Voxel-based morphometry reveals immune-metabolic dysregulation driving adaptive cortical gray matter remodeling in patients with esophageal cancer

Kaihua Zhang¹Wei Su¹Jiayu Lin¹Yingli Gao¹Chunming Gu²Ye Li³Ning Jiang⁴Yingtao Hao⁴Hai Zhong⁵Weiquan Zhang^4*

• ¹School of Psychology, Shandong Normal University, Jinan, China
• ²Department of Radiology, Mayo Clinic, Rochester, MN, United States
• ³Department of Pediatrics, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
• ⁴Department of Thoracic Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
• ⁵Department of Radiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

Esophageal cancer (EC), a highly prevalent malignant cancer, is frequently accompanied by cancer-related cognitive impairment (CRCI), yet its underlying neural mechanisms remain poorly understood. This study integrated inflammatory biomarkers and nutritional index with structural magnetic resonance imaging (MRI) to investigate the characteristics of brain structural alterations in EC patients and their association with systemic inflammation and nutritional metabolism. A total of 49 treatment-naive EC patients and 31 healthy controls (HC) were enrolled. High-resolution T1-weighted MRI scans and peripheral blood indices (including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR)) were collected. Voxel-based morphometry (VBM) was employed to assess gray matter volume differences, and correlations between GM volume, inflammatory markers and nutritional index were analyzed. Results demonstrated that the EC group exhibited significantly elevated monocyte counts and PLR, alongside reduced lymphocytes, albumin levels, and prognostic nutritional index compared to HC (p < 0.05). Structural MRI revealed significantly increased GM volume in bilateral occipital lobes, basal ganglia, pre-/postcentral gyri, and the right temporal lobe in EC patients, and decreased GM volume in bilateral parahippocampa gyri, amygdala, and cerebellum Posterior Lobe (FDR correction, p < 0.05). Partial correlation analysis indicated a negative association between GM volume in the right basal ganglia and PLR (r = - 0.464, p = 0.005). These findings suggest that brain structural alterations in EC patients may be driven by systemic inflammation and nutritional imbalance, reflecting a dynamic equilibrium between neuroplastic compensation and neuroinflammatory injury. The negative correlation between GM volume and PLR provides neuroimaging evidence for inflammation-mediated CRCI mechanisms, offering novel targets for the development of early intervention strategies.