Objective

To evaluate directional diffusivities within the optic nerve in a first event of acute optic neuritis to determine whether decreased axial diffusivity (AD) would predict 6-month visual outcome and optic nerve integrity measures.

Design

Cohort study.

Setting

Academic multiple sclerosis center.

Patients

Referred sample of 25 individuals who presented within 31 days after acute visual symptoms consistent with optic neuritis. Visits were scheduled at baseline, 2 weeks, and 1, 3, 6, and 12 months.

Main Outcome Measures

Visual acuity, contrast sensitivity, visual evoked potentials (VEPs), and thickness of the retinal nerve fiber layer (RNFL).

Results

An incomplete 6-month visual recovery was associated with a lower baseline AD (1.50 μm2/ms [95% confidence interval {CI}, 1.36–1.64 μm2/ms for incomplete recovery vs 1.75 μm2/ms [95% CI, 1.67–1.83 μm2/ms] for complete recovery). Odds of complete recovery decreased by 53% (95% CI, 27%–70%) for every 0.1-unit decrease in baseline AD. A lower baseline AD correlated with worse 6-month visual outcomes in visual acuity (r=0.40, P=.03), contrast sensitivity (r=0.41, P=.02), VEP amplitude (r=0.55, P<.01), VEP latency (r=−0.38, P=.04), and RNFL thickness (r=0.53, P=.02). Radial diffusivity increased between months 1 and 3 to become higher in those with incomplete recovery at 12 months than in those with complete recovery (1.45 μm2/ms [95% CI, 1.31–1.59 μm2/ms] vs 1.19 μm2/ms [95% CI, 1.10–1.28 μm2/ms]).

Conclusions

Decreased AD in acute optic neuritis was associated with a worse 6-month visual outcome and correlated with VEP and RNFL measures of axon and myelin injury. Axial diffusivity may serve as a marker of axon injury in acute white matter injury.

The contrast provided by diffusion-sensitive magnetic resonance offers the promise of improved tumor localization in organ-confined human prostate cancer (PCa). Diffusion tensor imaging (DTI) measurements of PCa were performed in vivo, in patients undergoing radical prostatectomy, and later, ex vivo, in the same patients’ prostatectomy specimens. The imaging data were coregistered to histological sections of the prostatectomy specimens, thereby enabling unambiguous characterization of diffusion parameters in cancerous and benign tissues. Increased cellularity, and hence decreased luminal spaces, in peripheral zone PCa led to approximately 40% and 50% apparent diffusion policy (ADC) decrease compared with benign peripheral zone tissues in vivo and ex vivo, respectively. In contrast, no significant diffusion anisotropy differences were observed between the cancerous and noncancerous peripheral zone tissues. However, the dense fibromuscular tissues in prostate, such as stromal tissues in benign prostatic hyperplasia in central gland, exhibited high diffusion anisotropy. A tissue classification method is proposed to combine DTI and T2-weighted image contrasts that may provide improved specificity of PCa detection over T2-weighted imaging alone. PCa identified in volume rendered MR images qualitatively correlates well with histologically determined PCa foci.

Optic nerve is often affected in patients with glaucoma and multiple sclerosis (MS). Conventional MRI can detect nerve damage but it does not accurately assess the underlying pathologies. Mean diffusivity and diffusion anisotropy indices derived from diffusion tensor imaging (DTI) have been shown to be sensitive to a variety of central nervous system (CNS) white matter pathologies. Despite being sensitive, the lack of specificity limits the ability of these measures to differentiate the underlying pathology in CNS white matter tissues. Directional (axial and radial) diffusivities, measuring water diffusion parallel and perpendicular to the axonal tracts, have been shown to be specific to axonal and myelin damages in mouse models of optic nerve injury, including retinal ischemia and experimental autoimmune encephalomyelitis (EAE). The progression of Wallerian degeneration has also been detected using directional diffusivities after retinal ischemia. However, translating these findings to human optic nerve is technically challenging. The current status of human optic nerve diffusion MRI, including the imaging sequences and protocols, are summarized herein. Despite lacking a consensus of the optimal sequence or protocol among different groups, increased mean diffusivity and decreased diffusion anisotropy has been observed in injured optic nerve from chronic optic neuritis patients. Decreased λ∥, correlating with visual function and recovery, was observed recently in acute optic neuritis patients in a pilot study, suggesting the specificity of λ∥ to axonal injury. From different mouse models of optic nerve injuries to the emerging studies on optic neuritis patients, directional diffusivities demonstrate great potential to be specific biomarkers for axonal and myelin injury.