A preliminary validation study of diffusion tensor imaging as a measure of functional brain injury

Background: Diffusion tensor imaging (DTI) characterizes multiple sclerosis (MS) tissue injury, although it has remained unproven whether DTI changes in disease have functional consequences. The medial longitudinal fasciculus (MLF) is a key brainstem pathway for ocular adduction and is commonly injured in patients with MS, typically resulting in internuclear ophthalmoparesis. Objective: To validate DTI as a physiologically relevant measure of brain tissue integrity. Design: A correlation study of ocular dysmotility and DTI conducted between January 2004 and September 2004. Setting: Multiple Sclerosis Center, University of Texas Southwestern Medical Center, Dallas. Patients: Six patients with chronic, unilateral, or bilateral internuclear ophthalmoparesis and 10 healthy control subjects. Main Outcome Measure: We used infrared oculography to correlate the velocity versional dysconjugacy index, defined as the ratio of the velocity of the abducting to adducting eye movements during horizontal saccades, and DTI measures within the MLF as measured through an anatomical overlay. Overall diffusion was measured by mean diffusivity, and anisotropy was measured by the lattice index. Results: Within the pontine MLF, the mean diffusivity was increased compared with healthy controls (P<.005), whereas the pontine lattice index was decreased (P<.03). Correlations were observed between the velocity versional dysconjugacy index and the mean diffusivity (left: r=0.65, P<.01; right: r=0.46, P=.07). Similar correlations were found between the versional dysconjugacy index and the lattice index (left: r=-0.43, P=.09; right: r=-0.65, P<.01). Conclusions: We identified DTI evidence of pathologic disruption of a small brainstem fiber pathway, which is crucial for accurate horizontal eye movements. In this small study, we observed correlations between the DTI changes and oculomotor dysfunction. Our preliminary observations provide criterion validity of DTI as a surrogate marker of brain tissue integrity.