Diffuse axonal injury in mild traumatic brain injury: a 3D multivoxel proton MR spectroscopy study
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Since mild traumatic brain injury (mTBI) often leads to neurological symptoms even without clinical MRI findings, our goal was to test whether diffuse axonal injury is quantifiable with multivoxel proton MR spectroscopic imaging (1H-MRSI). T1- and T2-weighted MRI images and three-dimensional 1H-MRSI (480 voxels over 360 cm3, about 30 % of the brain) were acquired at 3 T from 26 mTBI patients (mean Glasgow Coma Scale score 14.7, 18–56 years old, 3–55 days after injury) and 13 healthy matched contemporaries as controls. The N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and myo-inositol (mI) concentrations and gray-matter/white-matter (GM/WM) and cerebrospinal fluid fractions were obtained in each voxel. Global GM and WM absolute metabolic concentrations were estimated using linear regression, and patients were compared with controls using two-way analysis of variance. In patients, mean NAA, Cr, Cho and mI concentrations in GM (8.4 ± 0.7, 6.9 ± 0.6, 1.3 ± 0.2, 5.5 ± 0.6 mM) and Cr, Cho and mI in WM (4.8 ± 0.5, 1.4 ± 0.2, 4.6 ± 0.7 mM) were not different from the values in controls. The NAA concentrations in WM, however, were significantly lower in patients than in controls (7.2 ± 0.8 vs. 7.7 ± 0.6 mM, p = 0.0125). The Cho and Cr levels in WM of patients were positively correlated with time since mTBI. This 1H-MRSI approach allowed us to ascertain that early mTBI sequelae are (1) diffuse (not merely local), (2) neuronal (not glial), and (3) in the global WM (not GM). These findings support the hypothesis that, similar to more severe head trauma, mTBI also results in diffuse axonal injury, but that dysfunction rather than cell death dominates shortly after injury.
KeywordsBrain injury Diffuse axonal injury Magnetic resonance spectroscopy
This work was supported by National Institutes of Health grants EB01015, NS39135, NS29029 and NS050520. Assaf Tal is also supported by the Human Frontiers Science Project. We thank Ms. Nissa Perry and Mr. Joseph Reaume for subject recruitment.
Conflicts of interest
The authors declare that they have no conflict of interest.
This work has been approved by the appropriate ethics committee and therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
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