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.

项目摘要 本提案的目标是开发一种新的定量磁共振成像（MRI）技术 用于表征心力衰竭（HF）和支持中的肌肉减少症、骨骼肌质量和功能丧失 研究者Brendan Eck博士在衰老和生物医学成像研究方面的职业发展。 研究：HF患者的肌肉减少症是不良结局的独立预测因素。虽然原发性肌肉减少症是一种 随着年龄的增长，HF中的肌肉减少症的发生率高于一般人群。病理生理 心脏和骨骼肌中的机制已被确定为将HF和肌肉减少症联系起来。当前工具 用于评估HF中的肌肉减少症是间接的，或者对早期发生的骨骼肌改变不敏感 疾病。定量MRI可以提供对组织性质潜在敏感的组织性质测量。 骨骼肌的病理变化。然而，现有的技术是不切实际的慢或不 可复制的磁共振指纹（MRF）已发展为一种快速，可重复的技术，用于定量 多种组织特性。然而，定量T1 rho，一种对蛋白质含量变化敏感的指标， 最近才被证明是可量化的MRF没有研究其在肌肉减少症的使用。这个项目 旨在开发T1 rho-MRF，以同时定量T1 rho和其他MRF衍生的骨骼肌 特性. T1 rho-MRF还将用于心脏成像，以研究影响 骨骼肌和心肌中的肌减少症与HF。在项目目标1中，T1 rho-MRF 将在模拟中开发和优化技术。T1 rho-MRF将在物理体模中进行确认 和人类受试者。还将采集骨骼肌活检，并将T1 rho-MRF与 组织特性，如纤维类型比例。在目标2中，健康对照和HF患者，具有肌肉减少症和 没有肌肉减少症，将使用T1 rho-MRF进行扫描。将比较各组之间的定量值， 表征患有肌肉减少症的HF患者。T1 rho-MRF测量值将与抓握功能相关 力量、6分钟步行和心肺功能测试。 职业发展：研究者具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。该研究项目开发关键技能， 为研究者的职业发展提供知识。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，了解 HF中的肌肉减少症，以及成像研究设计和执行。培训包括教学和 经验成分。一个多元化的导师团队，顾问和合作者贡献互补 发展候选人的跨学科研究计划的技能。 总结：该提案将提供新的成像工具，以评估HF中的肌肉减少症，并支持职业生涯 研究者的发展，成为一个独立的研究人员在老化和生物医学成像。