VEGFR2-Targeted Ultrasound Molecular Imaging of Angiogenesis to Evaluate Liver Allograft Fibrosis

Abstract

Background: 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 insensitive to early-stage pathological changes, which affects its diagnosis accuracy of LAF. Herein, based on a thorough comparison with US elastography at multiple disease stages, VEGFR2-targeted US molecular imaging (USMI) was validated to be highly potent for LAF early diagnosis and staging. Methods: The VEGFR2-targeted microbubbles (MBs) were fabricated as a specific probe for angiogenesis, and a LAF rodent model was induced. Then, VEGFR2-targeted USMI and US elastography were compared in terms of evaluating the LAF progress. Findings: The quantitative USMI result (NID) displayed much higher linear correlation with histological standards including Metavir fibrosis score (R2 = 0.7723 vs 0.3504) and VEGFR2 semi-quantitative counting (IOD) (R2 = 0.7801 vs 0.4902) than US elastography measurements. Interpretation: The results demonstrated a greatly improved diagnosis accuracy owing to the advantages of VEGF receptor-2 (VEGFR2) targeted USMI in reducing the inflammatory influence as well as increasing the sensitivity to early-stage pathological changes. The study overcame the intrinsic limitations of US elastography, thus highlighting the potential of VEGFR2-targeted USMI as an effective monitoring tool for LAF surveilling. Funding: This work was supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangdong Province and Fundamental Research Funds for the Central Universities. Declaration of Interests: The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. Ethics Approval Statement: All animal studies in the research were approved by the Sun Yat-sen University Animal Care Committee and followed standard guidelines.