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Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap

Pontillo, Giuseppe
Author Pontillo, Giuseppe ORCID From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Prados, Ferran
Author Prados, Ferran ORCID From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Colman, Jordan
Author Colman, Jordan From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Kanber, Baris
Author Kanber, Baris From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Abdel-Mannan, Omar
Author Abdel-Mannan, Omar ORCID From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Al-Araji, Sarmad
Author Al-Araji, Sarmad From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Bellenberg, Barbara
Author Bellenberg, Barbara ORCID From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Bianchi, Alessia
Author Bianchi, Alessia ORCID From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Bisecco, Alvino
Author Bisecco, Alvino ORCID From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom
Brownlee, Wallace J
Author Brownlee, Wallace J ORCID From the Queen Square Multiple Sclerosis Centre (G.P., F.P., J.C., B.K., O.A.-M., S.A.-A., A. Bianchi, W.J.B., R. Christensen, E.C., S. Collorone, M.A.F., Y.H., A.H., S. Mohamud, R.N., A.T.T., J.W., C.Y., O.C., F.B.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, United Kingdom MS Center Amsterdam (G.P., H.V., F.B.), Radiology and Nuclear Medicine, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Departments of Advanced Biomedical Sciences and Electrical Engineering and Information Technology (G.P., A. Brunetti, S. Cocozza), University of Naples "Federico II," Italy Centre for Medical Image Computing (F.P., B.K., F.B.), Department of Medical Physics and Biomedical Engineering, University College London, United Kingdom E-Health Center (F.P.), Universitat Oberta de Catalunya, Barcelona, Spain Institute of Neuroradiology (B.B., C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Department of Advanced Medical and Surgical Sciences (A. Bisecco, A.G.), University of Campania "Luigi Vanvitelli," Naples, Italy Translational Imaging in Neurology (ThINK) Basel (A.C., C. Granziera), Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel, University of Basel Neurologic Clinic and Policlinic (A.C., C. Granziera, J.K.), MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Switzerland Department of Neurosciences, Biomedicine and Movement Sciences (M. Calabrese, M. Castellaro), University of Verona Department of Information Engineering (M. Castellaro), University of Padova Department of Medicine, Surgery and Neuroscience (R. Cortese, N.D.S.), University of Siena, Italy Department of Neurology (C.E., D.P.), Medical University of Graz, Austria Neuroimaging Research Unit (M.F., M.A.R., P.V.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Neurology Unit, Neurorehabilitation Unit, Neurophysiology Service, IRCCS San Raffaele Scientific Institute Vita-Salute San Raffaele University (M.F., M.A.R., P.V.), Milan Department of Neurosciences (C. Gasperini, S.R.), San Camillo-Forlanini Hospital, Rome, Italy Department of Neurology (G.G.-E., S.G.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany Department of Neurology (H.F.F.H., E.A.H., G.O.N.), Oslo University Hospital Institute of Clinical Medicine (H.F.F.H., E.A.H., G.O.N.), and Department of Psychology (E.A.H.), University of Oslo, Norway Neuroimmunology and Multiple Sclerosis Unit Laboratory of Advanced Imaging in Neuroimmunological Diseases (ImaginEM) (S.L., E.M.-H.), Hospital Clinic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Su, Barcelona, Spain Department of Neurology (C.L.), St. Josef Hospital, Ruhr-University Bochum, Germany Nuffield Department of Clinical Neurosciences (S. Messina, J.P.), University of Oxford, United Kingdom Department of Molecular Medicine and Medical Biotechnology (M.M.), and Department of Neurosciences and Reproductive and Odontostomatological Sciences (M.P.), University of Naples "Federico II" Department of Human Neurosciences (M.P.), Sapienza University of Rome, Italy Section of Neuroradiology (A.R.), Department of Radiology, and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (J.S.-G.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain MS Center Amsterdam (E.M.M.S.), Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Department of Neurology and Center of Clinical Neuroscience (T.U.), and Department of Radiology (M.V.), First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic MS Center Amsterdam (M.M.S.), Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, the Netherlands Centre for Medical Image Computing (J.H.C.), Department of Computer Science, and Dementia Research Centre (J.H.C., F.B.), UCL Queen Square Institute of Neurology, University College London, United Kingdom

Neurology. 2024 ; 103 (10) : e209976. [pub] 20241104

ISSN 1526-632X
Medvik
Source

BACKGROUND AND OBJECTIVES: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS. METHODS: In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS). RESULTS: We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00-0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51-0.59], p < 0.001). DD gap significantly explained EDSS changes (B = 0.060 [0.038-0.082], p < 0.001), adding to BAG (ΔR2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change (r = 0.50 [0.39-0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (ΔR2 = 0.064, p < 0.001). DISCUSSION: The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression.

MeSH
Deep Learning * MeSH
Adult MeSH
Middle Aged MeSH
Humans MeSH
Longitudinal Studies MeSH
Magnetic Resonance Imaging * MeSH
Brain * diagnostic imaging pathology MeSH
Neurodegenerative Diseases diagnostic imaging MeSH
Cross-Sectional Studies MeSH
Retrospective Studies MeSH
Multiple Sclerosis * diagnostic imaging pathology MeSH
Aging * pathology physiology MeSH
Check Tag
Adult MeSH
Middle Aged MeSH
Humans MeSH
Male MeSH
Female MeSH
Publication type
Journal Article MeSH
Multicenter Study MeSH

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