Preclinical Water-Mediated Ultrasound Platform using Clinical FOV for Molecular Targeted Contrast-Enhanced Ultrasound

Abstract

Background: This protocol introduces an ultrasound (US) configuration for whole-body 3D dynamic contrast-enhanced ultrasound (DCE-US) imaging in preclinical applications. The set-up relies on a clinical abdominal matrix US probe to enable mice imaging beyond current preclinical systems that are generally unable to capture whole-body volumetric and dynamic imaging. We demonstrate via this protocol the feasibility of volumetric contrast-enhanced and molecular 3D imaging in the entire lower body of mouse, as well as the capability of imaging multiple lesions in the same animal simultaneously with a single contrast bolus injection. Methods: We modified a silicone cup with a 101.6 mm inner diameter and 6.4 mm wall thickness, to a height of 76.2 mm and cut out a rectangular side window (12.7 mm x 15.9 mm) at the lower part of the cup. Mice were positioned with their head and the two front legs outside of the cup while the rest of the body remained inside the cup and submerged under water; the edges around the mouse's body in contact with the cup's wall were sealed with Vaseline to prevent water leakage, and the cup was filled with warm water to maintain the mouse's body heat. Imaging was conducted using a portable clinical ultrasound system (EPIQ 7 Philips) with an abdominal matrix-array transducer (PM mode, X6-1) inserted into the top of the cup, and positioned to visualize the entire of the mouse's abdomen. The mice were imaged before and after the injection of P-selectin-targeted microbubbles. Results: Here, in nude mice with two adjacent tumors, we demonstrate that a commercially available clinical matrix transducer can be utilized to achieve whole-body 3D DCE-US and molecular US imaging, as well as capture independent qualitative and quantitative information from several lesions or organs at different locations in the animal, through a single bolus injection.