Characterization of sarcopenia in heart failure by T1rho magnetic resonance fingerprinting

项目摘要 这项提议的目标是开发一种新的定量磁共振成像(MRI)技术 用于心力衰竭(HF)和支持中骨骼肌质量和功能丧失的骨骼肌减少的特征 研究人员Brendan Eck博士在老龄化和生物医学成像研究方面的职业发展。 研究：心力衰竭患者的骨钙素减少独立预测不良预后。虽然原发性骨质疏松症是一种 在老龄化条件下，心力衰竭患者的骨质疏松率高于普通人群。病理生理学 心脏和骨骼肌中的机制已被确定为心衰和骨质疏松症之间的联系。当前工具 用于评估HF患者的骨骼肌减少是间接的，或者对早期发生的骨骼肌变化不敏感 在疾病中。定量核磁共振可以提供潜在敏感的组织特性测量 骨骼肌的病理变化。然而，现有的技术要么慢得不切实际，要么不慢。 可重现的。磁共振指纹图谱(MRF)已经发展成为一种快速、可重复性的定量技术 多种组织属性。然而，定量T1rho，一种对蛋白质含量变化敏感的指标， 直到最近才被MRF证明是可以量化的，还没有关于它在石棺减少症中的使用的研究。这个项目 旨在开发T1rho-MRF以同时定量T1rho和其他MRF衍生的骨骼肌 属性。T1rho-MRF还将被开发用于心脏成像，以研究影响 肌萎缩症合并心力衰竭时骨骼肌和心肌均可见。在该项目的目标1中，T1rho-MRF 技术将在模拟中开发和优化。T1rho-MRF将在物理模型中得到验证 在人类实验对象中也是如此。还将获得骨骼肌活组织检查，并将T1rho-MRF与 组织属性如纤维类型比例。在目标2中，健康对照组和心力衰竭患者，有石棺减少和 若无石棺减少，则行T1rho-MRF扫描。数量值将在组之间进行比较，以 心力衰竭患者的石棺减少的特征。T1Rho-MRF测量将与GRIP的功能相关 体力、6分钟步行和心肺测试。 职业发展：调查员有定量心血管成像的技术背景， 旨在过渡到衰老和生物医学成像研究。这项研究项目培养了关键技能和 了解调查员的职业发展。职业发展计划提供生物学方面的培训 衰老，骨骼肌生物学，与临床医生接触，以了解临床评估 骨质疏松症在HF，影像研究研究的设计和实施。培训包括说教和培训 体验式组件。多元化的指导团队、顾问和合作者相辅相成 开发应聘者跨学科研究项目的技能。 摘要：该提案将提供新的成像工具来评估心力衰竭患者的骨骼减少症，并支持职业生涯 将研究人员发展成为衰老和生物医学成像领域的独立研究人员。

Project Summary The goals of this proposal are to develop a novel quantitative magnetic resonance imaging (MRI) technology for characterization of sarcopenia, loss of skeletal muscle mass and function, in heart failure (HF) and support the career development of the investigator, Brendan Eck, PhD, in aging and biomedical imaging research. Research: Sarcopenia in HF is independently predictive of poor outcomes. Although primary sarcopenia is a condition of aging, rates of sarcopenia in HF are greater than the general population. Pathophysiological mechanisms in the heart and skeletal muscle have been identified that link HF and sarcopenia. Current tools for assessing sarcopenia in HF are indirect or are not sensitive to alterations in skeletal muscle that occur early in disease. Quantitative MRI can provide tissue property measurements that are potentially sensitive to pathological changes in skeletal muscle. However, existing techniques are impracticably slow or not reproducible. MR fingerprinting (MRF) has developed as a rapid, reproducible technique for quantification of multiple tissue properties. However, quantitative T1rho, a measure sensitive to alterations in protein content, has only recently been shown to be quantifiable by MRF with no study of its use in sarcopenia. This project aims to develop T1rho-MRF to simultaneously quantify T1rho and other MRF-derived skeletal muscle properties. T1rho-MRF will also be developed for cardiac imaging to investigate tissue alterations affecting both skeletal muscle and myocardium in sarcopenia with HF. In Aim 1 of the project, the T1rho-MRF technology will be developed and optimized in simulations. T1rho-MRF will be validated in physical phantoms and in human subjects. Skeletal muscle biopsy will also be acquired and T1rho-MRF will be compared to tissue properties such as fiber type proportion. In Aim 2, healthy controls and HF patients, with sarcopenia and without sarcopenia, will be scanned with T1rho-MRF. Quantitative values will be compared between groups to characterize HF patients with sarcopenia. T1rho-MRF measurements will be correlated with function from grip strength, 6-minute walk, and cardiopulmonary tests. Career development: The investigator has a technical background in quantitative cardiovascular imaging and aims to transition to aging and biomedical imaging research. This research project develops critical skills and knowledge for the investigator’s career development. The career development plan provides training in biology of aging, biology of skeletal muscle, engagement with clinicians to understand clinical assessments of sarcopenia in HF, and imaging research study design and execution. Training includes both didactic and experiential components. A diverse mentorship team, consultant, and collaborators contribute complementary skills toward developing the candidate’s interdisciplinary research program. Summary: The proposal will provide novel imaging tools to assess sarcopenia in HF and support the career development of the investigator to become an independent researcher in aging and biomedical imaging.