Molecular Imaging of Atherosclerosis in Peripheral Artery Disease

PROJECT SUMMARY The long-term goal of this work is to develop a translatable imaging paradigm that enables comprehensive assessment of multiple anatomical and physiological parameters in patients with peripheral artery disease (PAD). Patients with lower extremity PAD are at increased risk of lifestyle limiting claudication, non-healing wounds, amputation, and death, which is often attributed to deficits in limb perfusion and high levels of vascular calcification above and below the knee. PAD patients with diabetes mellitus (DM) have accelerated progression of peripheral vascular calcification, which reduces lower extremity muscle perfusion, limits options for revascularization, reduces technical success rates of revascularization procedures, and increases risk for amputation. Despite this knowledge, an ongoing challenge for the vascular medicine community is the lack of standardized non-invasive imaging tests that quantify regional perfusion abnormalities as well as vessel- specific calcific disease progression in PAD patients. Our team recently developed a novel dual-phase (i.e., combined dynamic and static) PET/CT imaging approach using 18F-NaF that quantifies both regional muscle perfusion and vessel-specific active arterial microcalcification in the lower extremities during a single imaging session using a single radioisotope dose injection. In the proposed projects, we will characterize the stages of peripheral atherosclerosis targeted by 18F-NaF using an existing biobank of human arterial specimens possessing varying degrees of calcium density and stiffness. We will then prospectively apply dual-phase 18F- NaF PET/CT imaging to PAD patients with and without DM to quantify muscle-specific perfusion abnormalities and vessel-specific calcium burden, and to predict vessel-specific calcium progression across a 1.5-year study period. Following clinical evaluation of our approach, we will test the performance of deep learning image segmentation methods for enabling efficient analysis of vessel-specific measures of active and established arterial calcification as well as muscle-specific deficits in lower extremity perfusion from PET/CT images. Completion of the proposed studies would lead to a comprehensive and scalable imaging approach that quantifies multiple anatomical and functional parameters associated with PAD severity, calcium progression, and clinical outcomes in PAD patients, which would improve the evaluation, monitoring, and risk assessment of PAD patients who are at elevated risk of adverse limb and cardiovascular events.