TY  - GEN
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/35224/
Y1  - 2024///
ID  - heidok35224
AV  - public
TI  - 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
CY  - Heidelberg
A1  - Boucsein, Marc Oliver
N2  - 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.
ER  -