SUPER-RESOLUTION ULTRASOUND LOCALIZATION MICROSCOPY ON A RABBIT LIVER VX2 TUMOR MODEL: AN INITIAL FEASIBILITY STUDY

Ultrasound localization microscopy can image microvasculature in vivo without sacrificing imaging penetration depth. However, the reliance on super-resolution inference limits the applicability of the technique because subpixel tissue motion can corrupt microvascular reconstruction. Consequently, the majority of previous pre-clinical research on this super-resolution procedure has been restricted to low-motion experimental models with ample motion correction or data rejection, which precludes the imaging of organ sites that exhibit a high degree of respiratory and other motion. In this article, we present a novel anesthesia protocol in rabbits that induces safe, controllable periods of apnea to enable the long image-acquisition times required for ultrasound localization microscopy. We apply this protocol to a VX2 liver tumor model undergoing sorafenib therapy and compare the results to super-resolution images from conventional high-dose isoflurane anesthesia. We find that the apneic protocol was necessary to correctly identify the poorly vascularized tumor cores, as verified by immunohistochemistry, and to reveal the tumoral microvascular architecture. (C) 2021 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

Automated summary

Ultrasound localization microscopy has the potential to image microvasculature in vivo without sacrificing imaging penetration depth, but has been limited by the reliance on super-resolution inference. This study presents a novel anesthesia protocol in rabbits to induce safe, controllable apnea periods for long image-acquisition times. The results demonstrate the necessity of the apneic protocol for correctly identifying poorly vascularized tumor cores and revealing tumoral microvascular architecture.