Abstract 312: Mapping the Inflammatory Macrophage Response during Arteriovenous Fistula Maturation by In Vivo Molecular Imaging

Abstract

Introduction Inflammation plays a critical role in neointimal hyperplasia (NH), which leads to arteriovenous fistula (AVF) failure in hemodialysis patients. However, the spatial distribution of macrophages in vivo post AVF creation remains unclear. In this study, we mapped the distribution of macrophages in AVF using intravital fluorescence microscopy (IVFM) and a fluorescence macrophage nanosensor, CLIO-VT680. We hypothesized that the intensity of CLIO-VT680 signals would illuminate the topography of AVF inflammation. Methods AVF was created in C57BL/6J mice (n=5) by end to side anastomosis between the jugular vein and the ipsilateral carotid artery. Mice were injected with CLIO-VT680 (10mg/kg) at day 13 post AVF creation and imaged by IVFM 24 hours later. AVF was resected at week 6, and Von Gieson (VVG) staining was performed. Mean CLIO signal intensity (MSI) was measured every 60μm from the anastomosis. Target to background ratios (TBRs) were calculated as the MSI of AVF divided by the MSI of the control artery. TBR ratio was calculated by the TBRs at different distance away from the anastomosis divided by the TBR at the anastomotic site. Results The survival rate of mice after AVF creation was 100%. The penetration depth of IVFM was 200μm. IVFM detected significantly higher TBRs of CLIO signals near the anastomotic site (p<0.05). There is a linear relationship between TBR ratios and the distance away from the anastomosis (R2=0.99). VVG staining of resected AVF showed the volume of NH decreased as the distance away from the anastomosis increased. Conclusion Macrophages response can be detected via CLIO-VT680 using IVFM. In vivo molecular imaging may be able to predict AVF failure.