Histotripsy is an ultrasound ablation method that depends on the initiation of a cavitation bubble cloud to fractionate soft tissue. Although previous work has provided significant insight into the process of intrinsic threshold histotripsy, the majority of these studies have used highly focused (i.e. f-number<0.6) transducers. In this study, we investigate the effects of f-number on the histotripsy intrinsic threshold and cavitation bubble cloud behavior using a 500 kHz array transducer, with the effective f-number of the transducer varied from 0.51 to 0.89. The intrinsic threshold did not significantly change with f-number, with the threshold remaining ~27–30 MPa for all conditions. The predictability of intrinsic threshold histotripsy was further demonstrated by experiments comparing the predicted and experimentally measured bubble cloud dimensions, with results showing close agreement for all f-numbers. Finally, the effects of f-number on “bubble density” and tissue fractionation efficiency were investigated, with results supporting the hypothesis that the density of the bubbles within the bubble cloud significantly decreases at higher f-numbers, resulting in decreased fractionation efficiency. Overall, this study provides significant insight into the effects of f-number on intrinsic threshold histotripsy that will help to guide the development of intrinsic threshold histotripsy for specific clinical applications.

Hepatocellular carcinoma (HCC) or liver cancer has the fastest growing incidence among 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. Recently, our group has investigated histotripsy as a non-invasive liver cancer ablation method. Histotripsy is a non-thermal ultrasonic ablation method that fractionates tissue through the control of acoustic cavitation. Previous experiments in an in vivo porcine model show that histotripsy can create well-confined lesions in the liver through ribcage obstruction without damaging the overlying ribs and other tissues. Histotripsy can also completely fractionate liver tissue surrounding major vessels while preserving the vessels. In this study, we investigate the long-term effects of histotripsy liver ablation in a rodent model. We hypothesize that the fractionated histotripsy lesion will be resorbed by the liver, resulting in effective tissue healing. To test this hypothesis, the livers of 20 healthy rats were treated with histotripsy using an 8-element 1 MHz histotripsy transducer. Rats were euthanized after 0, 3, 7, 14, and 28 days (n=4). In vivo and post mortem results showed histotripsy lesions were successfully generated in all 20 rats through the intact abdomen. MRI demonstrated primarily negative contrast on day 0, positive contrast on day 3, and rapid normalization of signal intensity thereafter (i.e. signal amplitude returned to baseline levels seen in healthy liver tissue). Histologically, lesions were completely fractionated into an acellular homogenate. The lesions had a maximum cross-sectional area of 17.2±1.9 mm2 and sharp boundaries between the lesion and the healthy surrounding tissue after treatment. As the animals recovered after treatment, the histotripsy tissue homogenate was almost completely replaced by regenerated liver parenchyma, resulting in a small fibrous lesion (<1 mm2 maximum cross-section) remaining after 28 days. The results of this study suggest that histotripsy has potential as a non-invasive liver ablation method for effective tissue removal.

No abstract

Thermal strain imaging (TSI) is demonstrated in two model systems mimicking two potential clinical applications. First, a custom ultrasound (US) microscope produced high-resolution TSI images of an excised porcine coronary artery. Samples were placed in a temperature-controlled water chamber and scanned transversely and longitudinally. Phase-sensitive, correlation-based speckle tracking was applied to map the spatial distribution of temporal strain across the sample. TSI differentiated fatty tissue from water-based arterial wall and muscle with high contrast and a spatial resolution of 60 microm for a 50-MHz transducer. Both transverse and longitudinal TSI images compared well with B-scans of arterial wall structures, including intima, media, adventitia, and overlying fatty tissue. A second model system was used to test the hypothesis that US can produce the heating pattern required for TSI of internal structures. A 2-D phased array with independent drive electronics was combined with a conventional US scanner (iU22, Philips, Bothell, WA) for these studies. This 513-element array, originally designed for the US therapy, acted as the US heat source. To quantify the temporal strain induced by this system, TSI was performed on a homogeneous rubber phantom. TSI temperature estimates were within 3% error for a 3.2 degrees C temperature rise produced within 2 s using a specially designed beamformer and pulse sequencer. The system was then used to produce TSI scanning of an excised kidney containing an intact piece of fat below the collecting system. These images were validated using an magnetic resonance imaging (MRI) pulse sequence designed for lipid quantification. TSI scans matched well MRI scans and histology both anatomically and quantitatively. Finally, to test the potential of US-induced TSI for a significant clinical problem, images were obtained on an excised canine aorta with fatty tissue inside the lumen. Both longitudinal and transversal TSI agreed well with anatomy. These in vitro results demonstrate the potential of high-resolution US-induced TSI with a small temperature change (<1 degrees C) for plaque characterization.

Background and Aims: Open liver resection requiring an upper abdominal incision is associated with significant opioid use due to postoperative pain. We tested the hypothesis that the intraoperative combination of low dose lidocaine and ketamine would reduce opioid consumption when given in conjunction with intrathecal morphine for liver resection surgery. Methods: In this triple blind, parallel group four-arm placebo-controlled trial, we randomized 124 adult ASA 2-4 liver resection patients to receive intraoperative lidocaine 0.33 mg/kg/h (group L), ketamine 70 µg/kg/h (group K), combination of lidocaine 0.33 mg/kg/h and ketamine 70 µg/kg/h (group KL) and saline (group P). All patients received 300 µg intrathecal morphine prior to induction of anesthesia. All infusions were started immediately after intubation and continued until the end of surgery. Primary outcome measurements included opioid consumption at 24-hours. Secondary outcomes included pain scores, opioid consumption at 48 and 72-hours and side effects including nausea, vomiting, dizziness, hallucinations, headaches and signs of local anaesthetic toxicity. Patients were followed up for 12 weeks.