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Published in: Strahlentherapie und Onkologie 11/2016

01-11-2016 | Original Article

Novel technique for high-precision stereotactic irradiation of mouse brains

Authors: J. Hartmann, J. Wölfelschneider, C. Stache, R. Buslei, A. Derer, M. Schwarz, T. Bäuerle, R. Fietkau, U. S. Gaipl, C. Bert, A. Hölsken, B. Frey

Published in: Strahlentherapie und Onkologie | Issue 11/2016

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Abstract

Background and purpose

Small animal irradiation systems were developed for preclinical evaluation of tumor therapy closely resembling the clinical situation. Mostly only clinical LINACs are available, so protocols for small animal partial body irradiation using a conventional clinical system are essential. This study defines a protocol for conformal brain tumor irradiations in mice.

Materials and methods

CT and MRI images were used to demarcate the target volume and organs at risk. Three 6 MV photon beams were planned for a total dose of 10 fractions of 1.8 Gy. The mouse position in a dedicated applicator was verified by an X‑ray patient positioning system before each irradiation. Dosimetric verifications (using ionization chambers and films) were performed. Irradiation-induced DNA damage was analyzed to verify the treatment effects on the cellular level.

Results

The defined treatment protocol and the applied fractionation scheme were feasible. The in-house developed applicator was suitable for individual positioning at submillimeter accuracy of anesthetized mice during irradiation, altogether performed in less than 10 min. All mice tolerated the treatment well. Measured dose values perfectly matched the nominal values from treatment planning. Cellular response was restricted to the target volume.

Conclusion

Clinical LINAC-based irradiations of mice offer the potential to treat orthotopic tumors conformably. Especially with respect to lateral penumbra, dedicated small animal irradiation systems exceed the clinical LINAC solution.
Literature
4.
go back to reference Derer A, Frey B, Fietkau R, Gaipl US (2015) Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother. doi:10.1007/s00262-015-1771-8 PubMed Derer A, Frey B, Fietkau R, Gaipl US (2015) Immune-modulating properties of ionizing radiation: rationale for the treatment of cancer by combination radiotherapy and immune checkpoint inhibitors. Cancer Immunol Immunother. doi:10.​1007/​s00262-015-1771-8 PubMed
5.
go back to reference De Ryck T, Van Impe A, Vanhoecke BW, Heyerick A, Vakaet L, De Neve W, Muller D, Schmidt M, Dorr W, Bracke ME (2015) 8‑prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis : cell culture and murine model. Strahlenther Onkol 191(5):429–436. doi:10.1007/s00066-014-0782-2 CrossRefPubMed De Ryck T, Van Impe A, Vanhoecke BW, Heyerick A, Vakaet L, De Neve W, Muller D, Schmidt M, Dorr W, Bracke ME (2015) 8‑prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis : cell culture and murine model. Strahlenther Onkol 191(5):429–436. doi:10.​1007/​s00066-014-0782-2 CrossRefPubMed
6.
go back to reference Muth C, Rubner Y, Semrau S, Ruhle PF, Frey B, Strnad A, Buslei R, Fietkau R, Gaipl US (2015) Primary glioblastoma multiforme tumors and recurrence: comparative analysis of the danger signals HMGB1, HSP70, and calreticulin. Strahlenther Onkol. doi:10.1007/s00066-015-0926-z PubMed Muth C, Rubner Y, Semrau S, Ruhle PF, Frey B, Strnad A, Buslei R, Fietkau R, Gaipl US (2015) Primary glioblastoma multiforme tumors and recurrence: comparative analysis of the danger signals HMGB1, HSP70, and calreticulin. Strahlenther Onkol. doi:10.​1007/​s00066-015-0926-z PubMed
7.
go back to reference Clarkson R, Lindsay PE, Ansell S, Wilson G, Jelveh S, Hill RP, Jaffray DA (2011) Characterization of image quality and image-guidance performance of a preclinical microirradiator. Med Phys 38(2):845–856CrossRefPubMedPubMedCentral Clarkson R, Lindsay PE, Ansell S, Wilson G, Jelveh S, Hill RP, Jaffray DA (2011) Characterization of image quality and image-guidance performance of a preclinical microirradiator. Med Phys 38(2):845–856CrossRefPubMedPubMedCentral
8.
go back to reference Wong J, Armour E, Kazanzides P, Iordachita U, Tryggestad E, Deng H, Matinfar M, Kennedy C, Liu ZJ, Chan T, Gray O, Verhaegen F, McNutt T, Ford E, DeWeese TL (2008) High-resolution, small animal radiation research platform with X‑ray tomographic guidance capabilities. Int J Radiat Oncol Biol Phys 71(5):1591–1599. doi:10.1016/j.ijrobp.2008.04.025 CrossRefPubMedPubMedCentral Wong J, Armour E, Kazanzides P, Iordachita U, Tryggestad E, Deng H, Matinfar M, Kennedy C, Liu ZJ, Chan T, Gray O, Verhaegen F, McNutt T, Ford E, DeWeese TL (2008) High-resolution, small animal radiation research platform with X‑ray tomographic guidance capabilities. Int J Radiat Oncol Biol Phys 71(5):1591–1599. doi:10.​1016/​j.​ijrobp.​2008.​04.​025 CrossRefPubMedPubMedCentral
9.
go back to reference Tillner F, Hietschold V, Khaless A, Pawelke J, Thute P, Enghardt W (2010) Characterization and optimization of the imaging and dosimetric properties of a image-guided precision irradiation device for small animals. Strahlenther Onkol 186:105–105 Tillner F, Hietschold V, Khaless A, Pawelke J, Thute P, Enghardt W (2010) Characterization and optimization of the imaging and dosimetric properties of a image-guided precision irradiation device for small animals. Strahlenther Onkol 186:105–105
11.
go back to reference Felix MC, Fleckenstein J, Kirschner S, Hartmann L, Wenz F, Brockmann MA, Glatting G, Giordano FA (2015) Image-guided radiotherapy using a modified industrial Micro-CT for preclinical applications. PLoS ONE 10(5):11. doi:10.1371/journal.pone.0126246 CrossRef Felix MC, Fleckenstein J, Kirschner S, Hartmann L, Wenz F, Brockmann MA, Glatting G, Giordano FA (2015) Image-guided radiotherapy using a modified industrial Micro-CT for preclinical applications. PLoS ONE 10(5):11. doi:10.​1371/​journal.​pone.​0126246 CrossRef
17.
go back to reference Stache C, Holsken A, Schlaffer SM, Hess A, Metzler M, Frey B, Fahlbusch R, Flitsch J, Buchfelder M, Buslei R (2015) Insights into the infiltrative behavior of adamantinomatous craniopharyngioma in a new xenotransplant mouse model. Brain Pathol 25(1):1–10. doi:10.1111/bpa.12148 CrossRefPubMed Stache C, Holsken A, Schlaffer SM, Hess A, Metzler M, Frey B, Fahlbusch R, Flitsch J, Buchfelder M, Buslei R (2015) Insights into the infiltrative behavior of adamantinomatous craniopharyngioma in a new xenotransplant mouse model. Brain Pathol 25(1):1–10. doi:10.​1111/​bpa.​12148 CrossRefPubMed
20.
go back to reference Stache C, Holsken A, Fahlbusch R, Flitsch J, Schlaffer SM, Buchfelder M, Buslei R (2014) Tight junction protein claudin-1 is differentially expressed in craniopharyngioma subtypes and indicates invasive tumor growth. Neuro-oncology 16(2):256–264. doi:10.1093/neuonc/not195 CrossRefPubMed Stache C, Holsken A, Fahlbusch R, Flitsch J, Schlaffer SM, Buchfelder M, Buslei R (2014) Tight junction protein claudin-1 is differentially expressed in craniopharyngioma subtypes and indicates invasive tumor growth. Neuro-oncology 16(2):256–264. doi:10.​1093/​neuonc/​not195 CrossRefPubMed
21.
go back to reference Low DA, Mutic S, Dempsey JF, Gerber RL, Bosch WR, Perez CA, Purdy JA (1998) Quantitative dosimetric verification of an IMRT planning and delivery system. Radiother Oncol 49(3):305–316CrossRefPubMed Low DA, Mutic S, Dempsey JF, Gerber RL, Bosch WR, Perez CA, Purdy JA (1998) Quantitative dosimetric verification of an IMRT planning and delivery system. Radiother Oncol 49(3):305–316CrossRefPubMed
25.
go back to reference Bache ST, Juang T, Belley MD, Koontz BF, Adamovics J, Yoshizumi TT, Kirsch DG, Oldham M (2015) Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters. Med Phys 42(2):846–855. doi:10.1118/1.4905489 CrossRefPubMedPubMedCentral Bache ST, Juang T, Belley MD, Koontz BF, Adamovics J, Yoshizumi TT, Kirsch DG, Oldham M (2015) Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters. Med Phys 42(2):846–855. doi:10.​1118/​1.​4905489 CrossRefPubMedPubMedCentral
26.
go back to reference Welch D, Harken AD, Randers-Pehrson G, Brenner DJ (2015) Construction of mouse phantoms from segmented CT scan data for radiation dosimetry studies. Phys Med Biol 60:3589–3598CrossRefPubMedPubMedCentral Welch D, Harken AD, Randers-Pehrson G, Brenner DJ (2015) Construction of mouse phantoms from segmented CT scan data for radiation dosimetry studies. Phys Med Biol 60:3589–3598CrossRefPubMedPubMedCentral
Metadata
Title
Novel technique for high-precision stereotactic irradiation of mouse brains
Authors
J. Hartmann
J. Wölfelschneider
C. Stache
R. Buslei
A. Derer
M. Schwarz
T. Bäuerle
R. Fietkau
U. S. Gaipl
C. Bert
A. Hölsken
B. Frey
Publication date
01-11-2016
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 11/2016
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-016-1014-8

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