Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI

Filippi, Massimo; Iannucci, Giuseppe; Tortorella, Carla; Minicucci, L.; Horsfield, Mark A.; Colombo, Bruno; Sormani, Maria Pia; Comı, Gıancarlo

doi:10.1212/wnl.52.3.588

Cited by 204 publications

(187 citation statements)

References 37 publications

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“…Such measures are sensitive in depicting subtle abnormalities in NAWM and NAGM and convincing evidence has emerged that increasing abnormality in these tissues is associated with clinical progression. 99,100 However, these subtle MR changes are pathologically nonspecific and could potentially represent the effects of inflammation, gliosis, or axonal loss, all of which occur in NAWM. 4,101 Although they may be valuable for monitoring clinically relevant disease progression they should not be considered as specific markers of neurodegeneration.…”

Section: Other Measuresmentioning

confidence: 99%

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Miller¹

2004

Neurotherapeutics

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Summary:Multiple sclerosis (MS) is a chronic disease of the CNS that most commonly affects young adults. It is usually characterized in the early years by acute relapses followed by partial or complete remission; in later years progressive and irreversible disability develops. Because of the protracted and unpredictable clinical course, biological surrogate markers are much needed to make clinical trials of potential disease-modifying treatments more efficient. Magnetic resonance (MR) outcome measures are now widely used to monitor treatment outcome in MS trials. Areas of multifocal inflammation are detected with a high sensitivity as new areas of gadolinium enhancement and T2 abnormality, and these may be considered as surrogate markers for clinical relapses. However, progressive disability is not clearly related to inflammatory lesions but rather to a progressive and diffuse process with increasing neuroaxonal loss. MR surrogate measures for neuroaxonal loss include atrophy (tissue loss in brain and spinal cord), N-acetyl aspartate, and T1 hypointense lesions. Diffuse abnormality in normal appearing brain tissue may also be monitored using magnetization transfer ratio and other quantitative MR measures. For treatment trials of new agents aimed at preventing disability, measures of neuroaxonal damage should be acquired, especially atrophy, which occurs at all stages of MS and which can be quantified in a sensitive and reproducible manner. Because the MR surrogates for neuroaxonal loss are not yet validated as predicting future disability, definitive trials should continue to monitor an appropriate disability endpoint.

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Section: Other Measuresmentioning

confidence: 99%

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Miller¹

2004

Neurotherapeutics

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“…MS lesions also have lower MTR values (typically 20 pu in this image dataset) and, therefore, the threshold selected was such that voxels in visible lesions were not removed by this process. Other workers [1]- [5] have used thresholds in a similar manner; we chose this after experimentation, selecting an aggressive value to reduce partial volume effects with CSF.…”

Section: ) Thresholdingmentioning

confidence: 99%

Classification of disease subgroup and correlation with disease severity using magnetic resonance imaging whole-brain histograms: application to magnetization transfer ratios and multiple sclerosis

Dehmeshki

Barker

Tofts

2002

IEEE Trans. Med. Imaging

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Abstract-This paper presents a new approach to characterize subtle diffuse changes in multiple sclerosis (MS) using histograms derived from magnetization transfer ratio (MTR) images. Two major parts dominate our histogram analysis; 1) Classification of MTR histograms into control and MS subgroups; 2) Correlation with current disability, as measured by the EDSS scale (a measure of disease severity). Two data reduction schemes are used to reduce the complexity of the analysis: linear discriminant analysis (LDA) and principal component analysis (PCA). LDA is better for the classification of MTR histograms as it takes into account the between-class variation. By using LDA, the space of MTR histograms is transformed to the optimal discriminant space for a nearest mean classifier. In contrast, PCA is useful for correlation with current disability as it takes into account the variation within each subgroup in its process. A multiple regression analysis is used to evaluate the multiple correlation of those principal components with the degree of disability in MS. This is the first application of such classification and correlation techniques to magnetic resonance imaging histogram data. Our MTR histogram analysis approach give improved classification success and improved correlation compared with methods that use traditional histogram features such as peak height and peak location.Index Terms-Histogram analysis, linear discriminant analysis, multiple sclerosis, principal component analysis.

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“…On the contrary, magnetic resonance imaging (MRI) has provided combersome and controversial results. In detail, the majority of the studies showed that the load of T 2 -visible lesions is similar between patients with BMS and those with other disease phenotypes, whereas the extent of normal-appearing brain tissue (NABT) damage was found to be less pronounced in patients with BMS than in other forms of the disease in some studies [Davie et al, 1999;De Stefano et al, 2006;Falini et al, 1998;Filippi et al, 1996Filippi et al, , 1999Filippi et al, , 2000, but not in others [Brass et al, 2004;Droogan et al, 1999;Horsfield et al, 1996;Traboulsee et al, 2003].…”

Section: Introductionmentioning

confidence: 99%

“…Such an approach was driven by two considerations: (a) to investigate cortical functional changes in patients with a ''real'' benign course (i.e., with no locomotor and cognitive impairment), and (b) to study the underlying functional cortical correlates of brain-mediated clinical aspects (contrary to cognition, locomotor ability is indeed likely to be associated to both brain and spinal cord integrity). Differently from previous studies based on an ''overall'' assessment of brain damage [Brass et al, 2004;Davie et al, 1999;De Stefano et al, 2006;Droogan et al, 1999;Falini et al, 1998;Filippi et al, 1996Filippi et al, , 1999Filippi et al, , 2000Horsfield et al, 1996;Traboulsee et al, 2003], we investigated the structural correlates of fMRI abnormalities, by using diffusion tensor (DT) tractography, since it is likely that damage of ''strategic'' white matter (WM) fiber bundles of the brain might be more strictly linked to functional cortical changes than ''overall'' NABT damage. DT MRI provides quantitative data on water molecular motion, a marker of tissue structure and organization.…”

Section: Introductionmentioning

confidence: 99%

Structural and functional MRI correlates of Stroop control in benign MS

Rocca

Valsasina

Ceccarelli

et al. 2007

Human Brain Mapping

113

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The objective of this study was to assess the functional and structural substrates of cognitive network changes in patients with benign multiple sclerosis (BMS), using an analysis of effective connectivity and MR tractography. Using a 3-Tesla scanner, we acquired dual-echo, diffusion tensor (DT) and functional MRI during the performance of the Stroop task from 15 BMS patients and 19 healthy controls. DT MRI tractography was used to calculate DT derived metrics from several white matter (WM) fiber bundles, thought to be involved in cognitive performance. DT MRI metrics from WM fiber bundles not directly related with cognitive performance were also derived. Effective connectivity analysis was performed using statistical parametric mapping. MS patients had significantly abnormal DT MRI metrics in all the structures analyzed. Compared with controls, MS patients had more significant activations of several areas of the cognitive network involved in Stroop performance, bilaterally. Compared with controls, BMS patients also had increased connectivity strengths between several cortical areas of the sensorimotor network and the right (R) inferior frontal gyrus and the R cerebellum, as well as decreased connectivity strengths with the anterior cingulate cortex. Coefficients of altered connectivity were moderately correlated with structural MRI metrics of tissue damage within intra-and inter-hemispheric cognitiverelated WM fiber bundles, while no correlations were found with the remaining fiber bundles studied, suggesting that functional cortical changes in patients with BMS might represent an adaptive response driven by damage of specific WM structures. Hum Brain Mapp 30:276-290, 2009. V V C 2007 Wiley-Liss, Inc.

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Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI

Cited by 204 publications

References 37 publications

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Classification of disease subgroup and correlation with disease severity using magnetic resonance imaging whole-brain histograms: application to magnetization transfer ratios and multiple sclerosis

Structural and functional MRI correlates of Stroop control in benign MS

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