In-vivo intravascular autoradiography with storage phosphor detector

描述(申请人提供)：大约70%的急性冠状动脉疾病是由不稳定的(脆弱的)斑块引起的，上面的冠层发炎，脂肪含量高。斑块发炎帽的破裂会导致血栓扩散到管腔内，动脉阻塞，急性缺血综合征或猝死。形态成像，如血管造影术或血管内超声，可以识别冠状动脉斑块，但不能确定其炎症状态。易损斑块对放射性示踪剂18F-FDG的摄取高于正常斑块、血液或组织。这种机制可以用来检测脆弱的斑块。然而，正电子发射断层扫描(PET)无法检测到FDG标记的斑块，原因是呼吸和心脏运动、斑块体积小和活性低(请注意，三分之二的急性缺血综合征是由相对较小且狭窄较少的斑块破裂引起的)。斑块可以使用插入动脉的微型粒子(正电子)探测器来检测。我们提出了一种新的探测器概念，用于在体冠状动脉内成像斑块。该探测器由绑在血管内导管末端的存储磷光体尖端组成。它可以插入动脉，从斑块中吸收18F-FDG正电子，从动脉中取出并读出。存储磷光体尖端的长度和直径是可变的，这取决于插入该尖端的动脉的长度和直径。初步实验和蒙特卡罗模拟表明，该系统的灵敏度和空间分辨率足以检测直径为2-3 mm的动脉中1-2 mm的易损斑块和16-32个NCI活动，曝光时间为1分钟。该提案的具体目标是：(1)开发基于存储荧光粉的血管内成像系统；(2)使用冠状动脉和斑块模体来评估系统的性能；(3)在猪动物模型中研究使用存储荧光粉尖端的血管内成像系统可以检测和量化冠状动脉斑块的假设；(4)设计临床适用的冠状动脉内成像原型。这项拟议的技术将允许确定冠状动脉斑块是否脆弱。如果斑块是脆弱的，那么急性缺血综合征是可以预见的，治疗是必要的。如果斑块不脆弱，那么患者可能没有问题，但斑块的状态可以定期验证。此外，拟议的技术将允许研究脆弱斑块的关键特征，并获得基于体内成像的斑块研究的基本知识和方法，目前基本上无法获得这些知识和方法。

DESCRIPTION (provided by applicant): Approximately 70% of acute coronary artery disease is caused by unstable (vulnerable) plaques with an inflammation of the overlying cap and high lipid content. A rupturing of inflamed cap of plaque results in propagation of the thrombus into the lumen, blockage of the artery and acute ischemic syndrome or sudden death. Morphological imaging, such as angiography or intravascular ultrasound, can identify coronary plaque but cannot determine its inflammation status. Uptake of radiotracer 18F-FDG in vulnerable plaque is higher than in normal plaque, blood or tissue. This mechanism could be used to detect a vulnerable plaque. However, positron emission tomography (PET) cannot detect the FDG-labeled plaques because of respiratory and heart motions, small size and low activity of the plaque (notice that two thirds of acute ischemic syndromes result from a rupturing of relatively small and less stenotic plaques). Plaques can be detected using a miniature particle (positron) detector inserted into the artery. We propose a new detector concept for in-vivo intracoronary imaging of plaque. The detector consists of a storage phosphor tip bound to the end of an intravascular catheter. It can be inserted into an artery, absorb the 18F-FDG positrons from the plaque, withdrawn from the artery and readout. The length and diameter of the storage phosphor tip are variable, depending on the length and diameter of the artery into which the tip is inserted. Preliminary experiments and Monte Carlo simulations show that the sensitivity and spatial resolution of the proposed system are sufficient to detect vulnerable plaques of 1-2 mm size and 16-32 nCi activities in the arteries with 2-3 mm diameter for a 1 minute exposure time. Specific aims of the proposal are: (1) development of an intravascular imaging system based on storage phosphor; (2) evaluation of the system performance using coronary artery and plaque phantoms; (3) investigation of the hypothesis that coronary plaques can be detected and quantified using the intravascular imaging system with storage phosphor tip in a swine animal model; (4) design of a clinically applicable prototype for intra-coronary imaging. The proposed technique will allow determination of whether or not the coronary artery plaque is vulnerable. If plaque is vulnerable, then acute ischemic syndrome can be anticipated and treatment becomes necessary. If plaque is not vulnerable, then the patient may not have a problem, but the status of the plaque could be verified periodically. Additionally, the proposed technique will allow studying the key characteristics of the vulnerable plaques, and gaining both basic knowledge and methodologies for in-vivo imaging-based investigations of the plaques that are largely unavailable at the present time.