In-vivo intravascular autoradiography with storage phosphor detector

描述（由申请人提供）：约70%的急性冠状动脉疾病是由不稳定（易损）斑块引起的，其上覆冠状动脉炎症和高脂质含量。斑块的发炎帽的破裂导致血栓传播到管腔中、动脉阻塞和急性缺血综合征或猝死。形态学成像，如血管造影或血管内超声，可以识别冠状动脉斑块，但不能确定其炎症状态。易损斑块中放射性示踪剂18F-FDG的摄取高于正常斑块、血液或组织。这种机制可用于检测易损斑块。然而，正电子发射断层扫描（PET）不能检测到FDG标记的斑块，因为呼吸和心脏运动，小尺寸和低活性的斑块（注意，三分之二的急性缺血综合征是由相对较小和狭窄程度较低的斑块破裂引起的）。可以使用插入动脉的微型粒子（正电子）探测器来检测斑块。我们提出了一种用于斑块体内冠状动脉内成像的新探测器概念。探测器由一个固定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，吸收斑块中的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，这取决于尖端插入其中的动脉的长度和直径。初步实验和Monte Carlo模拟表明，所提出的系统的灵敏度和空间分辨率足以检测易损斑块的1-2 mm的大小和16-32 nCi的活动，在动脉直径为2-3 mm的曝光时间为1分钟。该提案的具体目标是：（1）开发基于存储磷光体的血管内成像系统;（2）使用冠状动脉和斑块模型评价系统性能;（3）在猪动物模型中研究使用具有存储磷光体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）设计一种临床上可应用的冠状动脉内成像原型。该技术将允许确定冠状动脉斑块是否是脆弱的。如果斑块是脆弱的，那么急性缺血综合征可以预期和治疗成为必要的。如果斑块不是脆弱的，那么患者可能没有问题，但是可以定期验证斑块的状态。此外，所提出的技术将允许研究易损斑块的关键特征，并获得基于体内成像的斑块研究的基本知识和方法，这些研究目前在很大程度上不可用。

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 It can be inserted into an artery, absorb the 18F-FDG positrons from the plaque, withdrawn from the artery and readout.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.