Radiation-induced hippocampal atrophy in patients with nasopharyngeal carcinoma early after radiotherapy: a longitudinal MR-based hippocampal subfield analysis

  • Xiaofei Lv
  • Haoqiang He
  • Yadi Yang
  • Lujun Han
  • Zheng Guo
  • Hong Chen
  • Jing Li
  • Yingwei QiuEmail author
  • Chuanmiao XieEmail author
Original Research


Increasing evidence indicates that radiation-induced injury to the hippocampus may play a critical role in neurocognitive dysfunction in patients with nasopharyngeal carcinoma (NPC). However, few studies have assessed RT-induced hippocampal structural alterations in these patients early after radiotherapy (RT). In this study, 58 NPC patients were longitudinally followed up prior to treatment initiation as well as 3 and 6 months after RT, respectively. Twenty comparable normal controls were recruited and followed up in parallel. A novel magnetic resonance imaging (MRI)-based automated method was used to label hippocampal subfields. The linear mixed model was employed to evaluate longitudinal changes in the volumes of the whole hippocampus and seven hippocampal subfields. Time-dependent volume reduction was observed in the bilateral hippocampus, as well as in the bilateral granule cell layer (GCL), bilateral cornu ammonis 1 (CA1), bilateral molecular layer (ML), and bilateral subiculum (SUB) in NPC patients, but not in controls. Moreover, volume deficits in the bilateral hippocampus, bilateral GCL, and right ML showed dose-dependent patterns, and high volume losses in the bilateral hippocampus, bilateral GCL, left SUB, and right ML were associated with a rapid decline in cognitive function. Our findings demonstrated that the hippocampal subfields were selectively injured by irradiation-related early neurotoxic effects, which might account for cognitive impairment in NPC patients at an early stage after RT. Further, structural MRI could serve as a potential noninvasive imaging biomarker for the early detection of radiation effects on the hippocampus in NPC patients after RT.


Radiotherapy Radiation-induced injury Nasopharyngeal carcinoma Hippocampus Hippocampal subfields Structural MRI 



This work was funded by grants from the Natural Scientific Foundation of China (grant numbers: 81401399, 81560283, and 81201084), Natural Scientific Foundation of Jiangxi Province, China (grant number: 20151BAB205049), Fundamental Research Funds for the Central Universities (Grant number: 15ykpy35), and Medical Scientific Research Foundation of Guangdong Province (Grant number: B2014162).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

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High resolution image (TIF 12030 kb)
11682_2018_9931_MOESM2_ESM.docx (119 kb)
ESM 2 (DOCX 118 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical ImagingSun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhouPeople’s Republic of China
  2. 2.Department of OncologyThe First Affiliated Hospital of Ganzhou Medical UniversityGanzhouPeople’s Republic of China
  3. 3.Department of Radiology, The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhouPeople’s Republic of China

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