The effect of interferon β-1b on quantities derived from MT MRI in secondary progressive MS

Inglese, Matilde; Waesberghe, J.H.T.M. van; Rovaris, Marco; Beckmann, Karola; Barkhof, Frederik; Hahn, Dietbert; Kappos, Ludwig; Miller, David H.; Polman, C.; Pozzilli, Carlo; Thompson, Alan J.; Yousry, Tarek; Wagner, Klaus; Comi, Giancarlo; Filippi, Massimo

doi:10.1212/01.wnl.0000049929.27032.29

Cited by 79 publications

(50 citation statements)

References 38 publications

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“…PET ligands targeting the 18 kDa translocator protein, which is upregulated with inflammation, detect neuroinflammation in human diseases including multiple sclerosis and in animal models, but the effectiveness of these PET markers remains to be seen (Banati et al, 2000;Papadopoulos et al, 2006;Chauveau et al, 2009Chauveau et al, , 2011Abourbeh et al, 2012;Xie et al, 2012). Promising advances in imaging myelination have been reported including myelin water imaging (MacKay et al, 1994;Du et al, 2007;Laule et al, 2008;Hwang et al, 2010;Prasloski et al, 2012), magnetization transfer (Inglese et al, 2003;Schmierer et al, 2004Schmierer et al, , 2007aDortch et al, 2011;Stikov et al, 2011;Underhill et al, 2011), optical imaging (Wang et al, 2011a) and myelin-specific PET markers (Wang et al, 2009;Wu et al, 2013). For specifically identifying axon injury and loss, reduced NAA content measured by magnetic resonance spectroscopy (MRS) has been used (De Stefano et al, 1999;Aboul-Enein et al, 2010;Wood et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis

Wang

Sun

Wang

et al. 2015

Brain

139

189

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Axon injury/loss, demyelination and inflammation are the primary pathologies in multiple sclerosis lesions. Despite the prevailing notion that axon/neuron loss is the substrate of clinical progression of multiple sclerosis, the roles that these individual pathological processes play in multiple sclerosis progression remain to be defined. An imaging modality capable to effectively detect, differentiate and individually quantify axon injury/loss, demyelination and inflammation, would not only facilitate the understanding of the pathophysiology underlying multiple sclerosis progression, but also the assessment of treatments at the clinical trial and individual patient levels. In this report, the newly developed diffusion basis spectrum imaging was used to discriminate and quantify the underlying pathological components in multiple sclerosis white matter. Through the multiple-tensor modelling of diffusion weighted magnetic resonance imaging signals, diffusion basis spectrum imaging resolves inflammation-associated cellularity and vasogenic oedema in addition to accounting for partial volume effects resulting from cerebrospinal fluid contamination, and crossing fibres. Quantitative histological analysis of autopsied multiple sclerosis spinal cord specimens supported that diffusion basis spectrum imaging-determined cellularity, axon and myelin injury metrics closely correlated with those pathologies identified and quantified by conventional histological staining. We demonstrated in healthy control subjects that diffusion basis spectrum imaging rectified inaccurate assessments of diffusion properties of white matter tracts by diffusion tensor imaging in the presence of cerebrospinal fluid contamination and/or crossing fibres. In multiple sclerosis patients, we report that diffusion basis spectrum imaging quantitatively characterized the distinct pathologies underlying gadolinium-enhanced lesions, persistent black holes, non-enhanced lesions and non-black hole lesions, a task yet to be demonstrated by other neuroimaging approaches. Diffusion basis spectrum imaging-derived radial diffusivity (myelin integrity marker) and non-restricted isotropic diffusion fraction (oedema marker) correlated with magnetization transfer ratio, supporting previous reports that magnetization transfer ratio is sensitive not only to myelin integrity, but also to inflammation-associated oedema. Our results suggested that diffusion basis spectrum imaging-derived quantitative biomarkers are highly consistent with histology findings and hold promise to accurately characterize the heterogeneous white matter pathology in multiple sclerosis patients. Thus, diffusion basis spectrum imaging can potentially serve as a non-invasive outcome measure to assess treatment effects on the specific components of underlying pathology targeted by new multiple sclerosis therapies. Keywords: diffusion basis spectrum imaging; diffusion tensor imaging; white matter injury; inflammation; multiple sclerosis Abbreviations: DTI = diffusion tensor imaging; DBSI = diffusion...

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Section: Discussionmentioning

confidence: 99%

Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis

Wang

Sun

Wang

et al. 2015

Brain

139

189

View full text Add to dashboard Cite

show abstract

“…57,58 Quantitative MRI techniques might enable measure ment and monitoring of disease related mechanisms that occur before the development of atrophy, which primarily occurs in the late stages of MS. To date, very few clin ical trials have included these metrics as outcome meas ures. [59][60][61][62] One method that was developed to monitor changes in the magnetization transfer ratio in individual lesion voxels revealed evidence consistent with demye lination and remyelination within the same lesion. Of note, signs of remyelination were still present in some lesions 3 years after their formation.…”

Section: Focal Lesionsmentioning

confidence: 99%

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

2015

Nat Rev Neurol

402

147

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“…Potential clinical applications of MT include early detection of neurologic involvement and response to treatment. In MS, for example, MT measurements have been used to evaluate drug effectiveness 44 and have been recommended as objective end points in large-scale MS trials. 45 It is possible, pending further study, that MT could be used to detect response to specific antiretrovirals.…”

Section: Correlations Of Mtr Measurements and Cognitive Status Measuresmentioning

confidence: 99%

Whole Brain and Localized Magnetization Transfer Measurements Are Associated with Cognitive Impairment in Patients Infected with Human Immunodeficiency Virus

Storey

Carrillo

et al. 2007

AJNR Am J Neuroradiol

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The effect of interferon β-1b on quantities derived from MT MRI in secondary progressive MS

Cited by 79 publications

References 38 publications

Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis

Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

Whole Brain and Localized Magnetization Transfer Measurements Are Associated with Cognitive Impairment in Patients Infected with Human Immunodeficiency Virus

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