Project Summary Heart disease is the leading cause of death in the US, resulting in over 600,000 deaths per year. The healthy heart is extremely metabolically active in order to supply its energetic needs, and alterations in cardiac metabolism have significant consequences for heart function. Metabolism is implicated in many heart diseases, including cardiomyopathies (hereditary hypertrophic cardiomyopathy, diabetic cardiomyopathy), diabetes, ischemia, HFpEF, and also as an early measure of systolic and diastolic heart failure. Measuring and quantifying heart metabolism would have significant implications on the diagnosis, understanding and management of these heart diseases, but there are no methods currently available to perform direct measurements of metabolism. This project aims to develop hyperpolarized 13C MRI as a human metabolic imaging for assessments of heart disease. This technology, utilizing 13C-pyruvate, has recently been shown to be safe and feasible in human subjects, with promising initial imaging in the heart. However, it still requires further development and in vivo validation to establish repeatable and reliable performance. This proposal includes Aim 1: Develop robust cardiac hyperpolarized 13C MRI methods. We propose imaging technology developments including real-time calibrations, fast imaging of multiple metabolites with whole heart coverage, image reconstructions with off-resonance correction, and cardiovascular signal models for quantifying metabolism. Aim 2: Perform in vivo validations in human subjects. We propose a series of studies that will establish robust imaging protocols and characterize the reproducibility and repeatability of this technique. These studies include evaluation of subject preparation methods, normalization of metabolic imaging data with correlative blood measurements, test-retest characterizations in healthy volunteers and patients, and same-session repeatability for multiple injection studies. The proposal also includes targeted performance measures to achieve with the proposed developments. Upon completion of this project, hyperpolarized 13C MRI has transformative potential for assessing heart diseases, adding new capabilities for quantifying metabolism in vivo.

Project Narrative Alterations in cardiac metabolism are implicated in a broad range of heart diseases, including cardiomyopathies, ischemia, and early heart failure. The project proposes to develop a novel imaging modality, hyperpolarized 13C MRI, for metabolic imaging to assess heart disease. Hyperpolarized 13C MRI has transformative potential by providing unique quantifications of metabolic fluxes for earlier and more precise diagnoses, improving understanding of pathogenesis, and rapid assessments of treatment response.