Ultrasound Imaging Based on Molecular Targeting for Quantitative Evaluation of Hepatic Ischemia–Reperfusion Injury

Abstract

The aim of the present study was to quantitatively diagnose and monitor the therapy response of hepatic ischemia–reperfusion injury (IRI) with the use of targeted ultrasound (US) imaging. Targeted microbubbles (MBs) were fabricated, and the binding of intracellular adhesion molecule 1 (ICAM-1) antibodies to MBs was observed. To establish a quantitative method based on targeted US imaging, contrast-enhanced US was applied for IRI rats. After andrographolide treatment, the IRI rats were subjected to the quantitative targeted US imaging for a therapeutic effect. Effective binding of ICAM-1 antibodies to MBs was observed. According to the quantitative targeted US imaging, the ICAM-1 normalized intensity difference (NID) in the IRI rats (38.74 ± 15.08%) was significantly higher than that in the control rats (10.08 ± 2.52%, p = 0.048). Further, different degrees of IRI (mild IRI, moderate to severe IRI) were distinguished by the use of the NID (37.14 ± 2.14%, 22.34 ± 1.08%, p = 0.002). Analysis of mRNA expression demonstrated the accuracy of analyzing the NID by using quantitative targeted US imaging (R2= 0.7434, p < 0.001). Andrographolide treatment resulted in an obviously weakened NID of ICAM-1 (17.7 ± 4.8% vs 34.2 ± 6.6%, p < 0.001). The study showed the potential of the quantitative targeted US imaging method for the diagnosis and therapeutic monitoring of IRI.