Ultrasonic perfusion imaging of peripheral vascular disease

项目摘要 我们的四年计划旨在发展一种新的超声多普勒方法，称为高阶灌注估计 （HOPE）成像。该技术的应用是微血管疾病的常规评估 伴有外周动脉疾病（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滤波技术，显著提高了灵敏度和特异性， 标准超声仪器对红细胞运动的空间无序模式进行检查， 添加造影剂。对缓慢灌注的血液的敏感性通过传输稀疏的规则信号而增加。 长持续时间（1- 10秒）的多普勒脉冲序列。为了抵消伴随的杂波信号的增加， 在灌注血液频率通道中的功率，首先将时空回波采集重新排列成3-D数据 阵列和3-D奇异值分解（3D-SVD）杂波滤波器形成的每个实验。我们 现在，这种方法成功地将微弱的灌注血液回波与其他回波信号源分离开来， 由于外周肌肉中杂波回波的特征带宽通常较窄， 使用回声模拟、微通道流动模型和小鼠临床前模型的初步结果 缺血性后肢和黑色素瘤病变表明，我们的方法是非常好的监测设计， 使用商业超声仪器（软件更新）稳定外周微血管血流模式。 提出了四个目标，以证明HOPE成像（功率和彩色流）用于测量的实用性 血流和灌注。目的1扩展了小鼠模型的初步研究，以评估灌注 在糖尿病动物中在12-24 MHz下的测量灵敏度，并揭示血管生成的机制。 组织对突然缺血的反应。目标2通过改善灌注继续开发HOPE成像- 在更一般的成像条件下的血液回波灵敏度和杂波滤波器性能（即，宽本征值 带宽杂波和3-D空间变化灌注）。目的3关注进行性缺血猪模型 使用5-12 MHz HOPE成像、MR血管造影和放射性微球技术进行校准， 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例患者的研究， 评价HOPE成像在评估PAD方面的诊断性能。整个项目旨在开发 将现有的超声仪器转变为用于评估微血管变化的高效工具， 残疾和重大心血管事件。本计划中提出的三项体内研究旨在 开发和评估HOPE成像，专门用于PAD诊断、分期和治疗监测。

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.