Diffusion tensor MRI as a diagnostic tool of upper motor neuron involvement in amyotrophic lateral sclerosis

Background: Clinical identification of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS) is often difficult, particularly early in the course of the disease, or when lower motor neuron (LMN) dysfunction is prominent. Diffusion tensor MR imaging (DTI) can provide unique information on axonal organization by measuring diffusion anisotropy and the directionally independent diffusion. Objective: The purpose of this study was to assess water diffusion changes along pyramidal tracts of the brainstem in patients with ALS and to investigate possible correlations between changes of diffusion properties and various clinical parameters. Methods: We studied 16 patients (M:F=9:7, 50.5±12.4 years) with ALS as defined by clinical and electrophysiological examinations. These patients were compared with 11 healthy, age and sex-matched controls (M:F=5:6, 54.5±9.9 years). DTI was performed using a single shot SE-EPI with 25 noncollinear diffusion gradient directions (b=1000 s/mm2) and with no diffusion gradient on a 3.0-T MR system. Results: By multifactorial ANOVA, the effects of group (patient versus control) and anatomical level on fractional anisotropy (FA) and mean diffusivity (MD) were significant (p<0.001 for both parameters), whereas the effect of side (left versus right) and interactions between factors (group by side and group by anatomical level) were not (p>0.05). In all subjects, FA and MD varied greatly depending on the anatomical level, and FA was highly variable even between contiguous slices in the pons and medulla, whereas relatively constant FA values were noted at the level of the midbrain. Cerebral peduncle was the only area that showed significant differences of diffusion properties between patients and controls (p<0.001 for FA, p=0.001 for MD). Correlation analysis revealed a significant inverse relationship between the FA value and the extent of UMN signs (r=-0.81, p<0.001). Conclusions: Alteration of diffusion properties in the cerebral peduncle in ALS may reflect pathological changes in structures rather than regional architectural variations of the corticospinal tracts or experimental artifacts.