Quantitative CT biomarkers for early outcome prediction in acute traumatic brain injury: a systematic review, meta-analysis, and meta-regression.

Acute traumatic brain injury (TBI) remains one of the leading causes of mortality worldwide, as well as long-term neurological deficits. Early and reliable prognostic measurements play an important role in clinical decision-making, triage procedures, and resource management in urgent care settings. Conventional computed tomography (CT)-based scoring systems, including Marshall, Rotterdam, and Helsinki, are widely used in practice; however, they may be limited by subjectivity and inter-observer variability due to their qualitative or semi-quantitative nature. The present study aimed to conduct a systematic review of the prognostic associations between quantitative CT biomarkers and early neurological outcomes, as well as mortality, in patients with acute TBI. A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases including PubMed, Scopus, Embase, and Web of Science were searched from inception until March 2025. Eligible studies included observational and interventional research reporting quantitative CT-derived biomarkers, such as lesion volume, midline shift, basal cistern compression, and ventricular ratios, along with clinical outcomes in adult patients with acute TBI. The QUADAS-2 tool and Newcastle–Ottawa Scale were used to assess risk of bias. Random-effects models were applied to estimate pooled odds ratios (ORs), and heterogeneity was explored using subgroup analyses and meta-regression. A total of 36 studies (n = 18,742 patients) met inclusion criteria, with 29 contributing to quantitative synthesis. Quantitative CT biomarkers were significantly associated with adverse neurological outcomes (pooled OR = 2.41, 95% CI = 1.98–2.93) and mortality (pooled OR = 2.67, 95% CI = 2.11–3.38). Lesion volume and midline shift demonstrated the largest pooled effect sizes among examined biomarkers. Meta-regression analyses identified patient age, injury severity, timing of CT imaging, and biomarker type as significant moderators of effect size. CT imaging performed within 24 h of injury was associated with stronger prognostic associations, likely reflecting acute injury burden rather than causation. Findings were consistent in sensitivity analyses, and no substantial publication bias was detected. The available evidence suggests that quantitative CT biomarkers provide clinically relevant prognostic associations with short-term neurological outcomes and mortality following acute TBI. These objective radiologic measures may complement existing CT-based scoring systems and support early risk stratification within emergency radiology practice. Nevertheless, prospective validation studies and standardized measurement protocols are required before broader clinical implementation.