In vivo histotripsy brain treatment.
In vivo histotripsy brain treatment.
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DOI：
10.3171/2018.4.jns172652
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发表时间：
2019-10
影响因子：
4.1
通讯作者：
Jonathan R. Sukovich;C. Cain;A. Pandey;N. Chaudhary;S. Camelo-Piragua;S. Allen;T. Hall;J. Snell;Zhiyuan Xu;J. Cannata;D. Teofilovic;J. Bertolina;N. Kassell;Zhen Xu
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文献类型：
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作者：
Jonathan R. Sukovich;C. Cain;A. Pandey;N. Chaudhary;S. Camelo-Piragua;S. Allen;T. Hall;J. Snell;Zhiyuan Xu;J. Cannata;D. Teofilovic;J. Bertolina;N. Kassell;Zhen Xu
目的：组织破碎术是一种基于超声的治疗方式，依赖于靶向空化气泡云的产生，其机械地使组织破裂。本研究的目的是研究体内可行性，包括剂量要求和安全性，利用组织破坏技术在猪脑内产生良好限制的破坏性病变。方法：在颅骨切除术打开通向大脑的声窗后，提供组织摧毁脉冲以在猪皮质中产生损伤。生成主要尺寸高达1 cm的大病变，以证明脑组织破坏病变的有效性。在不同的应用剂量和超声成像引导下产生脑回局限性病变，以确保它们准确地靶向并包含在单个脑回内。在急性（≤ 6小时）和亚急性（≤ 72小时）恢复期评估了临床评价以及MRI和组织学结局。结果：组织破坏术能够在皮质中产生主要尺寸达1 cm的病变。观察到组织破坏病变界限清楚，治疗和未治疗组织之间边界清晰，所有病例中损伤的组织学证据均从其边界延伸≤ 200 µm。在病变局限于脑回的动物中，未观察到治疗导致的大出血或其他并发症。72小时时，MRI显示极轻微至无水肿，病灶周围区域无炎症变化的放射学证据。组织学评价显示组织破坏病变与亚急性梗死相似。结论：组织摧毁术可用于在猪皮质中产生任意形状和大小的清晰定义的病变。局限于脑回内的病变在急性或亚急性时间间隔内未导致治疗部位的显著出血或水肿反应。
OBJECTIVE: Histotripsy is an ultrasound-based treatment modality relying on the generation of targeted cavitation bubble clouds, which mechanically fractionate tissue. The purpose of the current study was to investigate the in vivo feasibility, including dosage requirements and safety, of generating well-confined destructive lesions within the porcine brain utilizing histotripsy technology. METHODS: Following a craniectomy to open an acoustic window to the brain, histotripsy pulses were delivered to generate lesions in the porcine cortex. Large lesions with a major dimension of up to 1 cm were generated to demonstrate the efficacy of histotripsy lesioning in the brain. Gyrus-confined lesions were generated at different applied dosages and under ultrasound imaging guidance to ensure that they were accurately targeted and contained within individual gyri. Clinical evaluation as well as MRI and histological outcomes were assessed in the acute (≤ 6 hours) and subacute (≤ 72 hours) phases of recovery. RESULTS: Histotripsy was able to generate lesions with a major dimension of up to 1 cm in the cortex. Histotripsy lesions were seen to be well demarcated with sharp boundaries between treated and untreated tissues, with histological evidence of injuries extending ≤ 200 µm from their boundaries in all cases. In animals with lesions confined to the gyrus, no major hemorrhage or other complications resulting from treatment were observed. At 72 hours, MRI revealed minimal to no edema and no radiographic evidence of inflammatory changes in the perilesional area. Histological evaluation revealed the histotripsy lesions to be similar to subacute infarcts. CONCLUSIONS: Histotripsy can be used to generate sharply defined lesions of arbitrary shapes and sizes in the swine cortex. Lesions confined to within the gyri did not lead to significant hemorrhage or edema responses at the treatment site in the acute or subacute time intervals.