New imaging techniques in the diagnosis of multiple sclerosis

Abstract

Background: Multiple sclerosis (MS) is a chronic disabling disorder histopathologically characterized by inflammation, demyelination and axonal loss. Conventional MRI has made most contributions to the diagnosis of MS. However, it is not sufficiently sensitive and specific to reveal the extent and severity of the damage in the disease. Other nuclear magnetic resonance (NMR) techniques including magnetic resonance spectroscopy, magnetization transfer imaging, diffusion weighted and diffusion tensor imaging, and functional MRI have provided additional information that improves the diagnosis and understanding of MS. Optical techniques including optical coherence tomography (OCT) and coherent anti-Stokes Raman scattering (CARS) microscopy have shown promise in diagnosis and mechanistic study of myelin diseases.

Objective: To review new imaging techniques and their potential in diagnosis of MS.

Method: The principles of three imaging techniques (MRI, OCT and CARS) and their applications to MS studies are described. Their advantages and disadvantages are compared.

Conclusion: Conventional MRI remains a critical tool in the diagnosis of MS. Alternative NMR/MRI techniques have improved specificity for the detection of lesions and provided more quantitative information about MS. Optical techniques including OCT and CARS microscopy are opening up new ways for diagnosis and mechanistic study of myelin diseases.

Keywords: coherent anti-Stokes Raman scattering microscopy; magnetic resonance imaging; multiple sclerosis; optical coherence tomography.

Figure 1. Coherent anti-Stokes Raman scattering (CARS) images of myelin fibers in ex vivo guinea-pig spinal cord and brain

A. Parallel myelin fibers were observed in spinal cord tissues. B. In brain, single myelinated axon was observed. C. With submicron resolution, a node of Ranvier flanked by paranodal myelin was observed by CARS microscopy, D. Three-dimensional reconstruction of myelinated fibers in spinal cord. E. Z stacks of CARS images in brain cortex showing myelinated axons in random orientations. F. Z stacks of CARS images in brain corpus callosum showing tightly packed axonal bundles. For A, C – F, bar = 10 μm. For B, bar = 5 μm.

Figure 2. Real-time coherent anti-Stokes Raman scattering (CARS) imaging of demyelination processes induced by lyso-PtdCho

A. CARS image of normal myelin sheath wrapping four parallel axons. B. CARS image of partially swollen myelin sheath acquired at 31 min alter incubation of the tissue in 100 mg/ml lyso-PtdCho solution. Below A and B are CARS intensity profiles of normal and swollen myelin fibers. Note the decrease of CARS intensity in the swollen region.