使用组织解剖学进行超声引导的无创胰腺消融：猪体内模型的可行性研究,International Journal of Hyperthermia

摘要

胰腺癌是一种恶性疾病，生存率低，近 80% 的肿瘤无法切除。化疗和放射治疗等治疗方法虽然有限，但总体上显示出改善的生存益处。组织解剖学是一种无创、非电离、非热聚焦超声消融方式，已显示出治疗肝脏肿瘤和其他恶性肿瘤的功效。在这项新颖的研究中，我们研究了猪模型中无创胰腺消融的组织解剖学。在两项研究中，使用连接到临床组织解剖系统的定制 32 元件、500 kHz 组织解剖传感器对 11 头猪的健康胰腺进行组织解剖，并在实时超声成像指导下进行治疗。在 3 头禁食的猪中进行了一项初步研究，并以 500 Hz 的脉冲重复频率 (PRF) 进行组织解剖。结果显示，由于肠道气体覆盖，同轴超声成像上没有胰腺可视化，导致脱靶损伤，并且没有胰腺损伤。为了尽量减少胀气，第二组猪（n  = 8）喂食含有西甲硅油和比沙可啶的蛋奶冻日粮。猪立即被安乐死 ( n = 4) 或 在治疗后 存活 1 周 ( n = 4)。使用大体形态学、组织学分析和 CT 成像来表征胰腺和周围组织的损伤。结果显示，在同轴超声（n  = 4）上视觉上维持的胰腺内部产生组织解剖气泡云，其中 2 头猪表现出脱靶损伤。对于慢性动物，结果显示治疗耐受性良好，没有并发症迹象或血液标记物发生变化。这项研究提供了初步证据，表明组织解剖学具有无创胰腺消融的潜力，并值得在更全面的研究中进行进一步评估。

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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.