Frontiers in Oncology (May 2021)

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,
  • Tatia Mei Chun Lee,
  • Anthony Pak Yin Liu,
  • Patrick Ip,
  • Vince Vardhanabhuti,
  • Kevin King Fai Cheng,
  • Daniel Yee Tak Fong,
  • Dorita Hue Fung Chang,
  • 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

DOI
https://doi.org/10.3389/fonc.2021.573798
Journal volume & issue
Vol. 11

Abstract

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BackgroundChildhood 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.MethodsDKI 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.ResultsThe 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.ConclusionOur 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.

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