title: An end-to-end pipeline to study and model proton radiation-induced effects of the central nervous system as a function of dose and linear energy transfer at the single-cell level in 3D creator: Boucsein, Marc Oliver subject: ddc-530 subject: 530 Physics description: Proton therapy is a promising form of brain radiotherapy due to its characteristic Bragg peak profile sparing normal tissue. However, late side effects have been observed and the underlying mechanisms are not fully understood. An end-to-end pipeline was first proposed to investigate late brain tissue-specific radiation-induced effects associated with the central nervous system (CNS) as a function of dose and linear energy transfer (LET) at the single-cell level in 3D for a well-established preclinical experiment mimicking patient treatment. This pipeline includes Monte Carlo-based dose and LET calculation, target delivery verification, image processing tasks in- cluding preprocessing, local-affine multi-step registrations, a topology-preserving segmentation, and analysis modules using 2-point density correlation functions, the Riemann elastic metric, and the CNS network size to measure compactness, shape and size heterogeneity. As a proof of principle, the pipeline was applied to investigate the observed radiation-induced astrogliosis segmented with a Dice coefficient of 0.86, achieving a maximum dose and LET uncertainty of 2.5 Gy and 2 keV/mum. In conclusion, the analysis reveals that the process of astrogliosis can be considered as a functional acting unit showing a radiation-induced late effect as a function of the brain tissue type, dose and LET indicating a variable relative biological effectiveness. date: 2024 type: Dissertation type: info:eu-repo/semantics/doctoralThesis type: NonPeerReviewed format: application/pdf identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/35224/1/PhD_Thesis_Marc_Boucsein.pdf identifier: DOI:10.11588/heidok.00035224 identifier: urn:nbn:de:bsz:16-heidok-352243 identifier: Boucsein, Marc Oliver (2024) An end-to-end pipeline to study and model proton radiation-induced effects of the central nervous system as a function of dose and linear energy transfer at the single-cell level in 3D. [Dissertation] relation: https://archiv.ub.uni-heidelberg.de/volltextserver/35224/ rights: info:eu-repo/semantics/openAccess rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html language: eng