Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Radiation Oncology, Radiotherapy & OncoImmunology Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands.
Ultrason Sonochem. 2017 Sep;38:1-8. doi: 10.1016/j.ultsonch.2017.02.035. Epub 2017 Feb 28.
Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft tissue into submicron fragments with limited temperature increase using the shock wave and cavitation effects of HIFU. Research on BH has been largely limited to ex vivo experiments. As a consequence, the in vivo pathology after BH treatment and the relation to preexistent tissue characteristics are not well understood. This study reports on in vivo MR guided BH treatment, either with 100 or 200 pulses per focal spot, in three different subcutaneous mouse tumor models: a soft-tissue melanoma (B16OVA), a compact growing thymoma (EL4), and a highly vascularized neuroblastoma (9464D). Extensive treatment evaluation was performed using MR imaging followed by histopathology 2h after treatment. T2 weighted MRI allowed direct in vivo visualization of the BH lesions in all tumor models. The 100-pulse treated area in the B16OVA tumors was larger than the predicted treatment volume (500±10%). For the more compact growing EL4 and 9464D tumors this was 95±13% and 55±33%, respectively. Histopathology after the 100-pulse treatment revealed completely disintegrated lesions in the treated area with sharp borders in the compact EL4 and 9464D tumors, while for B16OVA tumors the lesion contained a mixture of discohesive (partly viable) clusters of cells, micro-vessel remainings, and tumor cell debris. The treatment of B16OVA with 200 pulses increased the fragmentation of tumor tissue. In all tumor types only micro-hemorrhages were detected after ablation (slightly higher after 200-pulse treatment for the highly vascularized 9464D tumors). Collagen staining revealed that the collagen fibers were to a greater or lesser extent still intact and partly clotted together near the lesion border in all tumor models. In conclusion, this study reveals effective mechanical fragmentation of different tumor types using BH without major hemorrhages. However, treatment settings may need to be adjusted to the tissue characteristics for optimal tissue fragmentation.
人们对机械高强度聚焦超声（HIFU）消融的兴趣正在迅速增长。沸腾空化爆破（BH）利用 HIFU 的冲击波和空化效应将软组织机械性地粉碎成亚微米级的碎片，同时升温有限。BH 的研究主要局限于离体实验。因此，BH 治疗后的体内病理学以及与预先存在的组织特征的关系尚不清楚。本研究报告了在三种不同的皮下小鼠肿瘤模型中，使用 100 或 200 个焦点脉冲进行的 MR 引导 BH 治疗：软组织黑素瘤（B16OVA）、致密生长的胸腺瘤（EL4）和高度血管化的神经母细胞瘤（9464D）。在治疗后 2 小时，通过 MR 成像和组织病理学进行了广泛的治疗评估。T2 加权 MRI 允许直接在所有肿瘤模型中对 BH 损伤进行体内可视化。B16OVA 肿瘤中 100 脉冲治疗区域大于预测的治疗体积（500±10%）。对于更致密生长的 EL4 和 9464D 肿瘤，这分别为 95±13%和 55±33%。100 脉冲治疗后的组织病理学显示，在致密的 EL4 和 9464D 肿瘤中，治疗区域的损伤完全解体，边界清晰，而在 B16OVA 肿瘤中，损伤包含离散（部分存活）的细胞簇、微血管残留物和肿瘤细胞碎片的混合物。用 200 脉冲治疗 B16OVA 增加了肿瘤组织的碎裂。在所有肿瘤类型中，消融后仅检测到微出血（高度血管化的 9464D 肿瘤的 200 脉冲治疗后略高）。胶原染色显示，在所有肿瘤模型中，胶原纤维或多或少仍完整，在损伤边界附近部分凝结在一起。总之，本研究揭示了使用 BH 对不同类型的肿瘤进行有效的机械性碎裂，而不会导致大出血。然而，为了实现最佳的组织碎裂，治疗参数可能需要根据组织特征进行调整。
