Article Text

other Versions

Download PDFPDF
Original research
Exploring in vivo multiple sclerosis brain microstructural damage through T1w/T2w ratio: a multicentre study
  1. Monica Margoni1,
  2. Elisabetta Pagani1,
  3. Alessandro Meani1,
  4. Loredana Storelli1,
  5. Sarlota Mesaros2,
  6. Jelena Drulovic2,
  7. Frederik Barkhof3,4,5,
  8. Hugo Vrenken3,4,
  9. Eva Strijbis4,
  10. Antonio Gallo6,
  11. Alvino Bisecco6,
  12. Deborah Pareto7,
  13. Jaume Sastre-Garriga8,
  14. Olga Ciccarelli5,
  15. Marios Yiannakas5,
  16. Jacqueline Palace9,
  17. Paolo Preziosa1,10,
  18. Maria A Rocca1,10,11,
  19. Massimo Filippi1,10,11,12,13
  20. MAGNIMS Study Group
  1. 1Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
  2. 2Clinic of Neurology, Faculty of Medicine, University of Belgrade, Beograd, Serbia
  3. 3Radiology and Nuclear Medicine, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  4. 4MS Center, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
  5. 5NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, London, UK
  6. 6Department of Advanced Medical and Surgical Sciences, and 3T MRI-Center, University of Campania "Luigi Vanvitelli", Naples, Italy
  7. 7Section of Neuroradiology, Department of Radiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
  8. 8Department of Neurology/Neuroimmunology, Multiple Sclerosis Centre of Catalonia, Hospital Universitari Vall d'Hebron, Barcelona, Spain
  9. 9Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  10. 10Neurology Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy
  11. 11Vita-Salute San Raffaele University, Milano, Italy
  12. 12Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
  13. 13Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy
  1. Correspondence to Massimo Filippi, Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy; filippi.massimo{at}hsr.it

Abstract

Objectives To evaluate white matter and grey matter T1-weighted (w)/T2w ratio (T1w/T2w ratio) in healthy controls and patients with multiple sclerosis, and its association with clinical disability.

Methods In this cross-sectional study, 270 healthy controls and 434 patients with multiple sclerosis were retrospectively selected from 7 European sites. T1w/T2w ratio was obtained from brain T2w and T1w scans after intensity calibration using eyes and temporal muscle.

Results In healthy controls, T1w/T2w ratio increased until 50–60 years both in white and grey matter. Compared with healthy controls, T1w/T2w ratio was significantly lower in white matter lesions of all multiple sclerosis phenotypes, and in normal-appearing white matter and cortex of patients with relapsing-remitting and secondary progressive multiple sclerosis (p≤0.026), but it was significantly higher in the striatum and pallidum of patients with relapsing-remitting, secondary progressive and primary progressive multiple sclerosis (p≤0.042). In relapse-onset multiple sclerosis, T1w/T2w ratio was significantly lower in white matter lesions and normal-appearing white matter already at Expanded Disability Status Scale (EDSS) <3.0 and in the cortex only for EDSS ≥3.0 (p≤0.023). Conversely, T1w/T2w ratio was significantly higher in the striatum and pallidum for EDSS ≥4.0 (p≤0.005). In primary progressive multiple sclerosis, striatum and pallidum showed significantly higher T1w/T2w ratio beyond EDSS=6.0 (p≤0.001). In multiple sclerosis, longer disease duration, higher EDSS, higher brain lesional volume and lower normalised brain volume were associated with lower lesional and cortical T1w/T2w ratio and a higher T1w/T2w ratio in the striatum and pallidum (β from −1.168 to 0.286, p≤0.040).

Conclusions T1w/T2w ratio may represent a clinically relevant marker sensitive to demyelination, neurodegeneration and iron accumulation occurring at the different multiple sclerosis phases.

  • multiple sclerosis
  • MRI
  • T1w/T2w-ratio

Data availability statement

Data are available on reasonable request. The dataset used and analysed during the current study are available from the corresponding author on reasonable request.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available on reasonable request. The dataset used and analysed during the current study are available from the corresponding author on reasonable request.

View Full Text

Footnotes

  • Correction notice This article has been corrected since it first published. Eva Strijbis has been added as author, guarantors have been added to the contributors section.

  • Collaborators The MAGNIMS Study Group (https://www.magnims.eu) is a group of European clinicians and scientists with an interest in undertaking collaborative studies using MRI methods in multiple sclerosis, independent of any other organisation and is run by a Steering Committee whose members are F. Barkhof (Amsterdam, London), O. Ciccarelli (London), N. de Stefano (Siena), C. Enzinger (Graz, Co-Chair), M. Filippi (Milan), C. Gasperini (Rome), L. Kappos (Basel), J. Palace (Oxford), M.A. Rocca (Milan, Co-Chair), À. Rovira (Barcelona), J. Sastre-Garriga (Barcelona), H. Vrenken (Amsterdam) and T. Yousry (London). The members of the MAGNIMS Study Group Steering Committee have reviewed, revised and approved the submitted paper.

  • Author Contributors Concept and design, guarantors: Filippi, Rocca. Acquisition, analysis or interpretation of data: Margoni, Pagani, Meani, Storelli, Mesaros, Drulovic, Barkhof Vrenken, Gallo, Bisecco, Pareto, Sastre-Garriga, Ciccarelli, Yiannakas, Palace, Rocca, Filippi. Drafting of the manuscript: Margoni, Pagani, Meani, Storelli, Preziosa, Rocca, Filippi. Critical revision of the manuscript for important intellectual content: Mesaros, Drulovic, Barkhof Vrenken, Gallo, Bisecco, Pareto, Sastre-Garriga, Ciccarelli, Yiannakas, Palace. Statistical analysis: Meani. Supervision: Filippi.

  • Competing interests M. Margoni reports grants and personal fees from Sanofi Genzyme, Merck Serono, Novartis and Almiral. She was awarded a MAGNIMS-ECTRIMS fellowship in 2020. E. Pagani received speakers’ honoraria from Biogen Idec. A. Meani received speakers’ honoraria from Biogen Idec. L. Storelli received speakers’ honoraria from Biogen Idec. She is supported by a senior research fellowship FISM—Fondazione Italiana Sclerosi Multipla—cod. 2019/BR/009 and financed or co-financed with the ‘5 per mille’ public funding. S. Mesaros has received travel funding from Merck, Bayer Schering, Medis and Genzyme Sanofi; has received speakers’ honoraria from Merck, Novartis, Medis, Sanofy Genzyme, Roche, Hemofarm. J. Drulovic received speaker’s honoraria from Merck Serono, Bayer, Teva, Genzyme Sanofi, Medis, Roche, Hemofarm and Novartis; and has also received research grant support from the Ministry of Education, Science, and Technological Development of the Republic of Serbia (project 200110). F. Barkhof acts as a consultant to Biogen-Idec, Janssen, Bayer, Merck, Roche, Novartis, IXICO, and Combinostics; he has received sponsorship from EU-H2020, Dutch MS research foundation, NIHR, EU-IMI, Biogen and GE Heatlthcare. H. Vrenken has received research grants from Merck Serono, Novartis and Teva, speaker honoraria from Novartis and consulting fees from Merck Serono; all funds paid directly to his institution. A. Gallo received speaker and consulting fees from Biogen, Sanofi-Genzyme, Merck Serono and Teva. A. Bisecco received speaker’s honoraria and/or compensation for consulting service and/or speaking activities from Biogen, Roche, Merck, Celgene, Coloplast and Genzyme. D. Pareto has received speaking honoraria from Novartis and Sanofi-Genzyme and a research contract from Biogen Idec. J. Sastre-Garriga declares grants and personal fees from Genzyme, Biogen, Celgene, Merck, Bayer, Biopass, Novartis and Roche outside the submitted work; Dr Sastre-Garriga is Associate Editor of Multiple Sclerosis Journal and Scientific Director of Revista de Neurologia, outside the submitted work. O. Ciccarelli receives grant support from the UK MS Society, National MS Society, NIHR, EU-H2020, Spinal Cord Research Foundation, Rosetrees Trust, Progressive MS Alliance, Bioclinica and GE Neuro. She received speaker’ honoraria from Biogen and Merck-Serono and is a consultant for Novartis. She is Deputy Editor of Neurology, for which she receives an honorarium. M. Yiannakas has nothing to declare. J. Palace has received support for scientific meetings and honorariums for advisory work from Merck Serono, Novartis, Chugai, Alexion, Roche, Medimmune, Argenx, UCB, Mitsubishi, Amplo, Janssen. Grants from Alexion, Roche, Medimmune, Amplo Biotechnology. Patent ref P37347WO and licence agreement Numares multimarker MS diagnostics Shares in AstraZenica. Acknowledges Partial funding by Highly specialised services NHS England. P. Preziosa received speakers’ honoraria from Biogen Idec, Novartis, Bristol, Myers Squibb, Genzyme, Roche and Excemed. M.A. Rocca received speakers’ honoraria from Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche and Teva, and receives research support from the MS Society of Canada and Fondazione Italiana Sclerosi Multipla. M. Filippi is Editor-in-Chief of the Journal of Neurology and Associate Editor of Radiology, Human Brain Mapping and Neurological Sciences; received compensation for consulting services and/or speaking activities from Almiral, Alexion, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck-Serono, Novartis, Roche, Sanofi, Takeda and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi, Almiral, Eli Lilly, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.