Imaging of multiple sclerosis: Role in neurotherapeutics

Abstract

Summary:Magnetic resonance imaging (MRI) plays an everexpanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normalappearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1-or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

Segmentation of gadolinium‐enhanced lesions on MRI in multiple sclerosis

“…The second strategy involves masking the binary map obtained after the application of a single threshold on the ratio map of the difference of post-and precontrast T1 images with precontrast T1 images. Published studies show that Gd-enhancement is nearly invariably associated with a hyperintense lesion in the same location on T2-weighted images (21,22). In those uncommon cases where Gd-enhancement is observed in the absence of corresponding T2 lesion (23), our algorithm does not identify it as a true enhancement.…”

Foundations of advanced magnetic resonance imaging

“…1). 6 Although diffusion tensor imaging has not yet been able to match the impact of DWI in stroke, it has proven to be a sensitive tool for detecting subtle abnormalities in the white matter of patients with diseases like multiple sclerosis 7,8 or ALS. 9 Despite DTI's sensitivity to white matter abnormalities shown in group comparisons, further work in this area is warranted to demonstrate its value for diagnosing individual patients.…”

“…Previously, the exclusive domain of the technology of positron emission tomography (PET), an important subset of MRI is now capable of mapping functional regions of the human cortex in real time during specific task activation. fMRI is now in use for the localization of visual, motor, and somatosensory responses in surgery of tumors, 138 localization of "handedness," and elucidation of brain function and metabolism altered by pathologies such as stroke, multiple sclerosis, 8 and Alzheimer's disease. 139 Given the large number of clinical MRI scanners operating worldwide, aside from fundamental new understanding in neuroscience, fMRI is used in clinical assessment of brain function.…”

“…In conjunction with other functional measures, particularly PET, electroencephalography and magnetoencephalography, one is able to map the unique structure-function correlates involved in cognitive processing and is poised to make great contributions to our theoretical and philosophical formulations of mental activities. Potential clinical applications of fMRI include: 1) mapping of distortions of the functional motor and somatosensory cortex and other cortical regions as a result of brain tumors; 138 2) observing the effect of degenerative diseases such as MS, 8 Alzheimer's disease, 139 stroke and others causing neuronal loss; 3) Parkinsonism; and 4) the critical area of rapidly and noninvasively mapping normal and pathologic brain reactivity to any number of mild, reversible stresses.…”

Neuroimaging: Anything to do with neurotherapeutics?

“…14 Neuroimaging is often essential to define the presence of the disease (state), as in the case of brain tumors or MS. 10,14 What is so obvious for these diseases, applies to the disorders that, as examples of major neurological disease categories, are discussed in this issue of NeuroRx. The individual subject with a well-defined neurological disease can then be enrolled in a clinical study to evaluate the effectiveness of a new therapeutic approach.…”