TY - JOUR
T1 - Brain Microstructural Changes Associated With Neurocognitive Outcome in Intracranial Germ Cell Tumor Survivors
AU - Tso, Winnie Wan Yee
AU - Hui, Edward Sai Kam
AU - Lee, Tatia Mei Chun
AU - Liu, Anthony Pak Yin
AU - Ip, Patrick
AU - Vardhanabhuti, Vince
AU - Cheng, Kevin King Fai
AU - Fong, Daniel Yee Tak
AU - Chang, Dorita Hue Fung
AU - Ho, Frederick Ka Wing
AU - Yip, Ka Man
AU - Ku, Dennis Tak Loi
AU - Cheuk, Daniel Ka Leung
AU - Luk, Chung Wing
AU - Shing, Ming Kong
AU - Leung, Lok Kan
AU - Khong, Pek Lan
AU - Chan, Godfrey Chi Fung
N1 - Funding Information:
This work was supported by Research Grants Council of the Hong Kong Special Administrative Region, China (No. HKU 17118815). The funder had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.
Publisher Copyright:
© Copyright © 2021 Tso, Hui, Lee, Liu, Ip, Vardhanabhuti, Cheng, Fong, Chang, Ho, Yip, Ku, Cheuk, Luk, Shing, Leung, Khong and Chan.
PY - 2021/5/26
Y1 - 2021/5/26
N2 - 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.
AB - 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.
KW - brain microstructure
KW - cognition
KW - diffusion kurtosis imaging
KW - functional outcome
KW - intracranial germ cell tumor
KW - neurotoxicity
UR - http://www.scopus.com/inward/record.url?scp=85108381927&partnerID=8YFLogxK
U2 - 10.3389/fonc.2021.573798
DO - 10.3389/fonc.2021.573798
M3 - Journal article
AN - SCOPUS:85108381927
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 573798
ER -
