Cytotoxic Edema Associated with Hemorrhage Predicts Poor Outcome after Traumatic Brain Injury

Abstract

Magnetic resonance imaging (MRI) is used rarely in the acute evaluation of traumatic brain injury (TBI) but may identify findings of clinical importance not detected by computed tomography (CT). We aimed to characterize the association of cytotoxic edema and hemorrhage, including traumatic microbleeds, on MRI obtained within hours of acute head trauma and investigated the relationship to clinical outcomes. Patients prospectively enrolled in the Traumatic Head Injury Neuroimaging Classification study (NCT01132937) with evidence of diffusion-related findings or hemorrhage on neuroimaging were included. Blinded interpretation of MRI for diffusion-weighted lesions and hemorrhage was conducted, with subsequent quantification of apparent diffusion coefficient (ADC) values. Of 161 who met criteria, 82 patients had conspicuous hyperintense lesions on diffusion-weighted imaging (DWI) with corresponding regions of hypointense ADC in proximity to hemorrhage. Median time from injury to MRI was 21 (10-30) h. Median ADC values per patient grouped by time from injury to MRI were lowest within 24 h after injury. The ADC values associated with hemorrhagic lesions are lowest early after injury, with an increase in diffusion during the subacute period, suggesting transformation from cytotoxic to vasogenic edema during the subacute post-injury period. Of 118 patients with outcome data, 60 had Glasgow Outcome Scale Extended scores ≤6 at 30/90 days post-injury. Cytotoxic edema on MRI (odds ratio [OR] 2.91 [1.32-6.37], p = 0.008) and TBI severity (OR 2.51 [1.32-4.74], p = 0.005) were independent predictors of outcome. These findings suggest that in patients with TBI who had findings of hemorrhage on CT, patients with DWI/ADC lesions on MRI are more likely to do worse.

Keywords: apparent diffusion coefficient; cytotoxic edema; diffusion-weighted imaging; hemorrhage; magnetic resonance imaging; traumatic brain injury.

FIG. 1.

Flowchart of study patient inclusion and exclusion. THINC, Traumatic Head Injury Neuroimaging Classification study (NCT01132937); MRI, magnetic resonance imaging; GCS, Glasgow Coma Scale; DWI, diffusion-weighted imaging; TMB, traumatic microbleed; GOSE, Glasgow Outcome Scale Extended; TBI, traumatic brain injury.

FIG. 2.

Types of acute traumatic brain injury lesions associated with magnetic resonance imaging findings. White arrows indicate the areas of interest. (A) Parenchymal hyperintensities on diffusion-weighted imaging (DWI), as seen in (i) coronal view, can be associated with acute traumatic microbleeds (TMBs) seen on (ii) gradient recalled echo (GRE) imaging, with (iii) axial DWI hyperintensities colocalizing with (iv) apparent diffusion coefficient (ADC) hypointensities. (B) Parenchymal (i) DWI hyperintensity and colocalizing (ii) ADC hypointensity can also occur adjacent to areas of subarachnoid hemorrhage, as seen on (iii) gradient recalled echo (GRE) imaging. (C) Similar changes can occur in parenchymal adjacent to areas of hemorrhage associated with contusion or intraparenchymal hematoma. (D) Isolated areas hyperintense on DWI and hypointense on ADC may also be observed in the absence of hemorrhage on GRE. (E) Frequency of visually conspicuous hyperintense lesions on DWI and hypointense lesions on ADC stratified by adjacent hemorrhagic lesion or seen in isolation. SAH, subarachnoid hemorrhage; TMB, traumatic microbleed; IPH, intraparenchymal hematoma.

FIG. 3.

Representative example of the evolution of magnetic resonance imaging findings associated with a traumatic microbleed from acute presentation to follow-up. (A) At 16 h after mild traumatic brain injury, near the traumatic microbleed on (i) gradient recalled echo (GRE), there is a hyperintense area on (ii) diffusion-weighed imaging (DWI) that is hypointense on initial (iii) apparent diffusion coefficient (ADC), indicative of cytotoxic edema. On follow-up (B), one week after injury, this same area remains hyperintense on DWI but is now hyperintense on ADC, suggesting that vasogenic edema has developed. The hemorrhage related to the traumatic microbleed is visible on both initial and follow-up GRE, with associated (iv) fluid-attenuated inversion recovery (FLAIR) hyperintensity.

FIG. 4.

Quantification of apparent diffusion coefficient (ADC) of water for all lesion types. (A) Scatter plot of ADC values of baseline presentation versus follow-up visit for all lesion types (one data point is off-scale). (B) Change in ADC for all volumes of interest stratified by quartiles based on baseline ADC value (minimum = 0.3954; 25th percentile = 0.6769; median = 0.7610; 75% = 0.8699; maximum = 1.419; n = 481). IPH, intraparenchymal hematoma; SAH, subarachnoid hemorrhage; TMB, traumatic microbleed. Color image is available online.

FIG. 5.

Quantification of apparent diffusion coefficient (ADC) of water for lesions in proximity to traumatic microbleeds. (A) The ADC values at baseline and follow-up visits for traumatic microbleeds are plotted based on the time from injury to magnetic resonance imaging (MRI), with reference values shown for comparison. (B) Box-whisker plot of ADC values grouped by baseline time from injury to MRI for traumatic microbleeds (*p < 0.001 for <24 h versus 24–72 h and versus >72 h). Color image is available online.