This pulsed cavitational ultrasound system is capable of transcutaneous nonthermal destruction of renal tissue. Refinement of this technology for noninvasive ablation of small renal masses is currently under way.

Purpose-This study evaluated histotripsy as a noninvasive, image-guided method of thrombolysis in a porcine model of deep vein thrombosis. Histotripsy therapy uses short, highintensity, focused ultrasound pulses to cause mechanical breakdown of targeted soft tissue by acoustic cavitation, which is guided by real-time ultrasound imaging. This paper is an in-vivo feasibility study of histotripsy thrombolysis.Methods and Materials-Acute thrombi were formed in the femoral vein of juvenile pigs weighing 30-40 kg by balloon occlusion with two catheters and thrombin infusion. A 10-cm diameter 1-MHz focused transducer was used for therapy. An 8 MHz ultrasound imager was used to align the clot with the therapy focus. Therapy consisted of 5 cycle pulses delivered at a rate of 1 kHz and peak negative pressure between 14-19 MPa. The focus was scanned along the long axis of the vessel to treat the entire visible clot during ultrasound exposure. The targeted region identified by a hyperechoic cavitation bubble cloud was visualized via ultrasound during treatment.Results-Thrombus breakdown was apparent as a decrease in echogenicity within the vessel in 10 of 12 cases, and in 7 cases, improved flow through the vein as measured by color Doppler. Vessel histology showed denudation of vascular endothelium and small pockets of hemorrhage in the vessel adventitia and underlying muscle and fatty tissue, but perforation of the vessel wall was never observed. Conclusions-The results indicate histotripsy has potential for development as a noninvasive treatment for deep vein thrombosis.

Hepatocellular carcinoma (HCC) or liver cancer is one of the fastest growing cancers in the United States. Current liver ablation methods are thermal-based and share limitations due to the heat sink effect from the blood flow through the highly vascular liver. In this study, we demonstrate the feasibility of using histotripsy for non-invasive liver ablation in the treatment of liver cancer. Histotripsy is a non-thermal ablation method that fractionates soft tissue through the control of acoustic cavitation. Twelve histotripsy lesions ~1cm3 were created in the livers of six pigs through an intact abdomen and chest in vivo. Histotripsy pulses of 10 cycles, 500 Hz pulse repetition frequency (PRF), and 14-17 MPa estimated in situ peak negative pressure were applied to the liver using a 1 MHz therapy transducer. Treatments were performed through 4-6 cm of overlying tissue with 30-50% of the ultrasound pathway covered by the ribcage. Complete fractionation of liver parenchyma was observed with sharp boundaries after 16.7 minute treatments. In addition, two larger volumes of 18 cm3 and 60 cm3 were generated within 60 minutes in two additional pigs. As major vessels and gallbladder have higher mechanical strength and are more resistant to histotripsy, the major hepatic vessels and gallbladder remained intact while the liver surrounding these structures was completely fractionated. This work demonstrates that histotripsy is capable of non-invasively fractionating liver tissue while preserving critical anatomical structures within the liver. Results suggest histotripsy has potential for the non-invasive ablation of liver tumors.

Acoustic droplet vaporization (ADV) shows promise for spatially and temporally targeted tissue occlusion. In this study, substantial tissue occlusion was achieved in operatively exposed and transcutaneous canine kidneys by generating ADV gas bubbles in the renal arteries or segmental arteries. Fifteen canines were anesthetized, among which 10 underwent laparotomy to externalize the left kidney and 5 were undisturbed for transcutaneous ADV. The microbubbles were generated by phase conversion of perfluoropentane droplets encapsulated in albumin or lipid shells in the blood. A 3.5 MHz single-element therapy transducer was aligned with an imaging array in a water tank with direct access to the renal artery or a segmental artery. In vivo color flow and spectral Doppler imaging were used to identify the target arteries. Tone bursts of 1 kHz pulse repetition frequency with 0.25% duty cycle vaporized the droplets during bolus passage. Both intracardiac (IC) and intravenous (IV) injections repeatedly produced ADV in chosen arteries in externalized kidneys, as seen by B-mode imaging. Concurrent with this in two cases was the detection by pulse wave Doppler of blood flow reversal, along with a narrowing of the waveform. Localized cortex occlusion was achieved with 87% regional flow reduction in one case using IC injections. Vaporization from IV injections resulted in a substantial echogenicity increase with an average half-life of 8 minutes per droplet dose. Gas bubbles sufficient to produce some shadowing were generated by transcutaneous vaporization of intra renal artery or IV administered droplets, with a tissue path up to 5.5 cm.