CT Method Development for Quantifying Myocardial Microvascular Flow Distribution

描述(由申请人提供)：本提案的目标是开发一种从心肌图像确定微血管血流分布的工具。这涉及到量化管腔直径在10-50？m范围内的微动脉树内血流的空间分布。高分辨率的Micro-CT成像将提供精确的微血管结构的3D几何映射，用于计算确定血流分布。这一“黄金标准”将用于校准通过临床MSCT心肌灌注图像的嵌套感兴趣区(NROI)分析获得的亚分辨率区域血流分布的估计值。这一建议的意义在于，它将使我们有可能更深入和更准确地探讨心肌和其他地方(如糖尿病、高血压和动脉粥样硬化)微循环疾病过程的机制。目前还没有一种成像方法能够以足够的分辨率定量评估人体微血管的状态，从而能够计算单个微血管水平上的血流分布。该方法将为探索新的诊断和治疗方法提供新的工具。这一建议的创新之处在于，它将首次提供亚分辨率微血管血流分布的3D映射 MSCT成像方法学经Micro-CT验证。 目的I-全身和Micro-CT图像数据的生成-Ia：使用猪，当造影剂通过冠状动脉循环时，生成MSCT图像序列。然后，在左前降支冠状动脉内注入腺苷的同时，重复此过程。下一步，在静息血流条件下向左心房注入15？m不透射线的微球(浸银)，然后在选定的腺苷递送速率下注入Au微球。IB：心脏将被取出，LAD将被注射微米非。几个1cm3的肌肉样本将从LAD灌注区取出。每个样本将以(4？m)3个体素分辨率进行扫描。目的II-微血管内对流血流分布的分析-IIa：标本的3DMicro-CT图像将被分割，以便我们的树分析程序可以提供血管管腔分支间段直径、长度、分支角度和分支层次，以便计算基于血流动力学的血流分布。IIB：微球将被数字隔离，以便它们的位置和密度可以用来提供基于微球的流量分布。IIC：将比较微球和基于血流动力学的血流分布，并考虑任何差异以确定真实的流量分布。目的III相同心肌区域内心肌灌注的空间不均一性分析-心肌的MSCT图像将进行nROI分析，用于计算心肌内血流量和血流量的空间分布，结果将由IIb，c的Micro-CT结果所得的血流和腔内血流量的分布来校准。

DESCRIPTION (provided by applicant): The objective of this proposal is to develop a tool for determining microvascular flow distribution from images of myocardium. This involves quantifying the spatial distribution of blood flow in arteriolar trees with lumen diameters in the range of 10 - 50 ¿m. High resolution micro-CT imaging will provide accurate 3D geometrical mapping of the microvascular architecture for a computational determination of the flow distribution. This "gold standard" will be used to calibrate estimates of sub-resolution regional blood flow distributions obtained by nested-region-of-interest (nROI) analysis of clinical MSCT images of myocardial perfusion. The significance of this proposal is that it will make it possible to probe deeper and more accurately into the mechanisms of microcirculatory disease processes in the myocardium and elsewhere (e.g., in diabetes mellitus, hypertension, and atherosclerosis). There is currently no imaging methodology for assessing quantitatively the state of microvasculature in humans with sufficient resolution as to allow the computation of flow distribution at the level of individual microvessels. The proposed method will provide a new tool for exploring novel diagnostic and treatment methods. The innovation in this proposal is that it will provide for the first time a 3D mapping of sub-resolution microvascular flow distribution with MSCT imaging methodology validated with micro-CT. AIM I - Generation of Whole-body and Micro-CT Image Data - Ia: Using pigs, generate an MSCT image sequence while the contrast bolus passes through the coronary circulation. Then, repeat this procedure while the LAD coronary artery is infused with adenosine. Next, inject 15 ¿m radiopaque microspheres (Ag impregnated) into the left atrium during resting flow conditions and then Au impregnated microspheres during the selected adenosine delivery rates. Ib: The heart will be removed and the LAD injected with Microfil. Several 1 cm3 muscle samples will be removed from the LAD perfusion territory. Each specimen will be scanned at (4 ¿m)3 voxel resolution. AIM II - Analysis of Convective Flow Distribution within the Microvasculature - IIa: The 3D micro-CT images of the specimens will be segmented so that our tree analysis program can provide the vascular lumen inter-branch segment diameter, length and branching angle and branch hierarchy in order to compute a hemodynamically-based flow distribution. IIb: The microspheres will be digitally isolated so that their location and density can be used to provide a microsphere-based flow distribution. IIc: The microsphere and hemodynamically based flow distributions will be compared and any differences will be accounted for to establish the true flow distribution. AIM III - Analysis of Spatial Heterogeneity of Myocardial Perfusion Within the Same Myocardial Regions -The MSCT images of the myocardium will be subjected to nROI analysis and used to compute the spatial distribution of intramyocardial blood volume and flow and the results will be calibrated by the distribution of flow and intraluminal blood volume as derived from the micro-CT results in IIb, c.