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

BackgroundMild 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).MethodsNine 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.ResultsThe 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.ConclusionsBlood 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.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

“…Mounting evidence demonstrates the microstructural damage in patients with mTBI. 8,[70][71][72][73] Our pilot data suggest that, in response to microstructural damage on the cingulate bundle shown on DTI, other regions of the brain tend to have higher FC with the anterior cingulate cortex on resting state fMRI signal. 74 This suggests a compensatory mechanism of brain injury.…”

Acute Temporal Profiles of Serum Levels of UCH-L1 and GFAP and Relationships to Neuronal and Astroglial Pathology following Traumatic Brain Injury in Rats

“…This study compared the acute time course of GFAP and UCH-L1 biomarkers using proprietary sandwich ELISA 11,14 for astrocyte and neuronal pathology, respectively in a model of moderate parasagittal fluid percussion TBI in rats. Levels of GFAP were significantly elevated in serum at 3 and 6 hours after TBI compared to baseline and time-matched sham-TBI animals while UCH-L1 was significantly elevated in serum only at 3 hours after TBI.…”

MR Imaging Applications in Mild Traumatic Brain Injury: An Imaging Update

“…Work by Kou et al examined serum in combination with imaging biomarkers and showed that glial biomarkers correlated with presence of intracranial hemorrhages detected with susceptibilityweighted imaging, while abnormal FA and WM volumes were correlated with impaired neurofunctional status (181). A recent pilot study using a multifeature classification algorithm showed that a multimodal evaluation achieved higher accuracy than the best single metric in differentiating mTBI patients from control subjects (76).…”