jats:titleAbstract</jats:title>jats:sec jats:titleBackground</jats:title> jats:pMagnetic resonance imaging (MRI) carries prognostic importance after traumatic brain injury (TBI), especially when computed tomography (CT) fails to fully explain the level of unconsciousness. However, in critically ill patients, the risk of deterioration during transfer needs to be balanced against the benefit of detecting prognostically relevant information on MRI. We therefore aimed to assess if day of injury serum protein biomarkers could identify critically ill TBI patients in whom the risks of transfer are compensated by the likelihood of detecting management-altering neuroimaging findings.</jats:p> </jats:sec>jats:sec jats:titleMethods</jats:title> jats:pData were obtained from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Eligibility criteria included: TBI patients aged ≥ 16 years, Glasgow Coma Score (GCS) < 13 or patient intubated with unrecorded pre-intubation GCS, CT with Marshall score < 3, serum biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1) sampled ≤ 24 h of injury, MRI < 30 days of injury. The degree of axonal injury on MRI was graded using the Adams-Gentry classification. The association between serum concentrations of biomarkers and Adams-Gentry stage was assessed and the optimum threshold concentration identified, assuming different minimum sensitivities for the detection of brainstem injury (Adams-Gentry stage 3). A cost–benefit analysis for the USA and UK health care settings was also performed.</jats:p> </jats:sec>jats:sec jats:titleResults</jats:title> jats:pAmong 65 included patients (30 moderate-severe, 35 unrecorded) axonal injury was detected in 54 (83%) and brainstem involvement in 33 (51%). In patients with moderate-severe TBI, brainstem injury was associated with higher concentrations of NSE, Tau, UCH-L1 and GFAP. If the clinician did not want to miss any brainstem injury, NSE could have avoided MRI transfers in up to 20% of patients. If a 94% sensitivity was accepted considering potential transfer-related complications, GFAP could have avoided 30% of transfers. There was no added net cost, with savings up to £99 (UK) or $612 (US). No associations between proteins and axonal injury were found in intubated patients without a recorded pre-intubation GCS.</jats:p> </jats:sec>jats:sec jats:titleConclusions</jats:title> jats:pSerum protein biomarkers show potential to safely reduce the number of transfers to MRI in critically ill patients with moderate-severe TBI at no added cost.</jats:p> </jats:sec>