Quantification and Characterization of Coronary Atherosclerotic Plaque by CT

描述(申请人提供)：扎德博士是马里兰州巴尔的摩约翰·霍普金斯医院的学术心脏病专家。他职业生涯的大部分时间都致力于以患者为导向的研究，特别关注冠状动脉疾病的诊断和预防。扎德博士在使用血管内超声、常规冠状动脉造影术和心脏计算机断层扫描来检测和表征冠状动脉疾病方面积累了相当多的专业知识。在约翰·霍普金斯医院心脏科任教的头三年里，他是一项多中心国际研究的组成部分，该研究旨在评估与传统冠状动脉造影术相比，多探测器计算机断层扫描(MDCT)检测阻塞性冠状动脉疾病的准确性。Zadeh博士现在是约翰·霍普金斯医院心脏CT的副主任和心脏CT冠状动脉造影核心实验室的主任，这是一项比较MDCT与核应力灌注成像和常规血管成像的第二项国际研究。扎德博士的长期职业目标是成为一名独立的临床研究员，其具体目标是将来自非侵入性冠状动脉成像的丰富的新信息转化为改进的心脏事件预测模型，用于基于人群的应用和患者管理。最终，他的目标是通过实施更好的预防策略，为降低我们社会和世界范围内的心肌梗死和心源性死亡的比率做出贡献。这一奖项申请旨在将扎德博士从一名在临床研究方面拥有坚实背景但在生物统计学和流行病学方面存在缺陷的指导研究员提升为一名能够根据冠状动脉成像和冠状动脉疾病方面的经验设计和进行临床结果研究的独立临床调查员。该奖项的目标将通过1)生物医学统计学和流行病学方面的全面教学培训计划和2)指导研究的经验来实现，这直接适用于他的长期目标。具体地说，该奖项头三年的重点将是彭博公共卫生学院在生物医学统计学、心血管流行病学和试验设计方面的密集课程工作，这些课程将在3年内获得公共卫生硕士学位。拟议的研究计划包括三个部分。第一部分是对参加CORE-多中心研究的32名患者的回顾分析，以验证多层螺旋CT对冠状动脉总斑块体积和斑块特征的评估与血管内超声的比较。这项分析的新方面是首次尝试通过MDCT与已建立的标准相比较来全面量化冠状动脉粥样硬化斑块的总负荷，并首次使用相对衰减测量来更有力地评估斑块特征。第二部分包括一项320层CT的前瞻性分析，用于评估30例心脏移植患者的冠状动脉总斑块体积和斑块特征，并与组织病理学进行比较。这将是第一次使用当代MDCT进行此类研究。与组织病理学相比，在心脏移植前分析和切除后即刻获得在体MDCT图像的独特机会将提供关于MDCT评估冠状动脉疾病的能力的宝贵信息。最后，在第三步中，这些经过验证的冠状动脉粥样硬化斑块体积和特征分析方法将用于预测参加CORE-320多中心研究的400名患者的心脏事件风险。CORE-320多中心研究是一项诊断准确性研究，旨在将MDCT对冠状动脉解剖和心肌负荷灌注成像的评估与传统的血管造影术和核负荷测试进行比较，为期5年。扎德博士在取得独立临床研究员地位方面的进展将受到他的导师、共同导师和一个指导顾问委员会的密切监督。约翰霍普金斯大学医学院和彭博公共学院提供了出色的培训环境，因此非常适合支持扎德博士转变为专注于以患者为中心的研究的独立研究员。

DESCRIPTION (provided by applicant): Dr. Zadeh is an academic cardiologist at the Johns Hopkins Hospital in Baltimore, Maryland. He devoted most of his career to patient oriented research with a particular focus on diagnosis and prevention of coronary artery disease. Dr. Zadeh gathered considerable expertise in the use of intravascular ultrasound, conventional coronary angiography, and cardiac computed tomography for the detection and characterization of coronary artery disease. During his first three years on the faculty in the Division of Cardiology at the Johns Hopkins Hospital he was an integral part of a multicenter, international study to evaluate the accuracy of multi-detector computed tomography (MDCT) to detect obstructive coronary artery disease in comparison to conventional angiography. Dr. Zadeh is now the Associate Director of Cardiac CT at the Johns Hopkins Hospital and the Director of the Cardiac CT coronary angiography core laboratory for a second international study comparing MDCT to nuclear stress perfusion imaging and conventional angiography. Dr. Zadeh's long term career goal is to become an independent clinical investigator with the specific objective to translate the new and abundant information from non-invasive coronary artery imaging into improved cardiac event prediction models for population based application and patient management. Ultimately, his goal is to contribute to a decrease in the rates of myocardial infarction and cardiac death in our society and worldwide by implementing better prevention strategies. This award application is designed to advance Dr. Zadeh from the status of a mentored researcher with a solid background in clinical research but with deficiencies in biostatistics and epidemiology to an independent clinical investigator who is able to design and conduct clinical outcome studies based on experience in coronary imaging and coronary artery disease. The objectives of this award will be accomplished through 1) a comprehensive didactic training program in biomedical statistics and epidemiology and 2) the experience of conducting supervised research, which is directly applicable to his long term goal. Specifically, the focus of the first three years of this award will be intensive course work in biomedical statistics, cardiovascular epidemiology, and trial design at the Bloomberg School of Public Health which will lead to a master degree in public health within 3 years. The proposed research plan consists of three parts. Part 1 consists of a retrospective analysis to validate MDCT assessment of total coronary atherosclerotic plaque volume and plaque characteristics compared to intravascular ultrasound in 32 patients enrolled in the CorE-64 multicenter study. The novel aspects of this analysis are the first attempt to fully quantify total coronary atherosclerotic plaque burden by MDCT in comparison to an established standard and the first use of relative attenuation measurements for a more robust assessment of plaque characterization. Part 2 includes a prospective analysis of 320-slice CT for the assessment of total coronary atherosclerotic plaque volume and plaque characteristics compared to histopathology in 30 patients scheduled to undergo heart transplantation. This will be the first such study using current generation MDCT. The unique opportunity to acquire MDCT images in vivo before heart transplantation analysis and ex vivo immediately after excision in comparison to histopathology will provide invaluable information regarding the ability of MDCT to assess coronary artery disease. Lastly, in a third step these validated methods of coronary atherosclerotic plaque volume and characteristics analysis will be applied to predict the risk of cardiac events in 400 patients who are being enrolled for the CorE-320 multicenter study, a diagnostic accuracy study to compare MDCT assessment of coronary anatomy and myocardial stress perfusion imaging to conventional angiography and nuclear stress testing, during a 5-year follow up. Dr. Zadeh's progress to achieving the status of an independent clinical investigator will be closely monitored by his mentor, co-mentor, and a mentoring advisory committee. The Johns Hopkins University School of Medicine and Bloomberg School of Public provide an outstanding training environment and thus are ideally suited to support Dr. Zadeh's transition to an independent investigator with focus on patient-oriented research.