Free-Breathing Diffusion Tensor MRI in Patients Following Myocardial Infarction

 描述（由申请人提供）：心力衰竭仍然是美国发病率和死亡率的主要原因。尽管医学治疗取得了进展，但大量前壁梗死患者的重塑不利，并发展为心力衰竭。我们推测肌纤维结构的明显变化在心力衰竭的发病机制中起重要作用。我们进一步假设，扩散张量MRI（DTI）的人体心脏在体内将允许这些变化的特点，从而阐明心肌重塑和心力衰竭的发展的微观结构基础。我们的小组以前已经开发了一个扩散编码的刺激回波脉冲序列进行DTI的心脏在体内。在这里，我们将对序列进行根本性的增强，以提高其速度，覆盖范围和准确性。我们的目标是在不到10分钟的时间内对整个心脏进行自由呼吸DTI采集。这将涉及同时多切片激励，梯度重新排序，并使用先进的时空配准技术。为了表征心肌结构的变化，我们将设计针对心脏DTI的新分析方法。这将包括开发心肌束和片结构量化的指标。我们假设这些措施，加上图像采集的改进，将允许随着时间的推移检测和跟踪肌纤维组织的细微变化，这将有助于确定新的治疗目标。该提案的目标1将涉及脉冲序列细化，以提高图像质量并缩短采集时间。在目标2中，我们将开发新的技术来表征心肌梗死（MI）后心脏重塑患者的微结构变化。这将包括设计用于检测梗死、边界和远端区域的指标，并表征相关的微结构改变。对于每个指标，我们将根据对健康志愿者的研究确定一组规范，并确定所开发指标的年龄和负荷依赖性。在目标3中，将对近期前壁心肌梗死患者进行研究。我们的初步数据显示，纤维和片状结构的显著异常 在这些患者梗死后不久的边缘区和远端区都可以看到。我们将随着时间的推移跟踪这些变化，以更好地了解它们与左心室扩张和心力衰竭发展的关系。该研究的完成将导致一组新的表型生物标志物的鉴定，这些生物标志物可以在微观结构水平上表征心肌重塑并预测心力衰竭的发展。这些生物标志物将在开发旨在预防和治疗心力衰竭的新疗法中发挥重要作用，这将具有重大的医学和公共卫生意义。

 DESCRIPTION (provided by applicant): Heart failure remains a leading cause of morbidity and mortality in the United States. Despite advances in medical therapy, a large number of patients with anterior infarcts remodel adversely and develop heart failure. We hypothesize that distinct changes in myofiber architecture play an important role in the pathogenesis of heart failure. We further hypothesize that diffusion tensor MRI (DTI) of the human heart in vivo will allow these changes to be characterized and thereby elucidate the microstructural basis for myocardial remodeling and the development of heart failure. Our group has previously developed a diffusion-encoded stimulated echo pulse sequence to perform DTI of the heart in vivo. Here we will make fundamental enhancements to the sequence to improve its speed, coverage and accuracy. We aim to perform a free-breathing DTI acquisition of the entire heart in vivo in less than 10 minutes. This will involve simultaneous multislice excitation, gradient reordering, and the use of advanced spatiotemporal registration techniques. To characterize changes in myocardial architecture, we will design novel analysis methods tailored to cardiac DTI. This will include the development of metrics for the quantification of myocardial tract and sheet architecture. We hypothesize that these measures, coupled with improvements in image acquisition, will allow subtle changes in myofiber organization to be detected and followed over time, which will help in identifying new targets for therapy. Aim 1 of the proposal will involve pulse sequence refinement to improve image quality and reduce acquisition time. In Aim 2, we will develop new techniques with which to characterize the microstructural changes seen in patients with cardiac remodeling after myocardial infarction (MI). This will include metrics designed to detect the infarct, border, and remote zones, and to characterize the associated microstructural alterations. For each metric, we will determine a set of norms based on the study of healthy volunteers, and also determine the age and load dependence of the developed metric. In Aim 3, patients with recent anterior myocardial infarcts will be studied in a longitudinl fashion. Our preliminary data reveal that significant abnormalities in fiber and sheet architecture are seen in both the border and remote zones in these patients soon after infarction. We will follow these changes over time to better understand their relationship with the development of left ventricular dilation and heart failure. Completion of the study will result in the identificaton of a new panel of phenotypic biomarkers that can characterize myocardial remodeling at the microstructural level and predict the development of heart failure. These biomarkers will play an important role in the development of new therapies designed to prevent and treat heart failure, which will be of major medical and public health significance.