Atherosclerotic Lesion Phantom (ALP) for MRI/A

描述（由申请人提供）： 基于图像的评估动脉粥样硬化性动脉疾病的状态和进展已被提出作为一个指标，以建立新兴的反向脂质转运（RLT）治疗的优点。确立新兴疗法益处的关键是：良好的临床方案依从性、低指数测量方差和多中心临床研究中心之间的高相关性。斑块体积、组成和大小目前被用作性能的主要和次要指标。IVUS是目前晚期冠状动脉疾病的成像标准，具有侵入性，并且存在限制临床试验期间性能和患者招募的缺陷。针对斑块可视化和量化进行了优化的MRI为IVUS提供了一种非侵入性替代方案，尤其是在颈动脉应用中。先进的ALP幻影，适当使用，将有助于实现统计上的结论性结果，加快心血管治疗的发展，在更短的时间内，以更低的成本。拟议的项目目标是开发一种高级的动脉粥样硬化病变治疗（ALP），用于RLT临床试验。在第一阶段，建立了概念验证，并引入了创新的制造技术。II期技术目标，解决制药合作伙伴要求的性能要求：1）基于临床数据的设计，2）定义的斑块形态，代表两种病变类型，包括与风险相关的三个关键斑块成分，3）重现与临床成像相关的困难的支持环境（解剖学杂乱、血流、血管和患者运动，4）与多个血管床（颈动脉、冠状动脉）兼容的先进材料和制造程序。在目前参与药物试验的地点构建原型并进行评价。目前，国内选定的胆固醇治疗市场超过190亿美元。临床试验每多运行一天，就需要400万美元的支出和收入损失。如果成功，ALP将满足未满足的临床需求，从而带来显著的经济和社会效益。

DESCRIPTION (provided by applicant): Image based assessment of atherosclerotic arterial disease status and progression has been proposed as an index to establish the merits of emerging reverse lipid transport (RLT) therapies. Key to establishing the benefits of emerging therapies are: good adherence to clinical protocols, low index measurement variance & high correlation between multi-center clinical sites. Plaque volume, composition and size are currently employed as primary and secondary indices of performance. IVUS, the current imaging standard for late stage coronary disease, is invasive and suffers from deficiencies that limit both performance and patient enrollment during clinical trials. MRI, optimized for plaque visualization and quantification provides a non invasive alternative to IVUS, especially in carotid applications. Advanced ALP phantoms, properly employed, will help achieve statistically conclusive results speeding the development of cardiovascular therapies in less time at lower costs. Proposed project goals are to develop an advanced class of Atherosclerotic Lesion Phantoms (ALP) for use RLT clinical trials. In Phase I, proof-of-concept was established and innovative manufacturing techniques introduced. Phase II technical aims, address performance requirements requested by Pharmaceutical partners: 1) designs based on clinical data, 2) defined plaque morphologies, representing two lesion types including three key plaque components associated with risk, 3) supporting environment which reproduces difficulties associated with clinical imaging (anatomic clutter, blood flow, vessel & patient motion, 4) advanced materials and manufacturing procedures compatible with multiple vascular beds (carotid, coronary). Prototypes are constructed and evaluated at sites currently involved in pharmaceutical trials. The current domestic market for selected cholesterol therapies exceeds $19 Billion. Each additional day a clinical trial must run requires $4 million in expenditures and lost revenue. If successful, ALP will fulfill an unmet clinical need, resulting in significant monetary and societal benefits.