Characterization of sarcopenia in heart failure by T1rho magnetic resonance fingerprinting

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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.