Characterization of sarcopenia in heart failure by T1rho magnetic resonance fingerprinting

T1rho 磁共振指纹图谱表征心力衰竭中的肌肉减少症

• 批准号: 10369408
• 负责人: Brendan Lee Eck
• 金额: $ 13.41万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10369408
• 关键词: Address; Affect; Aging; Biological Assay; Biology; Biology of Aging; Biopsy; Biopsy Specimen; Blood capillaries; Cardiac; Cardiopulmonary; Characteristics; Chronic Disease; Chronology; Clinical; Clinical Management; Clinical assessments; Consumption; Deposition; Deterioration; Development; Development Plans; Diabetes Mellitus; Disease; Doctor of Philosophy; Dual-Energy X-Ray Absorptiometry; Edema; Elderly; Evaluation; Exhibits; Fatty acid glycerol esters; Fiber; Fibrosis; Fingerprint; Functional disorder; General Population; Goals; Hand Strength; Heart; Heart failure; Hypertension; Image; Imaging Device; Imaging Techniques; Imaging technology; Impairment; Individual; Interdisciplinary Study; Knowledge; Link; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Mentorship; Metabolic; Methods; Mitochondria; Morphologic artifacts; Muscle; Muscle function; Muscular Atrophy; Myocardial tissue; Myocardium; Noise; Organ; Outcome; Pathologic; Pathway interactions; Patients; Performance; Population; Process; Property; Proteins; Quality of life; Questionnaires; Relaxation; Reporting; Reproducibility; Research; Research Design; Research Personnel; Research Project Grants; Scanning; Site; Skeletal Muscle; Techniques; Technology; Testing; Thigh structure; Time; Tissues; Training; Walking; X-Ray Computed Tomography; aging population; biomedical imaging; bone imaging; cardiac magnetic resonance imaging; cardiovascular imaging; career development; density; grasp; healthy volunteer; heart imaging; human subject; improved; in vivo evaluation; insight; mitochondrial dysfunction; mortality; muscle form; novel; programs; research study; sarcopenia; simulation; skeletal muscle wasting; skills; tool

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.

项目概要 该提案的目标是开发一种新型定量磁共振成像（MRI）技术 用于表征心力衰竭 (HF) 中的肌少症、骨骼肌质量和功能丧失以及支持 研究者 Brendan Eck 博士在衰老和生物医学成像研究领域的职业发展。 研究：心力衰竭中的肌肉减少症是不良预后的独立预测因素。虽然原发性肌少症是一种 在老龄化的情况下，心力衰竭中肌肉减少症的发生率高于一般人群。病理生理学 心脏和骨骼肌中的机制已被确定，这些机制与心力衰竭和肌肉减少症有关。当前工具 用于评估心力衰竭肌少症的方法是间接的，或者对早期发生的骨骼肌改变不敏感 在疾病中。定量 MRI 可以提供对以下因素可能敏感的组织特性测量： 骨骼肌的病理变化。然而，现有技术速度慢或不切实际 可重现。 MR 指纹识别 (MRF) 已发展成为一种快速、可重复的技术，用于量化 多种组织特性。然而，定量 T1rho（一种对蛋白质含量变化敏感的测量方法） 直到最近才被证明可以通过 MRF 进行量化，但尚未研究其在肌肉减少症中的应用。这个项目 旨在开发 T1rho-MRF 以同时量化 T1rho 和其他 MRF 衍生的骨骼肌 特性。 T1rho-MRF 还将开发用于心脏成像，以研究影响心脏的组织变化 心力衰竭肌肉减少症的骨骼肌和心肌。在该项目的目标 1 中，T1rho-MRF 技术将在模拟中得到开发和优化。 T1rho-MRF 将在物理体模中得到验证 以及在人类受试者中。还将获得骨骼肌活检并将 T1rho-MRF 与 组织特性，例如纤维类型比例。在目标 2 中，健康对照者和患有肌肉减少症和心力衰竭的患者 无肌肉减少症，将使用 T1rho-MRF 进行扫描。定量值将在组之间进行比较 描述患有肌肉减少症的心力衰竭患者。 T1rho-MRF 测量结果将与握力功能相关 力量、6 分钟步行和心肺测试。 职业发展：研究者具有定量心血管成像的技术背景和 旨在过渡到衰老和生物医学成像研究。该研究项目培养关键技能和 研究者职业发展的知识。职业发展计划提供生物学培训 衰老、骨骼肌生物学、与临床医生合作以了解临床评估 HF 中的肌肉减少症以及影像学研究的设计和执行。培训包括教学和 体验成分。多元化的指导团队、顾问和合作者贡献互补 开发候选人跨学科研究计划的技能。 摘要：该提案将提供新颖的成像工具来评估心衰肌少症并支持职业生涯 使研究者成为衰老和生物医学成像领域的独立研究者。