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Disability in optic neuritis correlates with diffusion tensor-derived directional diffusivities

From the Departments of Neurology (R.T.N., J.X., N.T.T., A.S., A.H.C.), Radiology (A.S., T.B., J. Shimony, S.-K.S.), Ophthalmology (J. Shepherd), and Biostatistics (K.T.), and Hope Center for Neurological Disorders (A.H.C., S.-K.S.), Washington University, Saint Louis, MO.

Address correspondence and reprint requests to Dr. Robert T. Naismith, Neurology, Box 8111, 660 S. Euclid Ave., St. Louis, MO 63110 naismithr{at}neuro.wustl.edu

Objective: To determine the potential of directional diffusivities from diffusion tensor imaging (DTI) to predict clinical outcome of optic neuritis (ON), and correlate with vision, optical coherence tomography (OCT), and visual evoked potentials (VEP).

Methods: Twelve cases of acute and isolated ON were imaged within 30 days of onset and followed prospectively. Twenty-eight subjects with a remote clinical history of ON were studied cross-sectionally. Twelve healthy controls were imaged for comparison. DTI data were acquired at 3T with a surface coil and 1.3 x 1.3 x 1.3 mm³ isotropic voxels.

Results: Normal DTI parameters (mean ± SD, µm²/ms) were axial diffusivity = 1.66 ± 0.18, radial diffusivity = 0.81 ± 0.26, apparent diffusion coefficient (ADC) = 1.09 ± 0.21, and fractional anisotropy (FA) = 0.43 ± 0.15. Axial diffusivity decreased up to 2.5 SD in acute ON. The decrease in axial diffusivity at onset correlated with visual contrast sensitivity 1 month (r = 0.59) and 3 months later (r = 0.65). In three subjects followed from the acute through the remote stage, radial diffusivity subsequently increased to >2.5 SD above normal, as did axial diffusivity and ADC. In remote ON, radial diffusivity correlated with OCT (r = 0.81), contrast sensitivity (r = 0.68), visual acuity (r = 0.56), and VEP (r = 0.54).

Conclusion: In acute and isolated demyelination, axial diffusivity merits further investigation as a predictor of future clinical outcome. Diffusion parameters are dynamic in acute and isolated optic neuritis, with an initial acute decrease in axial diffusivity. In remote disease, radial diffusivity correlates with functional, structural, and physiologic tests of vision.

Abbreviations: ADC = apparent diffusion coefficient; CI = confidence interval; CS = contrast sensitivity; DTI = diffusion tensor imaging; EAE = experimental autoimmune encephalitis; FA = fractional anisotropy; MD = mean diffusivity; MS = multiple sclerosis; NAWM = normal-appearing white matter; OCT = optical coherence tomography; ON = optic neuritis; RA = relative anisotropy; rFOV = reduced field of view; RNFL = retinal nerve fiber layer; ROI = region of interest; SD = standard deviation; SNR = signal-to-noise ratio; VA = visual acuity; VEP = visual evoked potentials.

Supplemental data at www.neurology.org

Editorial, page 584

e-Pub ahead of print on December 10, 2008, at www.neurology.org.

*These authors contributed equally.

Funding included K23NS052430 (R.T.N.), K12RR02324902 (R.T.N.), K24 RR017100 (A.H.C.), P30 NS048056 (A.Z.S.), and UL1 RR024992 from the NIH, and CA1012 (A.H.C., S.K.S.), RG 3670 (S.K.S.), and FG1782A1 (J.X.) from the National MS Society USA. A.H.C. was supported in part by the Manny and Rosalyn Rosenthal-Dr. John L. Trotter Chair in Neuroimmunology.

Disclosure: The authors report no disclosures.

Received April 18, 2008. Accepted in final form August 4, 2008.

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