High-resolution magnetization transfer weighted cardiac MRI of myocardial fibrosis using endogenous contrast mechanisms.

Fibrotic remodeling in the heart profoundly heightens the risk of deadly sudden cardiac arrhythmias1, 2 in patients with diabetes3-5, and in particular in those who undergo hemodialysis9. Cardiac magnetic resonance imaging (CMR) with gadolinium contrast agents, termed late gadolinium enhancement (LGE), is the state of the art technique for detection of myocardial fibrosis11, and is highly prognostic of deadly arrhythmias1, 2. However, the toxic side effects of gadolinium12-16 contraindicate diagnosis in many high risk patients including diabetic patients with reduced renal function. For those patients, diagnosis relies upon measurement of contractile dysfunction that is only present at late stages of heart failure3, 17, obstructing treatment during early disease stages. The inability to repeatedly assess fibrosis in these patients limits our understanding of how fibrotic remodeling leads to adverse cardiac events, and is a major barrier to the development of potential treatments. As a result, development of new approaches for non-invasive imaging of myocardial fibrosis, particularly in patients with reduced renal function, remains a high priority and unmet clinical need that could significantly reduce mortality from adverse cardiac events. Fibrotic collagen exchanges magnetization with bulk water through an endogenous process termed magnetization transfer (MT)18-20. We have developed a high resolution MT-weighted CMR approach (Figure 1) for rapid and gadolinium-free in vivo measurement of fibrosis, termed the Fibrotic Index (FI). Highly promising preliminary studies have demonstrated elevated Fibrotic Index in tissue identified as fibrotic using the standard of care LGE method. We seek to further validate measurement of the Fibrotic Index against LGE of both focal and diffuse fibrosis in patients. In addition, utilizing an existing cohort of 450 patients with chronic kidney disease (CKD) enrolled in an ongoing R01 funded longitudinal study at our institution as a model for diabetic cardiomyopathy, we will measure the Fibrotic Index in CKD patients, and test the prognostic capacity of Fibrotic Index for predicting adverse cardiac events in CKD patients.