Divergent effects of irradiation on brain cortical morphology in patients with nasopharyngeal carcinoma: one-year follow-up study using structural magnetic resonance imaging

Abstract

Background: Increasing evidence indicates that radiotherapy (RT)-induced brain cortical deficits may play a critical role in developing radiation encephalopathy in patients with nasopharyngeal carcinoma (NPC). However, the evolutional processes of RT-induced cortical injury have not been sufficiently investigated. This study investigates RT-induced effects on cortical morphology using longitudinal structural magnetic resonance imaging (MRI) in NPC patients.

Methods: Using MRI-based morphometry with surface-based measures, we evaluated the longitudinal alterations of cortical volume (CV), cortical thickness (CT), and cortical surface area (CSA) in 104 NPC patients at pre-RT (n=104), within 3 months post-RT (n=92), 6 months post-RT (n=71), and 9-12 months post-RT (n=52). Twenty healthy controls were also evaluated in parallel. Linear mixed models were used to investigate the trajectories of RT-related changes in cortical brain morphology and its association with irradiation dose, with healthy controls data being used to construct a normal age-related benchmark. The level of statistical significance was set at P<0.05, corrected for multiple comparisons.

Results: The results showed that RT-related longitudinal alterations in cortical morphology underwent two diverse patterns during the first year of follow up in NPC patients. The temporal cortices (including the bilateral superior temporal gyrus, middle temporal gyrus, temporal pole, parahippocampal and fusiform gyrus, and the right inferior temporal and right transverse temporal gyrus), the basal occipital cortices (the right lingual gyrus and lateral occipital gyrus), and the basal frontal cortices (the right lateral orbitofrontal gyrus) showed time-dependent attenuation in cortical morphology indices. Furthermore, these effects on multiple cortices were dose-dependent, suggesting they were RT-associated. In contrast, in the left rostral middle frontal gyrus, there was a time-dependent increase in CT.

Conclusions: Our preliminary findings revealed divergent effects of irradiation on cortical brain morphology. These results contribute to a more comprehensive understanding of the underlying neural mechanisms of irradiation-related neurotoxic effects on cortical brain morphology and will help guide the investigation of critically neuroprotective strategies.

Keywords: Cortical thickness (CT); cortical surface area (CSA); cortical volume (CV); nasopharyngeal carcinoma (NPC); radiotherapy (RT).

Figure 1

Enrollment and follow-up procedures for patients with NPC and healthy controls. CCR, concurrent chemoradiotherapy; RT, radiotherapy; Ms, months; NCCR, neoadjuvant/adjuvant chemotherapy combined with concurrent chemoradiotherapy; NPC, nasopharyngeal carcinoma; T, time-point.

Figure 2

Linear mixed effects model revealed a significant group × time interaction for cortical morphology in multiple brain regions during 12-months follow-up. Using healthy control data as normal age-related benchmark, NPC patients showed a steeper decrease in CV in some sub-regions of the temporal, occipital, and frontal lobe (A-N); and steeper decrease in CT and CSA in the temporal sub-regions, while steeper increase in CT was observed in the left rostral middle frontal gyrus in NPC patients (O-V). CV, cortical volume; CT, cortical thickness; CSA, cortical surface area; STG, superior temporal gyrus; MTG, middle temporal gyrus; TP, temporal pole; PHG, parahippocampal gyrus; ITG, inferior temporal gyrus; FG, fusiform gyrus; LOG, lateral occipital gyrus; LOFG, lateral orbitofrontal gyrus; RMFG, rostral middle frontal gyrus; TTG, transverse temporal gyrus; LG, lingual gyrus; L, left; R, right.

Figure 3

Correlation between changes in cortical morphology (CV/CT/CSA) and radiation dosage. Dose-dependent volume reductions of the left fusiform gyrus (A), the left parahippocampal gyrus (B), the right transverse temporal gyrus (C), the right lateral occipital gyrus (D), the right lateral orbitofrontal gyrus (E), dose-dependent reductions of CT in the left superior temporal gyrus (F), and the dose-dependent reductions of CSA in the right inferior temporal gyrus (G) were observed. Each point represents the subject-level longitudinal change in cortical morphology (CV/CT/CSA) (y-axis; higher values indicate greater loss) and the corresponding mean dose to the brain regions (x-axis). CV, cortical volume; CT, cortical thickness; CSA, cortical surface area; FG, fusiform gyrus; PHG, parahippocampal gyrus; TTG, transverse temporal gyrus; LOG, lateral occipital gyrus; LOFG, lateral orbitofrontal gyrus; L, left; R, right.