Spatio-Temporal Flow and Wall Shear Stress Mapping Based on Incoherent Ensemble-Correlation of Ultrafast Contrast Enhanced Ultrasound Images

In this study, a technique for high-frame-rate ultrasound imaging velocimetry (UIV) is extended first to provide more robust quantitative flow velocity mapping using ensemble correlation of images without coherent compounding, and second to generate spatio-temporal wall shear stress (WSS) distribution. A simulation model, which couples the ultrasound simulator with analytical flow solution, was implemented to evaluate its accuracy. It is shown that the proposed approach can reduce errors in velocity estimation by up to 10-fold in comparison with the coherent correlation approach. Mean errors (ME) of 3.2% and 8.6% were estimated under a steady flow condition, while 3.0% and 10.6% were found under a pulsatile condition for the velocity and wall shear rate (WSR) measurement, respectively. Appropriate filter parameters were selected to constrain the velocity profiles before WSR estimations and the effects of incorrect wall tracking were quantified under a controlled environment. Although accurate wall tracking is found to be critical in WSR measurement (as a 200?µm deviation from the wall may yield up to a 60% error), this can be mitigated by HFR imaging (of up to 10?kHz) with contrast agents, which allow for improved differentiation of the wall-fluid boundaries. In vitro investigations on two carotid bifurcation phantoms, normal and diseased, were conducted, and their relative differences in terms of the flow patterns and WSR distribution were demonstrated. It is shown that high-frame-rate UIV technique can be a non-invasive tool to measure quantitatively the spatio-temporal velocity and WSS distribution.     

Microbubble Void Imaging: A Non-invasive Technique for Flow Visualisation and Quantification of Mixing in Large Vessels Using Plane Wave Ultrasound and Controlled Microbubble Contrast Agent Destruction

There is increasing recognition of the influence of the flow field on the physiology of blood vessels and their development of pathology. Preliminary work is reported on a novel non-invasive technique, microbubble void imaging, which is based on ultrasound and controlled destruction of microbubble contrast agents, permitting flow visualisation and quantification of flow-induced mixing in large vessels. The generation of microbubble voids can be controlled both spatially and temporally using ultrasound parameters within the safety limits. Three different model vessel geometries—straight, planar-curved and helical—with known effects on the flow field and mixing were chosen to evaluate the technique. A high-frame-rate ultrasound system with plane wave transmission was used to acquire the contrast-enhanced ultrasound images, and an entropy measure was calculated to quantify mixing. The experimental results were cross-compared between the different geometries and with computational fluid dynamics. The results indicated that the technique is able to quantify the degree of mixing within the different configurations, with a helical geometry generating the greatest mixing, and a straight geometry, the lowest. There is a high level of concordance between the computational fluid dynamics and experimental results. The technique could also serve as a flow visualisation tool.     

Ultrasound Imaging Velocimetry: Effect of Beam Sweeping on Velocity Estimation

As an emerging flow-mapping tool that can penetrate deep into optically opaque media such as human tissue, ultrasound imaging velocimetry has promise in various clinical applications. Previous studies have shown that errors occur in velocity estimation, but the causes have not been well characterised. In this study, the error in velocity estimation resulting from ultrasound beam sweeping in image acquisition is quantitatively investigated. The effects on velocity estimation of the speed and direction of beam sweeping relative to those of the flow are studied through simulation and experiment. The results indicate that a relative error in velocity estimation of up to 20% can be expected. Correction methods to reduce the errors under steady flow conditions are proposed and evaluated. Errors in flow estimation under unsteady flow are discussed.     

Quantitative Analysis of Helical Flow with Accuracy Using Ultrasound Speckle Image Velocimetry: In Vitro and in Vivo Feasibility Studies

Venous valve dysfunction and induced secondary abnormal flows are closely associated with venous diseases. Thus, detailed analysis of venous valvular flow is invaluable from biological and medical perspectives. However, most of the previous studies on venous perivalvular flows were based on qualitative analysis. On the contrary, quantitative analysis of perivalvular flows has not been fully understood. In this study, we used the ultrasound speckle image velocimetry (SIV) technique, which utilizes the speckle patterns of red blood cells (RBCs) created by ultrasound waves to measure 3-D valvular flows quantitatively. The flow structures obtained with the proposed SIV technique for an in vitro model were compared with those obtained by numerical simulation and the color Doppler method to validate the measurement accuracy of the ultrasound SIV technique. Blood flow in the human great saphenous vein was then measured at various distances from the valve with and without exercise. 3-D valvular flow was analyzed in accordance with the dimensionless index, helical intensity. The results obtained by the proposed method matched well with those obtained by numerical simulation and the color Doppler method. The hemodynamic characteristics of 3-D valvular helical flow which were analyzed experimentally using the SIV method would be used for quantitative diagnosis of venous valvular diseases.     

Treatment of Microvascular Micro-embolization Using Microbubbles and Long-Tone-Burst Ultrasound: An in Vivo Study

Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction. In 16 rats, an imaging transducer was placed on the biceps femoris muscle, perpendicular to a single-element 1-MHz treatment transducer. Ultrasound contrast perfusion imaging was performed at baseline and after micro-embolization. Therapeutic ultrasound (5000 cycles, pulse repetition frequency = 0.33 Hz, 1.5 MPa) was delivered to nine rats for two 10-min sessions during intra-arterial infusion of lipid-encapsulated microbubbles; seven control rats received no ultrasound–microbubble therapy. Ultrasound contrast perfusion imaging was repeated after each treatment or control period, and microvascular volume was measured as peak video intensity. There was a 90% decrease in video intensity after micro-embolization (from 8.6 ± 4.8 to 0.7 ± 0.8 dB, p < 0.01). The first and second ultrasound–microbubble sessions were respectively followed by video intensity increases of 5.8 ± 5.1 and 8.7 ± 5.7 dB (p < 0.01, compared with micro-embolization). The first and second control sessions, respectively, resulted in no significant increase in video intensity (2.4 ± 2.3 and 3.6 ± 4.9) compared with micro-embolization (0.6 ± 0.7 dB). We have developed an in vivo model that simulates the distal thrombotic microvascular obstruction that occurs after primary percutaneous coronary intervention. Long-pulse-length ultrasound with microbubbles has a therapeutic effect on microvascular perfusion and may be a valuable adjunct to reperfusion therapy for acute myocardial infarction.     

Combining Subharmonic and Ultraharmonic Modes for Intravascular Ultrasound Imaging: A Preliminary Evaluation

Contrast-enhanced intra-vascular ultrasound (CE-IVUS) imaging could provide clinicians a valuable tool to assess cardiovascular risk and guide the choice of therapeutic strategies. In this technical note, we evaluated the feasibility of combining subharmonic and ultraharmonic imaging to improve the performance of CE-IVUS. Vessel phantoms perfused with phospholipid-shelled ultrasound contrast agents were visualized using subharmonic, ultraharmonic and combined CE-IVUS modes with commercial peripheral and coronary imaging catheters. Flow channels as small as 0.8 mm and 0.5 mm were imaged at 12-MHz and 30-MHz transmit frequencies, respectively. Subharmonic and ultraharmonic imaging modes achieved a contrast-to-tissue ratio (CTR) up to 18.1 ± 1.8 dB and 19.6 ± 1.9 dB at 12-MHz, and 8.8 ± 1.8 and 12.5 ± 1.1 dB at 30-MHz transmit frequencies, respectively. Combining these modes improved the CTR to 32.5 ± 3.0 dB and 25.0 ± 1.6 dB at 12-MHz and 30-MHz transmit frequencies. These results underscore the potential of combined-mode CE-IVUS imaging. Furthermore, the demonstration of this approach with commercial catheters may serve as a first step toward the clinical translation of CE-IVUS.     

Two-Dimensional Flow Imaging in the Carotid Bifurcation Using a Combined Speckle Tracking and Phase-Shift Estimator: A Study Based on Ultrasound Simulations and in vivo Analysis

A two-dimensional (2-D) blood velocity estimator is presented combining speckle tracking (ST) and phase-shift estimation (PE) to measure lateral (vx) and axial (vz) velocities respectively. Estimator properties were assessed in a carotid bifurcation using ultrasound simulations based on computational fluid dynamics, allowing validation toward a ground truth. Simulation results were supported with in vivo data of a healthy carotid. ST and PE estimates were combined as: (1) vx from 2D-ST and vz from PE, (2) vx from 2D-ST and vz from PE with aliasing correction based on ST and (3) vz from PE and only lateral ST for vx. Regression analysis showed a 35% to 77% decrease in standard deviation for vz for PE compared with ST. Aliasing correction based on ST improved results but also introduced spurious artifacts. A marginal decrease in performance was observed when only tracking laterally. Further work will focus on in vivo trials in patients with carotid plaques. (E-mail: abigail.swillens@ugent.be)