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      [ 18F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis

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          We evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [ 18F]florbetapir PET-MR imaging.


          We included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [ 18F]florbetapir PET-MR and both a clinical and cognitive assessment. [ 18F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70–90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling.


          [ 18F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion ( P < 0.001), correlated with fractional anisotropy and with mean, axial and radial diffusivity within T2 lesions ( coeff. = −0.15, P < 0.001, coeff. = −0.12, P < 0.001 and coeff. = −0.16, P < 0.001, respectively). Cerebral blood flow was reduced in white matter damaged areas compared to white matter in healthy controls (−10.9%, P = 0.005). SUV 70–90 and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26).


          Our findings demonstrate that [ 18F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [ 18F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.

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          The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has focussed on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data. The majority of the research laid out in this paper has been implemented as freely available software tools within FMRIB's Software Library (FSL).
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            Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

            New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use. Ann Neurol 2011
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              Multiple sclerosis.

              Multiple sclerosis is primarily an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons. Initially, inflammation is transient and remyelination occurs but is not durable. Hence, the early course of disease is characterised by episodes of neurological dysfunction that usually recover. However, over time the pathological changes become dominated by widespread microglial activation associated with extensive and chronic neurodegeneration, the clinical correlate of which is progressive accumulation of disability. Paraclinical investigations show abnormalities that indicate the distribution of inflammatory lesions and axonal loss (MRI); interference of conduction in previously myelinated pathways (evoked electrophysiological potentials); and intrathecal synthesis of oligoclonal antibody (examination by lumbar puncture of the cerebrospinal fluid). Multiple sclerosis is triggered by environmental factors in individuals with complex genetic-risk profiles. Licensed disease modifying agents reduce the frequency of new episodes but do not reverse fixed deficits and have questionable effects on the long-term accumulation of disability and disease progression. We anticipate that future studies in multiple sclerosis will provide a new taxonomy on the basis of mechanisms rather than clinical empiricism, and so inform strategies for improved treatment at all stages of the disease.

                Author and article information

                Eur J Nucl Med Mol Imaging
                Eur. J. Nucl. Med. Mol. Imaging
                European Journal of Nuclear Medicine and Molecular Imaging
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                21 October 2019
                21 October 2019
                : 47
                : 2
                : 366-378
                [1 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Neurodegeneration Imaging Group, , Maurice Wohl Clinical Neuroscience Institute, IoPPN, King’s College London, ; 125 Coldharbour Lane, Camberwell, London, SE5 9NU UK
                [2 ]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Multiple sclerosis Clinical Care and Research Centre, Department of Neuroscience, , Federico II University, ; Naples, Italy
                [3 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, , King’s College London, ; London, UK
                [4 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, King’s College London & Guy’s and St Thomas’ PET Centre, School of Biomedical Engineering and Imaging Sciences, Faculty of Life Sciences and Medicine, , King’s College London, St Thomas’ Hospital, ; London, UK
                [5 ]GRID grid.429705.d, ISNI 0000 0004 0489 4320, Department of Neurology, , King’s College Hospital NHS Foundation Trust, ; London, UK
                © The Author(s) 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                Funded by: King's College London
                Original Article
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                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Radiology & Imaging

                multiple sclerosis, pet, [18f]florbetapir, demyelination, pathology


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