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Dose-dependent volume loss in subcortical deep grey matter structures after cranial radiotherapy

By Steven H.J. Nagtegaal, Szabolcs David, Marielle E.P. Philippens, Tom J. Snijders, Alexander Leemans, Joost J.C. Verhoeff

Posted 24 Jul 2020
medRxiv DOI: 10.1101/2020.07.23.20160606

Background and purpose The relation between radiotherapy (RT) dose to the brain and morphological changes in healthy tissue has seen recent increased interest. There already is evidence for changes in the cerebral cortex and white matter, as well as selected subcortical grey matter (GM) structures. We studied this relation in all deep GM structures, to help understand the aetiology of post-RT neurocognitive symptoms. Materials and methods We selected 31 patients treated with RT for glioma. Pre-RT and post-RT 3D T1 MRIs were automatically segmented, and the changes in volume of the following structures were assessed: amygdala, nucleus accumbens, caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus. The volumetric changes were related to the mean RT dose received by each structure. Hippocampal volumes were entered into a population-based nomogram to estimate hippocampal age. Results A significant relation between RT dose and volume loss was seen in all examined structures, except the caudate nucleus. The volume loss rates ranged from 0.16-1.37 %/Gy, corresponding to 4.9-41.2% per 30 Gy. Hippocampal age, as derived from the nomogram, was seen to increase by a median of 11 years. Conclusion Almost all subcortical GM structures are susceptible to radiation-induced volume loss, with more volume loss being observed with increasing dose. Volume loss of these structures is associated with neurological deterioration, including cognitive decline, in neurodegenerative diseases. To support a causal relationship between radiation-induced deep GM loss and neurocognitive functioning in glioma patients, future studies are needed that directly correlate volumetrics to clinical outcomes.

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