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

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.