In Vivo Myocardial Microcirculatory Function

体内心肌微循环功能

• 批准号: 6724049
• 负责人: Erik Leo Ritman
• 金额: $ 36.88万
• 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/6724049
• 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）： 本提案的目的是开发一种基于 CT 的快速方法，用于微创定量心肌内微循环的区域功能特征及其并发心肌功能。该方法将克服其他方法的局限性，例如体内、心外膜和心内膜微循环的直接、侵入、可视化。此外，由于这些表面位置的机械力可能与壁内的机械力不同，我们提出的断层扫描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与从成像完整心肌中测量的基于 CT 的指示剂稀释曲线得出的参数之间存在独特的关系。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独特相关，因此可以以适合推进体内心肌微循环的生理和临床研究的特异性和灵敏度进行定量。我们建议通过微循环数学模型来实现我们的目标，该数学模型具有分支几何参数，该模型是通过使用微 CT 成像直接测量原位心肌微循环而得出的。 我们将通过三个目标来开发和验证该模型： (1) 该模型的开发将基于在静脉注射造影剂期间使用快速 CT 对猪进行扫描后对心肌“活组织检查”进行显微 CT 成像。 (2)模型结构方面的验证将通过体内心肌微循环的微栓塞来闭塞选定的血管直径，其中非放射性微球的直径选择为闭塞微血管及其灌注区域的已知部分。 (3) 通过对心肌微循环和正性肌力状态进行受控药物调节来评估局部左室壁功能的变化（基于快速CT的室壁增厚率和心肌耗氧指数定量），从而确定导管和交换微血管在心肌性能中的相对作用。 成功结果的意义在于检测出冠状动脉疾病的早期微血管阶段，如动脉粥样硬化、糖尿病和高血压。该工具还应适用于可以获得组织指示剂稀释曲线的其他成像方式。