Abstract 17797: Noninvasive Optical Imaging of Response to On-Demand Antioxidant Therapy in a Model of Peripheral Arterial Disease

Abstract

Peripheral arterial disease is often modeled by surgical induction of hind limb ischemia (HLI) in mice to study collateral vessel development. However, there is a need for methodologies that provide intravital, multifunctional, quantitative data on ischemic recovery for robust evaluation of new therapeutics. Here, we apply hyperspectral imaging and optical coherence tomography (OCT) to longitudinally assess hemoglobin oxygen saturation (SaO 2 ) and vessel morphology in response to a novel therapy. Injectable microspheres loaded with curcumin were synthesized from reactive oxygen species (ROS)-responsive poly(propylene) sulfide (PPS) to provide “on demand”, local release of the antioxidant drug curcumin to reduce tissue-damaging oxidative stress in a mouse model of diabetic HLI. Curcumin-PPS microspheres significantly reduced intracellular ROS in LPS-activated RAW 264.7 macrophages and rescued viability of 3T3 fibroblasts treated with cytotoxic levels of H 2 O 2 in vitro . HLI was induced in FVB mice with streptozotocin-induced diabetes, and curcumin-PPS or blank-PPS microspheres were injected into the ischemic limb. Curcumin-PPS significantly improved recovery of SaO 2 in the ischemic footpad relative to blank-PPS and vehicle (saline) groups over a one week time course evaluated with hyperspectral imaging (n≥8/group, p<0.05). Vessel structure in the gastrocnemius was imaged noninvasively with OCT at day 7 (Figure), revealing trends toward increased vessel area density and vessel length fraction in the curcumin-PPS group (n=5/group). The vessel diameter distribution was also extracted from OCT data. Our collective data indicate that sustained, on demand curcumin delivery has significant therapeutic promise for improving ischemic tissue recovery. Also, the hyperspectral and OCT imaging methods showcased provide quantitative, noninvasive monitoring of vasculature and can accelerate screening of novel therapies.