Serial evaluation of cardioprotective effects of exercise training in heart failure using cardiac diffusion tensor MRI

项目摘要/摘要 在美国，心力衰竭(HF)占死亡人数的九分之一，目前影响到约600万人 患病率为25万-40万，发病率为7万-12万。目前的治疗方法并没有解决 潜在的功能性心肌丧失和不利的结构重塑。一种新的潜在的治疗方法 HF是一种运动(有氧)疗法，已显示出各种心脏保护特性，可停止并潜在地 扭转不利的结构性重塑。然而，运动疗法的剂量仍然是一个挑战，因为每个 个体的内在差异，因此，对治疗的连续非侵入性监测将是 有必要对结构重塑的变化进行评估。此外，目前的非侵入性技术 用替代措施表征结构重建，因此，在单一的临床上没有共识 黄金标准。如果没有一个工具来监测和表征结构重塑的程度，评估 运动疗法在心力衰竭患者中的治疗潜力不能完全实现，这是一个未得到满足的需求。 最终改善治疗。拟议的项目旨在改善运动训练的治疗监测。 应用心脏弥散张量揭示心衰对微结构重构的影响 磁共振成像(DT-MRI)。DT-MRI是一种独特的、非侵入性的技术，能够表征心肌纤维 定向和直接反映微结构改造。然而，尽管取得了重大进展，但仍有 限制当前心脏DT-MRI方法在心脏疾病中广泛应用的基本挑战 临床环境。在这个项目中，将开发一种创新的5分钟“按钮”DT-MRI方法， 克服了这些限制。我们还利用机构优势进一步量化体内试验的准确性 DT-MRI利用新型组织清晰度3D组织学显示心肌微结构中心假说 解决这些主要的技术挑战将使心脏DT-MRI的临床翻译能够服务于 作为监测HF对微结构重塑的治疗效果的工具。这是通过扩展 先前开发的用于使用扩散加权MRI检测心肌纤维化的技术。这个 拟议的项目旨在系统地开发一种创新的和健壮的临床dt-mri方法学。 并在临床前环境中严格验证运动疗法对微结构重建的影响 从而为优化运动疗法的剂量奠定了基础。

Project Summary / Abstract Heart failure (HF) is accounts for 1 in 9 deaths in the United States and currently affects ~6 million with a prevalence of 250,00-400,000 and incidence of 70,000-120,000. Current therapy does not address the underlying loss of functional heart muscle and adverse structural remodeling. One novel potential treatment of HF is exercise (aerobic) therapy that has demonstrated various cardioprotective properties to halt and potentially reverse adverse structural remodeling. However, dosing of exercise therapy remains a challenge due to each individual's inherent differences and consequentially, serial non-invasive monitoring of the therapy would be necessary to evaluate the change on structural remodeling. Furthermore, current non-invasive technologies characterize structural remodeling with surrogate measures and thus, there is no consensus on a single clinical gold-standard. Without a tool to monitor and characterize the degree of structural remodeling, the evaluation of the therapeutic potential of exercise therapy in HF patients cannot be fully realized representing an unmet need in ultimately improving therapy. The proposed project aims to improve the therapy monitoring of exercise training to cardioprotect against HF by revealing its effect on microstructural remodeling with cardiac diffusion tensor MRI (DT-MRI). DT-MRI is a unique, non-invasive technology capable of characterizing myocardial fiber orientation and directly reflecting microstructural remodeling. However, despite major advances, there are fundamental challenges that limit the capability of current cardiac DT-MRI methods to be applied robustly in a clinical setting. In this project, an innovative 5-min “push button” DT-MRI method will be developed that overcomes such limitations. We also leverage institutional strengths to further quantify the accuracy of in vivo DT-MRI in revealing myocardial microstructure using novel tissue cleared 3D histology. The central hypothesis is that addressing these major technical challenges will allow for clinical translation of cardiac DT-MRI to serve as a tool to monitor the therapeutic effects of HF on microstructural remodeling. This is achieved by extending previously developed technologies used for myocardial fibrosis detection with diffusion-weighted MRI. The proposed project is designed to systematically develop an innovative and robust clinical DT-MRI methodology and rigorously validate in a pre-clinical setting the effects of exercise therapy on the microstructural remodeling of HF thereby laying the groundwork for potential optimization of dosing exercise therapy.