Super‐Resolution Ultrasound Imaging of Renal Microcirculation in a Murine Model of Renal Fibrosis

OBJECTIVES: Peripheral kidney microvascular damage and chronic perfusion dysfunction in kidney fibrosis are demonstrated in most chronic kidney diseases. There is an urgent clinical need to develop an in vivo, noninvasive, and quantitative diagnostic tool to monitor the renal microcirculation. The present study aims to investigate the feasibility of super-resolution ultrasound (SRU) imaging in the visualization and quantification of renal microvascular and microcirculation in mice of unilateral ureteral obstruction (UUO). METHODS: The SRU for renal micro-vessels imaging in healthy mice was performed and compared with conventional power Doppler ultrasound (US) and micro-computed tomography (CT). Renal fibrosis was prepared in vivo using UUO. B-mode, conventional power Doppler US, and SRU imaging were performed on the sham kidneys and UUO models at 3, 7, and 14 days. Then these kidneys were followed by histopathologic analysis and comparisons with SRU quantification parameters. RESULTS: SRU helped to evaluate the function and structure of vessels in progressive renal disease via quantifying the renal microvascular. The quantitative parameters of SRU based on total blood flow of the kidney were calculated in the sham group, 3, 7, and 14 days after UUO. Renal cortical vessel density (r = 0.881), vessel curvature (r = -0.506), cortical perfusion index (PI) (r = 0.668) showed correlations with pathologically derived vessel density labeled with the expression of CD31. Vessel density (r = -0.615) and cortical curvature (r = -0.842), cortical PI (r = -0.508) also showed correlations with Masson's trichrome stain. Vessel curvature (r = -0.591) showed correlations with the expression of Col-1. CONCLUSION: SRU imaging provides the noninvasive, dynamic, and longitudinal monitoring of vessel functionality and can provide quantification of renal microvascular changes in a murine model of renal fibrosis.