Brain Microstructural Changes Associated With Neurocognitive Outcome in Intracranial Germ Cell Tumor Survivors

Winnie Wan Yee Tso, Edward Sai Kam Hui, Tatia Mei Chun Lee, Anthony Pak Yin Liu, Patrick Ip, Vince Vardhanabhuti, Kevin King Fai Cheng, Daniel Yee Tak Fong, Dorita Hue Fung Chang, Frederick Ka Wing Ho, Ka Man Yip, Dennis Tak Loi Ku, Daniel Ka Leung Cheuk, Chung Wing Luk, Ming Kong Shing, Lok Kan Leung, Pek Lan Khong, Godfrey Chi Fung Chan (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Article number573798
JournalFrontiers in Oncology
Publication statusPublished - 26 May 2021


  • brain microstructure
  • cognition
  • diffusion kurtosis imaging
  • functional outcome
  • intracranial germ cell tumor
  • neurotoxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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