Journal Article

DKFZ-2022-00335

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neuroprotective Effects of Ultra-High Dose Rate FLASH Bragg Peak Proton Irradiation.

Dokic, I. (First author)DKFZ* ; Meister, S.DKFZ* ; Bojcevski, J.DKFZ* ; Tessonnier, T.Extern* ; Walsh, D.DKFZ* ; Knoll, M.DKFZ* ; Mein, S.DKFZ* ; Tang, Z.DKFZ* ; Vogelbacher, L.DKFZ* ; Rittmueller, C.DKFZ* ; Moustafa, M.DKFZ* ; Krunic, D.DKFZ* ; Brons, S. ; Haberer, T. ; Debus, J.DKFZ* ; Mairani, A. ; Abdollahi, A. (Last author)DKFZ*

2022
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ijrobp.2022.02.020

Abstract: To investigate brain tissue response to ultra-high dose rate (uHDR, FLASH) and standard dose rate (SDR) proton irradiations in the Bragg peak region.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 (LETD ranging from 4.5 keV µm-1 to 10.2 keV µm-1). Radiation induced injury of neuronal tissue was assessed by studying the DNA double strand break (DSB) 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 HMGB1) in healthy C57BL/6 mouse brains.Averaged dose rate achieved were 0.17 Gy/s (SDR) and 120 Gy/s (uHDR). The fraction of RIF positive cells increased after SDR ∼10-fold, while significantly lower fraction of RIF positive cells was found after uHDR vs. SDR (∼2 fold, p< 0.0001). Moreover, uHDR substantially preserved the microvascular architecture and reduced microglia/macrophage regulated associated inflammation as compared to SDR.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.

Keyword(s): Bragg-peak ; FLASH ; brain ; neurotoxicity ; proton

Note: #EA:E210#LA:E210# / 2022 Jul 1;113(3):614-623

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Contributing Institute(s):

1. E210 Translationale Radioonkologie (E210)
2. Lichtmikroskopie (W210)
3. E050 KKE Strahlentherapie (E050)
4. DKTK HD zentral (HD01)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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