title: Combining biochemical and imaging markers to improve diagnosis and characterization of mild traumatic brain injury in the acute setting: results from a pilot study.
abstract: BACKGROUND
  Mild traumatic brain injury (mTBI) is a significant healthcare burden and its diagnosis remains a challenge in the emergency department. Serum biomarkers and advanced magnetic resonance imaging (MRI) techniques have already demonstrated their potential to improve the detection of brain injury even in patients with negative computed tomography (CT) findings. The objective of this study was to determine the clinical value of a combinational use of both blood biomarkers and MRI in mTBI detection and their characterization in the acute setting (within 24 hours after injury).
  
  
  METHODS
  Nine patients with mTBI were prospectively recruited from the emergency department. Serum samples were collected at the time of hospital admission and every 6 hours up to 24 hours post injury. Neuronal (Ubiquitin C-terminal Hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels were analyzed. Advanced MRI data were acquired at 9 ± 6.91 hours after injury. Patients' neurocognitive status was assessed by using the Standard Assessment of Concussion (SAC) instrument.
  
  
  RESULTS
  The median serum levels of UCH-L1 and GFAP on admission were increased 4.9 folds and 10.6 folds, respectively, compared to reference values. Three patients were found to have intracranial hemorrhages on SWI, all of whom had very high GFAP levels. Total volume of brain white matter (WM) with abnormal fractional anisotropy (FA) measures of diffusion tensor imaging (DTI) were negatively correlated with patients' SAC scores, including delayed recall. Both increased and decreased DTI-FA values were observed in the same subjects. Serum biomarker level was not correlated with patients' DTI data nor SAC score.
  
  
  CONCLUSIONS
  Blood biomarkers and advanced MRI may correlate or complement each other in different aspects of mTBI detection and characterization. GFAP might have potential to serve as a clinical screening tool for intracranial bleeding. UCH-L1 complements MRI in injury detection. Impairment at WM tracts may account for the patients' neurocognitive symptoms.
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, United States of America ; Department of Radiology, School of Medicine, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Kou
authors.forename: Ramtilak
authors.initials: R
authors.lastname: Gattu
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
authors.forename: Robert D
authors.initials: RD
authors.lastname: Welch
authors.forename: Brian J
authors.initials: BJ
authors.lastname: O'Neil
authors.forename: John L
authors.initials: JL
authors.lastname: Woodard
authors.forename: Syed Imran
authors.initials: SI
authors.lastname: Ayaz
authors.forename: Andrew
authors.initials: A
authors.lastname: Kulek
authors.forename: Robert
authors.initials: R
authors.lastname: Kas-Shamoun
authors.forename: Valerie
authors.initials: V
authors.lastname: Mika
authors.forename: Conor
authors.initials: C
authors.lastname: Zuk
authors.forename: Francesco
authors.initials: F
authors.lastname: Tomasello
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
mesh_terms: D000328:Adult; D016880:Anisotropy; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D003071:Cognition / Q000502:physiology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000097:blood / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood; D010865:Pilot Projects; D043222:Ubiquitin Thiolesterase / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase