Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models

• Published in: Liver research 2023-12, Vol.7 (4), p.342-351
• Main Authors: Sha, Tingting, You, Yujia, Miao, Xiaoyan, Deng, Huan, Zhang, Wei, Ye, Huolin, Wang, Ping, Zheng, Rongqin, Ren, Jie, Yin, Tinghui
• Format: Article
• Language: English
• Subjects: CD36; Intercellular adhesion molecule-1 (ICAM-1); Non-alcoholic steatohepatitis (NASH); Noninvasive diagnosis; Ultrasound molecular imaging (USMI)
• ISSN: 2542-5684; 2542-5684
• DOI: 10.1016/j.livres.2023.11.002

Background and objective: Noninvasive non-alcoholic steatohepatitis (NASH) assessment is a clinical challenge to the management of non-alcoholic fatty liver disease. We aim to develop diagnostic models based on sequential ultrasound molecular imaging (USMI) for the noninvasive identification of NASH in mouse models. Methods: Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University. Forty-nine C57BL/6 mice were divided into normal control, non-alcoholic fatty liver, NASH, and hepatitis groups. Sequential USMI was implemented using CD36-targeted microbubbles (MBs-CD36) and intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles (MBs-ICAM-1) to visualize hepatic steatosis and inflammation. The targeting signal of USMI was quantified as the normalized intensity difference (NID) with the destruction-replenishment method. Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBs-ICAM-1 and pathological inflammation score. Finally, diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis. Results: MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice. NID-MBs-CD36 values increased with the progression of steatosis, while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation. A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade (rs = 0.9078, P