Dynamic contrast enhanced MRI for characterization of blood-brain-barrier dysfunction after traumatic brain injury

Abstract

Background and purpose: Dysfunction of the blood-brain-barrier (BBB) is a recognized pathological consequence of traumatic brain injury (TBI) which may play an important role in chronic TBI pathophysiology. We hypothesized that BBB disruption can be detected with dynamic contrast-enhanced (DCE) MRI not only in association with focal traumatic lesions but also in normal-appearing brain tissue of TBI patients, reflecting microscopic microvascular injury. We further hypothesized that BBB integrity would improve but not completely normalize months after TBI.

Materials and methods: DCE MRI was performed in 40 adult patients a median of 23 days after hospitalized TBI and in 21 healthy controls. DCE data was analyzed using Patlak and linear models, and derived metrics of BBB leakage including the volume transfer constant (K^trans) and the normalized permeability index (NPI) were compared between groups. BBB metrics were compared with focal lesion distribution as well as with contemporaneous measures of symptomatology and cognitive function in TBI patients. Finally, BBB metrics were examined longitudinally among 18 TBI patients who returned for a second MRI a median of 204 days postinjury.

Results: TBI patients exhibited higher mean K^trans (p = 0.0028) and proportion of suprathreshold NPI voxels (p = 0.001) relative to controls. Tissue-based analysis confirmed greatest TBI-related BBB disruption in association with focal lesions, however elevated K^trans was also observed in perilesional (p = 0.011) and nonlesional (p = 0.044) regions. BBB disruption showed inverse correlation with quality of life (rho = -0.51, corrected p = 0.016). Among the subset of TBI patients who underwent a second MRI several months after the initial evaluation, metrics of BBB disruption did not differ significantly at the group level, though variable longitudinal changes were observed at the individual subject level.

Conclusions: This pilot investigation suggests that TBI-related BBB disruption is detectable in the early post-injury period in association with focal and diffuse brain injury.

Keywords: Blood–brain-barrier; Dynamic contrast-enhanced MRI; Microvascular injury; TBI.