In Vivo Myocardial Microcirculatory Function

体内心肌微循环功能

• 批准号: 6970899
• 负责人: Erik Leo Ritman
• 金额: $ 36.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6970899
• 关键词: blood volume; computed axial tomography; diagnosis quality /standard; electrodes; heart circulation; heart disorder diagnosis; heart function; heart imaging /visualization /scanning; indicator dilution test; mathematical model; method development; microcirculation; myocardium; rapid diagnosis; swine

DESCRIPTION (provided by applicant): It is the intent of this proposal to develop a fast CT-based method for minimally invasively quantitating the regional functional characteristics of the intramyocardial microcirculation and its concurrent myocardial function. This method would overcome the limitations of other methods such as the direct, invasive, visualization of, in vivo, epicardial and endocardial microcirculations. Moreover, as the mechanical forces in those surface locations are likely different from those within the wall, our proposed tomographic perfusion imaging approach is more likely to provide data representative of the intramural micrccirculation. Our preliminary data indicate that a unique relationship exists linking the myocardial microcirculatory branching geometry and the parameters derived from the CT-based indicator dilution curve measured in the imaged intact myocardium. As a consequence, our hypothesis is that a myocardial CT-based indicator dilution curve is uniquely related to the patho-physiological behavior of the transmural myocardial microcirculation and can therefore be quantitated with a specificity and sensitivity that is suitable for advancing physiological and clinical investigation of the in vivo myocardial microcirculation. We propose to achieve our goal by a mathematical model of the microcirculation with branching geometry parameters to be derived from direct measurements of the in situ myocardial microcirculation using micro-CT imaging. We will develop and validate this model by three aims: (1) Development of the model will be based on micro-CT imaging of "biopsies" of the myocardium after we have scanned the pigs using fast-CT during an intravenous injection of contrast agent. (2) Validation of the structural aspects of the model will be performed by occlusion of selected vessel diameters by microembolization of the in vivo myocardial microcirculation with non-radioactive microspheres of diameters selected to occlude a known fraction of microvessels and their perfusion territories. (3) Change in local LV wall function (fast CT-based quantitation of rate of wall thickening and index of myocardial oxygen consumption) will be evaluated with controlled pharmacological modulation of the myocardial microcirculation and inotropic state so as to establish relative roles of conduit and exchange microvessels in myocardial performance. The significance of a successful outcome would be detection of an early, microvascular, stage of coronary disease as occurs in atherosclerosis, diabetes mellitus, and hypertension. This tool should also be applicable to other imaging modalities from which tissue indicator dilution curves can be obtained.

描述(由申请人提供)： 本研究的目的是开发一种快速的基于CT的方法，用于微创量化心肌内微循环的局部功能特征及其并发的心肌功能。这种方法克服了其他方法的局限性，如直接、有创、活体显示心外膜和心内膜微循环。此外，由于这些表面位置的机械力可能与壁内的不同，我们建议的断层灌注成像方法更有可能提供代表壁内微循环的数据。 我们的初步数据表明，心肌微循环分支几何形状和基于CT的指示剂稀释曲线在成像完整心肌中测量的参数之间存在着独特的联系。因此，我们的假设是，基于心肌CT的指示剂稀释曲线与跨壁心肌微循环的病理生理行为唯一相关，因此可以以适合于推进活体心肌微循环的生理和临床研究的特异度和灵敏度来定量。我们建议通过一个微循环的数学模型来实现我们的目标，该模型的分支几何参数将通过使用Micro-CT成像对原位心肌微循环的直接测量得到。 我们将通过三个目标来开发和验证该模型： (1)在静脉注射造影剂的过程中，我们使用FAST-CT对猪进行扫描后，心肌活检的显微CT成像将基于该模型的开发。 (2)模型的结构方面的验证将通过体内心肌微循环的微栓塞术来闭塞选定的血管直径，选择直径的非放射性微球闭塞已知的部分微血管及其灌注区。 (3)评价局部室壁功能的改变(基于CT的室壁增厚率和心肌耗氧指数的快速定量)将通过对心肌微循环和变力状态的受控药物调节来评估，以确定管道和交换微血管在心肌功能中的相对作用。 成功结果的重要意义在于发现早期的微血管病变，如动脉粥样硬化、糖尿病和高血压。该工具还应适用于可获得组织指示剂稀释曲线的其他成像方式。