Novel Technology Enables Diagnostic Ultrasound Machine to Treat Hepatocellular Carcinoma in Mice

An off-the-shelf diagnostic transducer (ULTRASONIX C5-2) was modified with custom-built circuitry to enable the transducer to produce therapeutic ultrasound in order to ablate hepatocellular carcinomas grown in immunodeficient athymic nude mice (25-35 g; Charles River Laboratories, Wilmington, MA, USA). The therapeutic antivascular ultrasound (AVUS) produced by the off-the-shelf abdominal transducer was unfocused, continuous 2.8MHz ultrasound targeting contrast-enhancing perflutren lipid microbubbles within tumor vasculature. Previous research with a dedicated physiotherapy ultrasound machine (D150 Plus, Dynatronics Corp., Salt Lake City, UT, USA) targeting similar hepatocellular carcinomas showed disrupted tumor neovasculature and irreparable dilation of tumor capillaries with subsequent intercellular edema and hemorrhage.1-3 In this study, the echointensity, peak enhancement (PE), perfusion index (PI), and area under curve (AUC) were measured using non-linear contrast B-mode images acquired before and after the sham or AVUS treatment. These measurements all showed the AVUS produced by the diagnostic transducer markedly decreased tumor blood flow (P \u3c 0.001). In addition, tumor temperature measurement in the live mice showed that AVUS treatment markedly increased tumor temperature with a thermal dose (CEM43) delivered by ultrasound treatment of 124.02 min versus sham of 0 min. Finally, histochemical staining of the tumor samples taken after AVUS treatment revealed several hemorrhagic pools in tumors while the sham-treated tumors lack such hemorrhagic pools. This study demonstrates diagnostic transducers can be enabled to produce AVUS with the ability to target mural hepatocellular carcinomas