Molecular imaging of vascular pathology

血管病理学的分子成像

• 批准号: 7135471
• 负责人: JOHN W CHEN
• 金额: $ 13.31万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7135471
• 关键词: atherosclerosis; atherosclerotic plaque; bioimaging /biomedical imaging; blood vessel disorder; cardiovascular imaging /visualization; chemical kinetics; chemical synthesis; clinical research; contrast media; enzyme activity; enzyme substrate; genetically modified animals; human subject; immunocytochemistry; laboratory mouse; magnetic resonance imaging; molecular /cellular imaging; molecular pathology; molecular probes; myeloperoxidase; pharmacokinetics; technology /technique development

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.

描述（由申请人提供）： 该建议描述了一项为期5年的培训计划，以开发分子成像研究的学术生涯。 首席研究人员已完成马萨诸塞州综合医院放射学的住院医师培训，并且是董事会认证的放射科医生。 主要研究人员现在将在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必需的理解和技能，该项目在科学上有奖励和临床相关的项目。 拉尔夫·韦森德（Ralph Weissleder）教授将成为主要研究者科学发展的主要导师。 Weissleder教授是马萨诸塞州综合医院分子成像研究中心主任。 他是分子成像研究的公认领导者，并拥有出色的培训记录。首席研究员将由公认的放射性药物和核/宠物/宠物放射学专家艾伦·菲奇曼（Alan Fischman）教授，以及中风专家迈克尔·莫斯科维茨（Michael Moskowitz）教授。高风险（“脆弱”）动脉粥样硬化斑块的特征是强烈的炎症和蛋白水解和氧化酶的产生。 该研究计划将重点介绍酶 - 感应磁共振成像（MRI）对比剂及其在体外和体内环境中的验证。 总体假设是，由这些“智能”剂测量的酶活性的体内MRI（例如过氧化物酶）将直接识别生物学上脆弱的（主动炎症性）动脉粥样硬化病变，从而极大地提高了MRI的能力，可以表征动脉粥样硬化的斑块。 具体而言，我们的目的是1）通过利用结构修饰来合成高度敏感的底物以进行MPO检测；到2）验证生物系统中最有希望的底物，并验证3）在建立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化研究相关。