Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction

Hum Brain Mapp. 2018 Jan;39(1):407-427. doi: 10.1002/hbm.23852. Epub 2017 Oct 23.

Abstract

Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc.

Keywords: amplitude of low-frequency fluctuations; diffusion tensor imaging; functional connectivity; functional magnetic resonance imaging; irradiation injury; nasopharyngeal carcinoma; prognosis; radiation therapy; resting state; structural connectivity.

MeSH terms

  • Adult
  • Aged
  • Brain / diagnostic imaging*
  • Brain / physiopathology
  • Brain / radiation effects
  • Brain Injuries / diagnostic imaging*
  • Brain Injuries / etiology
  • Brain Injuries / physiopathology
  • Carcinoma / diagnostic imaging
  • Carcinoma / physiopathology
  • Carcinoma / radiotherapy*
  • Cross-Sectional Studies
  • Diffusion Tensor Imaging
  • Dose-Response Relationship, Radiation
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Models, Biological
  • Multimodal Imaging
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / diagnostic imaging
  • Nasopharyngeal Neoplasms / physiopathology
  • Nasopharyngeal Neoplasms / radiotherapy*
  • Prognosis
  • Radiation Injuries / diagnostic imaging*
  • Radiation Injuries / etiology
  • Radiation Injuries / physiopathology
  • Radiotherapy Dosage
  • Rest
  • Retrospective Studies
  • Young Adult