A multi-shell multi-tissue diffusion study of brain connectivity in early multiple sclerosis

The potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple sclerosis (MS) has scarcely been investigated. To test, in patients with a clinically isolated syndrome (CIS), whether multi-shell imaging-derive...

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Veröffentlicht in:Multiple sclerosis Jg. 26; H. 7; S. 774
Hauptverfasser: Tur, Carmen, Grussu, Francesco, Prados, Ferran, Charalambous, Thalis, Collorone, Sara, Kanber, Baris, Cawley, Niamh, Altmann, Daniel R, Ourselin, Sébastien, Barkhof, Frederik, Clayden, Jonathan D, Toosy, Ahmed T, Wheeler-Kingshott, Claudia Am Gandini, Ciccarelli, Olga
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Sprache:Englisch
Veröffentlicht: England 01.06.2020
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ISSN:1477-0970, 1477-0970
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Abstract The potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple sclerosis (MS) has scarcely been investigated. To test, in patients with a clinically isolated syndrome (CIS), whether multi-shell imaging-derived connectivity metrics can differentiate patients from controls, correlate with clinical measures, and perform better than metrics obtained with conventional single-shell protocols. Nineteen patients within 3 months from the CIS and 12 healthy controls underwent anatomical and 53-direction multi-shell diffusion-weighted 3T images. Patients were cognitively assessed. Voxel-wise fibre orientation distribution functions were estimated and used to obtain network metrics. These were also calculated using a conventional single-shell diffusion protocol. Through linear regression, we obtained effect sizes and standardised regression coefficients. Patients had lower mean nodal strength (  = 0.003) and greater network modularity than controls (  = 0.045). Greater modularity was associated with worse cognitive performance in patients, even after accounting for lesion load (  = 0.002). Multi-shell-derived metrics outperformed single-shell-derived ones. Connectivity-based nodal strength and network modularity are abnormal in the CIS. Furthermore, the increased network modularity observed in patients, indicating microstructural damage, is clinically relevant. Connectivity analyses based on multi-shell imaging can detect potentially relevant network changes in early MS.
AbstractList The potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple sclerosis (MS) has scarcely been investigated.BACKGROUNDThe potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple sclerosis (MS) has scarcely been investigated.To test, in patients with a clinically isolated syndrome (CIS), whether multi-shell imaging-derived connectivity metrics can differentiate patients from controls, correlate with clinical measures, and perform better than metrics obtained with conventional single-shell protocols.OBJECTIVETo test, in patients with a clinically isolated syndrome (CIS), whether multi-shell imaging-derived connectivity metrics can differentiate patients from controls, correlate with clinical measures, and perform better than metrics obtained with conventional single-shell protocols.Nineteen patients within 3 months from the CIS and 12 healthy controls underwent anatomical and 53-direction multi-shell diffusion-weighted 3T images. Patients were cognitively assessed. Voxel-wise fibre orientation distribution functions were estimated and used to obtain network metrics. These were also calculated using a conventional single-shell diffusion protocol. Through linear regression, we obtained effect sizes and standardised regression coefficients.METHODSNineteen patients within 3 months from the CIS and 12 healthy controls underwent anatomical and 53-direction multi-shell diffusion-weighted 3T images. Patients were cognitively assessed. Voxel-wise fibre orientation distribution functions were estimated and used to obtain network metrics. These were also calculated using a conventional single-shell diffusion protocol. Through linear regression, we obtained effect sizes and standardised regression coefficients.Patients had lower mean nodal strength (p = 0.003) and greater network modularity than controls (p = 0.045). Greater modularity was associated with worse cognitive performance in patients, even after accounting for lesion load (p = 0.002). Multi-shell-derived metrics outperformed single-shell-derived ones.RESULTSPatients had lower mean nodal strength (p = 0.003) and greater network modularity than controls (p = 0.045). Greater modularity was associated with worse cognitive performance in patients, even after accounting for lesion load (p = 0.002). Multi-shell-derived metrics outperformed single-shell-derived ones.Connectivity-based nodal strength and network modularity are abnormal in the CIS. Furthermore, the increased network modularity observed in patients, indicating microstructural damage, is clinically relevant. Connectivity analyses based on multi-shell imaging can detect potentially relevant network changes in early MS.CONCLUSIONConnectivity-based nodal strength and network modularity are abnormal in the CIS. Furthermore, the increased network modularity observed in patients, indicating microstructural damage, is clinically relevant. Connectivity analyses based on multi-shell imaging can detect potentially relevant network changes in early MS.
The potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple sclerosis (MS) has scarcely been investigated. To test, in patients with a clinically isolated syndrome (CIS), whether multi-shell imaging-derived connectivity metrics can differentiate patients from controls, correlate with clinical measures, and perform better than metrics obtained with conventional single-shell protocols. Nineteen patients within 3 months from the CIS and 12 healthy controls underwent anatomical and 53-direction multi-shell diffusion-weighted 3T images. Patients were cognitively assessed. Voxel-wise fibre orientation distribution functions were estimated and used to obtain network metrics. These were also calculated using a conventional single-shell diffusion protocol. Through linear regression, we obtained effect sizes and standardised regression coefficients. Patients had lower mean nodal strength (  = 0.003) and greater network modularity than controls (  = 0.045). Greater modularity was associated with worse cognitive performance in patients, even after accounting for lesion load (  = 0.002). Multi-shell-derived metrics outperformed single-shell-derived ones. Connectivity-based nodal strength and network modularity are abnormal in the CIS. Furthermore, the increased network modularity observed in patients, indicating microstructural damage, is clinically relevant. Connectivity analyses based on multi-shell imaging can detect potentially relevant network changes in early MS.
Author Ciccarelli, Olga
Kanber, Baris
Ourselin, Sébastien
Collorone, Sara
Altmann, Daniel R
Clayden, Jonathan D
Charalambous, Thalis
Grussu, Francesco
Tur, Carmen
Cawley, Niamh
Barkhof, Frederik
Wheeler-Kingshott, Claudia Am Gandini
Prados, Ferran
Toosy, Ahmed T
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  givenname: Carmen
  orcidid: 0000-0003-1849-3184
  surname: Tur
  fullname: Tur, Carmen
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK
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  givenname: Francesco
  orcidid: 0000-0002-0945-3909
  surname: Grussu
  fullname: Grussu, Francesco
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK/Centre for Medical Image Computing, Department of Computer Science, University College London (UCL), London, UK
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  givenname: Ferran
  surname: Prados
  fullname: Prados, Ferran
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK/Translational Imaging Group, Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London (UCL), London, UK
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  givenname: Thalis
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  givenname: Sara
  orcidid: 0000-0003-1506-8983
  surname: Collorone
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  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK
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  givenname: Baris
  surname: Kanber
  fullname: Kanber, Baris
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK/Translational Imaging Group, Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London (UCL), London, UK
– sequence: 7
  givenname: Niamh
  surname: Cawley
  fullname: Cawley, Niamh
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK
– sequence: 8
  givenname: Daniel R
  surname: Altmann
  fullname: Altmann, Daniel R
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK/Department of Medical Statistics, London School of Hygiene and Tropical Medicine, University of London, London, UK
– sequence: 9
  givenname: Sébastien
  surname: Ourselin
  fullname: Ourselin, Sébastien
  organization: Translational Imaging Group, Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London (UCL), London, UK/School of Biomedical Engineering & Imaging Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
– sequence: 10
  givenname: Frederik
  surname: Barkhof
  fullname: Barkhof, Frederik
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK/Translational Imaging Group, Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London (UCL), London, UK/Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands/National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, UK
– sequence: 11
  givenname: Jonathan D
  surname: Clayden
  fullname: Clayden, Jonathan D
  organization: UCL Great Ormond Street Institute of Child Health, University College London (UCL), London, UK
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  givenname: Ahmed T
  surname: Toosy
  fullname: Toosy, Ahmed T
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK
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  givenname: Claudia Am Gandini
  surname: Wheeler-Kingshott
  fullname: Wheeler-Kingshott, Claudia Am Gandini
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, 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
– sequence: 14
  givenname: Olga
  surname: Ciccarelli
  fullname: Ciccarelli, Olga
  organization: Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, University College London (UCL), London, UK/National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, UK
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Issue 7
Keywords Diffusion-weighted imaging
multi-shell acquisitions
tractography
multi-shell multi-tissue constrained spherical deconvolution
clinically isolated syndrome
multiple sclerosis
Language English
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PublicationTitle Multiple sclerosis
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Snippet The potential of multi-shell diffusion imaging to produce accurate brain connectivity metrics able to unravel key pathophysiological processes in multiple...
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SubjectTerms Adult
Cognitive Dysfunction - diagnostic imaging
Cognitive Dysfunction - etiology
Cognitive Dysfunction - pathology
Diffusion Tensor Imaging - methods
Female
Gray Matter - diagnostic imaging
Gray Matter - pathology
Humans
Male
Middle Aged
Multiple Sclerosis - complications
Multiple Sclerosis - diagnostic imaging
Multiple Sclerosis - pathology
Nerve Net - diagnostic imaging
Nerve Net - pathology
Retrospective Studies
White Matter - diagnostic imaging
White Matter - pathology
Title A multi-shell multi-tissue diffusion study of brain connectivity in early multiple sclerosis
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