Evaluating Network-Level Functional and Neurovascular Alterations in Mild Traumatic Brain Injury: A Comparative Resting-State SAGE fMRI Pilot Study

Background/Objectives: Mild traumatic brain injury (mTBI) is frequently associated with persistent cognitive and neurobehavioral symptoms despite the absence of abnormalities on conventional structural imaging. Increasing evidence suggests that these symptoms arise from distributed functional and neurovascular alterations rather than focal damage. The goal of this pilot study was to investigate network-level functional alterations in subacute mTBI by evaluating resting-state functional MRI (rs-fMRI) combined with spin- and gradient-echo (SAGE) imaging to compare contrast-specific patterns across canonical resting-state networks. Methods: Rs-fMRI data from 20 subacute mTBI patients and 20 healthy controls were analyzed using independent component analysis across five canonical resting-state networks. SAGE-derived T2-weighted and T2*-weighted multi-echo contrasts were evaluated alongside conventional TE2 functional connectivity to differentiate microvascular from macrovascular contributions. Principal component analysis was applied within each network for dimensionality reduction, and multivariate patterns were compared across contrasts and networks to map group-level alterations. Results: The analysis revealed distinct, contrast-dependent spatial patterns of neurovascular alterations across multiple canonical networks. The T2-weighted contrast, reflecting microvascular weighting, identified pronounced differences in executive control, visual, and default mode networks, whereas conventional TE2 contrasts primarily highlighted alterations within sensorimotor and cerebellar circuits. Conclusions: This pilot study demonstrates the utility of evaluating SAGE-derived hemodynamic contrasts alongside canonical resting-state networks to characterize distinct spatial patterns of microvascular and macrovascular disruptions in subacute mTBI. These findings highlight the value of contrast-specific neuroimaging to disentangle complex neurovascular alterations following mild head injury.