Cardiac Magnetic Resonance to Detect Apoptosis in Vivo using Magnetic Labeling.

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DESCRIPTION: The candidate's immediate career goal is to obtain an Assistant Professor position at an academic Cardiology Division that allows for protected (75%) research time with a 25% clinical obligation. Ideally, the research will be translational work aimed toward improved diagnosis and treatment of cardiovascular disease. Because the candidate is trained in advanced cardiac imaging, the opportunity to employ these imaging skills in both the clinical and investigational settings will be critical. Long-term, the candidate hopes to establish a diverse and robust research program that validates new molecular imaging targets at the bench, and then tests the utility of those targets in clinical trials. This research proposal will examine the ability of non-invasive molecular imaging to detect cell death and cardiac remodeling in vivo. Specifically, cardiac magnetic resonance (CMR), which provides superior depth penetration and spatial resolution, will be used to image magnetically-labeled Annexin V (ANX-SPIO), which has been shown to bind cells early in apoptosis. The major hypothesis is that systemically delivered ANX-SPIO will be able to track to and monitor (by MRI) areas of myocardial cell death following either myocardial infarction or cardiotoxic doxorubicin exposure. This methodology is novel in its approach, and pursuit of this critical frontier in cardiac molecular imaging may lead to a new platform from which cardiovascular disease is both studied and treated. This proposal incorporates significant career development for the candidate. Through critical interactions with a rich cohort of mentors in Cardiac MRI, molecular imaging, and cardiac apoptosis/cell biology, the candidate will obtain invaluable and broad technical training in the fields that will lay the foundation for an independent research program in cardiac molecular imaging. The research environment at UCSF is ideally suited for this endeavor. Combined with concurrent coursework in biostatistics and various molecular imaging techniques (bioluminescence, MR-SPECT), these experiences will help the candidate compete for R01 funding to establish the aforementioned independent research program. RELEVANCE (See instructions): Using magnetic labeling to detect heart muscle damage may allow real-time adjustments to chemotherapy regimens, thereby preventing the irreversible heart failure that can result from these treatments. A similar strategy to monitor stem cell protection of threatened myocardium after heart attacks may also be possible. Thus, the ability to detect cardiac cell death through MRI may positively impact patient care and outcomes. (End of abstract)