Detecting heart failure from B-mode ultrasound characterization of arterial pulse waves.

This study investigated the sensitivity and specificity of identifying heart failure with reduced ejection fraction (HFrEF) from measurements of the intensity and timing of arterial pulse waves. Previously validated methods combining ultrafast B-mode ultrasound, plane-wave transmission, singular value decomposition (SVD), and speckle tracking were used to characterize the compression and decompression ("S" and "D") waves occurring in early and late systole, respectively, in the carotid arteries of outpatients with left ventricular ejection fraction (LVEF) < 40%, determined by echocardiography, and signs and symptoms of heart failure, or with LVEF ≥ 50% and no signs or symptoms of heart failure. On average, the HFrEF group had significantly reduced S-wave intensity and energy, a greater interval between the R wave of the ECG and the S wave, a reduced interval between the S and D waves, and an increase in the S-wave shift (SWS), a novel metric that characterizes the shift in timing of the S wave away from the R wave of the ECG and toward the D wave (all P < 0.01). Receiver operating characteristics (ROCs) were used to quantify for the first time how well wave metrics classified individual participants. S-wave intensity and energy gave areas under the ROC of 0.76-0.83, the ECG-S-wave interval gave 0.85-0.88, and the S-wave shift gave 0.88-0.92. Hence the methods, which are simple to use and do not require complex interpretation, provide sensitive and specific identification of HFrEF. If similar results were obtained in primary care, they could form the basis of techniques for heart failure screening.NEW & NOTEWORTHY We show that heart failure with reduced ejection fraction can be detected with excellent sensitivity and specificity in individual patients by using B-mode ultrasound to detect altered pulse wave intensity and timing in the carotid artery.

Capillary-Scale Hydrogel Microchannel Networks by Wire Templating.

Microvascular networks are essential for the efficient transport of nutrients, waste products, and drugs throughout the body. Wire-templating is an accessible method for generating laboratory models of these blood vessel networks, but it has difficulty fabricating microchannels with diameters of ten microns and narrower, a requirement for modeling human capillaries. This study describes a suite of surface modification techniques to  selectively control the interactions amongst wires, hydrogels, and world-to-chip interfaces. This wire templating method enables the fabrication of perfusable hydrogel-based rounded cross-section capillary-scale networks whose diameters controllably narrow at bifurcations down to 6.1 ± 0.3 microns in diameter. Due to its low cost, accessibility, and compatibility with a wide range of common hydrogels of tunable stiffnesses such as collagen, this technique may increase the fidelity of experimental models of capillary networks for the study of human health and disease.

Super-Resolution Ultrasound Localization Microscopy of Microvascular Structure and Flow for Distinguishing Metastatic Lymph Nodes - An Initial Human Study.

PURPOSE: Detecting and distinguishing metastatic lymph nodes (LNs) from those with benign lymphadenopathy are crucial for cancer diagnosis and prognosis but remain a clinical challenge. A recent advance in super-resolution ultrasound (SRUS) through localizing individual microbubbles has broken the diffraction limit and tracking enabled in vivo noninvasive imaging of vascular morphology and flow dynamics at a microscopic level. In this study we hypothesize that SRUS enables quantitative markers to distinguish metastatic LNs from benign ones in patients with lymphadenopathy. MATERIALS AND METHODS: Clinical contrast-enhanced ultrasound image sequences of LNs from 6 patients with lymph node metastasis and 4 with benign lymphadenopathy were acquired and motion-corrected. These were then used to generate super-resolution microvascular images and super-resolved velocity maps. From these SRUS images, morphological and functional measures were obtained including micro-vessel density, fractal dimension, mean flow speed, and Local Flow Direction Irregularity (LFDI) measuring the variance in local flow direction. These measures were compared between pathologically proven reactive and metastasis LNs. RESULTS: Our initial results indicate that the difference in the indicator of flow irregularity (LFDI) derived from the SRUS images is statistically significant between the two groups. The LFDI is 60% higher in metastatic LNs compared with reactive nodes. CONCLUSION: This pilot study demonstrates the feasibility of super-resolution ultrasound for clinical imaging of lymph nodes and the potential of using the irregularity of local blood flow directions afforded by SRUS for the characterization of LNs.

3D Super-Resolution US Imaging of Rabbit Lymph Node Vasculature in Vivo by Using Microbubbles.

Background Variations in lymph node (LN) microcirculation can be indicative of metastasis. The identification and quantification of metastatic LNs remains essential for prognosis and treatment planning, but a reliable noninvasive imaging technique is lacking. Three-dimensional super-resolution (SR) US has shown potential to noninvasively visualize microvascular networks in vivo. Purpose To study the feasibility of three-dimensional SR US imaging of rabbit LN microvascular structure and blood flow by using microbubbles. Materials and Methods In vivo studies were carried out to image popliteal LNs of two healthy male New Zealand white rabbits aged 6-8 weeks. Three-dimensional, high-frame-rate, contrast material-enhanced US was achieved by mechanically scanning with a linear imaging probe. Individual microbubbles were identified, localized, and tracked to form three-dimensional SR images and super-resolved velocity maps. Acoustic subaperture processing was used to improve image contrast and to generate enhanced power Doppler and color Doppler images. Vessel size and blood flow velocity distributions were evaluated and assessed by using Student paired t test. Results SR images revealed microvessels in the rabbit LN, with branches clearly resolved when separated by 30 µm, which is less than half of the acoustic wavelength and not resolvable by using power or color Doppler. The apparent size distribution of most vessels in the SR images was below 80 µm and agrees with micro-CT data, whereas most of those detected with Doppler techniques were larger than 80 µm in the images. The blood flow velocity distribution indicated that most of the blood flow in rabbit popliteal LN was at velocities lower than 5 mm/sec. Conclusion Three-dimensional super-resolution US imaging using microbubbles allows noninvasive nonionizing visualization and quantification of lymph node microvascular structures and blood flow dynamics with resolution below the wave diffraction limit. This technology has potential for studying the physiologic functions of the lymph system and for clinical detection of lymph node metastasis. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Power Doppler Quantification in Assessing Gestational Trophoblastic Neoplasia.

PURPOSE: The FIGO score cannot accurately stratify low-risk gestational trophoblastic neoplasia (GTN) patients who develop chemoresistance to single agent methotrexate chemotherapy. Tumour vascularisation is a key risk factor and its quantification may provide non-invasive way of complementing risk assessment. MATERIALS AND METHODS: 187 FIGO-staged, low-risk GTN patients were prospectively recruited. Power Doppler ultrasound was analysed using a quantification program. Four diagnostic indicators were obtained comprising the number of colour pixels (NCP), mean dB, power Doppler quantification (PDQ), and percentage of colour pixels (%CP). Each indicator performance was assessed to determine if they could distinguish the subset of low-risk patients who became chemoresistant. RESULTS: There were 111 non-resistant and 76 resistant patients. NCP performed best at distinguishing these two groups where the non-resistant group had an average 3435 (±â€Š2060) pixels and the resistant group 6151 (±â€Š3192) pixels (p < 0.001). PDQ and %CP showed significant differences (p < 0.001) but had poorer performance (area under ROC curves were 72 % and 67 % respectively compared with 75 % for NCP). The mean dB index was not significantly different (p = 0.133). CONCLUSION: Power Doppler ultrasound quantification shows potential for non-invasive assessment of tumour vascularity and can distinguish low-risk GTN patients who become chemoresistant from those who have an uncomplicated course with first line treatment.

Mapping microbubble viscosity using fluorescence lifetime imaging of molecular rotors.

Encapsulated microbubbles are well established as highly effective contrast agents for ultrasound imaging. There remain, however, some significant challenges to fully realize the potential of microbubbles in advanced applications such as perfusion mapping, targeted drug delivery, and gene therapy. A key requirement is accurate characterization of the viscoelastic surface properties of the microbubbles, but methods for independent, nondestructive quantification and mapping of these properties are currently lacking. We present here a strategy for performing these measurements that uses a small fluorophore termed a "molecular rotor" embedded in the microbubble surface, whose fluorescence lifetime is directly related to the viscosity of its surroundings. We apply fluorescence lifetime imaging to show that shell viscosities vary widely across the population of the microbubbles and are influenced by the shell composition and the manufacturing process. We also demonstrate that heterogeneous viscosity distributions exist within individual microbubble shells even with a single surfactant component.

Rapid short-pulse sequences enhance the spatiotemporal uniformity of acoustically driven microbubble activity during flow conditions.

Despite the promise of microbubble-mediated focused ultrasound therapies, in vivo findings have revealed over-treated and under-treated regions distributed throughout the focal volume. This poor distribution cannot be improved by conventional pulse shapes and sequences, due to their limited ability to control acoustic cavitation dynamics within the ultrasonic focus. This paper describes the design of a rapid short-pulse (RaSP) sequence which is comprised of short pulses separated by µs off-time intervals. Improved acoustic cavitation distribution was based on the hypothesis that microbubbles can freely move during the pulse off-times. Flowing SonoVue® microbubbles (flow velocity: 10 mm/s) were sonicated with a 0.5 MHz focused ultrasound transducer using RaSP sequences (peak-rarefactional pressures: 146-900 kPa, pulse repetition frequency: 1.25 kHz, and pulse lengths: 5-50 cycles). The distribution of cavitation activity was evaluated using passive acoustic mapping. RaSP sequences generated uniform distributions within the focus in contrast to long pulses (50 000 cycles) that produced non-uniform distributions. Fast microbubble destruction occurred for long pulses, whereas microbubble activity was sustained for longer durations for shorter pulses. High-speed microscopy revealed increased mobility in the direction of flow during RaSP sonication. In conclusion, RaSP sequences produced spatiotemporally uniform cavitation distributions and could result in efficient therapies by spreading cavitation throughout the treatment area.

Tracking shear waves in turbid medium by light: theory, simulation, and experiment.

Shear wave propagation provides rich information for material mechanical characterization, including elasticity and viscosity. This Letter reports tracking of shear wave propagation in turbid media by laser-speckle-contrast analysis. The theory is described, and a Monte Carlo simulation of light shear wave interaction was developed. Simulation and experiments on tissue-mimicking phantoms agree well and show tracking of shear wave at the phantom surface and at depth as well as multiple shear waves interacting within the object. The relationship between speckle contrast value and shear wave amplitude is also investigated.

Understanding the effects of microbubble concentration on localization accuracy in super-resolution ultrasound imaging.

Super-resolution ultrasound (SRUS) through localising and tracking of microbubbles (MBs) can achieve sub-wavelength resolution for imaging microvascular structure and flow dynamics in deep tissuein vivo. The technique assumes that signals from individual MBs can be isolated and localised accurately, but this assumption starts to break down when the MB concentration increases and the signals from neighbouring MBs start to interfere. The aim of this study is to gain understanding of the effect of MB-MB distance on ultrasound images and their localisation. Ultrasound images of two MBs approaching each other were synthesised by simulating both ultrasound field propagation and nonlinear MB dynamics. Besides the distance between MBs, a range of other influencing factors including MB size, ultrasound frequency, transmit pulse sequence, pulse amplitude and localisation methods were studied. The results show that as two MBs approach each other, the interference fringes can lead to significant and oscillating localisation errors, which are affected by both the MB and imaging parameters. When modelling a clinical linear array probe operating at 6 MHz, localisation errors between 20 and 30µm (∼1/10 wavelength) can be generated when MBs are ∼500µm (2 wavelengths or ∼1.7 times the point spread function (PSF)) away from each other. When modelling a cardiac probe operating at 1.5 MHz, the localisation errors were as high as 200µm (∼1/5 wavelength) even when the MBs were more than 10 wavelengths apart (2.9 times the PSF). For both frequencies, at smaller separation distances, the two MBs were misinterpreted as one MB located in between the two true positions. Cross-correlation or Gaussian fitting methods were found to generate slightly smaller localisation errors than centroiding. In conclusion, caution should be taken when generating and interpreting SRUS images obtained using high agent concentration with MBs separated by less than 1.7 to 3 times the PSF, as significant localisation errors can be generated due to interference between neighbouring MBs.

ULM-MbCNRT: In vivo Ultrafast Ultrasound Localization Microscopy by Combining Multi-branch CNN and Recursive Transformer.

Ultrasound localization microscopy (ULM) overcomes the acoustic diffraction limit by localizing tiny microbubbles (MBs), thus enabling the microvascular to be rendered at sub-wavelength resolution. Nevertheless, to obtain such superior spatial resolution, it is necessary to spend tens of seconds gathering numerous ultrasound (US) frames to accumulate MB events required, resulting in ULM imaging still suffering from trade-offs between imaging quality, data acquisition time and data processing speed. In this paper, we present a new deep learning (DL) framework combining multi-branch CNN and recursive Transformer, termed as ULM-MbCNRT, that is capable of reconstructing a super-resolution image directly from a temporal mean low-resolution image generated by averaging much fewer raw US frames, i.e., implement an ultrafast ULM imaging. To evaluate the performance of ULM-MbCNRT, a series of numerical simulations and in vivo experiments are carried out. Numerical simulation results indicate that ULM-MbCNRT achieves high-quality ULM imaging with ~10-fold reduction in data acquisition time and ~130-fold reduction in computation time compared to the previous DL method (e.g., the modified sub-pixel convolutional neural network, ULM-mSPCN). For the in vivo experiments, when comparing to the ULM-mSPCN, ULM-MbCNRT allows ~37-fold reduction in data acquisition time (~0.8 s) and ~2134-fold reduction in computation time (~0.87 s) without sacrificing spatial resolution. It implies that ultrafast ULM imaging holds promise for observing rapid biological activity in vivo, potentially improving the diagnosis and monitoring of clinical conditions.

Broad Elevation Projection Super-Resolution Ultrasound (BEP-SRUS) Imaging With a 1-D Unfocused Linear Array.

Super-resolution ultrasound (SRUS) through localizing spatially isolated microbubbles (MBs) has been demonstrated to overcome the wave diffraction limit and reveal the microvascular structure and flow information at the microscopic scale. However, 3-D SRUS imaging remains a challenge due to the fabrication and computational complexity of 2-D matrix array probes. Inspired by X-ray radiography which can present information within a volume in a single projection image with much simpler hardware than X-ray computerized tomography (CT), this study investigates the feasibility of broad elevation projection super-resolution (BEP-SR) ultrasound using a 1-D unfocused linear array. Both simulation and in vitro experiments were conducted on 3-D microvessel phantoms. In vivo demonstration was done on the Rabbit kidney. Data from a 1-D linear array with and without an elevational focus were synthesized by summing up row signals acquired from a 2-D matrix array with and without delays. A full 3-D reconstruction was also generated as the reference, using the same data of the 2-D matrix array but without summing row signals. Results show that using an unfocused 1-D array probe, BEP-SR can capture significantly more information within a volume in both vascular structure and flow velocity than the conventional 1-D elevational-focused probe. Compared with the 2-D projection image of the full 3-D SRUS results using the 2-D array probe with the same aperture size, the 2-D projection SRUS image of BEP-SR has similar volume coverage, using 32 folds fewer independent elements. This study demonstrates BEP-SR's ability of high-resolution imaging of microvascular structures and flow velocity within a 3-D volume at significantly reduced costs. The proposed BEP method could significantly benefit the clinical translation of the SRUS imaging technique by making it more affordable and repeatable.

Frequency-Domain Robust PCA for Real-Time Monitoring of HIFU Treatment.

High intensity focused ultrasound (HIFU) is a thriving non-invasive technique for thermal ablation of tumors, but significant challenges remain in its real-time monitoring with medical imaging. Ultrasound imaging is one of the main imaging modalities for monitoring HIFU surgery in organs other than the brain, mainly due to its good temporal resolution. However, strong acoustic interference from HIFU irradiation severely obscures the B-mode images and compromises the monitoring. To address this problem, we proposed a frequency-domain robust principal component analysis (FRPCA) method to separate the HIFU interference from the contaminated B-mode images. Ex-vivo and in-vivo experiments were conducted to validate the proposed method based on a clinical HIFU therapy system combined with an ultrasound imaging platform. The performance of the FRPCA method was compared with the conventional notch filtering method. Results demonstrated that the FRPCA method can effectively remove HIFU interference from the B-mode images, which allowed HIFU-induced grayscale changes at the focal region to be recovered. Compared to notch-filtered images, the FRPCA-processed images showed an 8.9% improvement in terms of the structural similarity (SSIM) index to the uncontaminated B-mode images. These findings demonstrate that the FRPCA method presents an effective signal processing framework to remove the strong HIFU acoustic interference, obtains better dynamic visualization in monitoring the HIFU irradiation process, and offers great potential to improve the efficacy and safety of HIFU treatment and other focused ultrasound related applications.

High Performance Wearable Ultrasound as a Human-Machine Interface for Wrist and Hand Kinematic Tracking.

OBJECTIVE: Non-invasive human machine interfaces (HMIs) have high potential in medical, entertainment, and industrial applications. Traditionally, surface electromyography (sEMG) has been used to track muscular activity and infer motor intention. Ultrasound (US) has received increasing attention as an alternative to sEMG-based HMIs. Here, we developed a portable US armband system with 24 channels and a multiple receiver approach, and compared it with existing sEMG- and US-based HMIs on movement intention decoding. METHODS: US and motion capture data was recorded while participants performed wrist and hand movements of four degrees of freedom (DoFs) and their combinations. A linear regression model was used to offline predict hand kinematics from the US (or sEMG, for comparison) features. The method was further validated in real-time for a 3-DoF target reaching task. RESULTS: In the offline analysis, the wearable US system achieved an average [Formula: see text] of 0.94 in the prediction of four DoFs of the wrist and hand while sEMG reached a performance of [Formula: see text]= 0.60. In online control, the participants achieved an average 93% completion rate of the targets. CONCLUSION: When tailored for HMIs, the proposed US A-mode system and processing pipeline can successfully regress hand kinematics both in offline and online settings with performances comparable or superior to previously published interfaces. SIGNIFICANCE: Wearable US technology may provide a new generation of HMIs that use muscular deformation to estimate limb movements. The wearable US system allowed for robust proportional and simultaneous control over multiple DoFs in both offline and online settings.

Ultrafast 3-D Transcutaneous Super Resolution Ultrasound Using Row-Column Array Specific Coherence-Based Beamforming and Rolling Acoustic Sub-aperture Processing: In Vitro, in Rabbit and in Human Study.

OBJECTIVE: This study aimed to realise 3-D super-resolution ultrasound imaging transcutaneously with a row-column array which has far fewer independent electronic channels and a wider field of view than typical fully addressed 2-D matrix arrays. The in vivo image quality of the row-column array is generally poor, particularly when imaging non-invasively. This study aimed to develop a suite of image formation and post-processing methods to improve image quality and demonstrate the feasibility of ultrasound localisation microscopy using a row-column array, transcutaneously on a rabbit model and in a human. METHODS: To achieve this, a processing pipeline was developed which included a new type of rolling window image reconstruction, which integrated a row-column array specific coherence-based beamforming technique with acoustic sub-aperture processing. This and other processing steps reduced the 'secondary' lobe artefacts, and noise and increased the effective frame rate, thereby enabling ultrasound localisation images to be produced. RESULTS: Using an in vitro cross tube, it was found that the procedure reduced the percentage of 'false' locations from ∼26% to ∼15% compared to orthogonal plane wave compounding. Additionally, it was found that the noise could be reduced by ∼7 dB and the effective frame rate was increased to over 4000 fps. In vivo, ultrasound localisation microscopy was used to produce images non-invasively of a rabbit kidney and a human thyroid. CONCLUSION: It has been demonstrated that the proposed methods using a row-column array can produce large field of view super-resolution microvascular images in vivo and in a human non-invasively.

3D Acoustic Wave Sparsely Activated Localization Microscopy With Phase Change Contrast Agents.

OBJECTIVE: The aim of this study is to demonstrate 3-dimensional (3D) acoustic wave sparsely activated localization microscopy (AWSALM) of microvascular flow in vivo using phase change contrast agents (PCCAs). MATERIALS AND METHODS: Three-dimensional AWSALM using acoustically activable PCCAs was evaluated on a crossed tube microflow phantom, the kidney of New Zealand White rabbits, and the brain of C57BL/6J mice through intact skull. A mixture of C 3 F 8 and C 4 F 10 low-boiling-point fluorocarbon gas was used to generate PCCAs with an appropriate activation pressure. A multiplexed 8-MHz matrix array connected to a 256-channel ultrasound research platform was used for transmitting activation and imaging ultrasound pulses and recording echoes. The in vitro and in vivo echo data were subsequently beamformed and processed using a set of customized algorithms for generating 3D super-resolution ultrasound images through localizing and tracking activated contrast agents. RESULTS: With 3D AWSALM, the acoustic activation of PCCAs can be controlled both spatially and temporally, enabling contrast on demand and capable of revealing 3D microvascular connectivity. The spatial resolution of the 3D AWSALM images measured using Fourier shell correlation is 64 µm, presenting a 9-time improvement compared with the point spread function and 1.5 times compared with half the wavelength. Compared with the microbubble-based approach, more signals were localized in the microvasculature at similar concentrations while retaining sparsity and longer tracks in larger vessels. Transcranial imaging was demonstrated as a proof of principle of PCCA activation in the mouse brain with 3D AWSALM. CONCLUSIONS: Three-dimensional AWSALM generates volumetric ultrasound super-resolution microvascular images in vivo with spatiotemporal selectivity and enhanced microvascular penetration.

Transthoracic ultrasound localization microscopy of myocardial vasculature in patients.

Myocardial microvasculature and haemodynamics are indicative of potential microvascular diseases for patients with symptoms of coronary heart disease in the absence of obstructive coronary arteries. However, imaging microvascular structure and flow within the myocardium is challenging owing to the small size of the vessels and the constant movement of the patient's heart. Here we show the feasibility of transthoracic ultrasound localization microscopy for imaging myocardial microvasculature and haemodynamics in explanted pig hearts and in patients in vivo. Through a customized data-acquisition and processing pipeline with a cardiac phased-array probe, we leveraged motion correction and tracking to reconstruct the dynamics of microcirculation. For four patients, two of whom had impaired myocardial function, we obtained super-resolution images of myocardial vascular structure and flow using data acquired within a breath hold. Myocardial ultrasound localization microscopy may facilitate the understanding of myocardial microcirculation and the management of patients with cardiac microvascular diseases.

ULTRA-SR Challenge: Assessment of Ultrasound Localization and TRacking Algorithms for Super-Resolution Imaging.

With the widespread interest and uptake of super-resolution ultrasound (SRUS) through localization and tracking of microbubbles, also known as ultrasound localization microscopy (ULM), many localization and tracking algorithms have been developed. ULM can image many centimeters into tissue in-vivo and track microvascular flow non-invasively with sub-diffraction resolution. In a significant community effort, we organized a challenge, Ultrasound Localization and TRacking Algorithms for Super-Resolution (ULTRA-SR). The aims of this paper are threefold: to describe the challenge organization, data generation, and winning algorithms; to present the metrics and methods for evaluating challenge entrants; and to report results and findings of the evaluation. Realistic ultrasound datasets containing microvascular flow for different clinical ultrasound frequencies were simulated, using vascular flow physics, acoustic field simulation and nonlinear bubble dynamics simulation. Based on these datasets, 38 submissions from 24 research groups were evaluated against ground truth using an evaluation framework with six metrics, three for localization and three for tracking. In-vivo mouse brain and human lymph node data were also provided, and performance assessed by an expert panel. Winning algorithms are described and discussed. The publicly available data with ground truth and the defined metrics for both localization and tracking present a valuable resource for researchers to benchmark algorithms and software, identify optimized methods/software for their data, and provide insight into the current limits of the field. In conclusion, Ultra-SR challenge has provided benchmarking data and tools as well as direct comparison and insights for a number of the state-of-the art localization and tracking algorithms.

Tailored photoacoustic apertures with superimposed optical holograms.

A new method of generating potentially arbitrary photoacoustic wavefronts with optical holograms is presented. This method uses nanosecond laser pulses at 1064 nm that are split into four time-delayed components by means of a configurable multipass optical delay apparatus, which serves to map the pulses onto phase-delayed regions of a given acoustic wavefront. A single spatial light modulator generates separate holograms for each component, which are imaged onto a photoacoustic transducer comprised of a thermoelastic polymer. As a proof of concept of the broader arbitrary wavefront construction technique, the spatially- and temporally-modulated holograms in this study produce a phased array effect that enables beam steering of the resulting acoustic pulse. For a first experimental demonstration of the method, as verified by simulation, the acoustic beam is steered in four directions by around 5 degrees.

Non-invasive Assessment by B-Mode Ultrasound of Arterial Pulse Wave Intensity and Its Reduction During Ventricular Dysfunction.

Arterial pulse waves contain clinically useful information about cardiac performance, arterial stiffness and vessel tone. Here we describe a novel method for non-invasively assessing wave properties, based on measuring changes in blood flow velocity and arterial wall diameter during the cardiac cycle. Velocity and diameter were determined by tracking speckles in successive B-mode images acquired with an ultrafast scanner and plane-wave transmission. Blood speckle was separated from tissue by singular value decomposition and processed to correct biases in ultrasound imaging velocimetry. Results obtained in the rabbit aorta were compared with a conventional analysis based on blood velocity and pressure, employing measurements obtained with a clinical intra-arterial catheter system. This system had a poorer frequency response and greater lags but the pattern of net forward-traveling and backward-traveling waves was consistent between the two methods. Errors in wave speed were also similar in magnitude, and comparable reductions in wave intensity and delays in wave arrival were detected during ventricular dysfunction. The non-invasive method was applied to the carotid artery of a healthy human participant and gave a wave speed and patterns of wave intensity consistent with earlier measurements. The new system may have clinical utility in screening for heart failure.

Acceleration-Based Kalman Tracking for Super-Resolution Ultrasound Imaging In Vivo.

Super-resolution ultrasound (SRUS) can image microvascular structure and flow at subwave-diffraction resolution based on localizing and tracking microbubbles (MBs). Currently, tracking MBs accurately under limited imaging frame rates and high MB concentrations remains a challenge, especially under the effect of cardiac pulsatility and in highly curved vessels. In this study, an acceleration-incorporated MB motion model is introduced into a Kalman tracking framework. The tracking performance was evaluated using simulated microvasculature with different MB motion parameters, concentrations, and acquisition frame rates, and in vivo human breast tumor US datasets. The simulation results show that the acceleration-based method outperformed the nonacceleration-based method at different levels of acceleration and acquisition frame rates and achieved significant improvement in true positive rate (TPR; up to 11.3%) and false negative rate (FNR; up to 13.2%). The proposed method can also reduce errors in vasculature reconstruction via the acceleration-based nonlinear interpolation, compared with linear interpolation (up to [Formula: see text]). The tracking results from temporally downsampled low frame rate in vivo datasets from human breast tumors show that the proposed method has better MB tracking performance than the baseline method, if using results from the initial high frame data as a reference. Finally, the acceleration estimated from tracking results also provides a spatial speed gradient map that may contain extra valuable diagnostic information.