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

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.