Optical Coherence Tomography: A Window Into the Mechanisms of Multiple Sclerosis

Elliot M. Frohman; James G. Fujimoto; Teresa C. Frohman; Peter A. Calabresi; Gary Cutter; Laura J. Balcer

Disclosures

Nat Clin Pract Neurol. 2008;4(12):664-675. 

In This Article

Summary and Introduction

The pathophysiology of multiple sclerosis (MS) is characterized by demyelination, which culminates in a reduction in axonal transmission. Axonal and neuronal degeneration seem to be concomitant features of MS and are probably the pathological processes responsible for permanent disability in this disease. The retina is unique within the CNS in that it contains axons and glia but no myelin, and it is, therefore, an ideal structure within which to visualize the processes of neurodegeneration, neuroprotection, and potentially even neurorestoration. In particular, the retina enables us to investigate a specific compartment of the CNS that is targeted by the disease process. Optical coherence tomography (OCT) can provide high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and, we believe, is ideal for precisely modeling the disease process in MS. In this Review, we provide a broad overview of the physics of OCT, the unique properties of this method with respect to imaging retinal architecture, and the applications that are being developed for OCT to understand mechanisms of tissue injury within the brain.

Multiple sclerosis (MS) is being increasingly recognized as a complex neurodegenerative disorder of the brain and spinal cord that involves autoimmune mechanisms that target both white and gray matter elements. The disease is characterized by demyelination, gliosis, axonal dysfunction, and, ultimately, neuronal loss.[1] The vast majority of individuals destined to have confirmed MS later in their lives will already exhibit disseminated plaque lesions, as revealed by conventional MRI techniques, at the time of their first inflammatory demyelinating event.[2] New and revised diagnostic criteria have enabled us to expedite the confirmation of MS, with substantial implications for early intervention with disease-modifying treatment.[2,3,4] However, the ability to accurately image both neurodegeneration and its prevention in MS would greatly facilitate the systematic evaluation of novel therapeutics and their efficacy over time.

In MS, a dissociation is widely acknowledged to exist between the lesional burden seen on MRI scans and the corresponding clinical deficits documented on formal neurological examination, a phenomenon referred to as the 'clinico-radiological paradox'.[5] Evidence has emerged that links early inflammation (e.g. clinical exacerbations and MRI lesions) with a likelihood of disease-related disability, and with the timescale of its evolution. For instance, we now recognize that patients with high MRI lesion burdens at presentation represent a high-risk group for early and substantial disability.[6] While substantial 'silent' disease activity is a classic feature of MS, the gradual accumulation of lesions will ultimately lead to the disconnection of disparate and clinically relevant neural pathways.

The application to MS of nonconventional MRI techniques such as magnetization transfer imaging, magnetic resonance spectroscopy, and diffusion tensor imaging, has led to modest achievements in linking imaging data with clinical measures of disease severity.[7] However, despite these improvements, until recently the progress in coupling specific clinical syndromes in MS with pathological changes within discrete tract systems was limited.[8,9,10] This Review describes a number of advancements in the application of optical coherence tomography (OCT), a technology that enables objective analysis of the processes of neurodegeneration within a highly discrete and eloquent CNS structure—the retina. OCT enables investigators to rapidly and reproducibly evaluate the structural composition of the retina and to provide unique insights into this structure. While already validated for the longitudinal assessment of glaucoma[11,12] and macular degeneration,[13] OCT is currently being investigated for its utility in tracking the progress of neurodegeneration in MS. Ultimately, OCT could substantially increase our understanding of the mechanisms of tissue injury in MS, could be used to identify new therapeutic strategies focused on neuroprotection of central axonal and neuronal structures, and could even enable the detection and monitoring of the processes of neurorestoration, a treatment goal not yet within the capability of the neurologist (but certainly a central goal in modern neurobiology).

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