Multimodal surface-based morphometry reveals diffuse cortical atrophy in traumatic brain injury

Abstract

Background: Patients with traumatic brain injury (TBI) often present with significant cognitive deficits without corresponding evidence of cortical damage on neuroradiological examinations. One explanation for this puzzling observation is that the diffuse cortical abnormalities that characterize TBI are difficult to detect with standard imaging procedures. Here we investigated a patient with severe TBI-related cognitive impairments whose scan was interpreted as normal by a board-certified radiologist in order to determine if quantitative neuroimaging could detect cortical abnormalities not evident with standard neuroimaging procedures.

Methods: Cortical abnormalities were quantified using multimodal surfaced-based morphometry (MSBM) that statistically combined information from high-resolution structural MRI and diffusion tensor imaging (DTI). Normal values of cortical anatomy and cortical and pericortical DTI properties were quantified in a population of 43 healthy control subjects. Corresponding measures from the patient were obtained in two independent imaging sessions. These data were quantified using both the average values for each lobe and the measurements from each point on the cortical surface. The results were statistically analyzed as z-scores from the mean with a p < 0.05 criterion, corrected for multiple comparisons. False positive rates were verified by comparing the data from each control subject with the data from the remaining control population using identical statistical procedures.

Results: The TBI patient showed significant regional abnormalities in cortical thickness, gray matter diffusivity and pericortical white matter integrity that replicated across imaging sessions. Consistent with the patient's impaired performance on neuropsychological tests of executive function, cortical abnormalities were most pronounced in the frontal lobes.

Conclusions: MSBM is a promising tool for detecting subtle cortical abnormalities with high sensitivity and selectivity. MSBM may be particularly useful in evaluating cortical structure in TBI and other neurological conditions that produce diffuse abnormalities in both cortical structure and tissue properties.

Figure 1

Representative axial slices from clinical MRI scans of the TBI patient. T1-weighted (top row), FLAIR (middle row) and T2-weighted images. The scans were interpreted as normal at the initial neuroradiological examination. Images are displayed according to radiological convention (right side of the brain is shown on the left side of figure).

Figure 2

SBM image processing steps: Surface reconstruction and alignment to standard template. A. High-resolution T1-weighted images were processed using FreeSurfer 3.0 to map the cortical surface. The image is a lateral view of the TBI patient's left hemisphere. B. Computerized reconstruction of the gray/white matter boundary. A smoothed and expanded view of the white matter surface is shown. The image has been intensity normalized, skull-stripped and the cerebellum has been removed. C. Inflation of the cortical surface to map gyral and sulcal anatomy. Gyral regions are shown in green and sulcal regions in red. D. Coregistration of the subject's cortical surface to a common spherical template. This step allows the assessment of cortical tissue properties with respect to a normative database using a common coordinate system.

Figure 3

Quantification of tissue properties in the cerebral cortex and in pericortical white matter. Two surfaces were defined from the T1-weighted anatomical images (left column): in mid-gray matter (red) and 2 mm below the gray-white matter boundary (blue). White matter fractional anisotropy (middle) was quantified 2-mm below the gray/white boundary and mean diffusivity (right) was quantified in both the cortical gray matter and the white matter surfaces. Parasagittal (left hemisphere) and axial (above the lateral ventricles) cross-sections from the TBI patient's first imaging session are shown. High intensity regions on the FA map correspond to major fiber bundles running parallel to the cortical surface. Cerebrospinal fluid surrounding the cortex appears bright on the MD map.

Figure 4

A, B. Cortical gray matter and pericortical tissue properties quantified along the cortical mantle in control subjects. Mean values (A) and variability (B, coefficient of variation) for cortical thickness, cortical mean diffusivity, and fractional anisotropy and mean diffusivity of pericortical white matter (2 mm below the gray-white boundary) for control subjects are shown for each point on the surfaces of the two hemispheres. The corpus callosum is cut out, and the regions with very low values (e.g., thickness < 1 mm, coefficient of variation < 1%) appear in gray.

Figure 5

Co-registration of the TBI patient's cortical surface anatomy with the Freesurfer atlas. An accurate parcellation of the cortical surface was produced by Freesurfer shown superimposed on the semi-inflated surface of the patient (sulci = dark, gyri light). Cortical regions are accurately labeled. Anatomical labels: Calc, calcarine sulcus; Cent, central sulcus; CinG, cingulate gyrus; CinS, cingulate sulcus; Cun, cuneus; IPS, interparietal sulcus; Ling, lingual gyrus; MFG, medial frontal gyrus; MTG, medial temporal gyrus; Pre, precentral gyrus; Post, postcentral gyrus; Orb, orbital sulcus; OTS, occipito-temporal sulcus; STG, superior temporal gyrus; STS, superior temporal sulcus; TOS, transverse occipital sulcus.

Figure 6

Histograms showing the lobar measurements from the patient in relation to the distributions for the control group. The distribution of cortical thickness, cortical mean diffusivity, and fractional anisotropy and mean diffusivity of pericortical white matter across 43 control subjects are shown for each lobe. The red dots indicate the corresponding measures from the patient's two imaging sessions.

Figure 7

Regional cortical gray matter abnormalities detected by SBM in the TBI patient. Reduced cortical thickness (A) and increased cortical gray matter diffusivity (B) were most pronounced in the frontal lobes in two imaging sessions. Each row shows lateral and medial inflated views of the two hemispheres. Color bar shows z-values.

Figure 8

Pericortical white matter abnormalities. Regions of low anisotropy (A) and high diffusivity (B) were broadly distributed underneath the cortical mantle, with similar spatial distributions in both sessions (point-wise, z > 1.5, shown without the cluster threshold).

Figure 9

Combined assessment of cortical abnormalities. Joint tests of significant cortical gray matter and pericortical white matter abnormalities using Fisher's combined probability test revealed extensive abnormalities, concentrated mainly in the frontal lobes and basal occipito-temporal regions. The spatial distribution of the abnormalities replicated on the two different imaging sessions.