Reduced neurite density in the brain and cervical spinal cord in relapsing–remitting multiple sclerosis: A NODDI study

Author:

Collorone Sara1ORCID,Cawley Niamh1,Grussu Francesco2ORCID,Prados Ferran2,Tona Francesca1,Calvi Alberto3,Kanber Baris4,Schneider Torben5,Kipp Lucas6,Zhang Hui4,Alexander Daniel C4,Thompson Alan J1,Toosy Ahmed1,Wheeler-Kingshott Claudia AM Gandini7,Ciccarelli Olga8

Affiliation:

1. NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK

2. NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/Centre for Medical Image Computing (CMIC), Department of Computer Science, University College London, London, UK

3. NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/Department of Pathophysiology and Transplantation, Neurodegenerative Disease Unit, La Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, University of Milan, Milan, Italy

4. Centre for Medical Image Computing (CMIC), Department of Computer Science, University College London, London, UK

5. NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/Philips UK, Guildford, UK

6. NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/Stanford MS Center, Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, CA, USA

7. NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy/Brain MRI 3T Research Centre, IRCCS Mondino Foundation, Pavia, Italy

8. NMR Research Unit, Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, UK

Abstract

Background: Multiple sclerosis (MS) affects both brain and spinal cord. However, studies of the neuraxis with advanced magnetic resonance imaging (MRI) are rare because of long acquisition times. We investigated neurodegeneration in MS brain and cervical spinal cord using neurite orientation dispersion and density imaging (NODDI). Objective: The aim of this study was to investigate possible alterations, and their clinical relevance, in neurite morphology along the brain and cervical spinal cord of relapsing–remitting MS (RRMS) patients. Methods: In total, 28 RRMS patients and 20 healthy controls (HCs) underwent brain and spinal cord NODDI at 3T. Physical and cognitive disability was assessed. Individual maps of orientation dispersion index (ODI) and neurite density index (NDI) in brain and spinal cord were obtained. We examined differences in NODDI measures between groups and the relationships between NODDI metrics and clinical scores using linear regression models adjusted for age, sex and brain tissue volumes or cord cross-sectional area (CSA). Results: Patients showed lower NDI in the brain normal-appearing white matter (WM) and spinal cord WM than HCs. In patients, a lower NDI in the spinal cord WM was associated with higher disability. Conclusion: Reduced neurite density occurs in the neuraxis but, especially when affecting the spinal cord, it may represent a mechanism of disability in MS.

Funder

Engineering and Physical Sciences Research Council

International Spinal Research Trust

Multiple Sclerosis Society

Publisher

SAGE Publications

Subject

Clinical Neurology,Neurology

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