The use of magnetic resonance imaging in multiple sclerosis: lessons learned from clinical trials

2004 ◽  
Vol 10 (4) ◽  
pp. 341-347 ◽  
Author(s):  
Filippo Martinelli Boneschi ◽  
Marco Rovaris ◽  
Giancarlo Comi ◽  
Massimo Filippi
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Magnetic Resonance ◽  
Lessons Learned ◽  
Secondary Outcome ◽  
Resonance Imaging ◽  
Quantitative Mr ◽  
Study Protocols ◽  
The Individual

Magnetic resonance imaging (MRI) is an important paraclinical tool for the diagnosis of multiple sclerosis (MS) and for monitoring its disease course. The efficacy of most of the available MS disease-modifying treatments has been tested in clinical trials where MRI-derived quantities served as primary or secondary outcome measures. However, conventional MRI measures (i.e., the number and volume of contrast-enhancing, the volumes of T2-hyperintense and T1-hypointense lesions and the assessment of brain volume changes) are limited in terms of pathological specificity and, as a consequence, are modestly correlated with clinical measures of disease activity and have a modest prognostic value as predictors of MS evolution. In the present review, we discuss the main factors potentially responsible for the so-called ‘clinicaluMRI paradox’ and how modern quantitative MR-based techniques might contribute to, at least partially, overcome it. The lessons learned from MS trials suggest that future applications of MRI to assess MS evolution should rely upon the use of composite measures thought to reflect the various components of the disease, as well as on study protocols specifically designed on the individual trial characteristics.

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.

Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year disability in multiple sclerosis

2016 ◽  
Vol 23 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Tomas Uher ◽  
Manuela Vaneckova ◽  
Lukas Sobisek ◽  
Michaela Tyblova ◽  
Zdenek Seidl ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Cumulative Risk ◽  
Resonance Imaging ◽  
Cox Models ◽  
T2 Lesions ◽  
Therapeutic Decisions ◽  
The Individual

Background: Disease progression and treatment efficacy vary among individuals with multiple sclerosis. Reliable predictors of individual disease outcomes are lacking. Objective: To examine the accuracy of the early prediction of 12-year disability outcomes using clinical and magnetic resonance imaging (MRI) parameters. Methods: A total of 177 patients from the original Avonex-Steroids-Azathioprine study were included. Participants underwent 3-month clinical follow-ups. Cox models were used to model the associations between clinical and MRI markers at baseline or after 12 months with sustained disability progression (SDP) over the 12-year observation period. Results: At baseline, T2 lesion number, T1 and T2 lesion volumes, corpus callosum (CC), and thalamic fraction were the best predictors of SDP (hazard ratio (HR) = 1.7–4.6; p ⩽ 0.001–0.012). At 12 months, Expanded Disability Status Scale (EDSS) and its change, number of new or enlarging T2 lesions, and CC volume % change were the best predictors of SDP over the follow-up (HR = 1.7–3.5; p ⩽  0.001–0.017). A composite score was generated from a subset of the best predictors of SDP. Scores of ⩾4 had greater specificity (90%–100%) and were associated with greater cumulative risk of SDP (HR = 3.2–21.6; p < 0.001) compared to the individual predictors. Conclusion: The combination of established MRI and clinical indices with MRI volumetric predictors improves the prediction of SDP over long-term follow-up and may provide valuable information for therapeutic decisions.

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.

scholarly journals Quantitative Magnetic Resonance Imaging of Cortical Multiple Sclerosis Pathology

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Christine L. Tardif ◽  
Barry J. Bedell ◽  
Simon F. Eskildsen ◽  
D. Louis Collins ◽  
G. Bruce Pike
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Resonance Imaging ◽  
Quantitative Magnetic Resonance Imaging ◽  
Quantitative Mr ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Study

Although significant improvements have been made regarding the visualization and characterization of cortical multiple sclerosis (MS) lesions using magnetic resonance imaging (MRI), cortical lesions (CL) continue to be under-detectedin vivo, and we have a limited understanding of the causes of GM pathology. The objective of this study was to characterize the MRI signature of CLs to help interpret the changes seenin vivoand elucidate the factors limiting their visualization. A quantitative 3D high-resolution (350 μm isotropic) MRI study at 3 Tesla of a fixedpost mortemcerebral hemisphere from a patient with MS is presented in combination with matched immunohistochemistry. Type III subpial lesions are characterized by an increase in T1, T2 and M0, and a decrease in MTR in comparison to the normal appearing cortex (NAC). All quantitative MR parameters were associated with cortical GM myelin content, while T1 showed the strongest correlation. The histogram analysis showed extensive overlap between CL and NAC for all MR parameters and myelin content. This is due to the poor contrast in myelin content between CL and NAC in comparison to the variability in myelo-architecture throughout the healthy cortex. This latter comparison is highlighted by the representation of T1 times on cortical surfaces at several laminar depths.

Magnetic resonance imaging metrics and their correlation with clinical outcomes in multiple sclerosis: a review of the literature and future perspectives

2008 ◽  
Vol 14 (6) ◽  
pp. 719-727 ◽  
Author(s):  
D Bar-Zohar ◽  
F Agosta ◽  
D Goldstaub ◽  
M Filippi
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Magnetic Resonance ◽  
Surrogate Endpoint ◽  
New Drugs ◽  
Phase Iii ◽  
Resonance Imaging ◽  
Disease Evolution ◽  
Conventional Mri

Magnetic resonance imaging (MRI) has revolutionized the diagnosis and management of patients with multiple sclerosis (MS). Conventional MRI metrics are employed as primary endpoints in proof-of-concept clinical trials evaluating new drugs for MS and as secondary endpoints in definitive phase III trials. Metrics derived from non-conventional MRI techniques are now emerging and hold significant promise since they appear to be more correlated with the most disabling features of MS. However, none of these has been approved for use as a surrogate endpoint for accumulation of physical disability, which is the most important clinical endpoint of this disease. Taking into account the large numbers of patients needed, the extensive exposure to placebo, and the relatively long duration required for phase III clinical trials to show a meaningful effect on progression of disability, the need for a valid, reliable, and objective paraclinical marker of disease evolution cannot be overemphasized. This paper reviews the most up-to-date data regarding MRI techniques, their relationship with central nervous system pathology, as well as with clinical endpoints, and proposes future insights into the use of MRI metrics as surrogate endpoints in clinical trials of MS.

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