Magnetization Transfer Contrast MRI of Myocardial Fibrosis

The 2-year event free survival rate of patients with myocardial fibrosis, as identified following intravenous (IV) infusion of the contrast agent gadolinium with delayed contrast enhanced (DCE)–MRI (1), is approximately 50% (19) (Fig 1). Myocardial fibrosis can be spatially variable at low densities (termed diffuse fibrosis), or spatially focalized at high densities (termed dense fibrosis), often transitioning from diffuse to dense states as part of disease progression. The sensitivity of DCE-MRI limits detection to dense fibrosis, obstructing a large window for potential therapeutic intervention (22). Recently, we developed a contrast agent free MRI method that uses MTC from collagen to image myocardial fibrosis, as well as software to quantify the degree of fibrosis from MTC-MR images. The proposed research seeks to validate this technique in preclinical imaging of diabetes induced diffuse myocardial fibrosis, and in translational imaging of fibrosis in patients. Completion of this work will significantly improve patient care by enabling noninvasive and early diagnosis of myocardial fibrosis, and by enabling expedited translational development of novel anti-fibrotic therapies (24, 25). I. HYPOTHESES 1) MTC-MRI enables detection of myocardial fibrosis in a mouse model of diabetes, and can provide an early predictor of fibrosis induced contractile dysfunction. 2) Automated assessment of fibrosis in the human heart with MTC-MRI agrees with DCE-MRI.