TY - JOUR
T1 - Impact of MR-guided boiling histotripsy in distinct murine tumor models
AU - Hoogenboom, Martijn
AU - Eikelenboom, Dylan C.
AU - van den Bijgaart, Renske J E
AU - Heerschap, Arend
AU - Wesseling, Pieter
AU - den Brok, Martijn H
AU - Fütterer, Jurgen J.
AU - Adema, Gosse J
N1 - Publisher Copyright:
© 2017
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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 2 h 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.
AB - 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 2 h 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.
KW - Boiling histotripsy
KW - High intensity focused ultrasound
KW - MRI
KW - Tumor ablation
UR - http://www.scopus.com/inward/record.url?scp=85014334515&partnerID=8YFLogxK
U2 - 10.1016/j.ultsonch.2017.02.035
DO - 10.1016/j.ultsonch.2017.02.035
M3 - Article
C2 - 28633808
AN - SCOPUS:85014334515
SN - 1350-4177
VL - 38
SP - 1
EP - 8
JO - Ultrasonics Sonochemistry
JF - Ultrasonics Sonochemistry
ER -