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-frequency noncontact low-intensity pulsed ultrasound modulates Ca2+-dependent transcription factors contributing to cell migration.

Chronic wounds have negative physical and psychological effects on patients and increase the health care burden. Consequently, chronic wound in the elderly population is an important issue. Ultrasound can be a great modality for treating chronic wounds because of its noninvasive and safety characteristics; it can accelerate in vitro and in vivo wound healing. In this study, we developed a novel noncontact ultrasound for wound treatment. We stimulated human epidermal keratinocyte migration using low-intensity pulsed ultrasound (LIPUS) with a noncontact transducer to avoid direct contact with the wound. We also compared the effects of 15-min contact and noncontact transducer stimulation, where a 1-MHz contact transducer (intensity = 40 or 200 mW/cm2) and a 0.45-MHz noncontact transducer (intensity = 30 mW/cm2) were used. Both contact and noncontact LIPUS considerably increased cell migration and activated the calcium (Ca2+)-dependent transcription factors cAMP-responsive element-binding protein (CREB) and nuclear factor of activated T cells (NFAT). Furthermore, noncontact transducer stimulation did not cause cell death or affect cell proliferation but significantly increased the Ca2+ influx-mediated intracellular Ca2+ levels. Ca2+-free medium and Ca2+ channel blockers effectively inhibited LIPUS-induced Ca2+-dependent transcription factor activation and cell migration.

Improving Image Quality for Single-Angle Plane Wave Ultrasound Imaging With Convolutional Neural Network Beamformer.

Ultrafast ultrasound imaging based on plane wave (PW) compounding has been proposed for use in various clinical and preclinical applications, including shear wave imaging and super resolution blood flow imaging. Because the image quality afforded by PW imaging is highly dependent on the number of PW angles used for compounding, a tradeoff between image quality and frame rate occurs. In the present study, a convolutional neural network (CNN) beamformer based on a combination of the GoogLeNet and U-Net architectures was developed to replace the conventional delay-and-sum (DAS) algorithm to obtain high-quality images at a high frame rate. RF channel data are used as the inputs for the CNN beamformers. The outputs are in-phase and quadrature data. Simulations and phantom experiments revealed that the images predicted by the CNN beamformers had higher resolution and contrast than those predicted by conventional single-angle PW imaging with the DAS approach. In in vivo studies, the contrast-to-noise ratios (CNRs) of carotid artery images predicted by the CNN beamformers using three or five PWs as ground truths were approximately 12 dB in the transverse view, considerably higher than the CNR obtained using the DAS beamformer (3.9 dB). Most tissue speckle information was retained in the in vivo images produced by the CNN beamformers. In conclusion, only a single PW at 0° was fired, but the quality of the output image was proximal to that of an image generated using three or five PW angles. In other words, the quality-frame rate tradeoff of coherence compounding could be mitigated through the use of the proposed CNN for beamforming.

Automatic Detection of Atherosclerotic Plaque and Calcification From Intravascular Ultrasound Images by Using Deep Convolutional Neural Networks.

Atherosclerosis is the major cause of cardiovascular diseases (CVDs). Intravascular ultrasound (IVUS) is a common imaging modality for diagnosing CVDs. However, an efficient analyzer for IVUS image segmentation is required for assisting cardiologists. In this study, an end-to-end deep-learning convolutional neural network was developed for automatically detecting media-adventitia borders, luminal regions, and calcified plaque in IVUS images. A total of 713 grayscale IVUS images from 18 patients were used as training data for the proposed deep-learning model. The model is constructed using the three modified U-Nets and combined with the concept of cascaded networks to prevent errors in the detection of calcification owing to the interference of pixels outside the plaque regions. Three loss functions (Dice, Tversky, and focal loss) with various characteristics were tested to determine the best setting for the proposed model. The efficacy of the deep-learning model was evaluated by analyzing precision-recall curve. The average precision (AP), Dice score coefficient, precision, sensitivity, and specificity of the predicted and ground truth results were then compared. All training processes were validated using leave-one-subject-out cross-validation. The experimental results showed that the proposed deep-learning model exhibits high performance in segmenting the media-adventitia layers and luminal regions for all loss functions, with all tested metrics being higher than 0.90. For locating calcified tissues, the best result was obtained when the focal loss function was applied to the proposed model, with an AP of 0.73; however, the prediction efficacy was affected by the proportion of calcified tissues within the plaque region when the focal loss function was employed. Compared with commercial software, the proposed method exhibited high accuracy in segmenting IVUS images in some special cases, such as when shadow artifacts or side vessels surrounded the target vessel.

Gap-filling method for suppressing grating lobes in ultrasound imaging: Experimental study with deep-learning approach.

Sparse arrays reduce the number of active channels that effectively increases the inter-element spacing. Large inter-element spacing results in grating lobe artifacts degrading the ultrasound image quality and reducing the contrast-to-noise ratio. A deep learning-based custom algorithm is proposed to estimate inactive channel data in periodic sparse arrays. The algorithm uses data from multiple active channels to estimate inactive channels. The estimated inactive channel data effectively reduces the inter-element spacing for beamforming, thus suppressing the grating lobes. Estimated inactive element channel data was combined with active element channel data resulting in a pseudo fully sampled array. The channel data was beamformed using a simple delay-and-sum method and compared with the sparse array and fully sampled array. The performance of the algorithm was validated using a wire target in a water tank, multi-purpose tissue-mimicking phantom, and in-vivo carotid data. Grating lobes suppression up to 15.25 dB was observed with an increase in contrast-to-noise (CNR) for the pseudo fully sampled array. Hypoechoic regions showed more improvement in CNR than hyperechoic regions. Root-mean-square error for unwrapped phase between fully sampled array and the pseudo fully sampled array was low, making the estimated data suitable for Doppler and elastography applications. Speckle pattern was also preserved; thus, the estimated data can also be used for quantitative ultrasound applications. The algorithm can improve the quality of sparse array images and has applications in small scale ultrasound devices and 2D arrays.

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.

Implementation of a Wearable Ultrasound Device for the Overnight Monitoring of Tongue Base Deformation during Obstructive Sleep Apnea Events.

Obstructive sleep apnea (OSA) is a breathing disorder characterized by the repeated collapse of the pharyngeal airway during sleep. Previous studies have reported that tongue base deformation may be a major contributing factor. However, overnight monitoring of tongue motion in patients with OSA has previously been impracticable. We developed a wearable ultrasound device for prolonged recording during natural sleep of the changes in tongue base thickness (TBT) in patients with OSA. The maximum TBT was fed into a polysomnography system so that physiologic signals and TBT data were simultaneously monitored. Subject trials revealed that TBT increased significantly during snoring, hypopnea and apnea events during natural sleep in patients with OSA. Moreover, the data revealed that the location of the maximum TBT during normal breathing was significantly different compared with the location during obstructive respiratory events, which implies a posterior or inferior displacement of the tongue base during sleep apnea.

40 MHz high-frequency ultrafast ultrasound imaging.

PURPOSE: Ultrafast high-frame-rate ultrasound imaging based on coherent-plane-wave compounding has been developed for many biomedical applications. Most coherent-plane-wave compounding systems typically operate at 3-15 MHz, and the image resolution for this frequency range is not sufficient for visualizing microstructure tissues. Therefore, the purpose of this study was to implement a high-frequency ultrafast ultrasound imaging operating at 40 MHz. METHODS: The plane-wave compounding imaging and conventional multifocus B-mode imaging were performed using the Field II toolbox of MATLAB in simulation study. In experiments, plane-wave compounding images were obtained from a 256 channel ultrasound research platform with a 40 MHz array transducer. All images were produced by point-spread functions and cyst phantoms. The in vivo experiment was performed from zebrafish. Since high-frequency ultrasound exhibits a lower penetration, chirp excitation was applied to increase the imaging depth in simulation. RESULTS: The simulation results showed that a lateral resolution of up to 66.93 µm and a contrast of up to 56.41 dB were achieved when using 75-angles plane waves in compounding imaging. The experimental results showed that a lateral resolution of up to 74.83 µm and a contrast of up to 44.62 dB were achieved when using 75-angles plane waves in compounding imaging. The dead zone and compounding noise are about 1.2 mm and 2.0 mm in depth for experimental compounding imaging, respectively. The structure of zebrafish heart was observed clearly using plane-wave compounding imaging. CONCLUSIONS: The use of fewer than 23 angles for compounding allowed a frame rate higher than 1000 frames per second. However, the compounding imaging exhibits a similar lateral resolution of about 72 µm as the angle of plane wave is higher than 10 angles. This study shows the highest operational frequency for ultrafast high-frame-rate ultrasound imaging.

The effect of flow acceleration on the cyclic variation of blood echogenicity under pulsatile flow.

It has been shown that the echogenicity of blood varies during a flow cycle under pulsatile flow both in vitro and in vivo. In general, the echogenicity of flowing whole blood increases during the early systole phase and then reduces to a minimum at late diastole. While it has been postulated that this cyclic variation is associated with the dynamics of erythrocyte aggregation, the mechanisms underlying this increasing echogenicity with flow velocity remain uncertain. The effect of flow acceleration has also been proposed as an explanation for this phenomenon, but no specific experiments have been conducted to test this hypothesis. In addition, the influence of ultrasonic attenuation on the cyclic variation of echogenicity requires clarification. In the present study, a Couette flow system was designed to simulate blood flowing with different acceleration patterns, and the flow velocity, attenuation, and backscattering coefficient were measured synchronously from 20%- and 40%-hematocrit porcine whole blood and erythrocyte suspensions using 35-MHz ultrasound transducers. The results showed ultrasonic attenuation exerted only minor effects on the echogenicity of blood under pulsatile flow conditions. Cyclic variations of echogenicity were clearly observed for whole blood with a hematocrit of 40%, but no variations were apparent for erythrocyte suspensions. The echogenicity did not appear to be enhanced when instantaneous acceleration was applied to flowing blood in any case. These findings show that flow acceleration does not promote erythrocyte aggregation, even when a higher peak velocity is applied to the blood. Comparison of the results obtained with different accelerations revealed that the cyclic variation in echogenicity observed during pulsatile blood flow may be jointly attributable to the effect of shear rate and the distribution of erythrocyte on aggregation.

A study of the adult zebrafish ventricular function by retrospective Doppler-gated ultrahigh-frame-rate echocardiography.

The zebrafish (Danio rerio) has become a preferred animal model for studying various human diseases, particularly those related to cardiovascular regeneration; therefore, a noninvasive imaging modality is needed for observing the cardiac function of zebrafish. Because of its high resolution, high-frequency ultrasound B-mode imaging has recently been used successfully to observe the heart of adult zebrafish. However, ultrahigh-frame-rate echocardiography combining Bmode imaging and color flow imaging is still needed to observe the detailed transient motions of the zebrafish ventricle. This study develops an 80-MHz ultrahigh-frame-rate echocardiography system for this purpose, based on retrospective Doppler- gated technology. B-mode and color flow images of the cardiovascular system of the zebrafish were reconstructed by two-dimensional autocorrelation at maximum frame rates of up to 40,000 and 400 fps, respectively. The timings of end diastole (E(D)) and end systole (E(S)) of ventricle can be determined by using this high-resolution image system. Two ventricular function parameters-fractional shortening (FS) and fractional area change (FAC)-were measured for evaluating the ventricular function by using E(D) and E(S) with their corresponding ventricular dimensions. The experimental results indicated that the measured FS values were 42 ± 4% (mean ± standard deviation) and 60 ± 13% for the long axis and short axis of the ventricle, respectively, and that FAC was 77 ± 9%. This is the first report of these ventricular function parameters for a normal adult zebrafish. The results showed that retrospective high-frequency echocardiography is a useful tool for studying the cardiac function of normal adult zebrafish.

Design and implementation of a smartphone-based portable ultrasound pulsed-wave Doppler device for blood flow measurement.

Blood flow measurement using Doppler ultrasound has become a useful tool for diagnosing cardiovascular diseases and as a physiological monitor. Recently, pocket-sized ultrasound scanners have been introduced for portable diagnosis. The present paper reports the implementation of a portable ultrasound pulsed-wave (PW) Doppler flowmeter using a smartphone. A 10-MHz ultrasonic surface transducer was designed for the dynamic monitoring of blood flow velocity. The directional baseband Doppler shift signals were obtained using a portable analog circuit system. After hardware processing, the Doppler signals were fed directly to a smartphone for Doppler spectrogram analysis and display in real time. To the best of our knowledge, this is the first report of the use of this system for medical ultrasound Doppler signal processing. A Couette flow phantom, consisting of two parallel disks with a 2-mm gap, was used to evaluate and calibrate the device. Doppler spectrograms of porcine blood flow were measured using this stand-alone portable device under the pulsatile condition. Subsequently, in vivo portable system verification was performed by measuring the arterial blood flow of a rat and comparing the results with the measurement from a commercial ultrasound duplex scanner. All of the results demonstrated the potential for using a smartphone as a novel embedded system for portable medical ultrasound applications.

Assessing the viscoelastic properties of thrombus using a solid-sphere-based instantaneous force approach.

The viscoelastic properties of thrombus play a significant role when the clot closes a leak in a vessel of the blood circulation. The common method used to measure the viscoelastic properties of a clot employs a rheometer but this might be unsuitable due to the clot fiber network being broken up by excessive deformation. This study assessed the feasibility of using a novel acoustic method to assess the viscoelastic properties of blood clots. This method is based on monitoring the motion of a solid sphere in a blood clot induced by an applied instantaneous force. Experiments were performed in which a solid sphere was displaced by a 1 MHz single-element focused transducer, with a 20 MHz single-element focused transducer used to track this displacement. The spatiotemporal behavior of the sphere displacement was used to determine the viscoelastic properties of the clot. The experimental system was calibrated by measuring the viscoelastic modulus of gelatin using different types of solid spheres embedded in the phantoms and, then, the shear modulus and viscosity of porcine blood clots with hematocrits of 0% (plasma), 20% and 40% were assessed. The viscoelastic modulus of each clot sample was also measured directly by a rheometer for comparison. The results showed that the shear modulus increased from 173 ± 52 (mean ± SD) Pa for 40%-hematocrit blood clots to 619.5 ± 80.5 Pa for plasma blood clots, while the viscosity decreased from 0.32 ± 0.07 Pa∙s to 0.16 ± 0.06 Pa∙s, respectively, which indicated that the concentration of red blood cells and the amount of fibrinogen are the main determinants of the clot viscoelastic properties.