Chengwu Huang

Ultrasound-Based Carotid Elastography for Detection of Vulnerable Atherosclerotic Plaques Validated by Magnetic Resonance Imaging

Ultrasound-based carotid elastography has been developed to estimate the mechanical properties of atherosclerotic plaques. The objective of this study was to evaluate the in vivo capability of carotid elastography in vulnerable plaque detection using high-resolution magnetic resonance imaging as reference. Ultrasound radiofrequency data of 46 carotid plaques from 29 patients (74 ± 5 y old) were acquired and inter-frame axial strain was estimated with an optical flow method. The maximum value of absolute strain rate for each plaque was derived as an indicator for plaque classification. Magnetic resonance imaging of carotid arteries was performed on the same patients to classify the plaques into stable and vulnerable groups for carotid elastography validation. The maximum value of absolute strain rate was found to be significantly higher in vulnerable plaques (2.15 ± 0.79 s(-1), n = 27) than in stable plaques (1.21 ± 0.37 s(-1), n = 19) (p < 0.0001). Receiver operating characteristic curve analysis was performed, and the area under the curve was 0.848. Therefore, the in vivo capability of carotid elastography to detect vulnerable plaques, validated by magnetic resonance imaging, was proven, revealing the potential of carotid elastography as an important tool in atherosclerosis assessment and stroke prevention.

Effects of parameters on the accuracy and precision of ultrasound-based local pulse wave velocity measurement: a simulation study

Quantification of arterial stiffness, such as pulse wave velocity (PWV), is increasingly used in the risk assessment of cardiovascular disease. Pulse wave imaging (PWI) is an emerging ultrasound-based technique to noninvasively measure the local PWV instead of the global PWV, as in conventional methods. In PWI, several key parameters, including the frame rate of ultrasound imaging, motion estimation rate (MER), number of scan lines, image width, PWV value, and sonographic signal-to-noise ratio (SNRs), play an important but still unclear role in the accuracy and precision of PWV measurement. In this study, computer simulations were performed to investigate the fundamental effects of these parameters on the PWV measurement. The pulse waveform was estimated by speckle tracking on ultrasound RF signals acquired at a frame rate of 2083 Hz from a location on the common carotid artery of a healthy subject. By applying different time delays on the estimated waveform based on specific PWI parameters, the pulse waveforms at others locations were simulated. Ultrasound RF signals of the artery during the pulse wave propagation were generated from a 2-D convolutional image formation model. The PWI technique was applied to estimate the PWV at different values of frame rate, MER, number of scan lines, image width, PWV, and SNRs. The performance of the PWV estimation was evaluated by measuring the relative error, coefficient of variation (CV) and coefficient of determination (R2). The results showed that PWVs could be correctly measured when the frame rate was higher than a certain value (i.e., minimum frame rate), below which the estimated error increased rapidly. The minimum frame rate required for PWV estimation was found to increase with the value of PWV. An optimal MER was found (i.e., about 200 Hz) and allowed better performance of PWV measurement. The CV of PWV estimation decreased and R2 increased with number of scan lines and image width, indicating that the performance of the PWV estimation could be improved with a larger number of scan lines and image width. For a given sufficiently high frame rate, a higher PWV value was found to deteriorate the PWV estimation, as indicated by an increasing CV and decreasing R2. The simulation results were in good agreement with the theoretical analysis. Finally, high-quality PWV estimation could be obtained as long as the SNRs was higher than about 30 dB. The quantitative effects of the key parameters obtained from this study might provide important guidelines for parameter optimization in ultrasound-based local PWV measurement in vivo.

Comparison of Different Pulse Waveforms for Local Pulse Wave Velocity Measurement in Healthy and Hypertensive Common Carotid Arteries in Vivo.

Pulse wave velocity (PWV), a measurement of arterial stiffness, can be estimated locally by determining the time delay of the pulse waveforms for a known distance as measured in an ultrasound image. Our aim was to compare three ultrasound-based methods for estimation of local PWV based on the measurement of diameter distension waveforms, displacement waveforms of the anterior wall and displacement waveforms of the posterior wall, respectively, in human common carotid arteries in vivo. The local PWVs at both systolic foot (PWVsf) and dicrotic notch (PWVdn) were estimated from ultrasound radiofrequency data of 25 healthy and 24 hypertensive patients for each method. PWV estimation using the distension waveform method was found to have the highest precision in both groups. Both PWVsf and PWVdn were significantly higher in the hypertensive group compared with the healthy group using the distension waveform method (PWVsf: 6.08 ± 1.70 m/s vs. 4.75 ± 0.92 m/s, p = 0.000014; PWVdn: 7.83 ± 2.26 m/s vs. 5.21 ± 0.95 m/s, p < 0.000001), whereas there was no significant difference at a significance level of 0.01 between the two groups when the anterior or posterior wall waveform method was used. Thus, the difference in arterial stiffness between the two groups could be discriminated well by the distension waveform method. The local PWV estimated using distension waveforms might be a promising index for arterial stiffness characterization and hypertension management.

High frame rate and high line density ultrasound imaging for local pulse wave velocity estimation using motion matching: A feasibility study on vessel phantoms

Pulse wave imaging (PWI) is an ultrasound-based method to visualize the propagation of pulse wave and to quantitatively estimate regional pulse wave velocity (PWV) of the arteries within the imaging field of view (FOV). To guarantee the reliability of PWV measurement, high frame rate imaging is required, which can be achieved by reducing the line density of ultrasound imaging or transmitting plane wave at the expense of spatial resolution and/or signal-to-noise ratio (SNR). In this study, a composite, full-view imaging method using motion matching was proposed with both high temporal and spatial resolution. Ultrasound radiofrequency (RF) data of 4 sub-sectors, each with 34 beams, including a common beam, were acquired successively to achieve a frame rate of ∼507 Hz at an imaging depth of 35 mm. The acceleration profiles of the vessel wall estimated from the common beam were used to reconstruct the full-view (38-mm width, 128-beam) image sequence. The feasibility of mapping local PWV variation along the artery using PWI technique was preliminarily validated on both homogeneous and inhomogeneous polyvinyl alcohol (PVA) cryogel vessel phantoms. Regional PWVs for the three homogeneous phantoms measured by the proposed method were in accordance with the sparse imaging method (38-mm width, 32-beam) and plane wave imaging method. Local PWV was estimated using the above-mentioned three methods on 3 inhomogeneous phantoms, and good agreement was obtained in both the softer (1.91±0.24 m/s, 1.97±0.27 m/s and 1.78±0.28 m/s) and the stiffer region (4.17±0.46 m/s, 3.99±0.53 m/s and 4.27±0.49 m/s) of the phantoms. In addition to the improved spatial resolution, higher precision of local PWV estimation in low SNR circumstances was also obtained by the proposed method as compared with the sparse imaging method. The proposed method might be helpful in disease detections through mapping the local PWV of the vascular wall.

Noninvasive measurement of regional pulse wave velocity in human ascending aorta with ultrasound imaging: an in-vivo feasibility study.

Objectives: Accurate and noninvasive techniques for measurement of local/regional pulse wave velocity (PWV), instead of global PWV, is desired for quantifying localized arterial stiffness and improving cardiovascular disease assessment. This study aimed at investigating the feasibility of regional PWV measurement in human ascending aorta in vivo using an ultrasound-based technique. Methods: Proximal ascending aortas of 76 healthy patients (23–71 years) were scanned with transthoracic echocardiography in parasternal long-axis view, and ultrasound radiofrequency data were acquired in a high temporal resolution (∼404 Hz). The PWV was derived from the determination of arrival times and identification of travel distances. Both PWVs in early systolic phase (PWVsf; pulse wave velocity measured using the systolic foot as characteristic time point) and late systolic phase (PWVdn; pulse wave velocity measured using the dicrotic notch as characteristic time point) were obtained. Results: The PWVsf and PWVdn were 4.58 ± 1.38 and 6.51 ± 1.90 m/s, respectively, and both were correlated with age (r = 0.30, P = 0.02 and r = 0.71, P < 0.0001). The measurements were reproducible, and PWVdn showed significant correlation with aortic diameter (r = 0.53, P < 0.0001), relative distension (r = −0.44, P = 0.0002), and local PWV derived from Bramwell–Hill equation (r = 35, P = 0.004). The PWV difference (PWVdn − PWVsf) reflected aortic stiffness change within cardiac cycle from early systole to late systole and was also correlated with age (r = 0.50, P < 0.0001). Conclusion: The feasibility of ascending aortic PWV measurement using ultrasound imaging was illustrated in vivo, suggesting the potential of the technique in characterization of regional aortic stiffness and assessment of aortic diseases.

Effects of key parameters on the accuracy and precision of local pulse wave velocity measurement by ultrasound imaging.

Quantification of arterial stiffness, such as pulse wave velocity (PWV), is increasingly used in the risk assessment of cardiovascular disease. Pulse wave imaging (PWI) is an emerging ultrasound-based technique to noninvasively measure the local PWV, instead of the global PWV as in conventional methods. In PWI, several key parameters, including the frame rate, number of scan lines, image width and PWV, play an important but still unclear role in the accuracy and precision of PWV measurement. In this study, computer simulations were performed to investigate the fundamental effects of these parameters on the PWV estimation. By applying different time delays on the pre-obtained pulse waveform based on specific PWI parameters, the pulse wave propagation along the artery was simulated and the ultrasound RF signals were generated from a convolutional image formation model. The PWI technique was applied to calculate the PWV at different values of key parameters. The performance is evaluated by measuring the bias, standard deviation (SD) and coefficient of determination (R2) of the estimated PWVs. The results show that PWVs can be correctly measured when the frame rate is higher than a certain value, below which the estimated PWVs become inaccurate. The SD decreases while R2 increases with number of scan lines and image width, indicating a better performance of the PWV estimation with a larger number of scan lines and image width. A higher value of PWV is found to deteriorate the PWV estimation. The quantitative effects of the key parameters obtained from this study may provide important guidelines for optimization of PWI parameters in vivo.

A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli

The use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Although many approaches have been reported to improve the maturation of hiPSC-CMs, the elucidation of the process of maturation is crucial. We applied a small-molecule-based differentiation method to generate cardiomyocytes (CMs) with multiple aggregation forms. The motion analysis revealed significant physical differences in the differently shaped CMs, and the net-shaped CMs had larger motion amplitudes and faster velocities than the sheet-shaped CMs. The net-shaped CMs displayed accelerated maturation at the transcriptional level and were more similar to CMs with a prolonged culture time (30 days) than to sheet-d15. Ion channel genes and gap junction proteins were up-regulated in net-shaped CMs, indicating that robust contraction was coupled with enhanced ion channel and connexin expression. The net-shaped CMs also displayed improved myofibril ultrastructure under transmission electron microscopy. In conclusion, different multicellular hPSC-CM structures, such as the net-shaped pattern, are formed using the conditioned induction method, providing a useful tool to improve cardiac maturation.

A Systematic Investigation of Lateral Estimation Using Various Interpolation Approaches in Conventional Ultrasound Imaging

Accurate lateral displacement and strain estimation is critical for some applications of elasticity imaging. Typically, motion estimation in the lateral direction is challenging because of low sampling frequency and lack of phase information in conventional ultrasound imaging. Several approaches have been proposed to improve the performance of lateral estimation, such as lateral interpolation on the radio frequency (RF) signals (Interp_RF), lateral interpolation on the cross-correlation function (Interp_CCF), and lateral interpolation on both the RF signals and cross-correlation function (Interp_Both). In this paper, the estimation performances of the above-mentioned three approaches are compared systematically in simulations and phantom experiments. In the simulations, the root-mean-square error (RMSE) of axial/lateral displacement and strain is utilized to assess the accuracy of motion estimation. In the phantom experiments, the displacement quality metric (DQM), defined as the normalized cross-correlation between the motion-compensated reference frame and the comparison frame, and the contrast-to-noise ratio (CNR) of axial/lateral strain are used as the evaluation criteria. The results show that the three approaches have similar performance in axial estimation. For lateral estimation, if the line density of ultrasound imaging is relatively high (i.e., >4.2 lines/mm), Interp_CCF is comparable to Interp_Both, and Interp_RF performs the worst. However, if the line density is relatively low (i.e., <2.8 lines/mm), Interp_Both performs the best as indicated by the lowest RMSEs or highest DQMs and CNRs in lateral estimation. The trend is consistent at different window sizes, applied strains, and sonographic signal-to-noise ratios (>20 dB). Besides, Interp_Both with a small interpolation factor (e.g., 3–5) is found to obtain the best tradeoff between the estimation accuracy and the computational cost, and thus is suggested for lateral motion estimation in the case of a low line density (i.e., <2.8 lines/mm).

Suppression of reflected waves with high-resolution Radon transform for accurate measurement of regional pulse wave velocity

Pulse wave velocity (PWV) is a reliable index of arterial stiffness. To date, reflected pulse wave interference is still a major challenge for regional PWV estimation using ultrasound imaging methods. In this study, a high-resolution Radon transform (HRT) method is proposed to eliminate the reflected wave interferences in PWV estimation.

Pulse wave velocity measurement in healthy and diseased carotid arteries in vivo

Pulse wave velocity (PWV), a measurement of arterial stiffness, is predictive of cardiovascular diseases and all-cause mortality. By determining the time-delay of pulse waveforms for a known distance measured in the ultrasound image, local PWV can be calculated. The aim of this study was to evaluate PWV estimation in both healthy and diseased common carotid arteries (CCAs) in vivo. Arterial wall displacements were estimated using speckle tracking on ultrasound radiofrequency (RF) data acquired from 26 young subjects (26 ± 4 yo) and 51 aged subjects (57 ± 7 yo). PWVs were estimated separately using diameter distension waveforms (distension PWV), displacement waveforms of anterior (near) wall (anterior PWV) and posterior (far) wall (posterior PWV) at both systolic foot (PWVsf) and dicrotic notch (PWVdn). According to the results, higher precision of PWV estimation was achieved using distension waveforms than using displacement waveforms of anterior or posterior wall. Both distension PWVsf and PWVdn were significantly higher in the aged subjects compared with the young subjects (p <; 0.0001), and correlated significantly with relative distension of the CCAs (r = -0.27, p = 0.002 and r = -0.62, p <; 0.00001, respectively), indicating the feasibility of the PWV estimation using arterial distension waveforms. In contrast, no significant difference of anterior or posterior PWVs was found between the two groups (all p > 0.01). The aged arteries were further divided into two groups based on the presence or absence of atherosclerotic plaques in the carotid arteries, and distension PWVdn was found to be significantly higher in arteries with visible plaques (8.94 ± 2.25 m/s) than that in plaque-free arteries (7.35 ± 1.99 m/s, p = 0.003). The preliminary results indicate that carotid PWV estimation using distension waveforms may be a valuable index for assessment of cardiovascular diseases.