Can a blood test safely reduce unnecessary CT imaging after a head injury?

Each year, millions of adults present to the emergency department (ED) after head injury, and most undergo CT imaging to evaluate for intracranial bleeding. Yet fewer than 10% of these scans reveal a clinically significant finding. The result is a high-volume, low-yield diagnostic pathway that increases costs, prolongs ED length of stay, contributes to crowding, and exposes patients to unnecessary radiation. This represents a clear gap in care, one that blood-based biomarkers are uniquely positioned to fill. What’s been missing is a reliable, scalable rule-out tool to safely identify patients with suspected mild traumatic brain injury (mTBI) who do not require imaging. 

That opportunity has driven interest in two brain-specific proteins: glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1). GFAP is released from astrocytes and UCH-L1 from neurons following injury. When the blood-brain barrier is disrupted during head trauma, these proteins enter the circulation and can be detected within hours. Importantly, these assays are intended to aid in determining the need for head CT imaging in patients with mTBI (e.g., Glasgow Coma Scale [GCS] 13–15) and are not designed to replace imaging in patients with moderate or severe injury. Since the first combined assay received FDA clearance in 2018, additional platforms, including both point-of-care devices and high-throughput laboratory analyzers, have expanded access to this testing and made integration into routine workflows increasingly feasible.

Our group recently evaluated the Abbott TBI assay on the Alinity i platform in patients with suspected mTBI. We analyzed remnant specimens from 97 ED patients presenting within 12 hours of blunt head trauma with mild symptoms (GCS 13–15), all of whom underwent CT imaging. Three emergency physicians independently reviewed each case, blinded to biomarker results. In this cohort, the assay achieved 100% sensitivity and 100% negative predictive value, and none of the eight patients with CT-confirmed intracranial injuries were missed. Results were available in under 20 minutes, compared to CT turnaround times exceeding one hour for most patients at our institution. Specificity, however, was limited at 32.6%, meaning many patients without intracranial injury still tested positive. This limitation was more pronounced in older adults, where specificity declined with age from 47.2% in patients under 65 to 11% in those 65 and older, likely reflecting higher baseline GFAP levels. Notably, GFAP alone improved specificity to 81.1% in younger patients while maintaining perfect sensitivity, suggesting a potential path toward more targeted use. 

So, what does this mean in practice? The sensitivity data are reassuring; this is a reliable rule-out tool when results fall below established cutoffs. However, specificity limitations, particularly in older adults, mean we shouldn’t simply report results without context. Successful implementation will require integration into clinical pathways, including age-stratified interpretive guidance and close collaboration with ED clinicians. Larger prospective studies are still needed to refine cutoffs and determine how biomarker testing complements established decision rules, such as the Canadian CT Head Rule. The direction is clear: laboratory medicine has a central role to play in making head injury evaluation faster, safer, and more efficient.

References

1. Mills CM, Roberts N, Fritsche K, et al. Clinical Evaluation of the TBI Assay in a Representative Emergency Department Cohort. J Appl Lab Med. 2026;11(1):26-35. doi:10.1093/jalm/jfaf159. 
2. Bazarian JJ, Biberthaler P, Welch, et al. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018;17(9):782-789. doi:10.1016/S1474-4422(18)30231-X.