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.

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.

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.

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.

Fast 3D Super-Resolution Ultrasound With Adaptive Weight-Based Beamforming.

OBJECTIVE: Super-resolution ultrasound (SRUS) imaging through localising and tracking sparse microbubbles has been shown to reveal microvascular structure and flow beyond the wave diffraction limit. Most SRUS studies use standard delay and sum (DAS) beamforming, where high side lobes and broad main lobes make isolation and localisation of densely distributed bubbles challenging, particularly in 3D due to the typically small aperture of matrix array probes. METHOD: This study aimed to improve 3D SRUS by implementing a new fast 3D coherence beamformer based on channel signal variance. Two additional fast coherence beamformers, that have been implemented in 2D were implemented in 3D for the first time as comparison: a nonlinear beamformer with p-th root compression and a coherence factor beamformer. The 3D coherence beamformers, together with DAS, were compared in computer simulation, on a microflow phantom and in vivo. RESULTS: Simulation results demonstrated that all three adaptive weight-based beamformers can narrow the main lobe, suppress the side lobes, while maintaining the weaker scatter signals. Improved 3D SRUS images of microflow phantom and a rabbit kidney within a 3-second acquisition were obtained using the adaptive weight-based beamformers, when compared with DAS. CONCLUSION: The adaptive weight-based 3D beamformers can improve the SRUS and the proposed variance-based beamformer performs best in simulations and experiments. SIGNIFICANCE: Fast 3D SRUS would significantly enhance the potential utility of this emerging imaging modality in a broad range of biomedical applications.

Fast and Selective Super-Resolution Ultrasound In Vivo With Acoustically Activated Nanodroplets.

Perfusion by the microcirculation is key to the development, maintenance and pathology of tissue. Its measurement with high spatiotemporal resolution is consequently valuable but remains a challenge in deep tissue. Ultrasound Localization Microscopy (ULM) provides very high spatiotemporal resolution but the use of microbubbles requires low contrast agent concentrations, a long acquisition time, and gives little control over the spatial and temporal distribution of the microbubbles. The present study is the first to demonstrate Acoustic Wave Sparsely-Activated Localization Microscopy (AWSALM) and fast-AWSALM for in vivo super-resolution ultrasound imaging, offering contrast on demand and vascular selectivity. Three different formulations of acoustically activatable contrast agents were used. We demonstrate their use with ultrasound mechanical indices well within recommended safety limits to enable fast on-demand sparse activation and destruction at very high agent concentrations. We produce super-localization maps of the rabbit renal vasculature with acquisition times between 5.5 s and 0.25 s, and a 4-fold improvement in spatial resolution. We present the unique selectivity of AWSALM in visualizing specific vascular branches and downstream microvasculature, and we show super-localized kidney structures in systole (0.25 s) and diastole (0.25 s) with fast-AWSALM outperforming microbubble based ULM. In conclusion, we demonstrate the feasibility of fast and selective imaging of microvascular dynamics in vivo with subwavelength resolution using ultrasound and acoustically activatable nanodroplet contrast agents.

Design and Construction of a Low-Frequency Ultrasound Acquisition Device for 2-D Brain Imaging Using Full-Waveform Inversion.

The main techniques used to image the brain and obtain structural data are magnetic resonance imaging and X-ray computed tomography. These techniques produce images with high spatial resolution, but with the disadvantage of requiring very large equipment with special installation needs. In addition, X-ray tomography uses ionizing radiation, which limits their use. Ultrasound imaging is a safe technology that is delivered using compact and mobile devices. However, conventional ultrasound reconstruction techniques have failed to obtain images of the brain because of, fundamentally, the presence of the skull and the distortion that it produces on ultrasound. Recent studies have indicated that full-waveform inversion, a computational technique originally from Earth science, has the potential to generate accurate 3-D images of the brain. This technology can overcome the limitations of conventional ultrasound imaging, but a prototype for transcranial applications does not yet exist. Here, we investigate different designs of an annular array of ultrasound transducers to optimize the number of elements and rotations needed to conduct transcranial imaging with full-waveform inversion. This device uses small-diameter, low-frequency transducers that readily propagate ultrasound through the skull with good signal-to-noise ratios. It also incorporates the use of rotations to produce a high-density coverage of the target and acquire redundant traces that are beneficial for full-waveform inversion. We have built a ring of 40 transducers to illustrate that this design is capable of reconstructing images of the brain, retrieving its anatomy and acoustic properties with millimeter resolution. Laboratory results reveal the ability of this device to successfully image a 2.5-D brain- and skull-mimicking phantom using full-waveform inversion. To our knowledge, this is the first prototype ever used for transcranial-like imaging. The importance of these findings and their implications for the design of a 3-D reconstruction system with possible clinical applications are discussed.

Ultrafast 3-D Ultrasound Imaging Using Row-Column Array-Specific Frame-Multiply-and-Sum Beamforming.

Row-column arrays have been shown to be able to generate 3-D ultrafast ultrasound images with an order of magnitude less independent electronic channels than traditional 2-D matrix arrays. Unfortunately, row-column array images suffer from major imaging artifacts due to high sidelobes, particularly when operating at high frame rates. This article proposes a row-column-specific beamforming technique, for orthogonal plane-wave transmissions, row-column-specific frame multiply and sum (RC-FMAS), that exploits the incoherent nature of certain row-column array artifacts. A series of volumetric images is produced using row or column transmissions of 3-D plane waves. The voxelwise geometric mean of the beamformed volumetric images from each row and column pair is taken prior to compounding, which drastically reduces the incoherent imaging artifacts in the resulting image compared to traditional coherent compounding. The effectiveness of this technique was demonstrated in silico and in vitro, and the results show a significant reduction in sidelobe level with over 16-dB improvement in sidelobe to main-lobe energy ratio. Significantly improved contrast was demonstrated with contrast ratio increased by ~10 dB and generalized contrast-to-noise ratio increased by 158% when using the proposed new method compared to the existing delay and sum during in vitro studies. The new technique allowed for higher quality 3-D imaging while maintaining high frame rate potential.

Volumetric Flow Estimation in a Coronary Artery Phantom Using High-Frame-Rate Contrast-Enhanced Ultrasound, Speckle Decorrelation, and Doppler Flow Direction Detection.

The coronary flow reserve (CFR), relating to the volumetric flow rate, is an effective functional parameter to assess the stenosis in the left anterior descending (LAD) coronary artery. We have recently proposed to use high-frame-rate (HFR) contrast-enhanced ultrasound (CEUS) to estimate the volumetric flow rate using ultrasound (US) speckle decorrelation (SDC) without any assumptions about the velocity profile. However, this method still has challenges in imaging deep and small vessels, such as LAD. In this study, we proposed to address the challenges and demonstrate the feasibility of volumetric flow rate measurement in a coronary mimicking phantom with pulsatile flow using a 1-D array cardiac probe, vector Doppler, and an optimal probe rotation/tilting for flow direction detection. Both simulations and in vitro experiments were conducted to validate the proposed method. It is shown that in-plane velocities estimated by vector Doppler under a 10° probe tilting resulted in smaller percentage error (+5.2%) in flow rate estimates than that in US imaging velocimetry (-20.2%) although their relative standard deviations were very close, being 2.6 and 2.8 ml/min, respectively. The flow rate estimated by SDC without direction detection had an error higher than 70%. A 10° tilting of the probe had the best results in flow rate estimation compared to the 5° or 15° tilting. Realistic global motions in the LAD increased the flow rate estimation error from 5.2% to 14.2%. It is concluded that it is feasible to measure the volumetric flow rate in a coronary artery flow phantom with a conventional cardiac probe, using HFR acquisition, Doppler, and SDC analysis. Potentially, this technique could also be applied to investigate the volumetric flow rate in other small vessels similar to the LAD.

3-D Super-Resolution Ultrasound Imaging With a 2-D Sparse Array.

High-frame-rate 3-D ultrasound imaging technology combined with super-resolution processing method can visualize 3-D microvascular structures by overcoming the diffraction-limited resolution in every spatial direction. However, 3-D super-resolution ultrasound imaging using a full 2-D array requires a system with a large number of independent channels, the design of which might be impractical due to the high cost, complexity, and volume of data produced. In this study, a 2-D sparse array was designed and fabricated with 512 elements chosen from a density-tapered 2-D spiral layout. High-frame-rate volumetric imaging was performed using two synchronized ULA-OP 256 research scanners. Volumetric images were constructed by coherently compounding nine-angle plane waves acquired at a pulse repetition frequency of 4500 Hz. Localization-based 3-D super-resolution images of two touching subwavelength tubes were generated from 6000 volumes acquired in 12 s. Finally, this work demonstrates the feasibility of 3-D super-resolution imaging and super-resolved velocity mapping using a customized 2-D sparse array transducer.

High-Frame-Rate Contrast Echocardiography Using Diverging Waves: Initial In Vitro and In Vivo Evaluation.

Contrast echocardiography (CE) ultrasound with microbubble contrast agents has significantly advanced our capability for assessment of cardiac function, including myocardium perfusion quantification. However, in standard CE techniques obtained with line by line scanning, the frame rate and image quality are limited. Recent research has shown significant frame-rate improvement in noncontrast cardiac imaging. In this work, we present and initially evaluate, both in vitro and in vivo, a high-frame-rate (HFR) CE imaging system using diverging waves and pulse inversion sequence. An imaging frame rate of 5500 frames/s before and 250 frames/s after compounding is achieved. A destruction-replenishment sequence has also been developed. The developed HFR CE is compared with standard CE in vitro on a phantom and then in vivo on a sheep heart. The image signal-to-noise ratio and contrast between the myocardium and the chamber are evaluated. The results show up to 13.4-dB improvement in contrast for HFR CE over standard CE when compared at the same display frame rate even when the average spatial acoustic pressure in HFR CE is 36% lower than the standard CE. It is also found that when coherent compounding is used, the HFR CE image intensity can be significantly modulated by the flow motion in the chamber.

Fully Automatic Myocardial Segmentation of Contrast Echocardiography Sequence Using Random Forests Guided by Shape Model.

Myocardial contrast echocardiography (MCE) is an imaging technique that assesses left ventricle function and myocardial perfusion for the detection of coronary artery diseases. Automatic MCE perfusion quantification is challenging and requires accurate segmentation of the myocardium from noisy and time-varying images. Random forests (RF) have been successfully applied to many medical image segmentation tasks. However, the pixel-wise RF classifier ignores contextual relationships between label outputs of individual pixels. RF which only utilizes local appearance features is also susceptible to data suffering from large intensity variations. In this paper, we demonstrate how to overcome the above limitations of classic RF by presenting a fully automatic segmentation pipeline for myocardial segmentation in full-cycle 2-D MCE data. Specifically, a statistical shape model is used to provide shape prior information that guide the RF segmentation in two ways. First, a novel shape model (SM) feature is incorporated into the RF framework to generate a more accurate RF probability map. Second, the shape model is fitted to the RF probability map to refine and constrain the final segmentation to plausible myocardial shapes. We further improve the performance by introducing a bounding box detection algorithm as a preprocessing step in the segmentation pipeline. Our approach on 2-D image is further extended to 2-D+t sequences which ensures temporal consistency in the final sequence segmentations. When evaluated on clinical MCE data sets, our proposed method achieves notable improvement in segmentation accuracy and outperforms other state-of-the-art methods, including the classic RF and its variants, active shape model and image registration.

Fast Nonlinear Ultrasound Propagation Simulation Using a Slowly Varying Envelope Approximation.

Medical systems usually consider linear propagation of ultrasound, an approximation of reality. However, numerous studies have attempted to accurately simulate the nonlinear pressure wave distortion and to evaluate the contribution of harmonic frequencies. In such simulations, the computation time is very large, except for the method based on the angular spectrum scheme where the derivative order is reduced using the Fourier transform. However, the harmonic computation is usually limited to the second harmonic because of quasi-linear approximation. In this paper, a slowly varying envelope approximation (SVEA) is used in the Fourier domain to compute the entire nonlinear distortion induced, including high harmonics and nonlinear mixing frequencies. The simulation by SVEA is evaluated by comparison with other simulation tools. The obtained deviation and difference remain low enough to fully validate such an approximation. Moreover, the simulator is implemented on a GPU to obtain a very fast tool, where the full nonlinear distorted [Formula: see text] field is computed in less than 10 s.

Thomson's multitaper approach combined with coherent plane-wave compounding to reduce speckle in ultrasound imaging.

In ultrasound imaging, the speckle pattern limits the image quality. Spatial and frequency compounding are commonly used to reduce speckle noise or improve the contrast. Although recent implementations can preserve a frame rate that is compatible with real-time imaging (e.g., synthetic aperture compounding), most classic compounding techniques are based on the coherent combination of several radiofrequency images from the same investigated area, which reduces the frame rate. Furthermore, Thomson's multitaper approach aims to smooth the speckle by incoherently combining the obtained B-mode images after applying different apodization windows on the same original data. With only one acquisition, the frame rate remains high, but the spatial resolution is decreased. To improve the resolution and contrast while reducing the speckle noise, this paper proposes combining the coherent plane-wave compounding technique (CPWC) with Thomson's multitaper method. The resulting multitaper coherent plane-wave compounding (MCPWC) takes advantage of coherent and incoherent approaches. Simulations and experimental results demonstrate that in terms of the signal-to-noise ratio, contrast, and resolution, the image quality is increased using plane wave emissions at approximately ten steering angles with three Thomson's tapers. Outside the focal area, the lateral resolution is improved by a factor of 2, and the contrast is increased by approximately 2dB compared with images obtained using a single focalization technique and Thomson's multitaper approach.