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

Abstract

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.

FEM deformable liver registration to facilitate CBCT guided histotripsy

“…[5] Surface geometries formed from each isosurface. [6] The complete liver geometry, including vertices on the surfaces of the liver, GB and vessels. [7] Iterative mesh generation of the principal surface geometry to optimize the liver's Gaussian smoothing kernel size and target element sizes.…”

“…[7] Iterative mesh generation of the principal surface geometry to optimize the liver's Gaussian smoothing kernel size and target element sizes. [8] The complete mesh generated from the geometric model ( [6]) and results of the iterative liver mesh generation ([7]).…”

“…Currently, histotripsy is typically guided by an integrated coaxially aligned diagnostic US probe. [5][6][7] However, the target can be difficult to visualize on US if the acoustic window for imaging is inadequate (e.g., for isoechoic tumors or due to blockage by bone or gas). 7 Importantly, it is still possible to deliver histotripsy treatment in most of these scenarios.…”

Investigation of Optimum Production Conditions and the Stability of β-Cyclodextrin–Perfluorocarbon Nanocone Clusters for Histotripsy Applications

“…Histotripsy can achieve precise liquefication of target tissue within the treatment zone through the homogenization of cells into acellular debris without destroying the tissue outside this targeted area . The promising potential of histotripsy is evident from the fact that it has been used clinically to treat liver cancer and investigated preclinically to treat a range of malignancies in the liver, , kidney, , breast, , prostate, pancreas, − brain, ,, and musculoskeletal system − along with other abnormal conditions such as kidney stones and thrombus obstruction. , …”