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Original research
Thalamic atrophy measured by artificial intelligence in a multicentre clinical routine real-word study is associated with disability progression
  1. Robert Zivadinov1,2,
  2. Niels Bergsland1,
  3. Dejan Jakimovski1,
  4. Bianca Weinstock-Guttman3,
  5. Ralph H B Benedict3,
  6. Jon Riolo4,
  7. Diego Silva4,
  8. Michael G. Dwyer1,2
  9. On behalf of the DeepGRAI Registry Study group
    1. 1Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA
    2. 2Center for Biomedical Imaging at Clinical and Translational Science Institute, University of Buffalo, State University of New York, Buffalo, New York, USA
    3. 3Jacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, New Jersey, USA
    4. 4Bristol Myers Squibb, New Jersey, USA
    1. Correspondence to Dr Robert Zivadinov, Department of Neurology, University at Buffalo, Buffalo NY 14203, New York, USA; Rzivadinov{at}bnac.net

    Abstract

    Background The thalamus is a key grey matter structure, and sensitive marker of neurodegeneration in multiple sclerosis (MS). Previous reports indicated that thalamic volumetry using artificial intelligence (AI) on clinical-quality T2-fluid-attenuated inversion recovery (FLAIR) images alone is fast and reliable.

    Objective To investigate whether thalamic volume (TV) loss, measured longitudinally by AI, is associated with disability progression (DP) in patients with MS, participating in a large multicentre study.

    Methods The DeepGRAI (Deep Grey Rating via Artificial Intelligence) Registry is a multicentre (30 USA sites), longitudinal, observational, retrospective, real-word study of relapsing-remitting (RR) MS patients. Each centre enrolled between 30 and 35 patients. Brain MRI exams acquired at baseline and follow-up on 1.5T or 3T scanners with no prior standardisation were collected. TV measurement was performed on T2-FLAIR using DeepGRAI, and on two dimensional (D)-weighted and 3D T1-weighted images (WI) by using FMRIB’s Integrated Registration and Segmentation Tool software where possible.

    Results 1002 RRMS patients were followed for an average of 2.6 years. Longitudinal TV analysis was more readily available on T2-FLAIR (96.1%), compared with 2D-T1-WI (61.8%) or 3D-T1-WI (33.2%). Over the follow-up, DeepGRAI TV loss was significantly higher in patients with DP, compared with those with disability improvement (DI) or disease stability (−1.35% in DP, −0.87% in DI and −0.57% in Stable, p=0.045, Bonferroni-adjusted, age-adjusted and follow-up time-adjusted analysis of covariance). In a regression model including MRI scanner change, age, sex, disease duration and follow-up time, DP was associated with DeepGRAI TV loss (p=0.022).

    Conclusions Thalamic atrophy measured by AI in a multicentre clinical routine real-word setting is associated with DP over mid-term follow-up.

    • MULTIPLE SCLEROSIS
    • CLINICAL NEUROLOGY

    Data availability statement

    All data relevant to the study are included in the article or uploaded as online supplemental information. N/A.

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as online supplemental information. N/A.

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    Footnotes

    • Collaborators Myassar Zarif and Mark Gudesblatt, Comprehensive Multiple Sclerosis Care Center, Patchogue, NY, USA, Mitch Freedman, Raleigh Neurology, Raleigh, NC; Samuel Hunter, Advanced Neurosciences Institute, Franklin, TN; Stanley Cohan, Providence Brain and Spine Institute, Portland, OR; Keith Edwards, MS Center of NE New York, Latham, NY; Brian Steingo, Infinity Clinical Research, LLC, Sunrise, FL; Rana Zabad, University of Nebraska Medical Center, Omaha, NE; Matthew Baker, Collier Neurologic Specialists, Naples, FL; Martin Belkin, Michigan Institute for Neurological Disorders (MIND), Farmington Hills, MI; Pavle Repovic, Swedish Neuroscience Institute, Seattle, WA; Amir Mazhari, Dent Neurology, Buffalo, NY, Abby Chase, Saunders Medical Center, Wahoo, NE; Jason Silversteen, Christiana Care Health Services, Inc., Newark, NJ; Derek Smith, Thames Neurological Institute, Norwich, CT; Donald Negroski, Negroski Neurology, LLP, Sarasota, Sarasota, FL; Marc Feinberg, SFM Clinical Research LLC, Boca Raton, FL; Stephen Newman, Island Neurological Association, Plainview, NY; Gabriel Pardo, Oklahoma Medical Research Foundation, Oklahoma City, OK; Evanthia Bernitsas, Department of Neurology, Wayne State University, Detroit, MI; Robert Krug, Mt. Sinai Rehabilitation Hospital, Hartford, CT; Peter Wade, Mercy Medical Center, Springfield, MA; Jennifer Ruiz, Saint Mary’s Hospital, Waterbury, CT; Bhupendra Khatri, Center for Neurological disorders at Ascension St. Francis, Milwaukee, WI; Bradley Jabour, Medical Imaging Center of Southern California, West Hollywood, CA; Tarun Singhal, Sturdy Memorial Hospital MS Center, Attleboro, MA; Flavia Nelson and Adam Carpenter, University of Minnesota, Minneapolis, MN; Francesca Bagnato and Margareta Clarke, Vanderbilt University, Nashville, TN; Jaqueline Nicholas and Andrew Smith, Ohio Health, MS Center, Riverside Methodist Hospital, Columbus, OH; Barry Singer, MS Center for Innovations in Care, Missouri Baptist Medical, St. Louis, MO.

    • Contributors RZ: study concept and design; analysis and interpretation; critical revision of the manuscript for important intellectual content; study supervision, author responsible for the overall content as the guarantor. NB: analysis and interpretation; critical revision of the manuscript for important intellectual content; study supervision. DJ: analysis and interpretation; statistical analysis; critical revision of the manuscript for important intellectual content; study supervision. BW-G: analysis and interpretation; critical revision of the manuscript for important intellectual content. RHBB: analysis and interpretation; critical revision of the manuscript for important intellectual content. JR: study concept and design; analysis and interpretation; critical revision of the manuscript for important intellectual content; study supervision. DS: study concept and design; analysis and interpretation; critical revision of the manuscript for important intellectual content; study supervision. MGD: analysis and interpretation; critical revision of the manuscript for important intellectual content.

    • Funding Study (RF AWARD NUMBER: 84309) was supported by a collaboration grant from Bristol Myers Squibb

    • Competing interests RZ has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Keystone Heart, Protembis and Novartis for speaking and consultant fees. He received financial support for research activities from Sanofi, Novartis, Bristol Myers Squibb, Octave, Mapi Pharma, Keystone Heart, Protembis and V-WAVE Medical. NB and and DJ have nothing to disclose. BW-G received honoraria as a speaker and/or as a consultant for Biogen Idec, Sanofi &Genzyme, Genentech, Novartis, BMS, Bayer, Horizon and Janssen. BW-G received research funds from Biogen Idec, Genentech and Novartis. RHBB has received consultation or speaking fees from Bristol Myer Squibb, Biogen, Merck, EMD Serono, Roche, Verasci, Immune Therapeutics, Novartis, and Sanofi-GenzymeJon Riolo and Diego Silva are employees of Bristol-Myers Squibb. MGD has received personal compensation from Keystone Heart for consultant fees. He received financial support for research activities from Bristol Myers Squibb, Mapi Pharma, Keystone Heart, Protembis and V-WAVE Medical.

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

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