Multivariate analysis of structural and diffusion imaging in traumatic brain injury.

RATIONALE AND OBJECTIVES Diffusion tensor (DT) and T1 structural magnetic resonance images provide unique and complementary tools for quantifying the living brain. We leverage both modalities in a diffeomorphic normalization method that unifies analysis of clinical datasets in a consistent and inherently multivariate (MV) statistical framework. We use this technique to study MV effects of traumatic brain injury (TBI). MATERIALS AND METHODS We contrast T1 and DT image-based measurements in the thalamus and hippocampus of 12 TBI survivors and nine matched controls normalized to a combined DT and T1 template space. The normalization method uses maps that are topology-preserving and unbiased. Normalization is based on the full tensor of information at each voxel and, simultaneously, the similarity between high-resolution features derived from T1 data. The technique is termed symmetric normalization for MV neuroanatomy (SyNMN). Voxel-wise MV statistics on the local volume and mean diffusion are assessed with Hotelling's T(2) test with correction for multiple comparisons. RESULTS TBI significantly (false discovery rate P < .05) reduces volume and increases mean diffusion at coincident locations in the mediodorsal thalamus and anterior hippocampus. CONCLUSIONS SyNMN reveals evidence that TBI compromises the limbic system. This TBI morphometry study and an additional performance evaluation contrasting SyNMN with other methods suggest that the DT component may aid normalization quality.