Abstract

A diagnostic ultrasound machine add-on module (AOM) was created to enable an off-the-shelf abdominal imaging transducer to perform contrast-enhanced therapeutic ultrasound. The AOM creates plane-wave ultrasound through an abdominal imaging transducer targeting intravascular microbubbles within tumors. This therapeutic antivascular ultrasound (AVUS) causes heating and cavitation effects that destroy tumor vasculature and starves it of nutrients. The AOM can switch between therapeutic and imaging modes for monitoring of AVUS treatment. The therapeutic capability of the AOM was validated in murine hepatocellular carcinomas (HCC) grown in adult mice. Contrast-enhanced ultrasound imaging performed before and after the therapeutic treatment evaluated the AVUS response of the treatment. The peak enhancement (PE), perfusion index (PI), and area under curve (AUC) were measured for the control and AOM treatment groups. The AOM group showed a substantial decrease in these parameters compared to the control group. The difference between the pre- and post-therapy was significant, (P < 0.001) for the AOM group and not significant (P > 0.5) for the control group. Tumor temperatures increased markedly for the AOM group with a thermal dose (CEM43) of 124.8 (± 2.5). Histochemical analysis of the excised HCC samples revealed several hemorrhagic pools in tumors from the AOM group, absent in the tumors of the control group. These results demonstrate the theranostic potential of the AOM to induce and monitor vascular disruption within murine tumors.

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