Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

Imaging techniques, in particular magnetic resonance imaging (MRI), play an important role in the diagnosis and management of multiple sclerosis (MS) and related demyelinating diseases. Findings on MRI studies of the brain and spinal cord are critical for MS diagnosis, are used to monitor treatment response and may aid in predicting disease progression in individual patients. In addition, results of imaging studies serve as essential biomarkers in clinical trials of putative MS therapies and have led to important insights into disease pathophysiology. Although they are useful tools and provide in vivo measures of disease-related activity, there are some important limitations of MRI findings in MS, including the non-specific nature of detectable white matter changes, the poor correlation with clinical disability, the limited sensitivity and ability of standard measures of gadolinium enhancing lesions and T2 lesions to predict future clinical course, and the lack of validated biomarkers of long term outcomes. Advancements that hold promise for the future include new techniques that are sensitive to diffuse changes, the increased use of higher field scanners, measures that capture disease related changes in gray matter, and the use of combined structural and functional imaging approaches to assess the complex and evolving disease process that occurs during the course of MS

Nonconventional MRI and microstructural cerebral changes in multiple sclerosis

MRI has become the most important paraclinical tool for diagnosing and monitoring patients with multiple sclerosis (MS). However, conventional MRI sequences are largely nonspecific in the pathology they reveal, and only provide a limited view of the complex morphological changes associated with MS. Nonconventional MRI techniques, such as magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) promise to complement existing techniques by revealing more-specific information on microstructural tissue changes. Past years have witnessed dramatic advances in the acquisition and analysis of such imaging data, and numerous studies have used these tools to probe tissue alterations associated with MS. Other MRI-based techniques-such as myelin-water imaging, 23 Na imaging, magnetic resonance elastography and magnetic resonance perfusion imaging-might also shed new light on disease-associated changes. This Review summarizes the rapid technical progress in the use of MRI in patients with MS, with a focus on nonconventional structural MRI. We critically discuss the present utility of nonconventional MRI in MS, and provide an outlook on future applications, including clinical practice. This information should allow appropriate selection of advanced MRI techniques, and facilitate their use in future studies of this disease