scholarly journals Using magnetic resonance imaging in animal models to guide drug development in multiple sclerosis

2013 ◽  
Vol 20 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Nabeela Nathoo ◽  
V Wee Yong ◽  
Jeff F Dunn
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Magnetic Resonance ◽  
Animal Models ◽  
Mr Imaging ◽  
Preclinical Studies ◽  
Resonance Imaging ◽  
Magnetic Resonance Imaging Mri ◽  
Potential Therapeutics

Major advances are taking place in the development of therapeutics for multiple sclerosis (MS), with a move past traditional immunomodulatory/immunosuppressive therapies toward medications aimed at promoting remyelination or neuroprotection. With an increase in diversity of MS therapies comes the need to assess the effectiveness of such therapies. Magnetic resonance imaging (MRI) is one of the main tools used to evaluate the effectiveness of MS therapeutics in clinical trials. As all new therapeutics for MS are tested in animal models first, it is logical that MRI be incorporated into preclinical studies assessing therapeutics. Here, we review key papers showing how MR imaging has been combined with a range of animal models to evaluate potential therapeutics for MS. We also advise on how to maximize the potential for incorporating MRI into preclinical studies evaluating possible therapeutics for MS, which should improve the likelihood of discovering new medications for the condition.

Voxelwise analysis of conventional magnetic resonance imaging to predict future disability in early relapsing–remitting multiple sclerosis

2012 ◽  
Vol 18 (11) ◽  
pp. 1585-1591 ◽  
Author(s):  
Delphine Wybrecht ◽  
Françoise Reuter ◽  
Wafaa Zaaraoui ◽  
Anthony Faivre ◽  
Lydie Crespy ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Physical Disability ◽  
Conventional Magnetic Resonance Imaging ◽  
Global Approach ◽  
Resonance Imaging ◽  
Conventional Magnetic Resonance ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Changes

Background: The ability of conventional magnetic resonance imaging (MRI) to predict subsequent physical disability and cognitive deterioration after a clinically isolated syndrome (CIS) is weak. Objectives: We aimed to investigate whether conventional MRI changes over 1 year could predict cognitive and physical disability 5 years later in CIS. We performed analyses using a global approach (T2 lesion load, number of T2 lesions), but also a topographic approach. Methods: This study included 38 patients with a CIS. At inclusion, 10 out of 38 patients fulfilled the 2010 revised McDonald’s criteria for the diagnosis of multiple sclerosis. Expanded Disability Status Scale (EDSS) evaluation was performed at baseline, year 1 and year 5, and cognitive evaluation at baseline and year 5. T2-weighted MRI was performed at baseline and year 1. We used voxelwise analysis to analyse the predictive value of lesions location for subsequent disability. Results: Using the global approach, no correlation was found between MRI and clinical data. The occurrence or growth of new lesions in the brainstem was correlated with EDSS changes over the 5 years of follow-up. The occurrence or growth of new lesions in cerebellum, thalami, corpus callosum and frontal lobes over 1 year was correlated with cognitive impairment at 5 years. Conclusion: The assessment of lesion location at the first stage of multiple sclerosis may be of value to predict future clinical disability.

Clinical and Magnetic Resonance Imaging Predictors of Disability in Primary and Secondary Progressive Multiple Sclerosis

1996 ◽  
Vol 1 (4) ◽  
pp. 218-222 ◽  
Author(s):  
NA Losseff ◽  
DPE Kingsley ◽  
WI McDonald ◽  
DH Miller ◽  
AJ Thompson
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Initial Study ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Secondary Progressive ◽  
Short Period ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Study

The role of magnetic resonance imaging (MRI) in predicting disability in multiple sclerosis (MS) remains unclear. In this study 21 patients with primary and secondary progressive MS were reviewed 5 years following a serial MRI study of 6 months duration. In the secondary progressive group (n=11) there was a significant relationship between the occurrence of enhancing lesions and clinical relapses during the initial 6 months and increase in diability 5 years later. For both groups change in disability over the initial study period was predictive of outcome. These results suggest that the presence and frequency of gadolinium enhancement (a marker of inflammation) and changes in disability over a short period are predictive of future deterioration in progressive patients.

scholarly journals Magnetic resonance imaging in multiple sclerosis animal models: A systematic review, meta-analysis, and white paper

2020 ◽  
Vol 28 ◽  
pp. 102371
Author(s):  
Benjamin V. Ineichen ◽  
Pascal Sati ◽  
Tobias Granberg ◽  
Martina Absinta ◽  
Nathanael J. Lee ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Systematic Review ◽  
Magnetic Resonance ◽  
Animal Models ◽  
Meta Analysis ◽  
White Paper ◽  
Resonance Imaging

scholarly journals Experimental design and sample size considerations in longitudinal magnetic resonance imaging-based biomarker detection for multiple sclerosis

2020 ◽  
Vol 29 (9) ◽  
pp. 2617-2628 ◽  
Author(s):  
Menghan Hu ◽  
Matthew K Schindler ◽  
Blake E Dewey ◽  
Daniel S Reich ◽  
Russell T Shinohara ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Magnetic Resonance ◽  
Sample Size ◽  
Disease Progression ◽  
Multiple Sclerosis Lesion ◽  
Resonance Imaging ◽  
Study Duration ◽  
Multiple Sclerosis Disease

Several modeling approaches have been developed to quantify differences in multiple sclerosis lesion evolution on magnetic resonance imaging to identify the effect of treatment on disease progression. These studies have limited clinical applicability due to onerous scan frequency and lengthy study duration. Efficient methods are needed to reduce the required sample size, study duration, and sampling frequency in longitudinal magnetic resonance imaging studies. We develop a data-driven approach to identify parameters of study design for evaluation of longitudinal magnetic resonance imaging biomarkers of multiple sclerosis lesion evolution. Our design strategies are considerably shorter than those described in previous studies, thus having the potential to lower costs of clinical trials. From a dataset of 36 multiple sclerosis patients with at least six monthly magnetic resonance imagings, we extracted new lesions and performed principal component analysis to estimate a biomarker that recapitulated lesion recovery. We tested the effect of multiple sclerosis disease modifying therapy on the lesion evolution index in three experimental designs and calculated sample sizes needed to appropriately power studies. Our proposed methods can be used to calculate required sample size and scan frequency in observational studies of multiple sclerosis disease progression as well as in designing clinical trials to find effects of treatment on multiple sclerosis lesion evolution.

Emerging tumefactive multiple sclerosis after switching therapy from natalizumab to fingolimod

2012 ◽  
Vol 18 (11) ◽  
pp. 1650-1652 ◽  
Author(s):  
Sebastian Jander ◽  
Bernd Turowski ◽  
Bernd C Kieseier ◽  
Hans-Peter Hartung
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Multiple Sclerosis Patient ◽  
Resonance Imaging ◽  
Mri Features ◽  
Switching Therapy ◽  
Magnetic Resonance Imaging Mri ◽  
First Time ◽  
Tumefactive Multiple Sclerosis

In this report we describe a multiple sclerosis patient who developed a relapse with magnetic resonance imaging (MRI) features of tumefactive demyelination after switching therapy from natalizumab to fingolimod. Tumefactive lesions emerged 16 weeks after stopping natalizumab and eight weeks after commencing fingolimod therapy but had been absent at the time of diagnosis and throughout the preceding course of the disease. Thus, the first-time occurrence of atypical lesion features may have been caused by the change in immunotherapy. The possible relevance of natalizumab withdrawal vs fingolimod introduction is discussed against the background of recently published case studies.

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