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High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis. 2010

Klaus Schmierer, and Harold G Parkes, and Po-Wah So, and Shu F An, and Sebastian Brandner, and Roger J Ordidge, and Tarek A Yousry, and David H Miller
UCL Institute of Neurology, Department of Neuroinflammation, NMR Research Unit, London, UK. k.schmierer@qmul.ac.uk

Multiple sclerosis is an inflammatory, degenerative disease of the central nervous system. The most obvious pathological change in multiple sclerosis is multifocal demyelination of the white matter, but grey matter demyelination may be of equal or even greater importance for its clinical manifestations. In order to assess the pathogenetic role of lesions in the grey and white matter, and to explore the association between demyelinated and non-lesional brain tissue, tools are needed to depict each of these tissue components accurately in vivo. Due to its sensitivity in detecting white matter lesions, T(2)-weighted magnetic resonance imaging at 1.5 T is important in the diagnosis of multiple sclerosis. However, magnetic resonance imaging at 1.5 T largely fails to detect grey matter lesions. In this study, we used T(2)-weighted magnetic resonance imaging at 9.4 T to detect grey matter lesions in fixed post-mortem multiple sclerosis motor cortex. Furthermore, we produced T(1), T(2) and magnetization transfer ratio maps, and correlated these indices with quantitative histology [neuronal density, intensity of immunostaining for myelin basic protein (reflecting myelin content) and phosphorylated neurofilament (reflecting axonal area)] using t-tests and multivariate regression. In 21 tissue samples, 28 cortical grey matter lesions were visible on both T(2)-weighted magnetic resonance imaging and sections immunostained for myelin basic protein, 15/28 being mixed white and grey matter and 11/28 subpial cortical grey matter lesions; 2/28 cortical grey matter lesions involved all layers of the cortex. Compared with non-lesional cortex, cortical grey matter lesions showed reduction of neuronal density (98/mm(2), SD = 34/mm(2;) versus 129/mm(2), SD = 44; P < 0.01), phosphorylated neurofilament (1/transmittance = 1.16; SD = 0.09 versus 1.24; SD = 0.1; P < 0.01) and magnetization transfer ratio (31.1 pu; SD = 11.9 versus 37.5 pu; SD = 8.7; P = 0.01), and an increase of T(2) (25.9; SD = 5 versus 22.6 ms; SD = 4.7; P < 0.01). Associations were detected between phosphorylated neurofilament and myelin basic protein (r = 0.58, P < 0.01), myelin basic protein and T(2) (r = -0.59, P < 0.01), and neuronal density and T(1) (r = -0.57, P < 0.01). All indices correlated with duration of tissue fixation, however, including the latter in the analysis did not fundamentally affect the associations described. Our data show that T(2)-weighted magnetic resonance imaging at 9.4 T enables detection of cortical grey matter lesion in post-mortem multiple sclerosis brain. The quantitative associations suggest that in cortical grey matter T(1) may be a predictor of neuronal density, and T(2) of myelin content (and-secondarily-axons). Successful translation of these results into in vivo studies using high field magnetic resonance imaging (e.g. 3 T and 7 T) will improve the assessment of cortical pathology and thereby have an impact on the diagnosis and natural history studies of patients with multiple sclerosis, as well as clinical trial designs for putative treatments to prevent cortical demyelination and neuronal loss.

UI MeSH Term Description Entries
D008279 Magnetic Resonance Imaging Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. Chemical Shift Imaging,MR Tomography,MRI Scans,MRI, Functional,Magnetic Resonance Image,Magnetic Resonance Imaging, Functional,Magnetization Transfer Contrast Imaging,NMR Imaging,NMR Tomography,Tomography, NMR,Tomography, Proton Spin,fMRI,Functional Magnetic Resonance Imaging,Imaging, Chemical Shift,Proton Spin Tomography,Spin Echo Imaging,Steady-State Free Precession MRI,Tomography, MR,Zeugmatography,Chemical Shift Imagings,Echo Imaging, Spin,Echo Imagings, Spin,Functional MRI,Functional MRIs,Image, Magnetic Resonance,Imaging, Magnetic Resonance,Imaging, NMR,Imaging, Spin Echo,Imagings, Chemical Shift,Imagings, Spin Echo,MRI Scan,MRIs, Functional,Magnetic Resonance Images,Resonance Image, Magnetic,Scan, MRI,Scans, MRI,Shift Imaging, Chemical,Shift Imagings, Chemical,Spin Echo Imagings,Steady State Free Precession MRI
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009044 Motor Cortex Area of the FRONTAL LOBE concerned with primary motor control located in the dorsal PRECENTRAL GYRUS immediately anterior to the central sulcus. It is comprised of three areas: the primary motor cortex located on the anterior paracentral lobule on the medial surface of the brain; the premotor cortex located anterior to the primary motor cortex; and the supplementary motor area located on the midline surface of the hemisphere anterior to the primary motor cortex. Brodmann Area 4,Brodmann Area 6,Brodmann's Area 4,Brodmann's Area 6,Premotor Cortex and Supplementary Motor Cortex,Premotor and Supplementary Motor Cortices,Anterior Central Gyrus,Gyrus Precentralis,Motor Area,Motor Strip,Precentral Gyrus,Precentral Motor Area,Precentral Motor Cortex,Premotor Area,Premotor Cortex,Primary Motor Area,Primary Motor Cortex,Secondary Motor Areas,Secondary Motor Cortex,Somatic Motor Areas,Somatomotor Areas,Supplementary Motor Area,Area 4, Brodmann,Area 4, Brodmann's,Area 6, Brodmann,Area 6, Brodmann's,Area, Motor,Area, Precentral Motor,Area, Premotor,Area, Primary Motor,Area, Secondary Motor,Area, Somatic Motor,Area, Somatomotor,Area, Supplementary Motor,Brodmann's Area 6s,Brodmanns Area 4,Brodmanns Area 6,Central Gyrus, Anterior,Cortex, Motor,Cortex, Precentral Motor,Cortex, Premotor,Cortex, Primary Motor,Cortex, Secondary Motor,Cortices, Secondary Motor,Gyrus, Anterior Central,Gyrus, Precentral,Motor Area, Precentral,Motor Area, Primary,Motor Area, Secondary,Motor Area, Somatic,Motor Areas,Motor Cortex, Precentral,Motor Cortex, Primary,Motor Cortex, Secondary,Motor Strips,Precentral Motor Areas,Precentral Motor Cortices,Premotor Areas,Primary Motor Areas,Primary Motor Cortices,Secondary Motor Area,Secondary Motor Cortices,Somatic Motor Area,Somatomotor Area,Supplementary Motor Areas
D009103 Multiple Sclerosis An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903) MS (Multiple Sclerosis),Multiple Sclerosis, Acute Fulminating,Sclerosis, Disseminated,Disseminated Sclerosis,Sclerosis, Multiple
D009413 Nerve Fibers, Myelinated A class of nerve fibers as defined by their structure, specifically the nerve sheath arrangement. The AXONS of the myelinated nerve fibers are completely encased in a MYELIN SHEATH. They are fibers of relatively large and varied diameters. Their NEURAL CONDUCTION rates are faster than those of the unmyelinated nerve fibers (NERVE FIBERS, UNMYELINATED). Myelinated nerve fibers are present in somatic and autonomic nerves. A Fibers,B Fibers,Fiber, Myelinated Nerve,Fibers, Myelinated Nerve,Myelinated Nerve Fiber,Myelinated Nerve Fibers,Nerve Fiber, Myelinated
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D012044 Regression Analysis Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable. Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell

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