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

Am J Transplant. 2017 Dec;17(12):3087-3097. doi: 10.1111/ajt.14345. Epub 2017 Jun 8.

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.

Keywords: animal models: canine; basic (laboratory) research/science; diagnostic techniques and imaging: ultrasound; liver transplantation/hepatology.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Disease Models, Animal
  • Diterpenes / pharmacology*
  • Intercellular Adhesion Molecule-1 / chemistry*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Molecular Targeted Therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / diagnostic imaging*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Ultrasonography / methods*

Substances

  • Anti-Inflammatory Agents
  • Diterpenes
  • ICAM1 protein, rat
  • Intercellular Adhesion Molecule-1
  • andrographolide