  Traumatic brain injury is a global public health problem associated with
chronic neurological complications and long-term disability. Biomarkers that
map onto the underlying brain pathology driving these complications are
urgently needed to identify individuals at risk for poor recovery and to inform
design of clinical trials of neuroprotective therapies. Neuroinflammation and
neurodegeneration are two endophenotypes associated with increases in brain
extracellular water content after trauma. The objective of this study was to
describe the relationship between a neuroimaging biomarker of extracellular
free water content and the clinical features of patients with traumatic brain
injury. We analyzed a cohort of 64 adult patients requiring hospitalization for
non-penetrating traumatic brain injury of all severities as well as 32 healthy
controls. Patients underwent brain MRI and clinical neuropsychological
assessment in the subacute (2-weeks) and chronic (6-months) post-injury period,
and controls underwent a single MRI. For each subject, we derived a summary
score representing deviations in whole brain white matter (1) extracellular
free water volume fraction (VF) and (2) free water-corrected fractional
anisotropy (fw-FA). The summary specific anomaly score (SAS) for VF was
significantly higher in TBI patients in the subacute and chronic post-injury
period relative to controls. SAS for VF significantly correlated with
neuropsychological functioning in the subacute, but not chronic post-injury
period. These findings indicate abnormalities in whole brain white matter
extracellular water fraction in patients with TBI and are an important step
toward identifying and validating noninvasive biomarkers that map onto the
pathology driving disability after TBI.
