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.
