Altered glymphatic function in nasopharyngeal carcinoma following radiotherapy: novel insights from choroid plexus volume and free-water fraction analyses

Background and purposeRadiotherapy (RT) often causes delayed radiation-induced brain injury (RBI) with unclear pathophysiology; emerging evidence links this to glymphatic dysfunction, but radiation effects on cerebrospinal fluid (CSF) dynamics and interstitial fluid-CSF exchange are unstudied. Thus, we used choroid plexus (CP) volume and free-water fraction (FWF) imaging to assess glymphatic changes in Nasopharyngeal carcinoma (NPC) patients after RT.Materials and methodsIn this cross-sectional cohort of 101 NPC patients (45 pre-RT and 56 post-RT) underwent 3 T MRI, including T1-weighted and diffusion tensor imaging. Automated CP segmentation and tract-specific FWF analysis are performed. Spearman correlation models assessed radiation-dose relationships with CP volume and Whiter matter (WM) FWF.ResultsWe observed that post-RT patients exhibited significant bilateral CP enlargement (total CP: 2560.56 ± 636.72 mm3, left: 1196.92 ± 334.53 mm3, right: 1363.64 ± 365.84 mm3; all p < 0.05) and elevated FWF in critical WM tracts, including the pontine crossing tract (PCT), bilateral corticospinal tracts (CST), middle cerebellar peduncle, right inferior cerebellar peduncle, and left medial lemniscus. Radiational dose exhibit strong dose-dependent correlations with CP volume and WM FWF. Maximum doses to the brainstem (MDRT_BS) and left temporal lobe (MDRT_LT) showed the strongest associations: MDRT_LT correlated with left CP volume (r = 0.599, p < 0.001), right CP volume (r = 0.585, p < 0.001), and bilateral CST FWF (left: r = 0.414, p = 0.005; right: r = 0.354, p = 0.017). CP volume positively correlated with FWF in the PCT and CST (left CST vs. total CP: r = 0.374, p = 0.011). These associations remained significant after adjusting for age, gender, and intracranial volume (r = 0.31–0.58, all p < 0.05).ConclusionThe observed association between choroid plexus enlargement and elevated white matter free-water fraction suggests RT-associated glymphatic dysfunction in NPC, offers a novel perspective on the pathogenesis of RBI.