Causal network analysis-based assessment of gray matter alteration in post-radiotherapy nasopharyngeal carcinoma patients using 3D T1-weighted MRI

Objectives: To explore the temporal and causal relationships underlying brain structural changes in post-radiotherapy (RT) nasopharyngeal carcinoma (NPC) patients. Methods: A total of 38 post-radiotherapy NPC patients (33 males, 5 females; median age: 50.0 years, range: 27-63 years; median time post-RT: 17.2 months, range: 0.5-108 months) and 23 healthy controls (16 males, 7 females; median age: 37 years, range: 24-61 years) underwent T1-weighted magnetic resonance (MR) images, and their images were evaluated. The causal structural covariance network (CaSCN) analysis approach was applied to assess the causal relationships underlying radiation-induced brain structural alterations in these patients. Granger causality (GC) analysis was employed to morphometric data derived from T1-weighted MR images, which were ordered by the time elapsed post-RT. Results: The source-like directed associations were observed in the bilateral parahippocampal gyrus (PHG), the right gyrus rectus (REC.R), and the right caudate nucleus (CAU.R). The directed network analysis revealed that the parahippocampal gyrus (PHG), REC.R and CAU.R exhibited typical source-like characteristics, and their structural changes exerted a key regulatory effect on GM volume alterations across multiple brain regions. While the left precuneus (PCUN.L), left temporal pole: middle temporal gyrus (TPOmid.L) and the left inferior temporal gyrus (ITG.L) were typical sink-like brain region that mainly received regulatory effects from source-like brain regions, acting as major target regions of structural damage. Conclusion: Over time, post-radiotherapy NPC patients exhibited progressive changes in GM volume, where the PHG.L, PHG.R, REC.R and CAU.R were core source-like brain regions. The PCUN.L, TPOmid.L, and ITG.L show distinct sink-like features, which mainly receive regulatory effects from source-like brain regions.