MRI Assessment of Radiation-Induced Delayed-Onset Microstructural Gray Matter Changes in Nasopharyngeal Carcinoma Patients.

Abstract

Background: The dynamic progression of gray matter (GM) microstructural alterations following radiotherapy (RT) in patients, and the relationship between these microstructural abnormalities and cortical morphometric changes remains unclear.

Purpose: To longitudinally characterize RT-related GM microstructural changes and assess their potential causal links with classic morphometric alterations in patients with nasopharyngeal carcinoma (NPC).

Study type: Prospective, longitudinal.

Population: Forty treatment-naïve patients with NPC (40.78 ± 9.15 years; 14 female) and 20 healthy controls (40.65 ± 9.76 years; 7 female).

Field strength/sequences: 3 T MRI with 3D T1-weighted gradient echo and multishell diffusion-weighted single-shot echo planar imaging.

Assessment: Multishell diffusion and structural MRIs were acquired from NPC patients at baseline, 0-3 months (acute), 6 months (early-delayed), and 12 months (late-delayed) post-RT, with healthy controls imaged at baseline. Temporal lobe (TL) radiation doses were extracted from dose-volume histograms. GM-based spatial statistics and surface-based morphometry analyses were used to quantify microstructural and macrostructural changes, respectively. TL subregions were extracted from the Desikan-Killiany atlas for the region-of-interest (ROI) analysis.

Statistical tests: Chi-squared tests, t-tests, repeated measures analysis of variance (ANOVA), Spearman correlation (r), and mediation analyses (p < 0.01 for voxel-wise analyses and p < 0.05 for others were considered significant).

Results: GM microstructural changes in TL regions were mainly observed to emerge at 6 months and to persist or first appear at 12 months post-RT, representing a delayed-onset pattern. ROI analyses showed dose-dependent alterations in diffusion metrics within the entorhinal cortex (EC) and temporal pole (TP) (|r| = 0.31-0.66). Morphometric analysis demonstrated widespread TL atrophy. Mediation analysis showed delayed-onset changes in EC and TP that mediated macrostructural abnormalities in multiple TL regions, including left middle and superior temporal gyri and right inferior temporal and parahippocampal gyri.

Data conclusions: This study showed delayed-onset, dose-sensitive microstructural changes in EC and TP that contribute to broader TL atrophy in NPC patients.

Evidence level: 2.

Technical efficacy: Stage 4.