VEGFR2-targeted ultrasound molecular imaging of angiogenesis to evaluate liver allograft fibrosis

Abstract

Liver allograft fibrosis (LAF) is a common challenge threatening patient survival after liver transplantation, making a potent imaging technique vital for clinical management. To date, ultrasound (US) elastography has been regarded as one of the most promising techniques for LAF monitoring. However, it is susceptible to inflammation and also insensitive to early-stage pathological changes, which affects its diagnostic accuracy of LAF. Herein, based on a thorough comparison with US elastography at multiple disease stages, VEGF receptor-2 (VEGFR2) targeted US molecular imaging (USMI) was validated to be highly potent for LAF early diagnosis and staging. The VEGFR2-targeted microbubbles (MBs) were fabricated as a specific probe for angiogenesis. Then, VEGFR2-targeted USMI and US elastography were compared in terms of evaluating the LAF progress in a rodent model. The quantitative USMI result displayed a much higher linear correlation with histological standards including the Metavir fibrosis score (R² = 0.77 vs. 0.35) and VEGFR2 semi-quantitative counting (R² = 0.78 vs. 0.49) than US elastography, which demonstrated a greatly improved diagnostic accuracy. The study not only revealed the mechanism of employing angiogenesis to describe LAF but also overcame the intrinsic limitations of US elastography, thus highlighting the potential of VEGFR2-targeted USMI as an effective monitoring tool for LAF surveilling.