Transcutaneous Imaging of Rabbit Kidney Using 3-D Acoustic Wave Sparsely Activated Localization Microscopy with a Row-Column-Addressed Array.

OBJECTIVE: Super-resolution ultrasound (SRUS) imaging through localizing and tracking microbubbles, also known as ultrasound localization microscopy (ULM), can produce sub-diffraction resolution images of micro-vessels. We have recently demonstrated 3-D selective SRUS with a matrix array and phase change contrast agents (PCCAs). However, this method is limited to a small field of view (FOV) and by the complex hardware required. METHOD: This study proposed 3-D acoustic wave sparsely activated localization microscopy (AWSALM) using PCCAs and a 128+128 row-column-addressed (RCA) array, which offers ultrafast acquisition with over 6 times larger FOV and 4 times reduction in hardware complexity than a 1024-element matrix array. We first validated this method on an in-vitro microflow phantom and subsequently demonstrated non-invasively on a rabbit kidney in-vivo. RESULTS: Our results show that 3-D AWSALM images of the phantom covering a 25×25×40 mm 3 volume can be generated under 5 seconds with an 8 times resolution improvement over the system point spread function. The full volume of the rabbit kidney can be covered to generate 3-D microvascular structure, flow speed and direction super-resolution maps under 15 seconds, combining the large FOV of RCA with the high resolution of SRUS. Additionally, 3-D AWSALM is selective and can visualize the microvasculature within the activation volume and downstream vessels in isolation. Sub-sets of the kidney microvasculature can be imaged through selective activation of PCCAs. CONCLUSION: Our study demonstrates large FOV 3-D AWSALM using an RCA probe. SIGNIFICANCE: 3-D AWSALM offers an unique in-vivo imaging tool for fast, selective and large FOV vascular flow mapping.

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.

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.

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.

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.