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Title: Brain microstructural changes associated with neurocognitive outcome in intracranial germ cell tumor survivors
Authors: Tso, WWY
Hui, ESK 
Lee, TMC
Liu, APY
Ip, P
Vardhanabhuti, V
Cheng, KKF
Fong, DYT
Chang, DHF
Ho, FKW
Yip, KM
Ku, DTL
Cheuk, DKL
Luk, CW
Shing, MK
Leung, LK
Khong, PL
Chan, GCF
Issue Date: May-2021
Source: Frontiers in oncology, May 2021, v. 11, 573798
Abstract: Background: Childhood intracranial germ cell tumor (GCT) survivors are prone to radiotherapy-related neurotoxicity, which can lead to neurocognitive dysfunctions. Diffusion kurtosis imaging (DKI) is a diffusion MRI technique that is sensitive to brain microstructural changes. This study aimed to investigate the association between DKI metrics versus cognitive and functional outcomes of childhood intracranial GCT survivors.
Methods: DKI was performed on childhood intracranial GCT survivors (n = 20) who had received cranial radiotherapy, and age and gender-matched healthy control subjects (n = 14). Neurocognitive assessment was performed using the Hong Kong Wechsler Intelligence Scales, and functional assessment was performed using the Lansky/Karnofsky performance scales (KPS). Survivors and healthy controls were compared using mixed effects model. Multiple regression analyses were performed to determine the effects of microstructural brain changes of the whole brain as well as the association between IQ and Karnofsky scores and the thereof.
Results: The mean Intelligence Quotient (IQ) of GCT survivors was 91.7 (95% CI 84.5 – 98.8), which was below the age-specific normative expected mean IQ (P = 0.013). The mean KPS score of GCT survivors was 85.5, which was significantly lower than that of controls (P < 0.001). Cognitive impairments were significantly associated with the presence of microstructural changes in white and grey matter, whereas functional impairments were mostly associated with microstructural changes in white matter. There were significant correlations between IQ versus the mean diffusivity (MD) and mean kurtosis (MK) of specific white matter regions. The IQ scores were negatively correlated with the MD of extensive grey matter regions.
Conclusion: Our study identified vulnerable brain regions whose microstructural changes in white and grey matter were significantly associated with impaired cognitive and physical functioning in survivors of pediatric intracranial GCT.
Keywords: Brain microstructure
Cognition
Diffusion kurtosis imaging
Functional outcome
Intracranial germ cell tumor
Neurotoxicity
Publisher: Frontiers Research Foundation
Journal: Frontiers in oncology 
EISSN: 2234-943X
DOI: 10.3389/fonc.2021.573798
Rights: © 2021 Tso, Hui, Lee, Liu, Ip, Vardhanabhuti, Cheng, Fong, Chang, Ho, Yip, Ku, Cheuk, Luk, Shing, Leung, Khong and Chan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The following publication Tso WWY, Hui ESK, Lee TMC, Liu APY, Ip P, Vardhanabhuti V, Cheng KKF, Fong DYT, Chang DHF, Ho FKW, Yip KM, Ku DTL, Cheuk DKL, Luk CW, Shing MK, Leung LK, Khong PL and Chan GC-F (2021) Brain Microstructural Changes Associated With Neurocognitive Outcome in Intracranial Germ Cell Tumor Survivors. Front. Oncol. 11:573798 is available at https://doi.org/10.3389/fonc.2021.573798
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