1st MAGNIMS virtual meeting

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Date/Time
Date(s) - 12/06/2020
3:00 pm - 6:00 pm


1st Virtual Meeting

12th June 2020

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12thJune 2020

15.00 pm-18.40

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Attendants list: via Web administration, 84 attendants

o   Apologies: Nicola de Stefano

 

Welcome and introduction – M. Rocca, C. Enzinger

Mara Rocca thanks Claudio for organising the meeting – important to keep flow in MAGNIMS projects. Hugo Vrenken taking care of the chat.  Thanks from CE to Alex Rovira for stepping in as co-chair during COVID-crisis and to Mara Rocca for taking main responsibility for MAGNIMS issues and current meeting

 

MAGNIMS/ECTRIMS Fellowships

2020 ECTRIMS/MAGNIMS fellowships – 4 proposals received, high-quality, external reviewers and internal MAGNIMS without COI

o   Antonio Carotenuto (Host: Milan), title of the project: Network Centrality in Multiple Sclerosis (participating centers: Milan, Amsterdam, Rome, Naples): Download file attached

  • from Naples, supervised by MR; presentation online by Antonio. Presentation of the aims of the project and working plan: fMRI, graph theory and voxel-wise approaches; large cohort of MS patients (n=800) and HC (n=420) currently from 4 cohorts: Milan, Amsterdam, Rome, Naples. Possibility to increase the numbers. Aims: evaluation of degree and eigenvector centrality abnormalities in MS and associations with clinical/NPS variables
  • EC submitted for core center; now other centres will be involved (DTA)
  • General aspects:Project postponed, September 2020 start appears realistic

o   Monica Margoni (Host: Milan), title of the project: Exploring in-vivo brain myelin content in patients with multiple sclerosis through the T1/T2 ratio mapping: a multicentre study (data from the MAGNIMS cord project: Milan, Amsterdam, London, Oxford, Barcelona): Download file attached

  • from Padua, supervised by MF; presentation online by Monica. Presentation of the aims of the project and working plan. In-vivo MRI method for studying tissue myelin content of cerebral WM and GM by quantifying T1/T2w ratio; easy to implement in clinical settings; post-mortem correlations established (e.g. Nakamura Ann Neurol 2017, Righart Ann Neurol 2017). Differences between T1/T2w ratio and MTR (Pareto AJNR 2020); large cohort of MS patients and HC from 3T data already available from recent collaborative MAGNIMS cord projects; 385 MS patients (216 RRMS, 31 CIS, 42 PPMS and 96 SPMS) and 161 HC. Aims: to compare T1/T2w ratio from different clinical MS phenotypes in comparison to HC; pipeline for analyses set (method by Ganzetti, Front Hum Neurosci 2014); comparisons between phenotypes and correlations between variables. Longitudinal data available for 168 MS patients and 34 HC
  • EC submitted for core center; now other centres will be involved (DTA)
  • General aspects:Project postponed, September 2020 start appears realistic

2019 MAGNIMS/ECTRIMS Fellowships 

o   Lukas Haider (Host: London), title of the project: Dirty” Virchow-Robin Spaces in Controls and Multiple Sclerosis – Histological and Clinical Validation of a Novel MRI Feature Download file attached

  • Collected in-vivo data from 34 HC, 31 MS, 30 AQP4 and 30 MOG. 1432 lesions analyzed. Radiological rating for DVRS lesions; DVRS association with age; some correlation in RRMS; absent in AQP4; percentage of lesions with DVRS: HC 87%, RRMS 42%, 55% AQP4, 48% MOG; lesion formation around VRS in 87% of all unspecific/small WML of HC; frequency increases with age in controls and RRMS; currently writing up (ECTRIMS abstract, paper)
  • Histological evaluation: cases with clinical MRI closely prior to death that went to autopsy (n=13) – MRI depicted VRS remain stable during death and fixation; writing up ECTRIMS abstract and manuscript

o   Rosa Cortese (Host: Siena), title of the project: Towards a better understanding of MOG-Antibody-associated disease and new MAGNIMS MRI criteria Download file attached

  • 30 MOGAD; 30 AQP4-NMOSD, 31 RRMS, 34 HC; scanning slowed down by COVID crisis
  • Possible other contributing centres? Total number ca 260; Last deadline to send data: 15 July 2020! See presentation
  • MOGAD onset most often unilateral ON onset; followed by bilateral ON; NMOSD: mostly unilateral ON and then SC
  • WM lesions in 100% MS, 79% NMOSD; 57% MOGAD; cortical lesions >>in RRMS compared to AQP4 and MOG; brain and cervical cord atrophy rates compared (all groups lower than HC)
  • Next steps: complete data collection, define differential lesion characteristics (Bulls-eye representation of lesion frequency)
  • Waiting for EC and DTA

 

MAGNIMS teaching activities 2020-21

  • NAIMS-MAGNIMS Workshop „Ultra-high Field MRI in Multiple Sclerosis“ July 14-17, 2020 Reykjavik, Iceland: Postponed to next year (summer 2021)
  • ECTRIMS/ACTRIMS 2020 Washington D. C., 9-12 September 2020: Only one proposal submitted (late), in collaboration with NAIMS and CMSC on MRI guidelines (1 Chair (CE, together with David Lee NAIMS); and 2 speakers from MAGNIMS – AR and MW); will be held virtually
  • ECTRIMS MAGNIMS joint teaching winter school 2020: Postponed to next year – great programme, still active
  • Virtual 6th EAN congress Paris (CE & MF):  Practical (hands-on) course in Paris on MS lesion identification (Speakers: Granziera, Enzinger, Celine Louape, Chair: Filippi,) – well attended (n=400), well received
  • ESNR: Plans for 2020 (TY): Round table in Lisbon on MRI guidelines (to be confirmed by TY) – virtual component does not contain round table discussion
  • ECTRIMS 2021 Vienna 13-15 October: CE Co-Chair National Program Committee – see programme; draft programme, many MAGNIMS proponents
  • EAN 2021 Vienna 19-22 June: CE Member National Program Committee; limited DOF; major hub EAN Panel NI in collaboration with other panels eg. MS (MF) and societies (ESNR); MOU underway; now definite proposals

 

New projects

o   Data-driven analysis of (neurodegeneration) subtypes in multiple sclerosis (Frederik Barkhof; Viktor Wottschel; Olga Ciccarelli, Amsterdam, London) – presented by FB, slides by VW; Event-based modelling (EBM) method as used in Brain paper has the disadvantage to postulate all MS patients undergo same evolution (paths could be different); SuStaIn – extension of EBM to identify multiple paths of progression: identify a sequence of events, identify clusters of subjects sharing a pathway; work plan: use MAGNIMS data for this (Arman and Viktor analyses: 1429 subjects in total; many analyses done) – and Amsterdam cohort (n=426) for validation. Preliminary results: model suggest 3 inherent subtypes of atrophy – occipito-temporal early, brain stem late; other brain stem early; ventricle/occipital onset; re-fitting model with AMS data gives similar but not identical clusters; test AMS data on MAGNIMS based model; correlation with clinical measures ongoing; Questions: CE clinical phenotypes – not done yet. AG WM lesions? MR how explain occipital data? Not clear; more than half 1.5 T; DTA to be verified. Download file attached

o   A multi-centric study of the combined sensitivity and specificity of cortical lesions and central vein sign for MS diagnosis and differential diagnosis (Cristina Granziera, Jens Wuerfel, Ludwig Kappos) – presented by Cristina, already presented in Basel; to assess value of combined detection of CLs and CV; inclusion criteria: MS, CIS, NMOSD, vasculitis, migraine, CSVD with 3T brain MRI; at least 10 MS and 10 MIMICS per center; automatic (CVSnet) and manual detection of central vein lesions (3 independent investigators); automatic (3D U-Net) and manual detection for cortical lesions (3 independent investigators) – participating centres see presentation, current aim 616 (317 MS), 103 HC; EC done. Call for participation; Q: FB dementia could be included; subjects with ≥2 lesions are requested; 3 raters Download file attached

o   COSMOS: aCcuracy Of central vein Sign in predicting Multiple sclerosis in nOn-typical preSentations (Nikos Evangelou, Jens Wuerfel, Massimo Filippi); presented by Afagh Garjani – changed acronym to COSMIC – pragmatic single-group prospective and retrospective; is central vein sing on 3T T2* or SWI more accurate than unpaired CSF-OCBs in prediction of MS; prospective. Inclusion criteria:  atypical CIS presentation, RIS, typical CIS older than 65, clinical typical but MRI atypical; lumbar puncture and MRI (T2* or SWI) acquired within 12 weeks apart one another; clinical follow-ups every 6 months (6-12-18 months). The study will stop at 30mths after start; retrospective: review of diagnosis. Discussion regarding the inclusion of RIS. Revised protocol needs to be send to SC after Basel. Download file attached

o   DECISIve – DiagnosE using the Central veInSIgn. A prospective diagnostic superiority study comparing T2* MRI and lumbar puncture in patients presenting with possible Multiple Sclerosis: a multicentre study (Nikos Evangelou, Jens Wuerfel, Massimo Filippi): Chris Allen presentation; protocol unchanged after Basel meeting, open in UK, but paused due to COVID-19; asks for other centres to participate; single typical event consistent with CIS OR one objectively demonstrable event; 18-65 subjects with typical CIS not already fulfilling 2017 Criteria -> research MRI scan, LP -> routine clinical care for 18mths. Q AR will you accept retrospective data? NO. Q HV datasharing process? All hospitals reviewing. Download file attached

o   Deep grey matter segmentation reference and challenge on longitudinal data (Hugo Vrenken): Amsterdam, Siena, Barcelona, Oxford, Oslo, Lindon, Rome; Boston – Alexandra de Sitter left, finished her thesis, slowed down as no immediate replacement available; MRI sequences needed: 3D T1 and 3D FLAIR – longitudinal with one year in between. Asks for more data. Q LK: What is DGM – A thalamus, Hc – LK e.g. doubts thalamus, no clear definition. Circulate final project. Download file attached

 

 

Updates on planned and on-going projects

o   Prognostic value of longitudinal network dynamics – Investigating their impact on emerging functional impairment (Sergiu Groppa, Mainz) – longitudinal study, CIS and RRMS with disease duration less than 5yrs; patients remaining stable and those who worsen needed; currently London, Oslo, Barcelona 2x, Bochum; invitation for further contributions. DTA approval needed. Q only 3T data? Yes. Download file attached

o   Restriction spectrum imaging as supplementary early demyelination detection technique (Daniel Rinker, HanneHarbo, Oslo). Update on Basel presentation. Any multishell would do, longitudinal data needed (1y FU). Technical data need to be resent. Suggestion (MR): acceleration of procedures for EC and DTA. Download file attached

o   Assessing treatment response to oral drugs for MS in real world setting (Serena Ruggieri, Claudio Gasperini, Rome). Presented by Serena Ruggieri. Retrospective study. Outcomes: 6mth CDP, switch. Data from Barc, London, Mainz, Milan, Naples, Nottingham, Rome, Siena – total 787 MS patients. Most on DMF (n=422), then Fingolimod (278) and Teri (n=87). Notification to local EC (no further procedures required in Rome). DTA to be defined. Download file attached

o   Comparison of the 2017 and 2010 revisions of the McDonald criteria in patients with CIS suggestive of MS: a multicentre study (Paolo Preziosa, Massimo Filippi, Alex Rovira). Presented by Paolo: current data collection CIS n=945, collection and update of clinical, CSF and MRI data completed. Next steps: presentation of analyses for ECTRIMS planned, EC and DTA. Download file attached

o   Spinal cord atrophy in MS – comparison of different approaches to enhance SC multicentre analysis (Carsten Lukas, Bochum). One slide update, 1st draft of 1st part of study circulated among SC (single-subject study) – asks for comments; part 2: MS-multiple subjects study – additional GBSI analysis for longitudinal examination (asked for in Basel) pending. Download file attached

o   Whole-cord and voxel-based assessment of cervical cord atrophy in MS patients with different clinical phenotypes: a multi-centre assessment (Paola Valsasina, Massimo Filippi, Mara Rocca, Milan). Presented by Paola: Paper in Neurology last year; collection of long-term 5yr FU data is ongoing; future steps: complete collection of 5-year FU clinical data and perform statistics; voxel-wise analysis: performed for 3 centers (Milan, Lugano and Mannheim): clusters of atrophy in MS patients compared to healthy controls. Longitudinal regional atrophy progression only in MS patients and not in HC. Future steps: pre-process data from remaining sites (London, Barcelona, Oxford, Naples) and finalize results. EC and DTA will be circulated according to new model. Download file attached

o   Crowd-sourced lesion segmentation (Hugo Vrenken, Amsterdam) – already shown

o   Periventricular white matter abnormalities and cortical thinning (Christian Enzinger, Graz). Data from Graz, London, Amsterdam, Barcelona, Milan, Rome, Paris, n = 898 subjects including CIS/RRMS/SPMS/PPMS; analyses for missing figure now finished (correlation between cortical thinning and periventricular lesions strongest in RRMS, also present in CIS, less strong in SP and missing in PPMS); currently paper drafting, will be circulated next month. DTA to be verified.

o   Study of the visual pathway in patients presenting with a CIS (Jaume Sastre-Garriga, Barcelona). A Vidal-Jordana; 112 patients included; data collection closed at this point. Next steps: performing analyses. Download file attached

o   Structural connectivity in MS phenotypes (Sara Llufriu, HC Barcelona) – 6 centres have provided MRI + clinical data; 467 MS patients (220 longitudinal), HB n=91. RR 262, CIS 38, SP 44, PP 7. Heterogeneity of data including site variability, harmonization done using ComBat (but this requires HC data not available in 2 centres). Need to increase progressive phenotypes. DTA already established. Download file attached

o   Non-invasive perfusion patterns in MS phenotypes (Ilaria Boscolo, Massimiliano Calabrese, Verona). Presented by Ilaria: 4 centres acquiring data (Verona, Basel, London, Bochum). Visual assessment and segmentation of cortical lesions; segmentation automated T2LL; ASL Data – 2D EPI pCASL  68 subjects analysed from three centres: Verona, London, Bochum. Morphometry results. Voxel based quantification of group maps, suggests global reduction of perfusion in patients. Ongoing: intensity normalisation for sequence bias field to reduce variability. Max Calabrese: need more patients and HC; DTA underway. Discussion on standardization among centers, magnitude of effect and variability of ASL and atrophy measures between sites. Download file attached

o   The role of automated lesion segmentation in CIS: Validation on multi-centre, multi-vendor MAGNIMS cohort at 1.5 and 3T (Frederik Barkhof, Olga Ciccarelli, Amsterdam, London)- update by FB, Paper about to be circulated.

o   Cortical remyelination in multiple sclerosis: a magnetization transfer ratio multicenter study (Bruno Stankoff, Paris). Update by Benedetta: 97 patients, 69 HC. Data from Graz, Paris, Siena, Milan. Progressive MS patients needed. FSL analyses started from scratch to make use of all data. Partial volume correction. Voxel classification (demyelinated, remyelinated) and indices of myelin content change for cortex and white matter. High heterogeneity in indices of myelin content change – even in patients with same phenotype. Correlations of cortical demyelination indices with EDSS changes. Significant only in CIS and RRMS, but low number of PMS patients. Next steps: cognitive data; especially PMS needed! DTA underway. Download file attached

 

 

Publication status

  • Review papers
  • Structural and functional connectivity (London workshop June 2017) (Declan Chard). Submitted, Nature Reviews Neurology
  • Big Data and Deep Learning: New Avenues for MRI in MS? (Amsterdam workshop 2018) (HV) – circulated today (2nd time for co-authors); asks for input on where to submit
  • Harmonization on MRI data in multicentre studies (Siena workshop November 2018) (NDS) – preliminary version circulated
  • Atypical MS (Graz workshop April 2019) (CE) – delayed, paper structure including request for contributions will follow over summer
  • MAGNIMS Guidelines (Graz workshop April 2019) (AR) Two papers submitted to the Lancet Neurology, Joint with NAIMS and CMSC
  • o   Quantitative MRI towards clinical application in multiple sclerosis (Basel workshop December 2019) (Cristina Granziera, LK). Submitted, Nature Reviews Neurology

 

  • Project papers
  • The role of pontine lesion location in differentiating multiple sclerosis from vascular risk factor related small vessel disease (Ruth Geraldes/Jackie Palace, Oxford) – short-report pontine lesion location sent to MSJ; comments sent back – revision
  • Predicting clinical conversion of CIS patients to MS using PRONTO (Deborah Pareto) – draft ready (results bad, accuracy 50%, no pattern identified to separate cohorts), will be circulated soon. DTA needed to be safe now. Download file attached
  • Development and evaluation of a manual segmentation protocol for deep grey matter in multiple sclerosis: towards accelerated semi-automated references (de Sitter/Burggraaff) – Circulated among co-authors Download file attached
  • Manual and automated tissue segmentation confirm the impact of thalamus atrophy on cognition in Multiple Sclerosis: a multicenter study (Burggraaff) – Submitted Neuroimage Clinical
  • Reduced accuracy of MRI deep grey matter segmentation in multiple sclerosis: An evaluation of four automated methods against manual reference segmentations in a multi-center cohort (de Sitter) – Working on revisions for Journal of Neurology
  • 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)  – Submitted, Neurology
  • Large-scale Assessment of Brain Volume Changes in Healthy Individuals (Marco Battaglini, Nicola De Stefano, Siena) – To be circulated among co-authors; Marco: drafting two papers, will be send before next MAGNIMS meeting
  • 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 – C. Lukas – Circulated among authors

 

  • Recently Published papers
  • MRI changes in MS with vascular disease additive or interactive: an age matched study of MS with and without vascular risk factors and vascular controls (Ruth Geraldes/Jackie Palace, Oxford) –Published, JNNP
  • The central vein sign in MS revisited at 3T MRI in a multi-center MAGNIMS study (T Sinnecker, J Würfel) – Published, JAMA Neurology
  • Improving longitudinal spinal cord atrophy measurements in multiple sclerosis using the generalised boundary shift integral (M Moccia, F Barkhof) – Published, Annals of Neurology
  • Effect of facial features removal on outcome measures (de Sitter) –Published, European Radiology
  • Individual prediction of clinically definitive MS in patients presenting with clinically isolated syndrome using machine learning (Viktor Wottschel, Olga Ciccarelli) – Published, Neuroimage Clinical
  • Clinically relevant cranio-caudal patterns of cervical cord atrophy evolution in MS (Mara Rocca, MassimoFilippi) – Published, Neurology
  • Single-subject structural cortical networks in clinically isolated syndrome (Collorone, Ciccarelli, Toosy) – Published, MSJ
  • Brain age in MS using machine learning (Raffel, Nicholas, Ciccarelli, London) – Published, Annals of Neurology
  • Value of 3T Susceptibility-Weighted Imaging in the Diagnosis of Multiple Sclerosis. (Clarke MA Rovira A) (ECTRIMS_MAGNIMS fellowship), Published in Am J Neuroradiol. 2020
  • Lifespan Normative Data on Rates of Brain Volume Changes – Battaglini – Published, Neurobiol Aging
  • Dynamic functional network connectivity and cognition (Alessandro D’Ambrosio, Mara Rocca, Massimo Filippi) – Published MSJ
  • Workshop – Brain atrophy in clinical practice 2016 (Barcelona) (JSG) – Published, Nature Reviews Neurology

 

Next MAGNIMS meetings: 

  • Meeting pipeline postponed – 36th meeting 25th-26thMarch 2021 Rome (CG)