Quantitative multivoxel proton MR spectroscopy for the identification of white matter abnormalities in mild traumatic brain injury: Comparison between regional and global analysis

Background: 3D brain proton MR spectroscopic imaging (¹H MRSI) facilitates simultaneous metabolic profiling of multiple loci, at higher, sub-1 cm³, spatial resolution than single-voxel ¹H MRS with the ability to separate tissue-type partial volume contribution(s). Purpose: To determine if: 1) white matter (WM) damage in mild traumatic brain injury (mTBI) is homogeneously diffuse, or if specific regions are more affected; 2) partial-volume-corrected, structure-specific ¹H MRSI voxel averaging is sensitive to regional WM metabolic abnormalities. Study Type: Retrospective cross-sectional cohort study. Population: Twenty-seven subjects: 15 symptomatic mTBI patients, 12 matched controls. Field Strength/Sequence: 3T using 3D ¹H MRSI over a 360-cm³ volume of interest (VOI) centered over the corpus callosum, partitioned into 480 voxels, each 0.75 cm³. Assessment: N-acetyl-aspartate (NAA), creatine, choline, and myo-inositol concentrations estimated in predominantly WM regions: body, genu, and splenium of the corpus callosum, corona radiata, frontal, and occipital WM. Statistical Tests: Analysis of covariance (ANCOVA) to compare patients with controls in terms of regional concentrations. The effect sizes (Cohen's d) of the mean differences were compared across regions and with previously published global data obtained with linear regression of the WM over the entire VOI in the same dataset. Results: Despite patients' global VOI WM NAA being significantly lower than the controls', no regional differences were observed for any metabolite. Regional NAA comparisons, however, were all unidirectional (patients' NAA concentrations < controls') within a narrow range: 0.3 ≤ Cohen's d ≤ 0.6. Data Conclusion: Since the patient group was symptomatic and exhibiting global WM NAA deficits, these findings suggest: 1) diffuse axonal mTBI damage; that is 2) below the ¹H MRSI detection threshold in small regions. Therefore, larger, ie, more sensitive, single-voxel ¹H MRS, placed anywhere in WM regions, may be well suited for mTBI ¹H MRS studies, given that these results are confirmed in other cohorts. Level of Evidence: 2. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2019;50:1424–1432.