Impairment of Cerebral Interstitial Fluid Dynamics after Whole-Brain Radiotherapy and Its Association with Leukoencephalopathy Development

Abstract

Purpose: To evaluate changes in cerebral interstitial fluid dynamics following whole-brain radiotherapy (WBRT) for brain metastases using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, and to investigate the relationship between these changes and the subsequent development of radiation-induced leukoencephalopathy (LEP). Materials and methods: A retrospective analysis was conducted on 50 patients who underwent WBRT for brain metastases. Baseline and post-WBRT DTI-ALPS indices were compared using paired t-tests. Univariate and multivariate linear regression analyses were performed to assess the relationship between changes in the DTI-ALPS index and clinical- and treatment-related factors. In a subset of 33 patients, univariate and multivariate logistic regression analyses were conducted to explore the association between the percentage change in the DTI-ALPS index and the development of LEP at 6-month follow-up, after adjustment for relevant clinical- and treatment-related factors. Results: The mean DTI-ALPS index decreased significantly following WBRT (baseline: 1.487 +/- 0.257; post-WBRT: 1.353 +/- 0.229; p<0.001). A higher baseline DTI-ALPS index was significantly associated with a greater decline in the index post-WBRT (p=0.023). In the logistic regression analysis, a greater percentage reduction in the DTI-ALPS index was the only factor significantly associated with LEP development at 6 months (p=0.048). Conclusion: WBRT is associated with impaired cerebral interstitial fluid dynamics, as reflected by a significant reduction in the DTI-ALPS index. A greater decline in the DTI-ALPS index was predictive of LEP development, suggesting its potential utility as a biomarker for early diagnosis of radiation-induced LEP.