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: 8697122
• 负责人: David E Sosnovik
• 金额: $ 72.67万
• 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/8697122
• 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）：左心室和右心室的压力超负荷最初导致自适应肥大。然而，这经常随后是适应不良的肥大，心力衰竭和死亡。我们在这里假设3D心肌体系结构的变化在从适应性到不良适应性肥大和心力衰竭的有害过渡中起着重要作用。我们进一步假设，体内扩散张量MRI（DTI）拖拉术将使心肌微观结构的异常变化在明显的过渡到心力衰竭之前，可以很好地检测到心肌微结构。 DT-Ti-Ti-Takography提供了3D Myofiber架构的独特读数，但迄今为止，迄今已限制了离体应用程序。在这里，我们 在暴露于压力期间，将对左心室（LV）进行串行的体内dt-dt-dt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-tt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dt-dtt摄影作用 超载。体内拖拉术数据将与LV质量，纤维化和应变（体内）以及分离的心肌细胞大小和功能在体内的变化相关。因此，基本的见解将被获得心肌结构与功能之间的关系。将野生型小鼠的过载过液的微观结构变化与转基因GQI小鼠中的小鼠的微观结构变化，这些小鼠对LV压力超负荷具有高度抗性。还将执行超载右心室（RV）的连续拖拉术，以确定为什么与LV不同，它适应压力超负荷。在AIM 1中，我们将比较运动，主动脉带和血管紧张素输注模型中生理和病理LV肥大中看到的微观结构变化。在AIM 2中，我们将确定RV纤维结构如何响应肺动脉带的响应，以及这与LV的反应，特别是在GQI小鼠中对主动脉束带的反应。在AIM 3中，我们将检查过载LV/RV的微观结构响应，以减少后负载减少（去除压力超负荷）。主动脉和肺动脉脱离将用于确定当肥厚和/或肢体失败时，肌纤维结构如何变化。肌纤维结构的变化将与心室功能，心肌纤维化和孤立的心肌细胞功能的变化相关。在这项研究中，小鼠模型的使用将使MRI发现与心肌的光学相干断层扫描和基本机械洞察力相关，并从转基因GQI小鼠中获得。该提案通过证明可以在体内进行心脏的手段来提高心脏成像的前沿，并可以为常见问题（例如高血压心脏病，舒张期LV衰竭和RV衰竭）提供重要的见解。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阻止从适应性肥大到心力衰竭和死亡的过渡。人体心脏的DT-ti-Dat-ti-Dactography是高度可行的，因此该提案具有主要的临床和公共健康意义。