  The trajectory of an individual's recovery after traumatic brain injury (TBI)
is heterogeneous, with complete recovery in some cases but persistent
disability in others. We hypothesized that changes in structural brain network
abnormalities guide the trajectory of an individual's recovery post-injury. Our
objective was to characterize the variability in recovery post-TBI by
identifying a putative neuroimaging biomarker of traumatic axonal injury (TAI)
in individuals with mild TBI.
  We analyzed 70 T1-weighted and diffusion MRIs longitudinally collected from
35 individuals during the subacute and chronic post-injury periods. Each
individual underwent longitudinal blood work to characterize blood protein
biomarkers of axonal and glial injury and assessment of post-injury recovery in
the subacute and chronic periods. By comparing the MRI data of individual cases
with 35 controls, we estimated the longitudinal change in structural brain
network abnormalities. We validated this proxy measure of TAI with independent
measures of acute intracranial injury estimated from head CT and blood protein
biomarkers.
  Post-injury structural network abnormality was significantly higher than
controls in both subacute and chronic periods, associated with an acute CT
lesion and subacute blood levels of glial fibrillary acid protein (r=0.5,
p=0.008) and neurofilament light (r=0.41, p=0.02). Longitudinal change in
abnormality associated with change in functional outcome status (r=-0.51,
p=0.003) and post-concussive symptoms (BSI: r=0.46, p=0.03; RPQ:r = 0.46,
p=0.02). Brain regions that most closely mapped onto symptom change over time
corresponded to structural network hubs or areas susceptible to neurotrauma.
  Structural network abnormalities might be a biomarker of TAI. Assessing
changes in brain network abnormality might enable better patient stratification
for monitoring recovery after neurotrauma.
