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.