Ultrasound-guided noninvasive pancreas ablation using histotripsy: feasibility study in an in vivo porcine model.

Pancreatic cancer is a malignant disease associated with poor survival and nearly 80% present with unresectable tumors. Treatments such as chemotherapy and radiation therapy have shown overall improved survival benefits, albeit limited. Histotripsy is a noninvasive, non-ionizing, and non-thermal focused ultrasound ablation modality that has shown efficacy in treating hepatic tumors and other malignancies. In this novel study, we investigate histotripsy for noninvasive pancreas ablation in a pig model. In two studies, histotripsy was applied to the healthy pancreas in 11 pigs using a custom 32-element, 500 kHz histotripsy transducer attached to a clinical histotripsy system, with treatments guided by real-time ultrasound imaging. A pilot study was conducted in 3 fasted pigs with histotripsy applied at a pulse repetition frequency (PRF) of 500 Hz. Results showed no pancreas visualization on coaxial ultrasound imaging due to overlying intestinal gas, resulting in off-target injury and no pancreas damage. To minimize gas, a second group of pigs (n = 8) were fed a custard diet containing simethicone and bisacodyl. Pigs were euthanized immediately (n = 4) or survived for 1 week (n = 4) post-treatment. Damage to the pancreas and surrounding tissue was characterized using gross morphology, histological analysis, and CT imaging. Results showed histotripsy bubble clouds were generated inside pancreases that were visually maintained on coaxial ultrasound (n = 4), with 2 pigs exhibiting off-target damage. For chronic animals, results showed the treatments were well-tolerated with no complication signs or changes in blood markers. This study provides initial evidence suggesting histotripsy's potential for noninvasive pancreas ablation and warrants further evaluation in more comprehensive studies.

Using load sensing insoles to identify knee kinetic asymmetries during landing in patients with an Anterior Cruciate Ligament reconstruction.

BACKGROUND: Knee extension moment asymmetry is a known second anterior cruciate ligament injury risk factor in patients who have had an anterior cruciate ligament reconstruction. Traditionally, assessing asymmetries requires motion capture and force platforms which are expensive and occupy a large space. Wireless force sensing insoles could be a feasible surrogate. METHODS: Twenty-nine patients following anterior cruciate ligament reconstruction performed ten bilateral stop jumps while insole forces, ground reaction forces, and lower extremity kinematics were collected. Peak knee extension moment symmetry was computed using the kinematic and kinetic data, and peak impact force symmetry and impulse symmetry were computed using both the insole force data and vertical ground reaction force data. The relationship between outcomes was analyzed using Pearson correlation coefficients. Patients were classified as symmetric or asymmetric for each outcome based on an 85% symmetry cutoff. The resulting classifications were qualitatively compared across outcome measures. FINDINGS: Peak knee extension moment symmetry had a strong association with the force plate symmetry outcomes (r = 0.72-0.96, p < 0.001) and a moderate to strong association with insole symmetry outcomes (r = 0.67-0.77, p < 0.001). There was strong agreement between insole and force plate symmetry outcomes (r = 0.69-0.90, p < 0.001). Four patients were identified as symmetric when using the peak knee extension moment symmetry, five when using force plate data, and eight when using insole data. INTERPRETATION: Force sensing insoles could be used as a surrogate for knee extension moment asymmetry in patients who have had an anterior cruciate ligament reconstruction.

Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in Dogs.

Osteosarcoma (OS) is a malignant bone tumor treated by limb amputation or limb salvage surgeries and chemotherapy. Histotripsy is a non-thermal, non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. Recent ex vivo and in vivo pilot studies have demonstrated the ability of histotripsy for ablating OS but were limited in scope. This study expands on these initial findings to more fully characterize the effects of histotripsy for bone tumors, particularly in tumors with different compositions. A prototype 500 kHz histotripsy system was used to treat ten dogs with suspected OS at an intermediate treatment dose of 1000 pulses per location. One day after histotripsy, treated tumors were resected via limb amputation, and radiologic and histopathologic analyses were conducted to determine the effects of histotripsy for each patient. The results of this study demonstrated that histotripsy ablation is safe and feasible in canine patients with spontaneous OS, while offering new insights into the characteristics of the achieved ablation zone. More extensive tissue destruction was observed after histotripsy compared to that in previous reports, and radiographic changes in tumor size and contrast uptake following histotripsy were reported for the first time. Overall, this study significantly expands our understanding of histotripsy bone tumor ablation and informs future studies for this application.