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.胰腺癌是一种预后不良的恶性疾病，约80%的患者确诊时已存在不可切除肿瘤。化疗、放疗等治疗手段虽可整体改善生存获益，但效果有限。组织碎石术（histotripsy）是一种无创、非电离、非热式的聚焦超声消融技术，已在肝肿瘤及其他恶性肿瘤的治疗中展现出疗效。本创新性研究旨在以猪为动物模型，探索组织碎石术用于胰腺无创消融的可行性。 两项子研究中，研究团队借助搭载于临床组织碎石术系统的定制化32阵元、500kHz组织碎石术换能器，在实时超声成像引导下，对11头健康猪的胰腺实施组织碎石术治疗。其中先导研究纳入3头禁食猪，以500Hz的脉冲重复频率（pulse repetition frequency, PRF）实施治疗。结果显示，由于肠道气体遮挡，同轴超声成像无法清晰显示胰腺，导致治疗脱靶，未造成胰腺损伤。 为减少肠道气体干扰，第二组共8头猪喂食含有二甲硅油和比沙可啶的蛋奶糊饮食。治疗后，4头猪即刻实施安乐死，剩余4头猪存活1周后安乐死。研究团队通过大体形态学观察、组织学分析及计算机断层扫描（CT）成像，对胰腺及周围组织的损伤情况进行评估。结果显示，在4头猪的胰腺内部成功生成组织碎石术气泡云，且同轴超声成像可清晰观测胰腺，其中2头猪出现脱靶损伤。对于存活1周的慢性实验组动物，治疗耐受性良好，未观察到并发症体征及血液标志物水平变化。 本研究初步证实了组织碎石术用于胰腺无创消融的潜力，有待在更大规模的系统性研究中进一步验证。