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

描述：候选人的近期职业目标是获得学术心脏病学部门的助理教授职位，允许保护（75%）的研究时间和25%的临床义务。理想情况下，这项研究将是旨在改善心血管疾病诊断和治疗的转化工作。由于候选人接受过高级心脏成像方面的培训，因此在临床和研究环境中使用这些成像技能的机会将至关重要。从长远来看，候选人希望建立一个多样化和强大的研究项目，在实验台上验证新的分子成像靶点，然后在临床试验中测试这些靶点的效用。本研究计划将检验非侵入性分子成像在体内检测细胞死亡和心脏重构的能力。具体来说，心脏磁共振（CMR）提供了优越的深度穿透和空间分辨率，将用于成像磁标记的膜联蛋白V (ax - spio)，该蛋白已被证明在细胞凋亡的早期结合细胞。主要的假设是，系统递送的anxo - spio将能够追踪和监测心肌梗死或心脏毒性阿霉素暴露后心肌细胞死亡的区域（通过MRI）。这种方法在方法上是新颖的，对心脏分子成像这一关键前沿的追求可能会为心血管疾病的研究和治疗提供一个新的平台。这份建议包含了候选人重要的职业发展。通过与心脏MRI、分子成像和心脏细胞凋亡/细胞生物学领域的丰富导师的重要互动，候选人将获得宝贵的广泛技术培训，为心脏分子成像的独立研究项目奠定基础。加州大学旧金山分校的研究环境非常适合这项工作。结合生物统计学和各种分子成像技术（生物发光，MR-SPECT）的并行课程，这些经验将有助于候选人竞争R01基金，以建立上述独立的研究计划。相关性（见说明）：使用磁标记检测心肌损伤可以实时调整化疗方案，从而防止这些治疗可能导致的不可逆心力衰竭。一个类似的策略来监测心脏病发作后干细胞对受威胁心肌的保护也是可能的。因此，通过MRI检测心脏细胞死亡的能力可能会对患者的护理和预后产生积极影响。（摘要结束）

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)