A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model

The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradia...

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Main Authors: Mariele Romano, Alberto Bravin, Alberto Mittone, Alicia Eckhardt, Giacomo E. Barbone, Lucie Sancey, Julien Dinkel, Stefan Bartzsch, Jens Ricke, Marianna Alunni-Fabbroni, Heidrun Hirner-Eppeneder, Dmitry Karpov, Cinzia Giannini, Oliver Bunk, Audrey Bouchet, Viktoria Ruf, Armin Giese, Paola Coan
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/19/4953
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author Mariele Romano
Alberto Bravin
Alberto Mittone
Alicia Eckhardt
Giacomo E. Barbone
Lucie Sancey
Julien Dinkel
Stefan Bartzsch
Jens Ricke
Marianna Alunni-Fabbroni
Heidrun Hirner-Eppeneder
Dmitry Karpov
Cinzia Giannini
Oliver Bunk
Audrey Bouchet
Viktoria Ruf
Armin Giese
Paola Coan
author_facet Mariele Romano
Alberto Bravin
Alberto Mittone
Alicia Eckhardt
Giacomo E. Barbone
Lucie Sancey
Julien Dinkel
Stefan Bartzsch
Jens Ricke
Marianna Alunni-Fabbroni
Heidrun Hirner-Eppeneder
Dmitry Karpov
Cinzia Giannini
Oliver Bunk
Audrey Bouchet
Viktoria Ruf
Armin Giese
Paola Coan
author_sort Mariele Romano
collection DOAJ
description The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS). XPCI-CT discriminates with high sensitivity the effects of MRT, MB and BB irradiations on both healthy and GBM-bearing brains producing a first-time 3D visualization and morphological analysis of the radio-induced lesions, MRT and MB induced tissue ablations, the presence of hyperdense deposits within specific areas of the brain and tumor evolution or regression with respect to the evaluation made few days post-irradiation with an in-vivo magnetic resonance imaging session. Histology, immunohistochemistry, SAXS/WAXS and XRF allowed identification and classification of these deposits as hydroxyapatite crystals with the coexistence of Ca, P and Fe mineralization, and the multi-technique approach enabled the realization, for the first time, of the map of the differential radiosensitivity of the different brain areas treated with MRT and MB. 3D XPCI-CT datasets enabled also the quantification of tumor volumes and Ca/Fe deposits and their full-organ visualization. The multi-scale and multi-technique approach enabled a detailed visualization and classification in 3D of the radio-induced effects on brain tissues bringing new essential information towards the clinical implementation of the MRT and MB radiation therapy techniques.
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spelling doaj.art-5f845436497f463597e9f918c2a4f2992023-11-22T15:54:49ZengMDPI AGCancers2072-66942021-10-011319495310.3390/cancers13194953A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical ModelMariele Romano0Alberto Bravin1Alberto Mittone2Alicia Eckhardt3Giacomo E. Barbone4Lucie Sancey5Julien Dinkel6Stefan Bartzsch7Jens Ricke8Marianna Alunni-Fabbroni9Heidrun Hirner-Eppeneder10Dmitry Karpov11Cinzia Giannini12Oliver Bunk13Audrey Bouchet14Viktoria Ruf15Armin Giese16Paola Coan17Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität, Am Coulombwall 1, München, 85748 Garching, GermanyEuropean Synchrotron Radiation Facility, 71 Avenue des Martyrs, 38000 Grenoble, FranceEuropean Synchrotron Radiation Facility, 71 Avenue des Martyrs, 38000 Grenoble, FranceDepartment of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität, Am Coulombwall 1, München, 85748 Garching, GermanyDepartment of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität, Am Coulombwall 1, München, 85748 Garching, GermanyCentre de Recherche UGA/INSERM U1209/CNRS UMR5309, Institute for Advanced Biosciences, 38700 La Tronche, FranceDepartment of Radiology, University Hospital, Ludwig-Maximilians-Universität, 81377 Munich, GermanyDepartment of Radiation Oncology, School of Medicine, Technical University of Munich, Klinikum Rechts der Isar, 81675 Munich, GermanyDepartment of Radiology, University Hospital, Ludwig-Maximilians-Universität, 81377 Munich, GermanyDepartment of Radiology, University Hospital, Ludwig-Maximilians-Universität, 81377 Munich, GermanyDepartment of Radiology, University Hospital, Ludwig-Maximilians-Universität, 81377 Munich, GermanyEuropean Synchrotron Radiation Facility, 71 Avenue des Martyrs, 38000 Grenoble, FranceInstitute of Crystallography, National Research Council, 70126 Bari, ItalySwiss Light Source, Paul Scherrer Institute, 5232 Villigen, SwitzerlandInserm U1296 Unit “Radiation: Defense, Health Environment”, 69008 Lyon, FranceCenter for Neuropathology and Prion Research, Ludwig-Maximilians-Universität, 81377 Munich, GermanyCenter for Neuropathology and Prion Research, Ludwig-Maximilians-Universität, 81377 Munich, GermanyDepartment of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität, Am Coulombwall 1, München, 85748 Garching, GermanyThe purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS). XPCI-CT discriminates with high sensitivity the effects of MRT, MB and BB irradiations on both healthy and GBM-bearing brains producing a first-time 3D visualization and morphological analysis of the radio-induced lesions, MRT and MB induced tissue ablations, the presence of hyperdense deposits within specific areas of the brain and tumor evolution or regression with respect to the evaluation made few days post-irradiation with an in-vivo magnetic resonance imaging session. Histology, immunohistochemistry, SAXS/WAXS and XRF allowed identification and classification of these deposits as hydroxyapatite crystals with the coexistence of Ca, P and Fe mineralization, and the multi-technique approach enabled the realization, for the first time, of the map of the differential radiosensitivity of the different brain areas treated with MRT and MB. 3D XPCI-CT datasets enabled also the quantification of tumor volumes and Ca/Fe deposits and their full-organ visualization. The multi-scale and multi-technique approach enabled a detailed visualization and classification in 3D of the radio-induced effects on brain tissues bringing new essential information towards the clinical implementation of the MRT and MB radiation therapy techniques.https://www.mdpi.com/2072-6694/13/19/4953X-ray phase-contrast imagingglioblastomaanimal modelhydroxyapatitevirtual histologyFLASH
spellingShingle Mariele Romano
Alberto Bravin
Alberto Mittone
Alicia Eckhardt
Giacomo E. Barbone
Lucie Sancey
Julien Dinkel
Stefan Bartzsch
Jens Ricke
Marianna Alunni-Fabbroni
Heidrun Hirner-Eppeneder
Dmitry Karpov
Cinzia Giannini
Oliver Bunk
Audrey Bouchet
Viktoria Ruf
Armin Giese
Paola Coan
A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model
Cancers
X-ray phase-contrast imaging
glioblastoma
animal model
hydroxyapatite
virtual histology
FLASH
title A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model
title_full A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model
title_fullStr A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model
title_full_unstemmed A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model
title_short A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model
title_sort multi scale and multi technique approach for the characterization of the effects of spatially fractionated x ray radiation therapies in a preclinical model
topic X-ray phase-contrast imaging
glioblastoma
animal model
hydroxyapatite
virtual histology
FLASH
url https://www.mdpi.com/2072-6694/13/19/4953
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