title: Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging.
abstract: The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many insights have been gained from such imaging studies: persisting inflammation in the absence of a damaged blood-brain barrier, activated microglia within and beyond lesions, increased mitochondrial activity after acute lesions, raised sodium concentrations in the brain, increased glutamate in acute lesions and normal-appearing white matter, different degrees of demyelination in different patients and lesions, early neuronal damage in grey matter, and early astrocytic proliferation and activation in lesions and white matter. Clinical translation of molecular and metabolic imaging and extension of these techniques will enable the assessment of novel drugs targeted at these disease mechanisms, and have the potential to improve health outcomes through the stratification of patients for treatments.
authors.affiliation: Queen Square MS Centre, University College London Institute of Neurology, London, UK; NIHR UCL/UCLH Biomedical Research Centre, London, UK. Electronic address: o.ciccarelli@ucl.ac.uk.
authors.forename: Olga
authors.initials: O
authors.lastname: Ciccarelli
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: ICM-Institut du Cerveau et de la Moelle épinière, Université Pierre et Marie Curie, Paris, France; Service Hospitalier Frédéric Joliot, DSV-I2BM, CEA, Orsay, France.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bodini
authors.affiliation: Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
authors.affiliation: Queen Square MS Centre, University College London Institute of Neurology, London, UK.
authors.forename: Xavier
authors.initials: X
authors.lastname: Golay
authors.affiliation: Biomedical NMR, Eindhoven University of Technology, Eindhoven, Netherlands.
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
authors.affiliation: Division of Neuro-immunology and Yale MS Center, Advanced Imaging in MS Laboratory, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.affiliation: Biomedical Engineering, Vanderbilt School of Engineering, Nashville, TN, USA.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Smith
authors.affiliation: Queen Square MS Centre, University College London Institute of Neurology, London, UK.
authors.forename: Claudia A M
authors.initials: CA
authors.lastname: Wheeler-Kingshott
authors.affiliation: ICM-Institut du Cerveau et de la Moelle épinière, Université Pierre et Marie Curie, Paris, France; Service Hospitalier Frédéric Joliot, DSV-I2BM, CEA, Orsay, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
authors.affiliation: Queen Square MS Centre, University College London Institute of Neurology, London, UK.
authors.forename: Tarek
authors.initials: T
authors.lastname: Yousry
authors.affiliation: Queen Square MS Centre, University College London Institute of Neurology, London, UK.
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
mesh_terms: D000818:Animals; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000639:trends; D057054:Molecular Imaging / Q000639:trends; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology