Yufan Zheng1, Jessica Dudman2, Jacqueline T Chen2, Kedar R Mahajan3, Danielle Herman2, Robert J Fox4, Daniel Ontaneda4, Bruce D Trapp2, Kunio Nakamura1. 1. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 2. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. 3. Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA/Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA. 4. Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Abstract
BACKGROUND: Detecting cortical demyelination using magnetic resonance imaging (MRI) in multiple sclerosis (MS) remains a challenge. Magnetization transfer ratio (MTR), T1-weighted/T2-weighted ratio (T1T2R), and T2-weighted (T2w) signal are sensitive to cortical demyelination, but their accuracy is unknown. OBJECTIVES: To quantify the sensitivity, specificity, and accuracy of postmortem T1T2R, MTR, and T2w in detecting cortical demyelination. METHODS: In situ postmortem MRIs from 9 patients were used to measure T1T2R, MTR, and T2w along the midline of cortical gray matter and classified as normal or abnormal. MRIs were co-registered and compared to hemispheric myelin staining. The sensitivity, specificity, and accuracy of T1T2R, MTR, and T2w in detecting cortical demyelination were measured. RESULTS: The mean age (standard deviation) at death was 64.7 (+/-13.7) years with a disease duration of 23.8 (+/-10.5) years. The sensitivity was 78% for MTR, 75% for T1T2R, and 63% for T2w. The specificity was 46% (T2w), 13% (T1T2R), and 29% (MTR). The accuracy was 71% (T2w), 39% (MTR), and 42% (T1T2R). There were no significant differences between different MRI measures in cortical demyelination or intracortical/subpial lesion detection. CONCLUSIONS: Although somewhat sensitive, the modest specificity of conventional MRI modalities for cortical demyelination indicates that they are influenced by cortical changes other than demyelination. Improved acquisition and post-processing are needed to reliably measure cortical lesion load.
BACKGROUND: Detecting cortical demyelination using magnetic resonance imaging (MRI) in multiple sclerosis (MS) remains a challenge. Magnetization transfer ratio (MTR), T1-weighted/T2-weighted ratio (T1T2R), and T2-weighted (T2w) signal are sensitive to cortical demyelination, but their accuracy is unknown. OBJECTIVES: To quantify the sensitivity, specificity, and accuracy of postmortem T1T2R, MTR, and T2w in detecting cortical demyelination. METHODS: In situ postmortem MRIs from 9 patients were used to measure T1T2R, MTR, and T2w along the midline of cortical gray matter and classified as normal or abnormal. MRIs were co-registered and compared to hemispheric myelin staining. The sensitivity, specificity, and accuracy of T1T2R, MTR, and T2w in detecting cortical demyelination were measured. RESULTS: The mean age (standard deviation) at death was 64.7 (+/-13.7) years with a disease duration of 23.8 (+/-10.5) years. The sensitivity was 78% for MTR, 75% for T1T2R, and 63% for T2w. The specificity was 46% (T2w), 13% (T1T2R), and 29% (MTR). The accuracy was 71% (T2w), 39% (MTR), and 42% (T1T2R). There were no significant differences between different MRI measures in cortical demyelination or intracortical/subpial lesion detection. CONCLUSIONS: Although somewhat sensitive, the modest specificity of conventional MRI modalities for cortical demyelination indicates that they are influenced by cortical changes other than demyelination. Improved acquisition and post-processing are needed to reliably measure cortical lesion load.
Authors: Laura Turati; Marco Moscatelli; Alfonso Mastropietro; Nicholas G Dowell; Ileana Zucca; Alessandra Erbetta; Chiara Cordiglieri; Greta Brenna; Beatrice Bianchi; Renato Mantegazza; Mara Cercignani; Fulvio Baggi; Ludovico Minati Journal: NMR Biomed Date: 2015-01-09 Impact factor: 4.044
Authors: David Pitt; Aaron Boster; Wei Pei; Eric Wohleb; Adam Jasne; Cherian R Zachariah; Kottil Rammohan; Michael V Knopp; Petra Schmalbrock Journal: Arch Neurol Date: 2010-07
Authors: A Seewann; E-J Kooi; S D Roosendaal; P J W Pouwels; M P Wattjes; P van der Valk; F Barkhof; C H Polman; J J G Geurts Journal: Neurology Date: 2012-01-04 Impact factor: 9.910
Authors: A Scott Nielsen; R Philip Kinkel; Emanuele Tinelli; Thomas Benner; Julien Cohen-Adad; Caterina Mainero Journal: J Magn Reson Imaging Date: 2011-11-01 Impact factor: 4.813
Authors: Iris D Kilsdonk; Laura E Jonkman; Roel Klaver; Susanne J van Veluw; Jaco J M Zwanenburg; Joost P A Kuijer; Petra J W Pouwels; Jos W R Twisk; Mike P Wattjes; Peter R Luijten; Frederik Barkhof; Jeroen J G Geurts Journal: Brain Date: 2016-03-08 Impact factor: 13.501
Authors: Ranjan Dutta; Kedar R Mahajan; Kunio Nakamura; Daniel Ontaneda; Jacqueline Chen; Christina Volsko; Jessica Dudman; Emilie Christie; Jordon Dunham; Robert J Fox; Bruce D Trapp Journal: J Vis Exp Date: 2019-07-19 Impact factor: 1.355
Authors: Jesper Hagemeier; Bianca Weinstock-Guttman; Mari Heininen-Brown; Guy U Poloni; Niels Bergsland; Claudiu Schirda; Christopher R Magnano; Cheryl Kennedy; Ellen Carl; Michael G Dwyer; Alireza Minagar; Robert Zivadinov Journal: Front Biosci (Elite Ed) Date: 2013-01-01
Authors: Ruthger Righart; Viola Biberacher; Laura E Jonkman; Roel Klaver; Paul Schmidt; Dorothea Buck; Achim Berthele; Jan S Kirschke; Claus Zimmer; Bernhard Hemmer; Jeroen J G Geurts; Mark Mühlau Journal: Ann Neurol Date: 2017-09-16 Impact factor: 10.422
Authors: Yara Kadria-Vili; Oara Neumann; Yage Zhao; Peter Nordlander; Gary V Martinez; James A Bankson; Naomi J Halas Journal: Proc Natl Acad Sci U S A Date: 2022-07-11 Impact factor: 12.779