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: 8858673
• 负责人: David E Sosnovik
• 金额: $ 73.36万
• 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 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8858673
• 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; Health; 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; cardiovascular visualization; coronary fibrosis; frontier; gadolinium oxide; heart function; hypertensive heart disease; in vivo; insight; mouse model; novel; pressure; prevent; 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）：左心室和右心室的压力超负荷最初导致适应性肥大。然而，随之而来的往往是适应不良性肥大、心力衰竭和死亡。我们在此假设，3D 心肌纤维结构的变化在从适应性肥厚到适应不良肥厚和心力衰竭的有害转变中发挥着重要作用。我们进一步假设，体内扩散张量 MRI (DTI) 纤维束成像将允许在明显转变为心力衰竭之前检测到心肌微观结构的异常变化。 DTI 纤维束成像提供了 3D 肌纤维结构的独特读数，但在心脏中，迄今为止仅限于离体应用。在这里，我们 将在暴露于压力期间对左心室 (LV) 进行连续体内 DTI 纤维束成像 超载。体内纤维束成像数据将与左心室质量、纤维化和应变（体内）的变化以及体外分离的心肌细胞大小和功能相关。因此将获得对心肌结构和功能之间关系的基本见解。野生型小鼠超负荷左心室的微观结构变化将与转基因 Gqi 小鼠的微结构变化进行比较，转基因 Gqi 小鼠对左心室压力超负荷具有高度抵抗力。还将对超负荷的右心室 (RV) 进行系列纤维束造影，以确定为什么它与 LV 不同，对压力超负荷的适应能力如此差。在目标 1 中，我们将比较运动、主动脉束带和血管紧张素输注模型中生理性和病理性左室肥厚的微观结构变化。在目标 2 中，我们将确定 RV 纤维结构如何响应肺动脉束带而变化，以及这与 LV（尤其是 Gqi 小鼠）对主动脉束带的反应有何不同。在目标 3 中，我们将检查超负荷 LV/RV 对强烈后负荷减少（消除压力超负荷）的微观结构响应。主动脉和肺动脉解带将用于确定当肥厚和/或衰竭的心室卸载时肌纤维结构如何变化。肌纤维结构的变化将与心室功能、心肌纤维化和离体心肌细胞功能的变化相关。本研究中使用小鼠模型将使 MRI 结果与心肌的光学相干断层扫描相关联，并从转基因 Gqi 小鼠中获得基本机制的见解。该提案通过证明心脏 DTI 纤维束成像可以在体内进行，并且可以为高血压心脏病、舒张性左心室衰竭和右心室衰竭等常见问题提供重要见解，从而推进了心脏成像的前沿。通过表征这些重要条件下的微观结构变化，我们希望更好地理解并最终预防从适应性肥大到心力衰竭和死亡的转变。人体心脏在体内的 DTI 纤维束成像具有很高的可行性，因此该提议具有重大的临床和公共卫生意义。