Hepatocyte Injury Induced by Contrast-Enhanced Diagnostic Ultrasound

J Ultrasound Med. 2019 Jul;38(7):1855-1864. doi: 10.1002/jum.14883. Epub 2018 Dec 13.

Abstract

Objectives: Contrast-enhanced diagnostic ultrasound (US) has a potential to induce localized biological effects. The potential for contrast-enhanced diagnostic US bioeffects in liver were researched, with guidance from a report by Yang et al (Ultrasonics 2012; 52:1065-1071).

Methods: Contact and standoff scanning was performed for 10 minutes with a diagnostic US phased array at 1.6 MHz during bolus injection or infusion of a contrast agent at a high dose. The impact of the imaging on rat liver was investigated by measuring enzyme release, microvascular leakage, and staining of injured hepatocytes.

Results: The results showed liver enzyme release at 30 minutes, indicating liver injury, and elevated extraction of Evans blue dye, indicating microvascular leakage. In addition, Evans blue and trypan blue vital-staining methods revealed scattered stained cells within the US scan plane. For the Evans blue method, fluorescent cell counts in frozen sections were greatest for standoff exposure with contrast infusion. The count decreased strongly with depth for bolus injection, which was probably reflective of the high attenuation noted for this agent delivery method.

Conclusions: The results qualitatively confirmed the report by Yang et al and additionally showed hepatocyte vital staining. Research is needed to determine the threshold for the effects and the contrast agent dose response.

Keywords: contrast-enhanced diagnostic ultrasound; diagnostic ultrasound adverse effects; liver ultrasound imaging; ultrasonic cavitation biology.

MeSH terms

  • Animals
  • Contrast Media / adverse effects*
  • Evans Blue
  • Hepatocytes / drug effects*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Ultrasonography*

Substances

  • Contrast Media
  • Evans Blue