A Molecular Imaging Strategy for In Vivo Monitoring of Vascular Remodeling in a Porcine Model of Femoral Artery Overdilation.

Abstract

Clinical use of endovascular interventions has increased in recent decades for treatment of peripheral artery disease (PAD); however, molecular imaging paradigms for monitoring inflammatory responses or adverse remodeling in targeted arteries have not been validated. Therefore, this study tested the utility of positron emission tomography (PET) imaging with fluorine-18 (¹⁸F)-fluorodeoxyglucose (FDG) for in vivo detection of peripheral angioplasty-induced arterial remodeling. Yorkshire pigs (n = 8) underwent fluoroscopy-guided overdilation of the right femoral artery using a balloon catheter inflated 1.25-1.85X the arterial diameter. ¹⁸F-FDG PET/CT imaging was performed 14 days post-angioplasty. Injured and control arteries were harvested immediately after imaging and sectioned for gamma counting (¹⁸F-FDG uptake) and stained with hematoxylin and eosin (H&E), alpha-smooth muscle actin (α-SMA), and CD64 for evaluation of arterial thickness, smooth muscle cell area, and macrophage infiltration. In vivo PET/CT imaging detected a significant increase in ¹⁸F-FDG uptake in injured versus control femoral arteries 14 days post-angioplasty (p = 0.008) that was confirmed by ex vivo gamma counting of vessels (p = 0.02). Ex vivo gamma counting of ¹⁸F-FDG uptake demonstrated a significant association with in vivo ¹⁸F-FDG uptake measured by PET/CT imaging (r = 0.92; p = 0.004). Image analysis for H&E, α-SMA, and CD64 revealed significant relative increases in vessel wall thickness (p < 0.0001), smooth muscle cell area (p = 0.0001), and CD64 area (p = 0.04) that were each significantly associated with ex vivo measures of ¹⁸F-FDG uptake. ¹⁸F-FDG PET/CT quantifies remodeling characteristics associated with angioplasty-induced injury, thereby providing a potential in vivo paradigm for monitoring and testing of emerging devices for PAD treatment.