Cardiac MRI-Tractography In Vivo: Integrated Imaging of Structure and Function

体内心脏 MRI 纤维束成像：结构和功能的综合成像

• 批准号: 8503669
• 负责人: David E Sosnovik
• 金额: $ 75.7万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8503669
• 关键词: Adult; Aldosterone; Angiotensin II; Angiotensins; Animals; Architecture; Arteries; Attenuated; Cardiac; Cardiac Myocytes; Cessation of life; Chronic; Cine Magnetic Resonance Imaging; Clinical; Data; Development; Diastolic heart failure; Diffusion; Excision; Exercise; Exposure to; Failure; Fiber; Fibrosis; Foundations; Gadolinium; Heart; Heart failure; Human; Hypertrophy; Image; Infusion procedures; Left; Left ventricular structure; Lung; Magnetic Resonance Imaging; Maps; Modeling; Mus; Muscle Fibers; Myocardial; Myocardium; Optical Coherence Tomography; Optics; Pathogenesis; Pattern; Physiological; Play; Prevention; Public Health; Pulmonary artery structure; Recovery; Reporting; Resistance; Right ventricular structure; Role; Structure; Techniques; Testing; Transgenic Mice; Transgenic Organisms; Ventricular Function; frontier; gadolinium oxide; heart function; hypertensive heart disease; in vivo; insight; mouse model; novel; pressure; prevent; public health relevance; response; tool

DESCRIPTION (provided by applicant): Pressure overload of the left and right ventricles initially leads to adaptive hypertrophy. This, however, is frequently followed by maladaptive hypertrophy, heart failure and death. We hypothesize here that changes in 3D myocardial fiber architecture play a significant role in the deleterious transition from adaptive to maladaptive hypertrophy and heart failure. We further hypothesize that in vivo diffusion tensor MRI (DTI) tractography will allow abnormal changes in myocardial microstructure to be detected well before the overt transition to heart failure. DTI-tractography provides a unique readout of 3D myofiber architecture but, in the heart, has been limited hitherto to ex vivo application. Here, we will perform serial in vivo DTI-tractography of the left ventricle (LV) during exposure to pressure overload. The in vivo tractography data will be correlated with changes in LV mass, fibrosis and strain (in vivo), and with isolated cardiomyocyte size and function ex vivo. Fundamental insights will thus be obtained into the relationship between myocardial structure and function. Microstructural changes in the overloaded LV of wildtype mice will be compared with those in transgenic Gqi mice, which are highly resistant to LV pressure overload. Serial tractography of the overloaded right ventricle (RV) will also be performed to determine why, unlike the LV, it adapts so poorly to pressure overload. In aim 1 we will compare the microstructural changes seen in physiological and pathological LV hypertrophy in models of exercise, aortic banding and angiotensin infusion. In aim 2 we will determine how RV fiber architecture changes in response to pulmonary artery banding, and how this differs from the response of the LV, particularly in Gqi mice, to aortic banding. In aim 3 we will examine the microstructural response of the overloaded LV/RV to intense afterload reduction (removal of the pressure overload). Aortic and pulmonary artery debanding will be used to determine how myofiber architecture changes when a hypertrophied and/or failing ventricle is unloaded. The changes in myofiber architecture will be correlated with changes in ventricular function, myocardial fibrosis and isolated cardiomyocyte function. The use of mouse models in this study will allow the MRI findings to be correlated with optical coherence tomography of the myocardium and fundamental mechanistic insights to be gained from the transgenic Gqi mice. The proposal advances the frontiers of cardiac imaging by demonstrating that DTI- tractography of the heart can be performed in vivo and can provide important insights into common problems such as hypertensive heart disease, diastolic LV failure and RV failure. By characterizing the microstructural changes in these important conditions we hope to better understand, and ultimately prevent, the transition from adaptive hypertrophy to heart failure and death. DTI-tractography of the human heart in vivo is highly feasible, and the proposal is thus of major clinical and public health significance.

描述（由申请人提供）：左、右心室压力过载最初导致适应性肥厚。然而，随之而来的往往是不适应性肥厚、心力衰竭和死亡。我们假设三维心肌纤维结构的改变在从适应性肥厚到非适应性肥厚和心力衰竭的有害转变中起着重要作用。我们进一步假设，体内弥散张量MRI （DTI）动脉束造影将允许在明显过渡到心力衰竭之前检测到心肌微观结构的异常变化。dti -肌腱束成像提供了独特的3D肌纤维结构读数，但在心脏中，迄今为止仅限于离体应用。在这里,我们