CT-Based Assessment of Brain Edema May Predict Which Patients with Traumatic Brain Injury May Benefit from Tranexamic Acid

BACKGROUND AND PURPOSE: Tranexamic acid (TXA) may reduce the progression of vasogenic edema in traumatic brain injury (TBI), potentially providing a survival benefit in specific patients. This study evaluates a CT-based quantitative imaging tool for identifying patients with acute TBI who may benefit from prehospital TXA. MATERIALS AND METHODS: This is a post hoc analysis of the Prehospital Tranexamic Acid Use for Traumatic Brain Injury trial, a multicenter, placebo-controlled trial that randomized patients with moderate or severe TBI to either a 1-g TXA bolus followed by 1-g infusion, a 2-g TXA bolus, or a placebo. CT images were analyzed using a novel Matlab-based algorithm to calculate the percentage of voxels within various density ranges. The region of interest was defined as the entire brain parenchyma after skull removal. The 10-20 HU range, identified as most representative of vasogenic edema based on correlation with mean ADC values in a subset of 102 patients, was used for further analysis. Logistic regression was performed to evaluate the relationship between voxel percentages in the 10-20 HU range and in-hospital mortality. Threshold analysis identified the minimum voxel percentage within the 10-20 HU range associated with significant TXA survival benefit. Relative risk reduction in mortality was calculated for patients above and below this threshold. RESULTS: In a cohort of 550 patients, logistic regression showed that the association between TXA use and in-hospital survival varied with the percentage of brain voxels in the 10-20 HU range (interaction P = .04). Threshold analysis identified a cutoff of 3% of brain parenchymal voxels in the 10-20 HU range, corresponding to approximately 40 mL of vasogenic edema, beyond which TXA administration was associated with a significant survival benefit (P = .04). In this subgroup, TXA was associated with a relative risk of mortality of 0.41 (95% CI, 0.17-0.99) compared with a placebo. CONCLUSIONS: A voxel percentage of ≥3% within the 10-20 HU CT density range serves as a promising imaging biomarker associated with a survival benefit from TXA in patients with acute TBI in the prehospital setting. Prospective validation is required to confirm these findings before integrating this biomarker into clinical decision-making for personalized TBI management.