Structural consequences of diffuse traumatic brain injury: a large deformation tensor-based morphometry study

Abstract

Traumatic brain injury (TBI) is one of the most common causes of long-term disability. Despite the importance of identifying neuropathology in individuals with chronic TBI, methodological challenges posed at the stage of inter-subject image registration have hampered previous voxel-based MRI studies from providing a clear pattern of structural atrophy after TBI. We used a novel symmetric diffeomorphic image normalization method to conduct a tensor-based morphometry (TBM) study of TBI. The key advantage of this method is that it simultaneously estimates an optimal template brain and topology preserving deformations between this template and individual subject brains. Detailed patterns of atrophies are then revealed by statistically contrasting control and subject deformations to the template space. Participants were 29 survivors of TBI and 20 control subjects who were matched in terms of age, gender, education, and ethnicity. Localized volume losses were found most prominently in white matter regions and the subcortical nuclei including the thalamus, the midbrain, the corpus callosum, the mid- and posterior cingulate cortices, and the caudate. Significant voxel-wise volume loss clusters were also detected in the cerebellum and the frontal/temporal neocortices. Volume enlargements were identified largely in ventricular regions. A similar pattern of results was observed in a subgroup analysis where we restricted our analysis to the 17 TBI participants who had no macroscopic focal lesions (total lesion volume >1.5 cm(3)). The current study confirms, extends, and partly challenges previous structural MRI studies in chronic TBI. By demonstrating that a large deformation image registration technique can be successfully combined with TBM to identify TBI-induced diffuse structural changes with greater precision, our approach is expected to increase the sensitivity of future studies examining brain-behavior relationships in the TBI population.

Figure 1

Illustration of the key stages of the approach employed by the current study. First, an optimized custom tem plate (c) is constructed by obtaining the shape and appearance average of the control (a) and patient (b) templates. A rigid-body transformed brain of a patient (one example brain is shown as d) is normalized to the custom template via SyN algorithm producing a large deformation field map (e). The resulting normalized brain (f) shows a high degree of alignment with the tem plate. A Jacobian map (g) is then calculated from the deformation field tensors to quantify the regional alterations of brain volume.

Figure 2

Areas of significant volume differences between TBI survivors and healthy controls displayed on the custom template brain (FDR p < .05 after multiple comparison correction; cluster size > 10 for display purpose). Volume losses are coded with hot colors (yellow and red) and volume enlargements with cold colors (green and blue).

Figure 3

Pattern of volume differences between TBI survivors and healthy controls in the subgroup analysis including only 17 TBI participants without macroscopic focal lesions (p < .005 uncorrected; cluster size > 10 for comparison purpose). Volume losses are coded with hot colors (red and yellow) and volume enlargements with cold colors (blue and green).

Figure 4

Pattern of volume differences between TBI survivors and healthy controls in the subgroup analysis including only 12 TBI participants with macroscopic focal lesions (p < .005 uncorrected; cluster size > 10 for comparison purpose). Volume losses are coded with hot colors (red and yellow) and volume enlargements with cold colors (blue and green).