HIFU plus contrast agent enhance non-thermal effects of ultrasound

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Pulsed, high-intensity focused ultrasound (PHIFU) with contrast agent can enhance non-thermal effects of ultrasound, according to research published Nov. 21, 2008 in the World Journal of Gastroenterology.

In recent years, HIFU has been widely used for the treatment of solid tumors, such as liver tumor, bone tumor and breast cancer. The mechanism for therapeutic actions of HIFU includes thermal effects and non-thermal effects with the latter dominated by cavitational effects, according to background information in the study.

Adjusting acoustic parameters of can control thermal effects and non-thermal effects; short duty cycle and high intensity favors the occurrence of cavitation. Ultrasound contrast agent (UCA) can enhance cavitational effects. Lesions caused by non-thermal effects have characteristic pathological changes quite different from those of thermal lesions, the authors noted.

The research group, led by Zhi-Biao Wang, MD, PhD, from the department of biomedical engineering of Chongqing Medical University in Chongqing, China, used PHIFU with short duty cycle and high-intensity combined with UCA SonoVue (Bracco of Milan, Italy) to damage rabbit liver VX2 tumor by non-thermal effect, and the non-thermal damage was evaluated by histopathology.

Liver VX2 tumor model were established in 20 rabbits, which researchers then divided randomly into PHIFU combined with UCA group (PHIFU+UCA group) and sham group, with 10 rabbits in each group.

In the PHIFU+UCA group, the investigators reported that 0.2 mL of SonoVue was injected intravenously, followed by rapid injection of 1 mL normal saline. Fifteen seconds after the injection, the tumors were exposed to HIFU with ISP 5900W/cm2 for 90 seconds. Rabbits were sacrificed one day after HIFU exposure. Specimens of the exposed tumor tissues were obtained and observed pathologically under light microscope and transmission electron microscope. The remaining exposed tumor tissues were sent for TTC staining.

Before TTC staining, tumor tissues in both the sham and the PHIFU+UCA group resembled gray fish meat; after TTC staining, the tumor tissues were uniformly stained red, with a clear boundary between tumor tissue and normal tissue, the authors wrote.

For PHIFU + UCA group, Wang and colleagues found that light microscopy displayed abundant vacuoles of various sizes in the cytoplasm and in some cells, chromatin margination and karyopyknosis were present. Electron microscopic examination revealed presence of karyopyknosis and chromatin margination in some cells, intercellular space widening, the presence of high electron-density apoptotic bodies and many vacuoles of various sizes in the cytoplasm.

“The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors,” the authors concluded.