Clinically Translatable Cardiac Diffusion MR for Non-Contrast Characterization of

描述（由申请人提供）：长期目标是开发一种创新的、临床上稳健的心脏弥散MRI序列，该序列对心肌组织微结构的变化敏感。表征心肌组织微观结构的能力将允许对心血管疾病（CVD）的病理生理学进展的独特见解，例如急性冠状动脉综合征、心肌炎和心肌病，这些疾病是美国发病率和死亡率的主要原因之一。传统的心脏MRI（CMR）技术已被证明是临床上有价值的，揭示心肌的形态学变化，同时提供良好的软组织对比。然而，用于心肌组织定征的经验证CMR技术需要使用造影剂。对于肾系统受损的患者，如慢性肾病（CKD）患者，这些患者无法从这些基于造影剂的技术中获益。此外，25%的CKD患者患有严重的CVD，导致左心室肥大（LVH），并可直接受益于心肌组织纤维化的表征。因此，需要一种能够对心肌纤维化进行非对比定量的新型MR技术，我们相信心脏弥散MRI可以实现这一点。在这个拟议的项目中，一个临床上可翻译的心脏 能够对人类心肌进行心肌纤维化表征的扩散MR技术将应用于已知具有经对比增强CMR验证的高度纤维化的肥厚型心肌病患者（HCM）。具体目标1解决了我们实验室开发的新建立的心脏弥散MR技术的临床转化的技术挑战，该技术需要更好的空间覆盖范围，空间分辨率和更短的扫描时间。具体目标2将具体目标1中开发的拟议技术应用于HCM患者，以表征心肌纤维化的程度，并将其与经验证的对比增强CMR方法进行比较。假设：心脏弥散MRI的临床转化需要重大的技术创新，证明该技术对CKD+LVH患者的临床实用性的关键应用是在不使用造影剂的情况下表征HCM患者的心肌纤维化。

DESCRIPTION (provided by applicant): The long-term objective is to develop an innovative and clinically robust cardiac diffusion MRI sequence that is sensitive to changes to myocardial tissue microstructure. The ability to characterize myocardial tissue microstructure will allow for unique insight to the pathophysiological progression of cardiovascular diseases (CVD) such as acute coronary syndrome, myocarditis, and cardiomyopathy, which are among the leading causes of morbidity and mortality of the US. Conventional cardiac MRI (CMR) techniques have shown to be clinically valuable in revealing morphological changes in the myocardium while providing excellent soft tissue contrast. However, validated CMR techniques used for myocardial tissue characterization require the use contrast agents. For patients with compromised renal systems such as those with Chronic Kidney Disease (CKD), these patients cannot benefit from these contrast-based techniques. Furthermore, 25% of CKD patients have a severe form of CVD that results in left ventricular hypertrophy (LVH) and can directly benefit from characterization of myocardial tissue fibrosis. Therefore, there is a need for a novel MR technique capable of non- contrast quantification of myocardial fibrosis, which we believe can be achieved with cardiac diffusion MRI. In this proposed project, a clinically translatable cardiac diffusion MR technique capable of myocardial fibrosis characterization of the human myocardium will be applied in hypertrophic cardiomyopathy patients (HCM) who are known to have high degree of fibrosis validated with contrast-enhanced CMR. Specific Aim 1 addresses the technical challenges of the clinical translation of a newly established cardiac diffusion MR technique developed by our lab, which requires better spatial coverage, spatial resolution, and shorter scan times. Specific Aim 2 will apply the proposed technique developed in Specific Aim 1 to HCM patients to characterize the extent of myocardial fibrosis and compare it with validated contrast-enhanced CMR methods. Hypothesis: Clinical translation of cardiac diffusion MRI requires major technical innovation, and a key application to demonstrate the technique's clinical utility for CKD+LVH patients would be to characterize myocardial fibrosis in HCM patients without the use of contrast agents.