Artificial control of the multistep oxidation reactions catalyzed by the cytochrome P450 enzyme RosC.

The cytochrome P450 monooxygenase RosC catalyzes the three-step oxidation reactions, which leads to the formation of a hydroxy, formyl, and carboxy group at C-20 during rosamicin biosynthesis in Micromonospora rosaria IFO13697. To determine if amino acid substitutions in RosC could allow for the control of the multistep oxidation reactions, we screened RosC random mutants. The RosC mutant RM30, with five amino acid substitutions (P107S, L176Q, S254N, V277A, and I319N), catalyzed only the first step of the oxidation reaction. Whole-cell assays using Escherichia coli cells expressing RosC mutants with single and double amino acid substitutions derived from RM30 indicated that P107S/L176Q, P107S/V277A, P107S/I319N, L176Q/V277A, L176Q/I319N, and S254N/V277A significantly reduced the catalytic activity of the second reaction, which is alcohol oxidation. Of the previously mentioned mutants, double mutants containing L176Q, which was presumed to occur in the FG loop region, lost the total catalytic activity of the third reaction (aldehyde oxidation). Additionally, an engineered M. rosaria strain with rosC disruption, which introduced the gene encoding the RosC mutants P107S/L176Q and P107S/V277A preferentially produced 20-dihydrorosamicin, which is formed after the first oxidation reaction of RosC.

Ultrasound measurement of fetal arterial pulse pressure using phased-tracking methods: A phantom study and clinical experience with antenatal corticosteroid therapy.

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.

Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction.

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 ß1-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.

Fast decomposition of two ultrasound longitudinal waves in cancellous bone using a phase rotation parameter for bone quality assessment: Simulation study.

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.

Haloperidol aggravates transverse aortic constriction-induced heart failure via mitochondrial dysfunction.

Haloperidol is an antipsychotic drug that inhibits the dopamine D2 receptor among others. Haloperidol also binds the sigma-1 receptor (σ1R) 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 σ1R. To test this, we treated neonatal rat cardiomyocytes with haloperidol, exposed them to angiotensin II and assessed hypertrophy, σ1R expression, mitochondrial Ca(2+) transport and ATP levels. In this context, haloperidol treatment altered mitochondrial Ca(2+) transport resulting in decreased ATP content by inactivating cardiac σ1R 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 σ1R inactivation or downregulation in response to haloperidol treatment impairs mitochondrial Ca(2+) mobilization, depleting ATP depletion from cardiomyocytes. These findings suggest a novel approach to mitigate haloperidol-related adverse effects in schizophrenia patients by ATP supplementation.

Assessing Fetal Cardiac Function by Measuring Myocardial Radial Velocity Using the Phased-Tracking Method.

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.

Stimulation of σ1-receptor restores abnormal mitochondrial Ca²âº mobilization and ATP production following cardiac hypertrophy.

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 (0.1-1µM) in cultured cardiomyocytes exposed to angiotensin II (Ang II). Then, to confirm the ameliorative effects of σ1R stimulation in vivo, we administered SA4503 (1.0mg/kg) and the σ1R antagonist NE-100 (1.0mg/kg) orally to TAC mice for 4weeks (once daily). RESULTS: σ1R stimulation with SA4503 significantly inhibited Ang II-induced cardiomyocyte hypertrophy. Ang II exposure for 72h impaired phenylephrine (PE)-induced Ca(2+) mobilization from the SR into both the cytosol and mitochondria. Treatment of cardiomyocytes with SA4503 largely restored PE-induced Ca(2+) mobilization into mitochondria. Exposure of cardiomyocytes to Ang II for 72h 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.

Expanding aliasing limit in measurement of tissue velocity using autocorrelation method.

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.

Estimation error in speed of sound caused by rotation of measured cross-section from short-axis plane of blood vessels: a preliminary study.

PURPOSE: Estimating the speed of sound (SoS) in ultrasound propagation media is important for improving the quality of B-mode images and for quantitative tissue characterization. We have been studying a method for estimating the SoS by measuring the reception time distribution of waves scattered from a scatterer at the elements in a probe. Previously, the measurement cross section was assumed to be perpendicular to the long axis of the blood vessel. In this study, we experimentally investigated the relationship between rotation angle [Formula: see text] of the probe relative to the short-axis plane of the blood vessel and the estimated SoS, [Formula: see text]. METHODS: Water tank and phantom experiments were conducted to investigate the characteristics of [Formula: see text] and element signals when the probe was rotated. RESULTS: The received signal powers at the elements around both edges greatly decreased as [Formula: see text] increased. We introduced a parameter representing the decrease in power, [Formula: see text], in the received signal at the elements at both edges relative to the center element. [Formula: see text] was estimated to be larger as [Formula: see text] increased, especially for [Formula: see text]. [Formula: see text] also increased as [Formula: see text] increased. An approximately proportional relationship existed between the errors in [Formula: see text] and [Formula: see text]. CONCLUSION: Based on these results, we can distinguish between the presence and the absence of SoS misestimations using the difference in power among the elements in the received signal. In the absence of misestimation, we can obtain the true SoS, even if the target has a non-negligible size, by applying our previously proposed methods.

A novel ultrasonic method for measuring minute sinusoidal displacement by network analyzer.

We developed a method for generating continuous sinusoidal displacements of an object to estimate viscoelastic parameters. However, the amplitude of the displacement caused by the ultrasonic excitation force under safe guidelines was small (a few micrometers), and it was difficult to stably measure the displacement. Therefore, to stably measure the amplitude of sinusoidal displacement as small as the order of micrometers, we proposed a novel method using a network analyzer. Ultrasonic waves were irradiated using an ultrasonic transducer on an object vibrating sinusoidally. The S parameter of the first reflected wave received from the surface of the object was measured using a network analyzer. The S parameter and the inverse Fourier transform were formulated theoretically, and the amplitude of the sinusoidal displacement of the object was estimated from the amplitude characteristics of the inverse Fourier-transformed signal. The proposed method was applied to measure sinusoidal displacements on the order of micrometers from 10 to 300 Hz on an object using a water tank experiment. The obtained sinusoidal displacement agreed well with the reference values measured using a laser displacement meter. The proposed method can accurately measure minute sinusoidal displacements that occur on an object.

Optimal treatment conditions for low-intensity pulsed ultrasound therapy for Alzheimer's disease: applications from mice to humans.

PURPOSE: We previously developed a novel therapy with low-intensity pulsed ultrasound (LIPUS) that ameliorates cognitive decline through upregulation of endothelial nitric oxide synthase (eNOS) in mouse models of Alzheimer's disease (AD). In a randomized, double-blind, placebo-controlled pilot trial, we demonstrated that whole-brain LIPUS therapy is safe and tends to suppress the cognitive decline in early AD patients. We herein report the findings of our basic experiments that we performed for the pilot trial in order to apply whole-brain LIPUS therapy to humans, as well. METHODS: First, we examined the relationship between bone density/thickness and ultrasound transmittance using human temporal bone. Next, based on the results of ultrasound transmittance, we further examined mRNA expression of VEGF, FGF2, and eNOS in response to variable ultrasound frequencies, duty cycles, and sound pressures. RESULTS: There was a significant correlation between bone thickness and transmittance (1.0 MHz, P < 0.001), while there was no significant correlation between bone density and transmittance (1.0 MHz, P = 0.421). At a frequency of 0.5 MHz, the optimum duty cycle was considered to be up to 20%. When the tissue amplitude was in the range of 0.05-0.5 MPa, VEGF, FGF2, and eNOS were significantly upregulated by LIPUS. Thus, the conditions necessary for LIPUS therapy for the human brain were identified as sound pressure just below the probe 1.3 MPa (tissue amplitude 0.15 MPa), duty cycle 5%, and frequency 0.5 MHz. CONCLUSION: We successfully identified the optimal treatment conditions for LIPUS therapy for patients with AD.

Influence of Power-Weighted Center of Echo Signal Within Window Function on Local Strain Rate Distribution in Left Ventricular Wall.

OBJECTIVE: The deviation of the power-weighted center of the echo signal from the geometric center within the velocity estimation window for calculating strain rate (SR) causes an estimation error. This study aimed to confirm whether an erroneous multilayer pattern in the SR distribution of the left ventricular wall could be corrected by considering the power-weighted center of the echo signal. METHODS: The SR distributions were measured locally in the transmural direction around the pre-ejection and early diastolic phases in healthy volunteers. The estimation error related to the power-weighted center of the echo signal was corrected using a previously proposed method, and the effectiveness of the correction was confirmed based on the accuracy of the estimated myocardial displacement. RESULTS: The SR distribution in early diastole was observed as multilayers of low- and high-amplitude negative SRs. However, this multilayer pattern disappeared after correction. In the pre-ejection phase, multilayers of positive and negative SRs were observed in the SR distributions with and without correction. This correction was sufficiently effective in accurately tracking the local peak of the echo signal. CONCLUSION: The multilayer pattern of low- and high-amplitude positive or negative SRs is caused by estimation errors related to the power-weighted center of the echo signal. The multilayer pattern of positive and negative SRs might not be caused by these errors and might relate to the actual change in myocardial thickness because the estimation errors do not convert the negative (positive) SR to positive (negative) in a homogeneous negative (positive) SR distribution.

Optimizing irradiation conditions for low-intensity pulsed ultrasound to upregulate endothelial nitric oxide synthase.

PURPOSE: Here we aimed to develop a minimally invasive treatment for ischemic heart disease and demonstrate that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia by promoting myocardial angiogenesis in a porcine model of chronic myocardial ischemia. Studies to date determined the optimal treatment conditions within the range of settings available with existing ultrasound equipment and did not investigate a wider range of conditions. METHODS: We investigated a broad range of five parameters associated with ultrasound irradiation conditions that promote expression of endothelial nitric oxide synthase (eNOS), a key molecule that promotes angiogenesis in human coronary artery endothelial cells (HCAEC). RESULTS: Suboptimal irradiation conditions included 1-MHz ultrasound frequency, 500-kPa sound pressure, 20-min total irradiation time, 32-48-[Formula: see text] pulse duration, and 320-[Formula: see text] pulse repetition time. Furthermore, a proposed index, [Formula: see text], calculated as the product of power and the total number of irradiation cycles applied to cells using LIPUS, uniformly revealed the experimental eNOS expression associated with the various values of five parameters under different irradiation conditions. CONCLUSION: We determined the suboptimal ultrasound irradiation conditions for promoting eNOS expression in HCAEC.

Measurement of regional pulse wave velocity using very high frame rate ultrasound.

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).

Lateral M-Mode: Ultrasound Visualization of Displacement Along Longitudinal Direction at Intima-Media Complex.

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.

Speed-of-sound estimation in ultrasound propagation medium by considering size of target scatterer.

PURPOSE: Accurate speed-of-sound (SoS) estimation in an ultrasound propagation medium improves imaging quality and contributes to better diagnosis of diseases. In conventional time-delay-based SoS estimation approaches studied by several groups, a received wave is assumed to be scattered from an ideal point scatterer. In these approaches, the SoS is overestimated when the target scatterer has a non-negligible size. In this paper, we propose the SoS estimation method that considers target size. METHODS: In the proposed method, the error ratio of the estimated SoS using the conventional time-delay-based approach is determined from measurable parameters using the geometric relationship between the received elements and target. Subsequently, the SoS erroneously estimated using conventional estimation, assuming the ideal point scatterer as a target, is corrected by the determined estimation error ratio. To validate the proposed method, the SoS in water was estimated for several wire sizes. RESULTS: The SoS in the water was overestimated using the conventional SoS estimation method, with a maximum positive error of 38 m/s. The proposed method corrected the SoS estimates, and the errors were suppressed to within 6 m/s, irrespective of the wire diameter. CONCLUSION: The present results demonstrate that the proposed method can estimate the SoS by considering the target size without using information on the true SoS, true target depth, and true target size, which is applicable to in vivo measurements.

Beneficial Effects of Low-Intensity Pulsed Ultrasound Therapy on Right Ventricular Dysfunction in Animal Models.

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.

A randomized, double-blind, placebo-controlled pilot trial of low-intensity pulsed ultrasound therapy for refractory angina pectoris.

BACKGROUND: Despite the advances in the treatment of cardiovascular diseases, effective treatment remains to be established to improve the quality of life and prognosis of patients with chronic coronary syndromes. This study was aimed to evaluate the effectiveness and safety of the low-intensity pulsed ultrasound (LIPUS) therapy, which we have developed as a novel non-invasive angiogenic therapy through upregulation of endothelial nitric oxide synthase (eNOS). METHODS AND FINDINGS: We conducted a randomized, double-blind, placebo-controlled (RCT) pilot trial of the LIPUS therapy for patients with refractory angina pectoris. The patients who received optimal medical therapy without indication of PCI or CABG due to the lack of graftability or complexity of coronary lesions were enrolled. They were randomly divided into the LIPUS treatment group (N = 31) and the placebo group (N = 25) in a 1:1 fashion. The LIPUS therapy was performed in a transthoracic manner for 20 min for 3 sections each (mitral, papillary muscle, and apex levels) under the conditions that we identified; frequency 1.875 MHz, intensity 0.25 MPa, and 32 cycles. The primary endpoint was weekly use of nitroglycerin. Secondary endpoints included stress myocardial perfusion imaging and others. The average weekly nitroglycerin use (times/week) was decreased from 5.50 to 2.44 in the LIPUS group and from 5.94 to 2.83 in the placebo group. The changes in the average weekly nitroglycerin use were comparable; -3.06 (95% CI: -4.481 to -1.648) in the LIPUS group (P<0.01) and -3.10 (95% CI: -4.848 to -1.356) in the placebo group (P<0.01). No adverse effects were noted. CONCLUSIONS: In the present study, the LIPUS therapy did not further ameliorate chest pain as compared with optimal medications alone in patients with refractory angina pectoris. The present findings need to be confirmed in another trial with a large number of patients. (Registration ID: UMIN000012369).

Appropriate Window Function and Window Length in Multifrequency Velocity Estimator for Rapid Motion and Locality of Layered Myocardium.

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.

Application of low-complexity generalized coherence factor to in vivo data.

PURPOSE: Beamforming using the generalized coherence factor (GCF) reduces sidelobe artifacts and provides an excellent contrast-to-noise ratio. We previously proposed GCFreal, a method to calculate GCF without generating analytic signals, and GCFbin, a method to calculate GCF by binarizing the received signals. In this study, we applied these methods to in vivo data and showed the effect of the computational complexity reduction on contrast performance. METHODS: Channel RF data were acquired from the human liver and gallbladder. We set up several observation points in each data set and investigated the mechanism that causes the differences in contrast performance among the methods based on the signals and their power spectra in the channel direction. RESULTS: For GCF and GCFreal, the obtained values were almost the same. However, there were large differences in GCFbin from GCF when the signals from the focus point or from outside the focus point were received on different channels. This is because the amplitudes of the signals with high coherence and those with low coherence were changed by binarizing the signals. CONCLUSION: While GCFbin can significantly reduce the computational complexity, there are differences in the values of GCFbin and GCF due to binarizing of the received signals. However, this difference resulted in GCFbin being superior to GCF in terms of artifact reduction. This is owing to the elimination of amplitude information in GCFbin, which makes it a new efficient coherence factor with different characteristics from GCF.