3rd MAGNIMS virtual meeting

Apologies sent by Chris, conflicting national meeting.

Mara asks for people to consider proposing new projects, since there are a limited number of new projects on the agenda currently.

Jaume shows the MAGNIMS website. Brief explanation of the MAGNIMS Project Tracker. Email with further details will be sent to members of the Steering Committee who are leaders of the different projects. They will receive the admin role of those particular projects and will be able to introduce other members of their centre to that role and thereafter introduce other members from other participating centres who are local keypersons for that particular project.The Project Tracker is now linked to the MAGNIMS website (accessible through https://www.magnims.eu ). This uses the same username and password. If you change username or password, it takes about one hour to update so you may briefly be unable to connect. However normally this is accessible straight away. Projects contain calendars, tasks, documents, etc.

Explanation of the procedures involved in the processing of each DTA (three documents –annex A, exhibit 1, exhibit 2-, one set for each data supplier). Important to make sure that the right person signs on behalf of each institution (sometimes PI, usually legal representative). Make also sure that the co-chairs sign the documents. All core and affiliate (except Paris) have accepted the agreement.Most centres have signed the Accession Document.Several questions on procedures, which transfers are allowed, etc.New affiliate centre Prague has to be added.

Title of the project: Towards a unified brain network model in multiple sclerosis: a multilayer coreness analysis of structural, diffusion, and resting-state functional MRI data – MAGNIMS PROJECT #27

Retrospective cross-sectional study on CIS, RRMS, SPMS, PPMS and HC using structural (3DT1, Flair), diffusion MRI, resting-state fMRI to correlate with clinical parameters (including cognition, which will be used to create composite scores). Initially: Naples, London and Amsterdam will contribute patients. Methods include use of these three modalities to produce a multilayer network which will be characterized through specific parameters and clinical correlations of such parameters will be tested by means of specific statistical tests. Hypothesis is that functional layers will moderate the impact of structural alterations on clinical parameters. Fellowship will begin on the 1st of June. An email with specific MRI and clinical data requested will be circulated among SC members.

Gerard Martí-Juan (Host: Barcelona) MAGNIMS PROJECT #28

Title of the project: The Virtual Brain: generative whole brain models in Multiple Sclerosis. The main aim of the project is to develop an automated pipeline for a virtual brain model of MS with the VIRTUAL BRAIN framework (https://www.thevirtualbrain.org/tvb/zwei). Parameters obtained in the creation of such models will be correlated with cognitive and disability parameters and connections between structural and functional changes and their clinical relevance will be explored. Initially, data from Milano, Hospital Clinic Barcelona, Mainz and Napoli will be collected; London has shown interest in participating. Protocol will be circulated using the tracker (3DT1, 3D-Flair, diffusion-weighted, resting-state fMRI). Start with generic model that has worked well for (other) neurodegenerative diseases.

Antonio Carotenuto (Host: Milan) MAGNIMS PROJECT #25

Title of the project: Network Centrality in Multiple Sclerosis (participating centres: Milan, Amsterdam, Rome, Naples). Some preliminary analyses (comparison between phenotypes, between cognitively preserved and impaired patients and regression analyses with EDSS) have been run with a restricted number of patients from a subgroup of centres. All analyses will be age, gender and centre adjusted. MRI data processing will be finished by end of April and the full cohort analyses will be run immediately after.

Monica Margoni (Host: Milan) MAGNIMS PROJECT #24

Title of the project: Exploring in-vivo brain myelin content in patients with multiple sclerosis through the T1/T2 ratio mapping: a multicentre study (participating centres: Milan, Amsterdam, London, Oxford, Barcelona). Baseline and follow-up data from 474 patients from 8 centres. T1/T2 ratio values have been obtained and from a small group of HC to show that this measure is stable. Variability of T1/T2 ratio between centres seems limited. Also values seem to be stable over time in healthy controls over 1 year. As this is a potential surrogate for myelin, focus has been put on corpus callosum, which is known to have different concentrations of myelin in different areas. However, results have not been consistent with CC myelin density. Rather than that, results are more congruent with T1/T2 ratios being a marker of dendrite density. Recent literature is also consistent with it. Clinical information is still in the collection state before full statistical analyses could be run on the whole sample. Suggestion to consider g ratio as well to see if it matches the observations better.

Lukas Haider (Host: London) MAGNIMS PROJECT #01

Title of the project: Dirty” Virchow-Robin Spaces in Controls and Multiple Sclerosis – Histological and Clinical Validation of a Novel MRI Feature –

In vivo study (RRMS vs HC) is already finished and ready to submit (data already presented at previous meetings). Clear distinction between HC and MS, many more lesions with dirty VRS in HC than MS. Pre/post-mortem study (80% reproducibility of VRS in vivo vs post-mortem – n=12). Awaiting more data from UK brain bank (10 HC & 10 MS patients). Work is still ongoing. Samples received and scanning now underway.

Rosa Cortese (Host: Siena; Home London Ciccarelli) MAGNIMS PROJECT #02

Title of the project: Towards a better understanding of MOG-Antibody-associated disease and new MAGNIMS MRI criteria – Data presented in previous meetings. An abstract to ECTRIMS 2021 will be soon circulated and the paper is about to be finalized.

COSMOS: aCcuracy Of central vein Sign in predicting Multiple sclerosis in nOn-typical preSentations (Nikos Evangelou, Jens Wuerfel, Massimo Filippi)

DECISIve – DiagnosE using the Central veInSIgn. A prospective diagnostic superiority studycomparing T2* MRI and lumbar puncture in patients presenting with possible Multiple Sclerosis: a multicentre study (Nikos Evangelou, Jens Wuerfel, Massimo Filippi). No further presentation from Nottingham on these projects. Clarifications are requested on their status. Should no response be received they shall be removed from the list.

(Frederik Barkhof; Olga Ciccarelli, Tarek Yousry, Olivia Goodkin, London) – MAGNIMS PROJECT #26

Machine learning method to predict chronological age with structural scans. Previous publication using 3D-T1. Present project tries to use same (and also advanced) methods on 3DFLAIR and compare to previous 3DT1 model. At present a healthy control dataset is being created.  A reminder of requested data is presented. Twelve centres have or will soon provide data. Discussion on availability of blood samples to correlate with body fluid biomarkers, particularly neurofilaments. Prague volunteered to participate.

(BrunoStankoff, Paris) – MAGNIMS PROJECT #23

Aim is to create a cortical demyelination index. Participating centres are Paris, Siena and Graz (Milano data was finally not used). Further aim was added last time – to see if EDSS at 5 years could be predicted. MTR-based classification of voxels; threshold determined based on randomized comparisons between MS and healthy controls. Inner and outer 25% of cortex was excluded; only central part analyzed. Statistical analyses have just started. Cortical de and remyelination are heterogeneous across patients. A mean of 4% of cortical voxels re and demyelinate over follow-up. No differences across phenotypes and treatment status. Longer disease duration is associated with a greater demyelination at baseline and developing over follow-up and lower remyelination over follow-up. Next step is to associate such changes with cortical volume loss. Cortical demyelination at baseline is not associated with cortical volume changes, but remyelination is associated with volume changes. EDSS change at five years have been used to associate with indices, with some significant results (e.g., higher demyelination at baseline is associated with greater probability of clinical progression – association with remyelination follows a more complex pattern). Once statistical analyses are finished, writing will start. Cortical atrophy assessed by FreeSurfer combined with Jacobian integration.

(Cristina Granziera, Jens Wuerfel, Ludwig Kappos) – MAGNIMS PROJECT #06

Still collecting data; a reminder of requested data is presented (at least one sequence to detect CLs and CVS plus conventional scans). Patients 18-80 years old; CIS, MS, NMOSD, and several other MS mimics.3T brain MRI with T1, T2/Flair, one of DIR/PSIR/MP2RAGE, and one of SWI/T2*. A total of 10 centres have committed to provide data (seven have already provided data). Sample includes 336 MS, 38 CIS, 62 NMOSD/MOGAD as well as mimics and HC (at least 10 each for centre). An overview of the different sequences received is presented and strategy for CLs and CVS detection is presented (including testing of automated pipelines).

Investigating their impact on emerging functional impairment (Sergiu Groppa, Mainz) – MAGNIMS PROJECT #10

A review of objectives and data requirements is presented. 1-year network changes impact on 5-year clinical disability. A total of 293 MS patients have been collected/committed from Mainz, Oslo, Barcelona, Bochum, London and Milano. Suggestions to consider only confirmed and sustained EDSS changes and include vascular risk factors and smoking in the predictive models.

(Daniel Rinker, Hanne Harbo, Oslo) – MAGNIMS PROJECT #12

A summary of current status is presented. London, Barcelona HUVH, Barcelona Clinic have sent/committed data. Preliminary results (38 cases) with some significant correlations with EDSS have been presented. An invitation to contribute more data is presented.

(Serena Ruggieri, Claudio Gasperini, Rome) – MAGNIMS PROJECT #13

Nine centres providing data and one more committed. A total of 1114 patients collected, but still lacking patients on some drugs (particularly teriflunomide and fingolimod). Statistical analyses will be performed trying to adjust for this unbalance. Different strategies to increase number of patients on such patients are discussed. Warning not to ask new centres for specific drugs but to send everything that they have to avoid bias.

(Paola Valsasina, Massimo Filippi, Mara Rocca, Milan) – MAGNIMS PROJECT #25

A summary of overall final results of this multifaceted project is presented. Two papers have been already published: cervical cord atrophy across phenotypes at baseline and over one-year follow up & SBM study of GM atrophy over baseline and follow-up. Recent analyses of cord VBM were presented in December (2nd virtual meeting) – paper has been recently submitted to Radiology. A further analysis on five year follow-up clinical data is planned with some centres already providing data (an abstract will be submitted to ECTRIMS this year).

(Christian Enzinger, Graz)

Brief recap by Stefan Ropele. Project has been completed. Paper draft will be circulated by Christian in the next few weeks.

(Àngela Vidal-Jordana, Barcelona) – MAGNIMS PROJECT #18

Design, hypothesis and objectives of this longitudinal study are reviewed. CIS in 6 months prior to inclusion. Complete visual pathway assessment, including OCT and VEP. An update of data collection is provided. Recruited was closed end 2020 – 5 centres with a total of 155 patients. Central reading of MRI data has finished recently and statistical analyses will start soon. Aim to submit to ECTRIMS.

(Sara Llufriu, HC Barcelona) – MAGNIMS PROJECT #20

A summary update of data collection is presented (8 centres with 467 MS patients – 339 with cognitive assessment and 202 longitudinal assessments, some with cognitive assessments as well). Progressive patients have been recently collected. Two centres have been recently included. Almost all MRI data received have been processed.

(Ilaria Boscolo, Massimiliano Calabrese, Verona) – MAGNIMS PROJECT #21

A brief update of design and objectives of the project is presented. Still collecting data from four centres (Verona, London, Bochum, Basel). Recruitment goal for RRMS and HC has been achieved, but still more PPMS patients are needed. Now 19 PPMS (goal was 30-40). 16 more PPMS have been scheduled in Verona until June 2021. Results will be presented in September in Rome.

o   Quantitative MRI towards clinical application in multiple sclerosis (Basel workshop December 2019) (Cristina Granziera, LK). Accepted, Brain.

o   Big Data and Deep Learning: New Avenues for MRI in MS? (Amsterdam workshop 2018) (HV).

Major revisions submitted to Neurology.

o   MAGNIMS Guidelines (Graz workshop April 2019) (AR). Accepted, Lancet Neurology.

Open access will be provided for free by Lancet Neurology.

o   Harmonization on MRI data in multicentre studies (Siena workshop November 2018) (NDS).

Paper rewritten. New version will be sent to Alex next week, then to other co-authors.

o   Atypical MS (Graz workshop April 2019) (CE).

Update by Michael Khalil. Contacted NRN editor in chief about the delay and still interested. Revisit literature, contact contributors, submit in autumn 2021.

o   Comparison of the 2017 and 2010 revisions of the McDonald criteria in patients with CIS suggestive of MS: a multicentre study (Massimo Filippi, Mara Rocca). Reviewer comments received (minor), Neurology.

o   Quantification of cervical cord cross-sectional area: which software? which vertebral level? spinal cord or brain MRI? A multi-center comparison on a healthy volunteer (Carsten Lukas, Bochum) – Submitted to Neuroimage Clinical. Was not sent for review, proposal to send to Frontiers in Neurology.

o   Characterizing 1-year development of cervical cord atrophy across different MS phenotypes: a voxel-wise, multicenter analysis (Paola Valsasina, Massimo Filippi, Mara Rocca). Under Review, Radiology.

o   Prognosis of a second clinical event from baseline MRI in patients with a CIS. A multicenter study using a machine learning approach (Deborah Pareto). Rejected from NeuroImage Clinical and AJNR. Will now try MSJ.

o   Development and evaluation of a manual segmentation protocol for deep grey matter in multiple sclerosis: towards accelerated semi-automated references (de Sitter/Burggraaff). Accepted by Neuroimage Clinical.

o   Large-scale Assessment of Brain Volume Changes in Healthy Individuals (Marco Battaglini, Nicola De Stefano, Siena).

Abstract for ECTRIMS will be circulated. Paper will be written afterwards

o    Characterization of MS-related grey matter atrophy in relevant networks of the human brain: a data-driven, multivariate analysis using source-based morphometry (Mara Rocca, Massimo Filippi, Milan).Published, Neurology

o    Structural and functional connectivity (London workshop June 2017) (Declan Chard).Published, Nature Reviews Neurology.

o    Manual and automated tissue segmentation confirm the impact of thalamus atrophy on cognition in Multiple Sclerosis: a multicenter study (Burggraaff).Published, Neuroimage Clinical.

o    FLAIR-only joint volumetric analysis of brain lesions and atrophy in clinically isolated syndrome (CIS) suggestive of multiple sclerosis (Olivia Goodkin).Published, Neuroimage Clinical.

o    Meeting pipeline postponed – 36th meeting 9-10 of September 2021, in Rome (depending on actual COVID situation). Workshop defined on:  The role of MRI to assess MS prognosis: what we know and what we need to know.

Unclear whether this is possible in September. Cancellation options should be arranged in case a venue is booked. Close contact within MAGNIMS and with Rome institution necessary to update our plans as time progresses. Suggestion to plan both as a virtual and a face-to-face meeting. Hybrid meeting could be difficult in terms of having the discussions.

o   Meeting pipeline postponed – 37th meeting 5-6th May 2022, in Oxford (depending on actual COVID situation). Workshop defined on: Identifying imaging features of MOGAD and differentiating it from MS.

o   SC TC Meeting May 2021.

FINALLY: Just a kind reminder to all presenters to send Jaume their slides for website upload. Many thanks!

jsastre-garriga@cem-cat.org

Thanks to Ludwig Kappos, Cristina Granziera and team for organising the conference!