PET/CT for Multidimensional Translational Cardiovascular Research

描述（由申请人提供）：心血管分子成像是一个快速发展的领域，为心脏和血管疾病患者的评估提供了可观的前景。虽然使用新型显像剂和微型PET在心脏病小鼠模型中进行了概念验证研究，但将其转化为人类和大型动物模型一直存在问题，因为人类心脏比人类大2000倍，剂量测定和示踪剂定位也有很大不同。该提案要求通过获得用于研究的混合正电子发射断层扫描（PET）和多探测器计算机断层扫描（CT）扫描仪来支持推进临床前和临床转化心血管分子成像。它将支持和加强七个主要用户正在进行的研究成像项目（由9个RO1奖和2个专注于心血管成像的K奖支持）。拟议的GE Discovery VCT是一种最先进的PET/CT扫描仪，将允许血管和心肌结构的临床前研究，并结合使用由UB正电子发射断层扫描中心开发的新型回旋加速器产生的放射性药物进行分子成像。布法罗大学的心血管医学研究中心和东芝中风中心是跨学科的心血管研究中心，在转化心血管成像方面是公认的领导者。美国国立卫生研究院支持的研究常规采用先进的心血管成像在猪模型慢性缺血性心脏病和中风的大型动物模型。除了基本的机制研究外，在血管支架、体内基因转移和干细胞（间充质干细胞和内皮祖细胞）心血管修复等治疗领域也有活跃的研究项目。还有一项正在进行的NIH支持的大型临床试验，通过使用11c -羟麻黄碱量化冬眠心肌的程度和交感神经的成像不均匀性来确定PET是否可以预测患者心源性猝死的风险（用正电子发射断层扫描预测心律失常事件）。在冬眠心肌、冠状动脉疾病、脑血管疾病和缺血性心肌病等大型动物疾病模型方面的专业知识，以及心脏PET、定量图像分析和放射化学合成等面向患者的研究，是该研究团队的独特优势。拟议的仪器和这两个团队之间的协同作用将促进应用于心血管系统的分子成像领域的快速发展。

DESCRIPTION (provided by applicant): Cardiovascular molecular imaging is a rapidly emerging area offering considerable promise for the evaluation of patients with heart and vascular disease. While proof of concept studies using novel imaging agents and micro PET have been conducted in mouse models of heart disease, their translation to humans and large animal models has been problematic since the human heart is 2000 times larger and dosimetry and tracer localization are considerably different. This proposal requests support to advance preclinical and clinical translational cardiovascular molecular imaging by acquiring a hybrid positron emission tomography (PET) and multidetector computed tomography (CT) scanner dedicated to research. It will support and enhance the ongoing investigational imaging programs of seven major users (supported by 9 RO1 awards and 2 K awards focused on cardiovascular imaging). The proposed GE Discovery VCT is a state of the art PET/CT scanner that will permit preclinical studies of vascular and myocardial structure coupled with molecular imaging using novel cyclotron generated radiopharmaceuticals developed at the adjacent UB Center for Positron Emission Tomography. The Center for Research in Cardiovascular Medicine and Toshiba Stroke Center at the University at Buffalo are interdisciplinary cardiovascular research centers that are recognized leaders in translational cardiovascular imaging. NIH supported studies routinely employ advanced cardiovascular imaging in porcine models of chronic ischemic heart disease and large animal models of stroke. Besides basic mechanistic research, active programs exist in therapeutics including vascular stents, in vivo gene transfer and cardiovascular repair with stem cells (mesenchymal stem cells and endothelial progenitor cells). There is also a large ongoing NIH supported clinical trial to determine if PET can predict the risk of sudden cardiac death in patients by quantifying the extent of hibernating myocardium and imaging inhomogeneity in sympathetic innervation using 11C-Hydroxyephedrine (Prediction of Arrhythmic Events with Positron Emission Tomography). The combined institutional expertise in large animal disease models including hibernating myocardium, coronary disease, cerebrovasular disease and ischemic cardiomyopathy along with patient oriented research in cardiac PET, quantitative image analysis and radiochemistry synthesis are unique strengths of this investigative team. The proposed instrument and synergy between these two teams will facilitate rapid advancements in the field of molecular imaging as applied to the cardiovascular system. PUBLIC HEALTH RELEVANCE: Heart disease continues to be one of the leading causes of death and disability. The proposed PET/CT system will advance bench to bedside research of potentially clinically relevant therapies by focusing on research at the preclinical to clinical translational interface. Such multilevel translational research ultimately has a high likelihood of directly impacting patient care and improving health outcomes. `