Abstract
Simple SummaryThis 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.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.
Highlights
Glioblastoma (GBM) is the most common and aggressive intra-axial primary tumor, accounting for about 60% of the cases [1] and causing around 2.7% of all cancerrelated deaths [2]
We report on a multi-technique analysis performed on both healthy and GBM-bearing rat brains after treatment with either Microbeam Radiation Therapy (MRT), Minibeam Radiation Therapy (MB) or standard broad beam radiation therapy (RT) (BB) for the assessment and classification of the specific radio-induced effects
X-ray Phase Contrast Imaging–Computed Tomography (XPCI-CT) coronal images of healthy Broad Beam (BB), MB and MRT irradiated brains acquired with a voxel size of 3.253 μm3 are presented in Figures 2 and 3 and correlated to histology results
Summary
Glioblastoma (GBM) is the most common and aggressive intra-axial primary tumor, accounting for about 60% of the cases [1] and causing around 2.7% of all cancerrelated deaths [2]. GBM treatment involves surgery, chemotherapy, and radiation therapy (RT); due to the radio- and chemo-resistance and highly infiltrative growth of GBM, present treatments are only able to slow down the development of the disease permitting an increase of the survival by a few months [7]. For all these reasons, there is the need for an effective therapy for the management of gliomas. These properties allow the delivery of radiation locally in micrometric windows at high speed, preventing beam smearing due to the cardio-synchronous pulsations [11,12]
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