Quantification and Characterization of Coronary Atherosclerotic Plaque by CT

简介（由申请人提供）：Zadeh博士是马里兰州巴尔的摩市约翰霍普金斯医院的学术心脏病专家。他的大部分职业生涯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。Zadeh博士在使用血管内超声、常规冠状动脉造影和心脏计算机断层扫描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病学系的前三年，他参与了一项多中心国际研究，评估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，并与传统血管造影进行比较。Zadeh博士现在是约翰霍普金斯医院心脏CT副主任和心脏CT冠状动脉造影核心实验室主任，负责第二项比较MDCT与核应激灌注成像和传统血管造影的国际研究。Zadeh博士的长期职业目标是成为一名独立的临床研究者，其具体目标是将新的和丰富的非侵入性冠状动脉成像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，为降低我们社会和全世界的心肌梗死和心脏死亡率做出贡献。该奖项申请旨在将Zadeh博士从具有扎实临床研究背景但在生物统计学和流行病学方面存在不足的指导研究人员提升为能够根据冠状动脉成像和冠状动脉疾病的经验设计和开展临床结果研究的独立临床研究人员。该奖项的目标将通过1)生物医学统计和流行病学的综合教学培训计划和2)进行监督研究的经验来实现，这直接适用于他的长期目标。具体而言，该奖项前三年的重点将是彭博公共卫生学院生物医学统计、心血管流行病学和试验设计方面的强化课程，这将使学生在三年内获得公共卫生硕士学位。拟定的研究计划由三部分组成。第一部分包括回顾性分析，以验证32名参加CorE-64多中心研究的患者的MDCT评估冠状动脉粥样硬化斑块总体积和斑块特征与血管内超声的比较。该分析的新颖之处在于，与已建立的标准相比，首次尝试通过MDCT全面量化冠状动脉粥样硬化斑块总负荷，并首次使用相对衰减测量来更可靠地评估斑块特征。第2部分包括对30例计划接受心脏移植的患者进行320层CT的前瞻性分析，以评估冠状动脉粥样硬化斑块总体积和斑块特征，并将其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，在心脏移植分析前和切除后立即获得体内MDCT图像的独特机会将为MDCT评估冠状动脉疾病的能力提供宝贵的信息。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被应用于预测400名参加CorE-320多中心研究的患者的心脏事件风险，该研究是一项诊断准确性研究，旨在比较5年随访期间MDCT对冠状动脉解剖和心肌应激灌注成像的评估与传统血管造影和核应激测试。Zadeh博士取得独立临床研究者地位的进展将由他的导师、共同导师和指导咨询委员会密切监测。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Zadeh博士过渡到专注于以患者为导向的研究的独立研究者。

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. PUBLIC HEALTH RELEVANCE: This research is likely to positively impact our health care system because it proposes and tests tools that may increase our ability to identify patients who are at increased risk of suffering cardiac events and who may benefit from more aggressive treatment. Conversely, the proposed tools may help identifying patients who are at very low risk of suffering cardiac events and in whom treatment can be safely omitted. Resources therefore could be allocated more efficiently and reduce the financial burden on our health care system.