Experimental Study Of Acoustic Droplet Vaporization Enhanced High Intensity Focused Ultrasound Treatment Of Tumor

Acoustic droplet vaporization (ADV) is a promising techniqueenhancing the therapeutic outcome of high intensity focused ultrasound(HIFU) treatment. When delivered in vivo, ADV is generated only withinthe focal region of HIFU, which increases the heat accumulation in a veryshort time, and correspondently overcome current disadvantage of theHIFU treatment which takes a long time for large tumors. The therapeuticeffects of the combined HIFU and ADV treatment of4T1tumors in micewas investigated in this paper.Tissue-mimicking phantoms were used to quantify the enhancementof the ADV technique and find the appropriate treatment parameters for invivo study. It was found addition of the droplets to the animal before HIFUtreatment could enlarge the lesion volume up to16times. And the acousticthreshold required to form visible thermal lesion was found to besignificantly reduced.Before treat the animals with the combined modality, tumor growthrate and the correspondent blood supply were followed. The growth curveand regions with sufficient blood supply inside the tumor were quantified.Based on the results, tumors grown for15days and21days were treated.Histological examination showed that the combination of HIFU and ADVgenerated a mean necrotic area in the tumor that was2.9-fold larger thanwith HIFU alone(n=6). A significant enhancement of necrosis was found inthe periphery of the tumor, where the blood supply was abundant. After treatment, the tumor volume was found to decrease very quickly. After7days following treatment, the tumors treated with combined HIFU andADV were30fold smaller in volume than tumors treated with HIFU alone.When changing the HIFU parameter, with focal distance enlarged, it wasfound the tumors treated with combined HIFU and ADV were mostlydestroyed, while for those treated with HIFU alone, most of the tumor cellswere still viable. The mean necrotic tumor area in the group withcombination of HIFU and ADV was3-fold larger than the one with HIFUalone(n=6). The study demonstrated that the microdroplets could bevaporized in vivo using current HIFU systems and addition of the dropletsto the animal before HIFU treatment could greatly enhance the HIFUtherapeutic effect in vivo tumor treatment.