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

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.

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

Prospective, longitudinal.

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

3 T MRI with 3D T1-weighted gradient echo and multishell diffusion-weighted single-shot echo planar imaging.

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.

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).

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.

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

2.

Stage 4.