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The Role of Blood Biomarkers for Magnetic Resonance Imaging Diagnosis of Traumatic Brain Injury

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94143, USA
Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital, San Francisco, CA 94110, USA
Department of Neurological Surgery, Columbia University Medical Center, New York, NY 10027, USA
Department of Neurological Surgery, University of California Diego, San Diego, CA 92093, USA
Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
Brain Rehabilitation Research Center (BRRC), Malcom Randall Veterans Affairs Medical Center, Gainesville, FL 32608, USA
Author to whom correspondence should be addressed.
Authors contributed equally to this work.
Medicina 2020, 56(2), 87;
Received: 20 December 2019 / Revised: 7 February 2020 / Accepted: 19 February 2020 / Published: 22 February 2020
Background and Objectives: The annual global incidence of traumatic brain injury (TBI) is over 10 million. An estimated 29% of TBI patients with negative computed tomography (CT−) have positive magnetic resonance imaging (MRI+) findings. Judicious use of serum biomarkers with MRI may aid in diagnosis of CT-occult TBI. The current manuscript aimed to evaluate the diagnostic, therapeutic and risk-stratification utility of known biomarkers and intracranial MRI pathology. Materials and Methods: The PubMed database was queried with keywords (plasma OR serum) AND (biomarker OR marker OR protein) AND (brain injury/trauma OR head injury/trauma OR concussion) AND (magnetic resonance imaging/MRI) (title/abstract) in English. Seventeen articles on TBI biomarkers and MRI were included: S100 calcium-binding protein B (S100B; N = 6), glial fibrillary acidic protein (GFAP; N = 3), GFAP/ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1; N = 2), Tau (N = 2), neurofilament-light (NF-L; N = 2), alpha-synuclein (N = 1), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor peptide (AMPAR; N = 1). Results: Acute GFAP distinguished CT−/MRI+ from CT−/MRI− (AUC = 0.777, 0.852 at 9–16 h). GFAP discriminated CT−/diffuse axonal injury (DAI+) from controls (AUC = 0.903). Tau correlated directly with number of head strikes and inversely with white matter fractional anisotropy (FA), and a cutoff > 1.5 pg/mL discriminated between DAI+ and DAI− (sensitivity = 74%/specificity = 69%). NF-L had 100% discrimination of DAI in severe TBI and correlated with FA. Low alpha-synuclein was associated with poorer functional connectivity. AMPAR cutoff > 0.4 ng/mL had a sensitivity of 91% and a specificity of 92% for concussion and was associated with minor MRI findings. Low/undetectable S100B had a high negative predictive value for CT/MRI pathology. UCH-L1 showed no notable correlations with MRI. Conclusions: An acute circulating biomarker capable of discriminating intracranial MRI abnormalities is critical to establishing diagnosis for CT-occult TBI and can triage patients who may benefit from outpatient MRI, surveillance and/or follow up with TBI specialists. GFAP has shown diagnostic potential for MRI findings such as DAI and awaits further validation. Tau shows promise in detecting DAI and disrupted functional connectivity. Candidate biomarkers should be evaluated within the context of analytical performance of the assays used, as well as the post-injury timeframe for blood collection relative to MRI abnormalities. View Full-Text
Keywords: blood-based biomarkers; diagnosis; magnetic resonance imaging; traumatic brain injury blood-based biomarkers; diagnosis; magnetic resonance imaging; traumatic brain injury
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Yue, J.K.; Upadhyayula, P.S.; Avalos, L.N.; Deng, H.; Wang, K.K.W. The Role of Blood Biomarkers for Magnetic Resonance Imaging Diagnosis of Traumatic Brain Injury. Medicina 2020, 56, 87.

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