Whole-brain proton MR spectroscopic imaging of mild-to-moderate traumatic brain injury and correlation with neuropsychological deficits

Abstract

Changes in the distribution of the magnetic resonance (MR)-observable brain metabolites N-acetyl aspartate (NAA), total choline (Cho), and total creatine (Cre), following mild-to-moderate closed-head traumatic brain injury (mTBI) were evaluated using volumetric proton MR spectroscopic imaging (MRSI). Studies were carried out during the subacute time period following injury, and associations of metabolite indices with neuropsychological test (NPT) results were evaluated. Twenty-nine subjects with mTBI and Glasgow Coma Scale (GCS) scores of 10-15 were included. Differences in individual metabolite and metabolite ratio distributions relative to those of age-matched control subjects were evaluated, as well as analyses by hemispheric lobes and tissue types. Primary findings included a widespread decrease of NAA and NAA/Cre, and increases of Cho and Cho/NAA, within all lobes of the TBI subject group, and with the largest differences seen in white matter. Examination of the association between all of the metabolite measures and the NPT scores found the strongest negative correlations to occur in the frontal lobe and for Cho/NAA. No significant correlations were found between any of the MRSI or NPT measures and the GCS. These results demonstrate that significant and widespread alterations of brain metabolites occur as a result of mild-to-moderate TBI, and that these measures correlate with measures of cognitive performance.

FIG. 1.

Structural and metabolite images from a subject with mild TBI. Data were acquired from a 22-year-old male (subject 10 in Table 1) with an initial GCS score of 13 at 53 days after injury. Images in the rows are: (a) axial T1-weighted MRI (5-mm slice thickness and matched to spectroscopic imaging (SI) slice location); (b) NAA; (c) Cho; (d) Cre; (e) NAA/Cre; (f) Cho/Cre; (g) Cho/NAA (GCS, Glasgow Coma Scale; NAA, N-acetyl aspartate; Cho, choline; Cre, creatine; MRI, magnetic resonance imaging; TBI, traumatic brain injury).

FIG. 2.

Proton magnetic resonance spectra from a 22-year-old male subject (subject 10 in Table 1) with mild traumatic brain injury (a and b), and a 23-year-old female control subject (c and d). Spectra were obtained from five contiguous axial slices ∼ 5.6 mm in thickness, and are shown at a fixed vertical scale. The R on the images indicates the right side of the subjects.

FIG. 3.

Proton magnetic resonance spectra from five contiguous axial slices inferior to the first slice shown in Figure 2 (c and d; a 23-year-old female control subject). The spectra are shown at a fixed vertical scale. The R and L on the image indicate the right and left side of the subject, respectively. Spectra R1–R5 and L1–L5 were obtained from the right and left hemispheres, respectively, and the arrows indicate their voxel locations. The spectra were obtained from voxels located in the frontotemporal GM (R1), occipital WM (R2), frontal WM (R3), frontal GM (R4), parietal GM (R5), brainstem (L1), cerebellum (L2), putamen (L3), occipital GM (L4), and parietal WM (L5) regions (GM, gray matter; WM, white matter).

FIG. 4.

Mean values of the metabolites and ratios in the white matter of control and mild traumatic brain injury (mTBI) groups, by brain region, with error bars for ± 1 standard deviation. Data are shown for control (black bars), TBI-1 (light gray bars), TBI-2 (white bars), and TBI-3 (dark gray bars) groups, with significant differences indicated (single triangle = p ≤ 0.05; two triangles = p ≤ 0.01). The y-axis scale for the metabolite values is in institutional units (i.u.). Abbreviations used for the hemispheric lobar regions are: the first letter R/L indicates the right/left side of the brain, and the second letter F/T/P/O indicate frontal/temporal/parietal/occipital lobes, respectively (NAA, N-acetyl aspartate; Cho, choline; Cre, creatine).

FIG. 5.

Mean values of the metabolites and ratios in the gray matter of control and mild traumatic brain injury (mTBI) groups, by brain region, with error bars for ± 1 standard deviation. Data are shown for control (black bars), TBI-1 (light gray bars), TBI-2 (white bars), and TBI-3 (dark gray bars) groups, with significant differences indicated (single triangle = p ≤ 0.05; two triangles = p ≤ 0.01). The y-axis scale for the metabolite values is in institutional units (i.u.). Abbreviations used for the hemispheric lobar regions are: the first letter R/L indicates the right/left side of the brain, and the second letter F/T/P/O indicate frontal/temporal/parietal/occipital lobes, respectively (NAA, N-acetyl aspartate; Cho, choline; Cre, creatine).

FIG. 6.

Mean values of the metabolites (A) and ratios (B) in the cerebellum of control and mild traumatic brain injury (mTBI) groups, with error bars for ± 1 standard deviation. Data are shown for control (black bars), TBI-1 (light gray bars), TBI-2 (white bars), and TBI-3 (dark gray bars) groups, with significant differences (single triangle = p ≤ 0.05; two triangles = p ≤ 0.01; NAA, N-acetyl aspartate; Cho, choline; Cre, creatine).

FIG. 7.

Comparison of the mean NPT z-score and the mean cerebral white-matter Cho/NAA ratio for all mild traumatic brain injury (mTBI) subjects. Points are coded according to total lesion volume, for the TBI-2 (circle) and TBI-3 (diamond) subject groups (NAA, N-acetyl aspartate; Cho, choline; NPT, neuropsychological test).