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Neuroprotective effects of ultra-high dose rate FLASH Bragg peak proton irradiation

Purpose - To investigate brain tissue response to ultra-high dose rate (uHDR, FLASH) and standard dose rate (SDR) proton irradiations in the Bragg peak region. - Methods and Materials - Active scanning uHDR delivery was established for proton beams for investigation of dose rate effects between clin...

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Hauptverfasser: Dokić, Ivana (VerfasserIn) , Meister, Sarah (VerfasserIn) , Bojcevski, Jovana (VerfasserIn) , Tessonnier, Thomas (VerfasserIn) , Walsh, Dietrich (VerfasserIn) , Knoll, Maximilian (VerfasserIn) , Mein, Stewart (VerfasserIn) , Tang, Zili (VerfasserIn) , Vogelbacher, Lena (VerfasserIn) , Rittmüller, Claudia (VerfasserIn) , Moustafa, Mahmoud (VerfasserIn) , Krunic, Damir (VerfasserIn) , Brons, Stephan (VerfasserIn) , Haberer, Thomas (VerfasserIn) , Debus, Jürgen (VerfasserIn) , Mairani, Andrea (VerfasserIn) , Abdollahi, Amir (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 20 February 2022
In: International journal of radiation oncology, biology, physics
Year: 2022, Jahrgang: 113, Heft: 3, Pages: 614-623
ISSN:1879-355X
DOI:10.1016/j.ijrobp.2022.02.020
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ijrobp.2022.02.020
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0360301622001663
Volltext
Verfasserangaben:Ivana Dokic, Sarah Meister, Jovana Bojcevski, Thomas Tessonnier, Dietrich Walsh, Maximilian Knoll, Stewart Mein, Zili Tang, Lena Vogelbacher, Claudia Rittmueller, Mahmoud Moustafa, Damir Krunic, Stephan Brons, Thomas Haberer, Jürgen Debus, Andrea Mairani, and Amir Abdollahi
Beschreibung
Zusammenfassung:Purpose - To investigate brain tissue response to ultra-high dose rate (uHDR, FLASH) and standard dose rate (SDR) proton irradiations in the Bragg peak region. - Methods and Materials - Active scanning uHDR delivery was established for proton beams for investigation of dose rate effects between clinical SDR and uHDR at ∼10 Gy in the Bragg peak region (dose-averaged linear energy transfer [LETD] ranging from 4.5 to 10.2 keV µm-1 ). Radiation- induced injury of neuronal tissue was assessed by studying the DNA double strand break repair kinetics surrogated by nuclear γH2AX staining (radiation induced foci [RIF]), microvascular density and structural integrity (MVD, CD31+ endothelium), and inflammatory microenvironmental response (CD68+ microglia/macrophages and high mobility group box protein 1[HMGB]) in healthy C57BL/6 mouse brains. - Results - Averaged dose rates achieved were 0.17 Gy/s (SDR) and 120 Gy/s (uHDR). The fraction of RIF-positive cells increased after SDR ∼10-fold, whereas a significantly lower fraction of RIF-positive cells was found after uHDR versus SDR (∼2 fold, P < .0001). Moreover, uHDR substantially preserved the microvascular architecture and reduced microglia/macrophage regulated associated inflammation as compared with SDR. - Conclusions - The feasibility of uHDR raster scanning proton irradiation is demonstrated to elicit FLASH sparing neuroprotective effects compared to SDR in a preclinical in vivo model.
Beschreibung:Gesehen am 17.09.2022
Beschreibung:Online Resource
ISSN:1879-355X
DOI:10.1016/j.ijrobp.2022.02.020

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