Ultrasonic perfusion imaging of peripheral vascular disease

项目摘要 我们为期4年的项目旨在开发一种新的超声多普勒方法，即高阶血流灌注估计 (希望)成像。这项技术的应用是微血管疾病的常规评估 有外周动脉疾病(PAD)症状的糖尿病患者的进展。技术进步包括 新的超声回波采样和过滤技术显著提高了诊断的敏感性和特异性 标准超声仪器用于检测红细胞运动的空间无序模式 添加造影剂。通过传递稀疏的规则来增加对缓慢血液灌流的敏感性 持续时间较长(1-10秒)的多普勒脉冲序列。为了应对随之而来的杂波信号的增加 在血流频率通道中，时空回波采集首先被重新排列成3-D数据 阵列和三维奇异值分解(3D-SVD)杂波滤波器用于每个实验。我们的 现在，该方法成功地将微弱的血液灌流回声与 外周血管病变，因为外周肌肉中杂乱回声的特征带宽通常很窄。 使用回声模拟、微通道流动模体和小鼠临床前模型的初步结果 后肢缺血和黑色素瘤病变表明，我们的方法非常适合用于监测。 使用商用超声仪器稳定的外周微血管血流模式(带软件更新)。 提出了四个目标来证明希望成像(能量和色流)在测量中的作用 血液流动和灌流。Aim 1扩大小鼠模型的初步研究以评估血流灌注 糖尿病动物12-24 MHz的测量灵敏度，并揭示血管生成的机制 组织对突发性缺血的反应。目标2通过改进灌流继续发展希望成像- 更一般成像条件下的血液回波灵敏度和杂波滤波性能(即，广义本征- 带宽杂乱和3-D空间变化的血流灌注)。目标3侧重于渐进性缺血的猪模型 使用5-12 MHz希望成像、磁共振血管造影术和放射性微球技术来校准和 将HOPE成像结果与标准临床方法进行比较。AIM 4是一项为期4年、150名患者参与的研究 目的：评价HOPE显像在评估PAD中的诊断性能。整个项目的目标是开发 现有的超声仪器成为评估微血管改变的高效工具，导致常见的 残疾和重大心血管事件。该计划中提出的三项体内研究旨在 开发和评估专门用于PAD诊断、分期和治疗监测的HOPE成像。

Project Summary Our 4-yr project aims to develop a new ultrasonic Doppler method named Higher-Order Perfusion Estimation (HOPE) imaging. Applications enabled by this technology are routine assessments of microvascular disease progression in diabetic patients with symptoms of peripheral artery disease (PAD). Technical advances include new ultrasonic echo sampling and filtering techniques that significantly increase the sensitivity and specificity of standard sonographic instruments to spatially disorganized patterns of red-blood-cell movement without the addition of contrast media. Sensitivity to slowly perfusing blood is increased by transmitting a sparse regular sequence of Doppler pulses over long durations (1-10s). To counter a concomitant increase in clutter-signal power in perfusing-blood frequency channels, spatiotemporal echo acquisitions are first rearranged into 3-D data arrays and a 3-D singular-value decomposition (3D-SVD) clutter filter is formed for each experiment. Our approach now successfully separates weak perfusing-blood echoes from other echo-signal sources in the peripheral vasculature because of the typically narrow eigen-bandwidth of clutter echoes in peripheral muscle. Preliminary results using echo simulation, microchannel flow phantoms, and preclinical models of mouse ischemic hindlimb and melanoma lesions demonstrate that our method is very well designed for monitoring steady peripheral microvascular flow patterns using commercial ultrasonic instruments (with software updates). Four aims are proposed to demonstrate the utility of HOPE imaging (both power and color-flow) for measuring blood flow and perfusion. Aim 1 expands preliminary studies in mouse models to evaluate perfusion measurement sensitivity at 12-24 MHz in diabetic animals, and to uncover mechanisms of the angiogenic response of tissues to sudden ischemia. Aim 2 continues development of HOPE imaging by improving perfusing- blood echo sensitivity and clutter-filter performance under more general imaging conditions (viz., broad eigen- bandwidth clutter and 3-D spatially varying perfusion). Aim 3 focuses on a progressively ischemic pig model using 5-12 MHz HOPE imaging, MR angiography, and radioactive microsphere techniques to calibrate and compare HOPE imaging results with standard clinical approaches. Aim 4 is a 4-yr, 150-patient study designed to evaluate the diagnostic performance of HOPE imaging at assessing PAD. The overall project aims to develop existing ultrasonic instruments into highly-effect tools for evaluating microvascular changes leading to common disabilities and major cardiovascular events. The three in vivo studies proposed in this plan are designed to develop and evaluate HOPE imaging specifically for PAD diagnosis, staging, and therapeutic monitoring.