# Serial evaluation of cardioprotective effects of exercise training in heart failure using cardiac diffusion tensor MRI

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $683,284

## Abstract

Project Summary / Abstract
 Heart failure (HF) is accounts for 1 in 9 deaths in the United States and currently affects ~6 million with
a prevalence of 250,00-400,000 and incidence of 70,000-120,000. Current therapy does not address the
underlying loss of functional heart muscle and adverse structural remodeling. One novel potential treatment of
HF is exercise (aerobic) therapy that has demonstrated various cardioprotective properties to halt and potentially
reverse adverse structural remodeling. However, dosing of exercise therapy remains a challenge due to each
individual's inherent differences and consequentially, serial non-invasive monitoring of the therapy would be
necessary to evaluate the change on structural remodeling. Furthermore, current non-invasive technologies
characterize structural remodeling with surrogate measures and thus, there is no consensus on a single clinical
gold-standard. Without a tool to monitor and characterize the degree of structural remodeling, the evaluation of
the therapeutic potential of exercise therapy in HF patients cannot be fully realized representing an unmet need
in ultimately improving therapy. The proposed project aims to improve the therapy monitoring of exercise training
to cardioprotect against HF by revealing its effect on microstructural remodeling with cardiac diffusion tensor
MRI (DT-MRI). DT-MRI is a unique, non-invasive technology capable of characterizing myocardial fiber
orientation and directly reflecting microstructural remodeling. However, despite major advances, there are
fundamental challenges that limit the capability of current cardiac DT-MRI methods to be applied robustly in a
clinical setting. In this project, an innovative 5-min “push button” DT-MRI method will be developed that
overcomes such limitations. We also leverage institutional strengths to further quantify the accuracy of in vivo
DT-MRI in revealing myocardial microstructure using novel tissue cleared 3D histology. The central hypothesis
is that addressing these major technical challenges will allow for clinical translation of cardiac DT-MRI to serve
as a tool to monitor the therapeutic effects of HF on microstructural remodeling. This is achieved by extending
previously developed technologies used for myocardial fibrosis detection with diffusion-weighted MRI. The
proposed project is designed to systematically develop an innovative and robust clinical DT-MRI methodology
and rigorously validate in a pre-clinical setting the effects of exercise therapy on the microstructural remodeling
of HF thereby laying the groundwork for potential optimization of dosing exercise therapy.

## Key facts

- **NIH application ID:** 10848235
- **Project number:** 5R01HL151704-06
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Christopher T Nguyen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $683,284
- **Award type:** 5
- **Project period:** 2022-11-04 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848235

## Citation

> US National Institutes of Health, RePORTER application 10848235, Serial evaluation of cardioprotective effects of exercise training in heart failure using cardiac diffusion tensor MRI (5R01HL151704-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10848235. Licensed CC0.

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