Diffusion tensor imaging of the right ventricle

The National Heart, Lung, and Blood Institute awarded The General Hospital Corporation, doing business as Massachusetts General Hospital, $802,156 under Project Grant R01HL183169 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837).

The award funds development of diffusion tensor magnetic resonance imaging (DTI) techniques to image the microstructure of the human right ventricle in vivo. The recipient will develop a diffusion-encoded MRI sequence compensated for the first three moments of motion (M3SE) to overcome motion artifacts that currently limit visualization of right ventricular microstructure. Current approaches using motion-compensated spin echo sequences (M2SE) achieve only 2.5×2.5 millimeter in-plane resolution, which under-resolves the thin right ventricular wall; recent free-breathing refinements improved visualization but remain limited by complex right ventricular motion patterns. The M3SE sequence is hypothesized to significantly improve right ventricular microstructure visualization by addressing the principal technical challenge of managing more complex gradient waveforms required for higher-order motion compensation.

Work is performed at Massachusetts General Hospital's Research Management Division in Boston, Massachusetts, from September 1, 2026, through May 31, 2030. The assistance type is a Project Grant.

Abstract

The right ventricle (RV) plays a central role in cardiovascular disease. In several conditions mechanical failure of the RV can result in severe morbidity or mortality, and IT can also be a source of lethal ventricular arrhythmias. Changes in the arrangement of cardiomyocytes in the RV could play an important role in these processes but cannot be characterized at present in the human heart. The microstructure of the RV has been examined histologically in animal models, but this has several major limitations. The RV is a thin and highly compliant chamber, and its microstructure could be influenced by its shape and loading conditions. A compelling need, therefore, exists to develop an approach to image the microstructure of the human RV in vivo. Diffusion tensor MRI (DTI) has been used with significant success to image the microstructure of the left ventricle (LV). We and others have used a spin echo sequence with diffusion-encoding gradients compensated for the first and second moments of motion (M2SE) to image the LV. Imaging with this approach is typically performed with an in-plane spatial resolution of 2.5X2.5MM, which severely under-resolves the thin RV wall. We have recently developed an approach to perform free-breathing M2SE of the heart with sub-millimeter in-plane resolution. This has improved the visualization of the RV, but its microstructure has remained difficult to fully resolve. We hypothesize here that DTI of the RV with M2SE is limited by the complex motion patterns of the RV, and that the diffusion-encoded images remain corrupted by motion. The key goal of this proposal is, therefore, to develop a diffusion-encoded sequence compensated for the first 3 moments of motion. We hypothesize that this M3SE sequence will result in a significant improvement in the visualization of RV microstructure. The principal challenge of M3SE lies in the potential of the more complex gradient waveforms to significantly lengthen the echo time (TE) of the sequence, which is not well tolerated in the heart. To address this, we will use convex optimization to design a M3-nulled gradient waveform with the shortest possible TE as well as commercial MRI scanners with 200MT/M whole body gradients. In aim 1 of the proposal, we will focus on the optimization of the M3SE sequence. In aim 2 we will use the sequence to characterize RV microstructure in heathy subjects. Particular attention will be paid to the impact of electrical and mechanical loading conditions on readouts of RV microstructure. In aim 3, we will use our approach to characterize RV microstructure in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Changes in RV microstructure will be correlated with mechanical and electrical manifestations of the disease. Execution of the study will not only advance the technical sophistication of diffusion tensor imaging, but also provide important insights into the pathophysiology of the RV and its role in a broad range a cardiovascular conditions.