Traumatic Brain Injury

Traumatic brain injury (TBI) is one of the most common causes of long-term disability. Each year, approximately 1.5 million people sustain TBI n the United States alone, causing billions of dollars of economic cost. Among the survivors, many individuals are left with significant long-term cognitive and motor disabilities. However, efforts to identify the neuropathologic correlates of these deficits have gained only limited success to date. The use of more sensitive and reliable in vivo neuroimaging protocols may facilitate the identification of specific brain-behavior relationships in the TBI population. Here we present two studies that explore novel methodologies for examining neuroimaging data to gain further insight into TBI.

1. Structural Consequences of Diffuse Traumatic Brain Injury: A Large Deformation Tensor-Based Morphometry Study
2. Multivariate Analysis of Thalamo-Cortical Connectivity Loss in TBI

Structural Consequences of Diffuse Traumatic Brain Injury: A Large Deformation Tensor-Based Morphometry Study

Despite the importance of identifying neuropathology in individual 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. 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.

Volumetric Differences Pattern of volume differences between TBI survivors and healthy controls in the subgroup analysis including only 17 TBI participants without macroscopic focal lesions (p b 0.005 uncorrected; cluster size N10 for comparison purpose). Volume losses are coded with hot colors (red and yellow) and volume enlargements with cold colors (blue and green). Click image to view fullsized version.

Multivariate Analysis of Thalamo-Cortical Connectivity Loss in TBI

Diffusion tensor (DT) images quantify connectivity patterns in the brain while the T1 modality provides high-resolution images of tissue interfaces. Our objective is to use both modalities to build subject-specific, quantitative models of fiber connections in order to discover effects specific to a neural system. We first use a population-specific average T1 and DT template to label the thalamus and cortical regions of interest. We then build an expected connection model within this template space that is transferred to subject space in order to provide a prior restriction on probabilistic tracking performed in subject space. This allows for the comparison of properties such as fractional anisotropy (FA) within a common framework along fiber pathways.

Multiple Views of Thalamo-Cortical Connectivity Model Thalamo-cortical connectivity models for the prefrontal lobe are created using deterministic tractograpy in a subject-specific atlas. BA's 9 (blue), 10 (purple) and 11 (pink) are used to label the streamlines that connect each region to the thalamus. Model connections are visualized as tubes with colors corresponding to their cortical regions. The streamlines used to determine the model connections are shown with complementary colors. Click on images to view fullsize images.

Fractional Anisotropy Differences Students t-test results after FDR correction at p<0.02 indicate that the left hemisphere connection between thalamus and Brodmann area 10 is affected by TBI. Arrows indicate regions where TBI survivors show reduced FA compared to controls. A sagittal slice from the T1 component of the template is shown for anatomical reference.