wall motion using ultrasound, the vibration mode is identified, which has a potential to noninvasively evaluate the movability and its transition property during one cardiac cycle.

There are many studies on measurement of tissue mechanical properties by applying an acoustic radiation force induced by ultrasound to an object. However, when the elastic modulus of the object is much higher than that of the surrounding tissue (such like a tumor in the breast tissue), an acoustic radiation force might generate only the change in position of the object and the strain of the object is hardly generated. In such cases, mechanical properties of the object cannot be evaluated. In this study, two cyclic acoustic radiation forces are simultaneously applied to an object to effectively generate the strain inside the object even when the object is much harder than the surrounding tissue.

Artery wall elasticity and intima-media thickness (IMT) are useful markers for diagnosis of atherosclerosis. However, the regional elasticity of intima-media complex have never been measured. Therefore, we developed a method for imaging the regional elasticity by measuring changes in wall thickness due to heartbeat. In this method, multiple points are assigned in the wall along each ultrasonic beam with a pitch of the sampling interval of received echoes just before the ejection of the heart. Then, the displacement of each point is estimated, and the change in thickness between two points (=layer) is obtained from the difference between estimated displacements at these two points. The initial distance between these two points is determined in consideration of the duration of ultrasonic pulse. A spatial distribution of changes in thickness is obtained by shifting the combination of two points along each ultrasonic beam with a pitch of sampling interval of echo. Although, the original thickness of each layer is determined by the duration of the ultrasonic pulse, the estimated change in thickness should not be divided by the original thickness based on the pulse duration because only two dominant echoes from lumen-intima and media-adventitia boundaries contribute to displacement estimation in the case of a healthy subject. To obtain the actual strain, measured changes in thickness should be divided by the intima-media thickness. In this study, the intima-media elasticity is obtained from measured changes in thickness combined with the automatic detection of the intima-media thickness.

Fourth Japan-America<br /> Frontiers of Engineering Symposium (JAFOE2004) (November 4-6, 2004, Kyoto, Japan)

American Heart Association Scientific Sessions 2004 (November 7-10, 2004, New Orleans, USA)

American Heart Association Scientific Sessions 2004 (November 7-10, 2004, New Orleans, USA)

The Third International Conference on the Ultrasonic Measurement and Imaging<br /> of Tissue Elasticity (October 17-20, 2004, Lake Windermere, Cumbria, United Kingdom)

Purpose. For noninvasive diagnosis of atherosclerosis, we attempted to evaluate the elasticity of the arterial wall by measuring small changes in thickness caused by the heartbeat. The elasticity of the arterial wall has been evaluated noninvasively by measuring the change in diameter of the artery or the pulse-wave velocity however, there is no method for noninvasively evaluating the elasticity of the arterial wall from changes in its thickness. Methods. Employing the phased tracking method that we developed, changes in thickness of less than 100 μm were measured in each regional area, which corresponded to the diameter of the ultrasonic beam. Results. The elasticity of the arterial wall could be evaluated with better spatial resolution from the change in thickness than from the change in diameter of the artery or pulse-wave velocity. We therefore propose a method for evaluating the elastic modulus of an arterial wall of nonuniform wall thickness. Conclusions. In basic experiments employing silicone rubber tubes with nonuniform wall thickness as arterial models, the elastic moduli of silicone rubber tubes were evaluated by measuring changes in wall thickness. These results confirm the value of the proposed method. © The Japan Society of Ultrasonics in Medicine 2004.

June 25, 2004, Sendai, Japan

To characterize tissues in atherosclerotic plaques, we have developed a method, the phased tracking method, for measuring the strain (change in wall thickness) and elasticity of the arterial wall. However, some types of tissue, such as lipids and blood clots, cannot be discriminated from each other based only on elasticity due to the small difference in their elasticity. For more precise tissue characterization, we have measured the regional viscoelasticity. To obtain the viscoelasticity, in this study, elastic moduli at multiple frequencies were measured with ultrasound by generating the change in internal pressure due to remote cyclic actuation. Furthermore, the viscoelasticity of the arterial wall was estimated from the measured elastic moduli at multiple actuation frequencies.

We have developed the phased tracking method [H. Kanai, M. Sato, Y. Koiwa and N. Chubachi: IEEE Trans. UFFC 43 (1996) 791.] for measuring the minute change in thickness during one heartbeat and the elasticity of the arterial wall with transcutaneous ultrasound. When this method is applied to a plane perpendicular to the axis of the artery (short-axis plane) using a linear-type probe, only an ultrasonic beam which passes through the center of the artery coincides with the direction of the change in thickness. At other beam positions, the wall motion cannot be accurately tracked because the direction of wall expansion slips off the beam. To obtain the cross-sectional image of elasticity in the short-axis plane using transcutaneous ultrasound, in this paper, the directions of ultrasonic beams are designed so that each beam always passes through the center of the artery; thus, they always coincide with the direction of the wall expansion. In basic experiments, the accuracy in elasticity measurement was evaluated using a silicone rubber tube. In in vivo experiments, the minute change in wall thickness was measured along each ultrasonic beam, and the cross-sectional image of elasticity was obtained in the short-axis plane with transcutaneous ultrasound.

Seventh Congress of the Asian Federation of Societies for Ultrasound in Medicine and Biology (AFSUMB 2004) May 17-21, 2004, Utsunomiya, Japan