Controlled Hyperthermia With High-Intensity Focused Ultrasound and Ultrasound Contrast Agent Microbubbles in Porcine Liver

Abstract

Objective: The objective of this work was to study microbubble-enhanced temperature elevation with high-intensity focused ultrasound (HIFU) at different acoustic pressures and under image guidance. The microbubbles were administered with either local or vascular injections (that mimic systemic injections) in perfused and non-perfused ex vivo porcine liver under ultrasound image guidance.

Methods: Porcine liver was insonified for 30 s with a single-element HIFU transducer (0.9 MHz, 0.413 ms, 82% duty cycle, focal pressures of 0.6-3.5 MPa). Contrast microbubbles were injected either locally or through the vasculature. A needle thermocouple at the focus measured temperature elevation. Diagnostic ultrasound (Philips iU22, C5-1 probe) guided placement of the thermocouple and delivery of microbubbles and monitored the procedure in real time.

Results: At lower acoustic pressures (0.6 and 1.2 MPa) in non-perfused liver, inertial cavitation of the injected microbubbles led to greater temperatures at the focus compared with HIFU-only treatments. At higher pressures (2.4 and 3.5 MPa) native inertial cavitation in the tissue (without injecting microbubbles) resulted in temperature elevations similar to those after injecting microbubbles. The heated area was larger when using microbubbles at all pressures. In the presence of perfusion, only local injections provided a sufficiently high concentration of microbubbles necessary for significant temperature enhancement.

Conclusion: Local injections of microbubbles provide a higher concentration of microbubbles in a smaller area, avoiding acoustic shadowing, and can lead to higher temperature elevation at lower pressures and increase the size of the heated area at all pressures.

Keywords: Acoustic shadowing; Heated area; High-intensity focused ultrasound; Hyperthermia; Microbubbles; Perfusion; Thermal lesion; Ultrasound contrast agents.