Russell Ouellette1,2,3,4, Gabriel Mangeat3,5, Ildiko Polyak6, Marcel Warntjes7,8, Yngve Forslin1,2, Åsa Bergendal1,9, Michael Plattén1,2,10, Martin Uppman1,2, Constantina Andrada Treaba3,4, Julien Cohen-Adad5, Fredrik Piehl1,11, Maria Kristoffersen Wiberg1,2, Sten Fredrikson1,11, Caterina Mainero3,4, Tobias Granberg1,2,3,4. 1. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. 2. Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden. 3. A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA. 4. Harvard Medical School, Boston, MA. 5. NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, Quebec, Canada. 6. Invicro, Boston, MA. 7. Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden. 8. SyntheticMR, Linköping, Sweden. 9. Department of Medical Psychology, Karolinska University Hospital, Stockholm, Sweden. 10. School of Engineering Sciences in Chemistry, Biology, and Health, Royal Institute of Technology, Stockholm, Sweden. 11. Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
Abstract
OBJECTIVE: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T1 /T2 relaxometry and proton density mapping in multiple sclerosis. METHODS: Rapid myelin imaging was applied using 3T MRI ex vivo in 3 multiple sclerosis brain samples and in vivo in a prospective cohort of 71 multiple sclerosis patients and 21 age/sex-matched healthy controls, with scan-rescan repeatability in a subcohort. Disability in patients was assessed by the Expanded Disability Status Scale and the Symbol Digit Modalities Test at baseline and 2-year follow-up. RESULTS: Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostaining and Luxol fast blue) and demonstrated good precision. Multiple sclerosis patients had, relative to controls, lower normalized whole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cognitive and physical disability. Longitudinally, these myelin fractions correlated with follow-up physical disability, even with correction for baseline disability. INTERPRETATION: Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination in normal-appearing tissue in multiple sclerosis, which is associated with both cognitive and clinical disability. Because the technique is fast, with automatic postprocessing and US Food and Drug Administration/CE clinical approval, it can be a clinically feasible biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyelination. ANN NEUROL 2020.
OBJECTIVE: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T1 /T2 relaxometry and proton density mapping in multiple sclerosis. METHODS: Rapid myelin imaging was applied using 3T MRI ex vivo in 3 multiple sclerosis brain samples and in vivo in a prospective cohort of 71 multiple sclerosispatients and 21 age/sex-matched healthy controls, with scan-rescan repeatability in a subcohort. Disability in patients was assessed by the Expanded Disability Status Scale and the Symbol Digit Modalities Test at baseline and 2-year follow-up. RESULTS: Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostaining and Luxol fast blue) and demonstrated good precision. Multiple sclerosispatients had, relative to controls, lower normalized whole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cognitive and physical disability. Longitudinally, these myelin fractions correlated with follow-up physical disability, even with correction for baseline disability. INTERPRETATION: Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination in normal-appearing tissue in multiple sclerosis, which is associated with both cognitive and clinical disability. Because the technique is fast, with automatic postprocessing and US Food and Drug Administration/CE clinical approval, it can be a clinically feasible biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyelination. ANN NEUROL 2020.
Authors: H Jang; Y-J Ma; E Y Chang; S Fazeli; R R Lee; A F Lombardi; G M Bydder; J Corey-Bloom; J Du Journal: AJNR Am J Neuroradiol Date: 2021-02-18 Impact factor: 3.825
Authors: Cristina Granziera; Jens Wuerfel; Frederik Barkhof; Massimiliano Calabrese; Nicola De Stefano; Christian Enzinger; Nikos Evangelou; Massimo Filippi; Jeroen J G Geurts; Daniel S Reich; Maria A Rocca; Stefan Ropele; Àlex Rovira; Pascal Sati; Ahmed T Toosy; Hugo Vrenken; Claudia A M Gandini Wheeler-Kingshott; Ludwig Kappos Journal: Brain Date: 2021-06-22 Impact factor: 13.501
Authors: Spyros Papapetropoulos; Angela Pontius; Elizabeth Finger; Virginija Karrenbauer; David S Lynch; Matthew Brennan; Samantha Zappia; Wolfgang Koehler; Ludger Schoels; Stefanie N Hayer; Takuya Konno; Takeshi Ikeuchi; Troy Lund; Jennifer Orthmann-Murphy; Florian Eichler; Zbigniew K Wszolek Journal: Front Neurol Date: 2022-02-03 Impact factor: 4.003
Authors: David W Nelson; Tobias Granberg; Pia Andersen; Elias Jokhadar; Jessica Kåhlin; Anna Granström; Helena Hallinder; Anna Schening; Charlotta Thunborg; Håkan Walles; Göran Hagman; Roya Shams-Latifi; Jimmy Yu; Sven Petersson; Antonios Tzortzakakis; Nicholas Levak; Malin Aspö; Fredrik Piehl; Henrik Zetterberg; Miia Kivipelto; Lars I Eriksson Journal: Acta Anaesthesiol Scand Date: 2022-04-02 Impact factor: 2.274