# DTI Histogram and Texture Features as Early Predictors of Post-Radiotherapy Cognitive Decline
## 1 Introduction  
Brain tumors, including high-grade gliomas and brain metastases, frequently require whole-brain radiation therapy (WBRT) or stereotactic irradiation (STI) as primary treatment modalities [1, 2]. While these interventions effectively control tumor growth and extend patient survival, they are frequently associated with neurotoxic effects. Notably, studies report that approximately 50% to 90% of patients experience varying degrees of cognitive dysfunction, including impairments in memory, attention, processing speed, and executive function, within 3 to 6 months following radiation therapy [3, 4, 5, 6]. The pathophysiological mechanisms underlying radiation-induced cognitive impairment are multifaceted. Radiation disrupts the integrity of cerebral white matter (WM) andgray matter through several biological processes, including vascular damage, demyelination, neuroinflammation, and, ultimately, necrosis of brain tissues [7,8]. Current assessment methods for post-radiation cognitive impairment primarily include neurocognitive function tests such as the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) [9,10]. WM, which consists of myelinated axonal tracts, is particularly susceptible to radiation-induced injury. Damage to WM disrupts signal transmission across critical neural pathways, affecting various cognitive domains. Studies have demonstrated that specific WM tracts, such as the corpus callosum, cingulum bundle, and superior longitudinal fasciculus, are particularly susceptible to radiation damage, correlating with deficits in semantic fluency, executive function, and processing speed [11,12,13]. Damage to the WM can be assessed using diffusion tensor imaging (DTI) [14], a magnetic resonance imaging (MRI) technique that quantifies the microstructural integrity of WM tracts by measuring the diffusion of water molecules around axons [15]. DTI provides four indices: fractional anisotropy (FA), which reflects fiber density and coherence and typically decreases in cases of WM damage; mean diffusivity (MD), which represents the average apparent diffusion coefficient across fiber directions and is negatively correlated with cell density and positively correlated with edema and WM degeneration; radial diffusivity (RD), which measures water diffusion perpendicular to axonal fibers and is particularly sensitive to demyelination processes; and axial diffusivity (AD), which quantifies water diffusion parallel to the principal fiber direction and often reflects axonal integrity. These DTI indices have been demonstrated to be effective in evaluating WM changes, offering insights into the extent and distribution of WM injury [16,17]. Importantly, studies have shown that FA reduction and RD increase in major WM tracts, including the posterior thalamic radiation, sagittal stratum, and corpus callosum, are closely linked to impairments in cognitive processing speed, memory, and executive function [18]. Moreover, advanced imaging analysis, such as histogram analysis and gray level co-occurrence matrix (GLCM)-based texture analysis, extends the diagnostic capabilities of DTI. Histogram analysis evaluates the distribution and frequency of voxel intensity values within tissue regions. In contrast, GLCM-based texture analysis captures the spatial relationships between neighboring voxels with similar intensities, providing information about tissue heterogeneity and structural disorganization [19,20]. [PERSON] et al. effectively utilized these methods to characterize tissue heterogeneity and microstructural organization in gliomas and successfully predicted genetic profiles and clinical outcomes with high accuracy [21]. Despite extensive research on radiation-induced WM changes, significant gaps remain regarding immediate post-treatment microstructural alterations and their cognitive correlates.