DTI Histogram and Texture Features as Early Predictors of Post-Radiotherapy Cognitive Decline

Background: Radiotherapy for brain tumors can induce cognitive decline, yet most studies examine white matter (WM) damage six months post-treatment, overlooking early microstructural changes. This study investigated whether early WM changes, as measured by diffusion tensor imaging (DTI) histogram and texture features, can predict later cognitive deficits. Methods: Nineteen adults with brain metastases underwent DTI before and immediately after radiotherapy. Ten features—eight histogram-based and two texture-based—were extracted from normal-appearing WM of major DTI indices. Changes (Δ) in these features, if any, were analyzed via multiple linear regression, correlating them with cognitive performance at four months after therapy. Results: Out of 40 features, four exhibited significant post-radiotherapy changes. These were the mean (ADmean) and skewness (ADskewness) of axial diffusivity and the kurtosis of mean diffusivity (MDkurtosis) and radial diffusivity (RDkurtosis). Regression identified ΔADmean (β = −3.303 × 104, p = 0.002) as negatively and ΔADskewness (β = 4.642, p = 0.006) and ΔRDkurtosis (β = −1.505, p = 0.027) as positively associated with semantic fluency. Conclusions: Early WM microstructural disruptions—particularly axonal damage and heterogeneous injury—correlate with declines in semantic fluency. DTI histogram and texture features may be promising as early non-invasive biomarkers for cognitive risk following radiotherapy.