Diffusion tensor imaging in multiple sclerosis: assessment of regional differences in the axial plane within normal-appearing cervical spinal cord

Abstract

Background and purpose: Evaluation of the spinal cord is important in the diagnosis and follow-up of patients with multiple sclerosis. Our purpose was to investigate diffusion tensor imaging (DTI) changes in different regions of normal-appearing spinal cord (NASC) in relapsing-remitting multiple sclerosis (RRMS).

Methods: Axial DTI of the cervical spinal cord was performed in 24 patients with RRMS and 24 age- and sex-matched control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated in separate regions of interest (ROIs) in the anterior, lateral, and posterior spinal cord, bilaterally, and the central spinal cord, at the C2-C3 level. Patients and control subjects were compared with respect to FA and MD with the use of an exact Mann-Whitney test. Logistic regression and receiver operating characteristic (ROC) curve analysis assessed the utility of each measure for the diagnosis of RRMS.

Results: DTI metrics in areas of NASC in MS were significantly different in patients compared with control subjects; FA was lower in the lateral (mean +/- SD of 0.56 +/- 0.10 versus 0.69 +/- 0.09 in control subjects, P < .0001), posterior (0.52 +/- 0.11 versus 0.63 +/- 0.10, P < .0001), and central (0.53 +/- 0.10 versus 0.58 +/- 0.10, P = .049) NASC ROIs. Assessing DTI metrics in the diagnosis of MS, a sensitivity of 87.0% (95% confidence interval [CI], 66.4 to 97.1) and a specificity of 91.7% (95% CI, 73.0 to 98.7) were demonstrated.

Conclusion: The NASC in RRMS demonstrates DTI changes. This may prove useful in detecting occult spinal cord pathology, predicting clinical course, and monitoring disease progression and therapeutic effect in MS.

Fig 1.

Diagram of the cervical spinal cord in cross-section (A) showing regions of interest (ROIs) placed for the measurement of fractional anisotropy (FA) and mean diffusivity in the anterior, lateral, and posterior spinal cord, bilaterally. B, Color FA map obtained in control patient at the C2-C3 level. C, The corresponding black and white FA map is shown with ROIs placed, including a central region of interest. Values have been scaled by a factor of 1000.

Fig 2.

Receiver operating characteristic (ROC) curve for diagnostic model using fractional anisotropy (FA)_mean, FA_ant,right, and FA_central (model 1, solid line in 2A and 2B, area under ROC curve (AUC), 0.928; 95% confidence interval [CI], 0.813 to 0.982), showing a significantly higher AUC compared with a model using only FA_mean (2A, thick dotted line, difference between AUCs = 0.180, P = .012) as well as a model using only FA_central (2B, thick dotted line, difference between AUCs = 0.274, P = .001). In other words, the best performing test is one in which multiple ROIs provide spatial information.

Fig 3.

Diffusion tensor imaging (DTI) metrics of healthy patients within ROIs placed in the anterior, lateral, and posterior spinal cord (bilaterally, with 2 data points per location per patient) at the C2-C3 level. Fractional anisotropy (FA) versus age (A) and mean diffusivity (MD) versus age (B). None of the FA or MD measures exhibited a significant association with patient age (P > .15).