a Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System , Washington , DC , USA.
b Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center , National Institutes of Health , Bethesda , MD , USA.
Int J Hyperthermia. 2018 Dec;34(8):1213-1224. doi: 10.1080/02656736.2018.1438672. Epub 2018 Feb 22.
High intensity focussed ultrasound (HIFU) can non-invasively treat tumours with minimal or no damage to intervening tissues. While continuous-wave HIFU thermally ablates target tissue, the effect of hundreds of microsecond-long pulsed sonications is examined in this work. The objective of this study was to characterise sonication parameter-dependent thermomechanical bioeffects to provide the foundation for future preclinical studies and facilitate clinical translation.
Acoustic power, number of cycles/pulse, sonication time and pulse repetition frequency (PRF) were varied on a clinical magnetic resonance imaging (MRI)-guided HIFU (MR-HIFU) system. Ex vivo porcine liver, kidney and cardiac muscle tissue samples were sonicated (3 × 3 grid pattern, 1 mm spacing). Temperature, thermal dose and T2 relaxation times were quantified using MRI. Lesions were histologically analysed using H&E and vimentin stains for lesion structure and viability.
Thermomechanical HIFU bioeffects produced distinct types of fractionated tissue lesions: solid/thermal, paste-like and vacuolated. Sonications at 20 or 60 Hz PRF generated substantial tissue damage beyond the focal region, with reduced viability on vimentin staining, whereas H&E staining indicated intact tissue. Same sonication parameters produced dissimilar lesions in different tissue types, while significant differences in temperature, thermal dose and T2 were observed between the parameter sets.
Clinical MR-HIFU system was utilised to generate distinct types of lesions and to produce targeted thermomechanical bioeffects in ex vivo tissues. The results guide HIFU research on thermomechanical tissue bioeffects, inform future studies and advice sonication parameter selection for direct tumour ablation or immunomodulation using a clinical MR-HIFU system.
高强度聚焦超声（HIFU）可以非侵入性地治疗肿瘤，对介入组织的损伤最小或没有损伤。虽然连续波 HIFU 通过热消融目标组织，但在这项工作中研究了数百个微秒长的超声脉冲的效果。本研究的目的是描述与超声参数相关的热机械生物效应，为未来的临床前研究提供基础，并促进临床转化。
在临床磁共振成像（MRI）引导的高强度聚焦超声（MR-HIFU）系统上改变声功率、脉冲数/周期、超声时间和脉冲重复频率（PRF）。对离体猪的肝、肾和心肌组织样本进行超声处理（3×3 网格模式，间隔 1 毫米）。使用 MRI 量化温度、热剂量和 T2 弛豫时间。使用 H&E 和波形蛋白染色对病变进行组织学分析，以评估病变结构和活力。
热机械 HIFU 生物效应产生了不同类型的分割组织损伤：固体/热、糊状和空泡样。在 20 或 60 Hz PRF 下进行超声处理会在焦域之外产生大量的组织损伤，波形蛋白染色显示活力降低，而 H&E 染色则表明组织完整。相同的超声参数在不同的组织类型中产生了不同的病变，而在参数设置之间观察到温度、热剂量和 T2 有显著差异。
临床 MRI-HIFU 系统用于产生不同类型的病变，并在离体组织中产生靶向热机械生物效应。研究结果指导了高强度聚焦超声在热机械组织生物效应方面的研究，为未来的研究提供了信息，并为使用临床 MRI-HIFU 系统进行直接肿瘤消融或免疫调节的超声参数选择提供了建议。
