Nonconventional Optic Nerve Imaging in Multiple Sclerosis

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Conventional MR imaging is, at present, the most important paraclinical modality for assessing the risk of MS in patients with acute demyelinating ON and for monitoring the progression of disease. However, there are limitations of conventional MR in imaging the optic nerve. Newer strategies, MT MR imaging, DT MR imaging, and OCT, show significant promise. Future investigations, including the use of nonconventional MR imaging techniques coupled with OCT and functional measures of anterior visual pathway function, will further assist in the early detection of clinical impairment. Serial analysis will allow for monitoring of disease progression, predict accumulation of disability, and ascertain the effects of candidate neuroprotective therapies.

Section snippets

Optic nerve anatomy

The paired optic nerves, each 50 mm in length, serve to transmit visual information from the retina to the optic chiasm. Each optic nerve, from the globe to the chiasm, is composed of four parts: intraocular (optic nerve head, 1 mm), intraorbital (25 mm), intracanalicular (traversing the optic canal, 9 mm), and intracranial (stretching from the canal to the optic chiasm, 4 to 16 mm). Each is composed of a bundle of nerve fibers that maintain a topical arrangement along their course from the

Optic neuritis: clinical presentation

In the absence of other symptoms of MS, acute demyelinating ON is referred to as one of the clinically isolated syndromes (CIS) suggestive of MS. Young to middle-aged persons (second through fourth decade) are most commonly affected. ON is approximately three times more common in women than in men.3, 6, 7 Patients present with vision loss that is acute or subacute. In greater than 90% of patients, pain exacerbated by eye movements is reported. The degree of vision loss is variable, with median

Conventional MR imaging: lesions of the optic nerve

The diagnosis of acute, monosymptomatic ON is often based on the appropriate clinical history and supportive examination findings, without the need for neuroimaging. However, data from the Optic Neuritis Treatment Trial (ONTT)12 and the Longitudinal Optic Neuritis Study (LONS)13, 14 have highlighted the utility of brain MR imaging in predicting the subsequent risk of developing MS. In atypical cases, MR imaging of the orbits should be obtained to exclude an alternate diagnosis, such as a

Optic nerve atrophy

While classically considered an inflammatory-demyelinating process, both acute and chronic phases of MS have been shown to result in axonal injury;1 this is the basis for progressive and permanent neurologic dysfunction as a consequence of demyelinating disease. Following the acute phase of ON (when the inflammatory process results in edema of the optic nerve), ongoing demyelination results in axon loss and atrophy. This process was first documented using conventional optic nerve imaging in

Magnetization transfer MR imaging

Magnetization transfer MR imaging (MT MR imaging) provides an analysis of the degree of tissue damage, both within and surrounding demyelinating lesions. By measuring macromolecular density, MT MR imaging is superior to conventional MR imaging in its specificity for detecting irreversible demyelination and axonal injury. The studies completed to date suggest that MT MR imaging correlates with functional outcome measures, and may be a useful technique for the longitudinal monitoring of patients

Diffusion tensor MR imaging

Advances in image acquisition and post-processing have allowed the use of DT MR imaging in the longitudinal study of patients with MS. As with other quantitative MR imaging techniques, it is noninvasive and can both detect and quantify tissue changes within and around demyelinating lesions. Application of this technique allows for quantification of the structural integrity of axons; as a result, DT MR imaging represents another potential surrogate for monitoring disease progression in MS.

The

Optical coherence tomography

As a technique for detecting subtle but important tissue changes brought about as a consequence of demyelinating disease, OCT has received significant attention. OCT allows for the direct visualization of the relevant tissues themselves; thus, the integrity of the optic nerve fibers as they originate from the retinal ganglion cells can be assessed. OCT circumvents the barrier of the skull, providing a “window” into the disease process and a reflection of alterations occurring elsewhere in the

Summary

It is well recognized that conventional MR imaging is, at present, the most important paraclinical modality for assessing the risk of MS in patients with acute demyelinating ON, and for monitoring the progression of disease. However, there are several limitations that limit the utility of conventional MR in imaging the optic nerve. Furthermore, conventional MR imaging is inadequate as an outcome metric for clinical trials of neuroprotective agents. Newer strategies, including measurement of

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      DTI is a surrogate marker of the structural integrity of the optic nerve, with increases in MD and reductions in FA in case of neuritis. DTI can also be applied to further detection of early optic nerve alterations, before abnormalities detected on conventional MR imaging.81 Despite the potential usefulness of DTI in the clinical scenario in the assessment of the optic nerve, its acquisition is still a technical challenge.

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      At present, MRI continues to be the most important paraclinical modality for assessing the risk of future MS and for monitoring disease progression in patients with acute demyelinating optic neuritis (Fig. 6.6B, C). However, newer imaging strategies, including magnetization transfer MRI, diffusion tensor MRI, and OCT, are being used alone and in combination for earlier detection of clinical impairment, monitoring disease progression, predicting disability, and ascertaining the effects of experimental neuroprotective therapies (Glisson and Galetta, 2009). OCT in particular can provide rapid, reproducible, high-resolution images of retinal anatomy, and is increasingly being used to model the axonal and neuronal degeneration that is now recognized as part of the disease process that contributes to permanent disability in MS (Frohman et al., 2008).

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