Increasing the Maximum Detectable Flow Velocity in High-Frequency Ultrasound Vector Doppler Imaging.

High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler imaging (VDI) has certain advantages for visualizing complex flow patterns independent of the Doppler angle. However, no commercial HFUS VDI system is currently available; therefore, several studies have connected an ultrasound research platform (Verasonics Vantage 256) with an HFUS array transducer for HFUS VDI. Unfortunately, the maximum frame rate of this system is only 10 kHz at an operational frequency of 40 MHz because of limitations related to data transmission hardware, thereby restricting the maximum detectable velocity of Doppler measurements. To address this drawback, in the present study, an electrocardiography (ECG)-gating-based HFUS VDI system was developed to avoid Doppler flow aliasing in data acquisition by ultrasound research platform at its maximum frame rate of 10 kHz. The developed method aligns all tilted plane waves with the ECG R-wave, which avoids the trade-off between frame rate and tilted angles number in conventional VDI. The performance of the proposed data acquisition method in HFUS VDI was verified using a steady-flow phantom, for which estimation errors were less than 10% under different flow settings. In animal studies, peak flow velocities in the carotid artery, left ventricle, and aortic arch of wild-type mice were measured (approximately 55, 655, and 765 mm/s, respectively). Also, the HFUS VDI from the mitral regurgitation mice model was obtained to present the complex flow patterns through the proposed method. In contrast to the conventional method, no Doppler aliasing occurs in the proposed method because the frame rate is sufficient. The experimental results indicate the developed HFUS VDI has the potential to become a useful tool for vector flow visualization in small animals, even under a high flow velocity.

High-Spatiotemporal-Resolution Ultrasound Flow Imaging to Determine Cerebrovascular Hemodynamics in Alzheimer's Disease Mice Model.

Although the relationships of cerebrovascular hemodynamic dysfunction with neurodegenerative diseases remain unclear, many studies have indicated that poor cerebral perfusion accelerates the progression of neurodegenerative diseases, such as Alzheimer's disease (AD). Small animal models are widely used in AD research. However, providing an imaging modality with a high spatiotemporal resolution and sufficiently large field of view to assess cerebrovascular hemodynamics in vivo remains a challenge. The present study proposes a novel technique for high-spatiotemporal-resolution vector micro-Doppler imaging (HVµDI) based on contrast-free ultrafast high frequency ultrasound imaging to visualize the cerebrovascular hemodynamics of the mouse, with a data acquisition time of 0.4 s, a minimal detectable vessel size of 38 µm, and a temporal resolution of 500 Hz. In vivo experiments are conducted on wild-type and AD mice. Cerebrovascular hemodynamics are quantified using the cerebral vascular density, diameter, velocity, tortuosity, cortical flow pulsatility, and instant flow direction variations. Results reveal that AD significantly change the cerebrovascular hemodynamics. HVµDI offers new opportunities for in vivo analysis of cerebrovascular hemodynamics in neurodegenerative pathologies in preclinical animal research.

Visualization of Pulse-Wave Velocity on Arterial Wall of Mice Through High-Frequency Ultrafast Doppler Imaging.

Arterial pulse-wave velocity (PWV) is widely used in clinical applications to assess cardiovascular diseases. Ultrasound methods have been proposed for estimating regional PWV in human arteries. Furthermore, high-frequency ultrasound (HFUS) has been applied to perform preclinical small-animal PWV measurements; however, electrocardiogram (ECG)-gated retrospective imaging is required to achieve high-frame-rate imaging, which might be affected by arrhythmia-related problems. In this article, HFUS PWV mapping based on 40-MHz ultrafast HFUS imaging is proposed to visualize PWV on mouse carotid artery to measure arterial stiffness without ECG gating. In contrast to most other studies that used cross-correlation methods to detect arterial motion, ultrafast Doppler imaging was applied in this study to measure arterial wall velocity for PWV estimations. The performance of the proposed HFUS PWV mapping method was verified using a polyvinyl alcohol (PVA) phantom with various freeze-thaw cycles. Small-animal studies were then performed in wild-type (WT) mice and in apolipoprotein E knockout (ApoE KO) mice that were fed a high-fat diet (for 16 and 24 weeks). The Young's modulus of the PVA phantom measured through HFUS PWV mapping was 15.3 ± 0.81, 20.8 ± 0.32, and 32.2 ± 1.11 kPa for three, four, and five freeze-thaw cycles, respectively, and the corresponding measurement biases (relative to theoretical values) were 1.59%, 6.41%, and 5.73%, respectively. In the mouse study, the average PWVs were 2.0 ± 0.26, 3.3 ± 0.45, and 4.1 ± 0.22 m/s for 16-week WT, 16-week ApoE KO, and 24-week ApoE KO mice, respectively. The PWVs of ApoE KO mice increased during the high-fat diet feeding period. HFUS PWV mapping was used to visualize the regional stiffness of mouse artery, and a histology confirmed that the plaque formation in the bifurcation region increased the regional PWV. All the results indicate that the proposed HFUS PWV mapping method is a convenient tool for investigating arterial properties in preclinical small-animal studies.

Measurement of local pulse wave velocity for carotid artery by using an ultrasound-based method.

Currently, pulse wave velocity (PWV) is an important physical index for characterizing the mechanical properties of arteries. Carotid-femoral PWV (cfPWV) is a clinically-approved parameter for evaluating the cardiovascular risk and therapeutic efficacy. However, cfPWV only provides global information about vessel properties. Many recent studies have indicated that local PWV measurements provide precise evaluation of artery conditions. Here, an ultrasound (US) method based on a novel vessel displacement waveform correction, is proposed for improving the accuracy of local carotid PWV measurement. A programmable US device and a commercial array transducer were used, which allow a user to excite transducer and receive US signals arbitrarily with different beam settings. The local PWV measurement accuracy was verified using a phantom. The number of US beams used for PWV measurements was also considered, which indicates that eight elements is the acceptable setting. Subsequently, local carotid PWV and cfPWV were measured in 35 healthy human subjects (age: 21.9 ± 2.4 years) by using the US method and SphygmoCor device, respectively. The cfPWV and local carotid PWV were 6.65 ± 0.74 and 4.63 ± 0.57 m/s, respectively. A good linear correlation was observed between the two aforementioned methods (r = 0.8) for the subjects. All the results indicated that when few US beams were used, the proposed method exhibited a reliable measurement of local PWV.