Molecular imaging of vascular pathology

描述（由申请人提供）： 该提案描述了一个为期5年的培训计划，以发展分子成像研究的学术生涯。 主要研究者在马萨诸塞州总医院完成了放射学住院医师培训，是一名委员会认证的放射科医生。 首席研究员现在将在一个独特的多学科环境和研究计划中扩展他的科学技能。该计划旨在促进对进行分子成像研究所需的理解和技能，在一个科学奖励和临床相关的项目中。 Ralph Weissleder教授将是首席研究员科学发展的主要导师。 Weissleder教授是马萨诸塞州综合医院分子影像研究中心主任。 他是分子成像研究领域公认的领导者，并拥有出色的培训记录。主要研究者将由公认的放射性药物和核/PET放射学专家Alan Fischman教授和世界知名的中风专家Michael Moskowitz教授共同指导。高危（“易损”）动脉粥样硬化斑块的特征在于强烈的炎症和蛋白水解酶和氧化酶的产生。 该研究计划将专注于酶敏感磁共振成像（MRI）造影剂的开发及其在体外和体内环境中的验证。 总的假设是，通过这些“智能”试剂测量的酶活性（例如过氧化物酶）的体内MRI将直接识别生物学上脆弱的（活动性炎症）动脉粥样硬化病变，从而显著提高MRI表征动脉粥样硬化斑块的能力。 具体而言，我们的目标是1）通过利用结构修饰合成用于MPO检测的高灵敏度底物; 2）验证生物系统中最有前途的底物; 3）在成熟的动脉粥样硬化动物模型中验证最佳底物，并与免疫组织化学和生物化学研究相关联。

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in molecular imaging research. The principal investigator has completed residency training in radiology at Massachusetts General Hospital, and is a board certified radiologist. The principal investigator will now expand his scientific skills in a unique multidisciplinary environment and research program. The program is designed to promote an understanding of and skills necessary to conduct molecular imaging research, in a project that is scientifically rewarding and clinically relevant. Professor Ralph Weissleder will be the primary mentor for the principal investigator's scientific development. Professor Weissleder is the Director of Center for Molecular Imaging Research at Massachusetts General Hospital. He is a recognized leader in molecular imaging research and has an outstanding training record. The principal investigator will be co-mentored by Professor Alan Fischman, a recognized expert in radiopharmaceuticals and nuclear/PET radiology, and by Professor Michael Moskowitz, a world-renowned expert in stroke. High-risk ("vulnerable") atherosclerotic plaques are characterized by intense inflammation and the production of proteolytic and oxidative enzymes. This research program will focus on the development of enzyme-sensing magnetic resonance imaging (MRI) contrast agents and their validation in in vitro and in vivo settings. The overall hypothesis is that in vivo MRI of enzyme activity (e.g. peroxidase) measured by these "smart" agents will directly identify biologically vulnerable (active inflammatory) atherosclerotic lesions, thereby dramatically improving MRI's capability to characterize atherosclerotic plaques. Specifically, we aim to 1) synthesize highly sensitive substrates for MPO detection by exploiting structural modifications; to 2) validate the most promising substrates in biological systems, and to 3) validate the optimal substrates in a well-established animal model of atherosclerosis and correlate with immunohistochemical and biochemical studies.