SBIR-STTR Award

Development of MRI techniques, optimized for cardiovascular disease (CVD) applications, are currently hampered by low signal to noise ratios (SNR), tissue motion and blood flow artifacts. The long term goal of this project is to develop an Atherosclerotic Lesion Phantom (ALP) to assist the MRI community develop non invasive applications to identify patients at risk for clinically acute CV syndromes. This will be accomplished by: 1) accurately modeling the morphology of key pathogenic features associated with high risk atherosclerotic lesions and 2) providing a controlled environment that reproduces the difficulties associated with clinical imaging. ALP combines the benefits of existing technologies with: an innovative artificial artery including multiple wall layers (Aim 1), stenotic lesions that mimic the morphology (Aim 2) and MRI content (T1, T2, contrast) of atherosclerotic lesions in a stable and well characterized manner (Aim 3). In Phase II, we focus on optimizing materials and procedures identified in Phase I in anticipation of constructing advanced flow phantoms for Phase III product evaluation. A comprehensive ALP will be critical for the development and validation of new clinical applications as well as in training medical personnel on using state of the art MRI screening protocols for atherosclerotic CVD. PROPOSED COMMERCIAL APPLICATION: The magnitude of the clinical need for a non invasive means to identify patients at risk for plaque rupture or erosion is so large and the commercial availability of adequate MRI tools so limited as to create a lucrative market niche for a highly advanced atherosclerotic lesion phantom targeted at cardiovascular disease. Products developed from this project will address current and future needs in clinical research, QA, and personnel training applications

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.

Thesaurus Terms:
atherosclerosis, atherosclerotic plaque, cardiovascular imaging /visualization, image enhancement, magnetic resonance imaging, model design /development, phantom model artery stenosis bioimaging /biomedical imaging, clinical research, human data