Format

Send to

Choose Destination
Ultrason Sonochem. 2017 Sep;38:1-8. doi: 10.1016/j.ultsonch.2017.02.035. Epub 2017 Feb 28.

Impact of MR-guided boiling histotripsy in distinct murine tumor models.

Author information

1
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: martijn.hoogenboom@radboudumc.nl.
2
Department of Radiation Oncology, Radiotherapy & OncoImmunology Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
4
Department of Pathology, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands; Department of Pathology, University Medical Center Utrecht, The Netherlands; Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
5
Department of Radiation Oncology, Radiotherapy & OncoImmunology Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Anesthesiology, Radboud University Medical Center, Nijmegen, The Netherlands.
6
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
7
Department of Radiation Oncology, Radiotherapy & OncoImmunology Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: gosse.adema@radboudumc.nl.

Abstract

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.

KEYWORDS:

Boiling histotripsy; High intensity focused ultrasound; MRI; Tumor ablation

PMID:
28633808
DOI:
10.1016/j.ultsonch.2017.02.035
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center