Proton MR Spectroscopy Correlates Diffuse Axonal Injury with Post-Concussive Symptoms in Mild Traumatic Brain Injury

Ivan I. Kirov¹, Assaf Tal¹, James S. Babb¹, Joseph Reaume¹, Tamara Bushnik², Teresa A. Ashman², Steven Flanagan², Robert I. Grossman¹, Oded Gonen¹

There are no established biomarkers for mild traumatic brain injury (mTBI), in part because post-concussive symptoms (PCS) are subjective and conventional imaging is typically unremarkable. To test whether diffuse axonal injury (DAI) quantified with three-dimensional (3D) proton magnetic resonance spectroscopic imaging (1H-MRSI) correlated with patients PCS we retrospectively studied 26mTBI patients (mean Glasgow Coma Scale score of 14.7), 1856 years old, 3 55 days post injury and 13 controls. All were scanned at 3 Tesla with T1-andT2-weighted MRI and 3D 1H-MRSI (480 voxels over 360 cm3, ~30% of the brain). On scan day patients completed a symptom questionnaire and those indicating at least one of the most common subacute mTBI symptoms (headache, dizziness, sleep disturbance, memory deficits, blurred vision) were grouped as PCS-positive. Global gray- and white matter (GM/WM) absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) in PCS-positive and PCS-negative patients were compared to age- and gender-matched controls using two-way analysis of variance. The results showed that PCS-negative group (n=11) and controls (n=8) did not differ in any GM or WM metabolite level. The PCS-positive patients (n=15) had lower WM NAA than the controls (n=12): 7.00.6 versus 7.90.5mM (p=0.0007). Global WM NAA, therefore, showed sensitivity to the DAI sequelae associated with common PCS in patients with mostly normal neuroimaging as well as GCS scores. This suggests a potential biomarker role in a patient population in which objective measures of injury and symptomatology are currently lacking.