A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model
by
, , , , , , , , , and
Mariele Romano
1
,
Alberto Bravin
2,3
,
Alberto Mittone
2,4,
Alicia Eckhardt
1,
Giacomo E. Barbone
1,5,
Lucie Sancey
6
,
Julien Dinkel
5,
Stefan Bartzsch
7,8
,
Jens Ricke
5,
Marianna Alunni-Fabbroni
5
,
Heidrun Hirner-Eppeneder
5,
Dmitry Karpov
2,9,
Cinzia Giannini
10
,
Oliver Bunk
9,
Audrey Bouchet
11,
Viktoria Ruf
12,
Armin Giese
12 and
Paola Coan
1,5,* 1
Department of Medical Physics, Faculty of Physics, Ludwig-Maximilians-Universität, Am Coulombwall 1, München, 85748 Garching, Germany
2
European Synchrotron Radiation Facility, 71 Avenue des Martyrs, 38000 Grenoble, France
3
Department of Physics, Faculty of Physics, University of Milano-Bicocca, 20126 Milan, Italy
4
CELLS-ALBA Synchrotron, 08290 Cerdanyola del Valles, Spain
5
Department of Radiology, University Hospital, Ludwig-Maximilians-Universität, 81377 Munich, Germany
6
Centre de Recherche UGA/INSERM U1209/CNRS UMR5309, Institute for Advanced Biosciences, 38700 La Tronche, France
7
Department of Radiation Oncology, School of Medicine, Technical University of Munich, Klinikum Rechts der Isar, 81675 Munich, Germany
8
Department of Radiation Sciences (DRS), Institute of Radiation Medicine (IRM), Helmholtz Zentrum München, 85764 Neuherberg, Germany
9
Swiss Light Source, Paul Scherrer Institute, 5232 Villigen, Switzerland
10
Institute of Crystallography, National Research Council, 70126 Bari, Italy
11
Inserm U1296 Unit “Radiation: Defense, Health Environment”, 69008 Lyon, France
12
Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität, 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(19), 4953; https://doi.org/10.3390/cancers13194953
Submission received: 5 August 2021
/
Revised: 23 September 2021
/
Accepted: 27 September 2021
/
Published: 1 October 2021
(This article belongs to the Special Issue Research in Spatially Fractionated Radiation Therapies for Cancers)
Simple Summary
This study aims at using a multi-technique approach to detect and analyze the effects of high dose rate spatially fractionated radiation therapies and to compare them to seamless broad beam irradiation targeting healthy and glioblastoma-bearing rat brains and delivering three different doses per each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray phase contrast imaging–computed tomography, histology, immunohistochemistry, X-ray fluorescence, and small- and wide-angle X-ray scattering to achieve detailed visualization, characterization and classification in 3D of the radio-induced effects on brain tissues. The original results bring new insights to the understanding of the response of cerebral tissue and tumors treated with high dose rate spatially fractioned radiotherapies and put the basis for channeling studies of in-vivo applications for monitoring RT effects.
Abstract
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.
