Department of Urology, University of Michigan, Ann Arbor, Michigan 48109-5330, USA.
J Endourol. 2010 Jul;24(7):1145-50. doi: 10.1089/end.2010.0123.
Histotripsy is an extracorporeal focused ultrasound (US) technology that uses controlled cavitation to induce nonthermal mechanical tissue fractionation. Feasibility of histotripsy ablation of normal renal tissue in an in vivo rabbit model has previously been demonstrated. Our specific objective in this study was to characterize the histologic effects of histotripsy on VX-2 tumor implanted in the kidneys of an in vivo rabbit model.
VX-2 tumor was implanted below the renal capsule in 15 New Zealand white rabbits. Two weeks after implantation, tumors were localized with diagnostic US imaging. Targeted volumes within the observed tumor were treated with short (3 micros) pulses of 1 MHz acoustic energy at a repetition frequency of 300 Hz. Twenty tumors were treated with histotripsy and 7 served as tumor controls. Three normal kidneys were also treated with histotripsy. Kidneys and lungs were harvested, grossly inspected, and processed for histopathologic analysis.
Real-time US imaging confirmed presence of cavitation during all histotripsy treatments. Examination of tumor and kidney specimens revealed 100% tumor growth with an average tumor diameter of 7 mm (range 2-12). In 16 of 20 tumors treated with histotripsy, acellular zones of debris and finely disrupted cellular architecture were present on histology. Kidneys harvested 24 hours after treatment revealed an extensive inflammatory reaction.
Transcutaneous application of histotripsy to implanted VX-2 tumor in rabbit kidney produced fractionation of malignant tissue. These findings support the further study and development of histotripsy for potential oncologic application.
组织破碎是一种体外聚焦超声（US）技术，它利用控制空化来诱导非热机械组织分割。先前已经证明了组织破碎消融活体兔模型中正常肾组织的可行性。我们在这项研究中的具体目标是描述组织破碎对活体兔模型中植入的 VX-2 肿瘤的组织学影响。
在 15 只新西兰白兔的肾包膜下植入 VX-2 肿瘤。植入后 2 周，使用诊断性 US 成像定位肿瘤。在观察到的肿瘤内的目标体积用 1 MHz 声能的短（3 微秒）脉冲以 300 Hz 的重复频率进行治疗。20 个肿瘤用组织破碎治疗，7 个作为肿瘤对照。还对 3 个正常肾脏进行了组织破碎治疗。收获肾脏和肺脏，进行大体检查，并进行组织病理学分析。
实时 US 成像证实所有组织破碎治疗过程中均存在空化。肿瘤和肾脏标本的检查显示 100%的肿瘤生长，平均肿瘤直径为 7 毫米（范围 2-12）。在 20 个用组织破碎治疗的肿瘤中，有 16 个肿瘤在组织学上存在无细胞的碎片区和精细破坏的细胞结构。治疗后 24 小时收获的肾脏显示出广泛的炎症反应。
经皮应用组织破碎技术对兔肾中植入的 VX-2 肿瘤进行治疗，可使恶性组织发生分割。这些发现支持进一步研究和开发组织破碎技术，以用于潜在的肿瘤治疗应用。
