Elevated apparent diffusion coefficient of extra-axial space in patients with traumatic brain injury

Abstract Background Following traumatic brain injury, the apparent diffusion coefficient (ADC) of fluid within extra-axial space was discovered to be elevated above that of water in “free space”. We aimed to characterize the prevalence, predictors, and temporal evolution of elevated ADC in extra-axial space. Meningeal injury occurs in ~ 50% of mild traumatic brain injury patients, we investigated whether diffusion-weighted magnetic resonance imaging (MRI) serves as a surrogate biomarker for acute injury-induced meningeal blood–cerebrospinal fluid barrier disruption. Methods We conducted a retrospective analysis of predominately Glasgow Coma Scale 13–15 patients with paired 3T MRI scans within 48 h and 30 days post-injury. Blinded raters qualitatively assessed ADC elevation and was confirmed by co-registered signal intensity-based segmentation. To estimate time to resolution, ADC elevation was evaluated on additional serial MRI scans out to one year. Meningeal injury was independently assessed on post-contrast MRI. Univariate and multivariable logistic regression explored predictors of ADC elevation. Results Among 186 patients analyzed (age 47 [31–59] years; 70% male), elevated ADC was detected more frequently at baseline than at 30-day follow-up, (73/186 [39%] vs. 41/186 [22%], P < 0.001). Dichotomous (presence/absence) qualitative ratings of ADC elevation showed high concordance with quantitative analysis. ADC values > 3.4 × 10⁻³ mm²/s were observed in 84% of patients with presence of elevation and in 20% of patients interpreted as absent elevation at baseline ( P < 0.001). At 30 days, corresponding rates were 73% and 7%, respectively ( P < 0.001). Stable ventricular ADC values supported the compartmental specificity of observed elevated ADC within the convexity and falx. Temporal analysis revealed ADC elevation was transient; more than half of patients with acute elevation had increased severity within the first week. Median duration of elevated ADC was ~ 18 days. Meningeal injury and elevated ADC at baseline were closely associated ( P < 0.001; odds ratio = 8.58) and typically resolved by 30 days post-injury. Conclusions Together, these findings suggest elevated ADC in extra-axial space following traumatic brain injury represents increased fluid dispersion associated with meningeal injury. Elevated ADC may serve as an alternative biomarker for meningeal injury, without the need for gadolinium administration.