Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations

PLOS ONE, Nov 2019

Purpose To implement a statistical framework for assessing the precision of several quantitative MRI metrics sensitive to myelin in the human spinal cord: T1, Magnetization Transfer Ratio (MTR), saturation imposed by an off-resonance pulse (MTsat) and Macromolecular Tissue Volume (MTV). Methods Thirty-three healthy subjects within two age groups (young, elderly) were scanned at 3T. Among them, 16 underwent the protocol twice to assess repeatability. Statistical reliability indexes such as the Minimal Detectable Change (MDC) were compared across metrics quantified within different cervical levels and white matter (WM) sub-regions. The differences between pathways and age groups were quantified and interpreted in context of the test-retest repeatability of the measurements. Results The MDC was respectively 105.7ms, 2.77%, 0.37% and 4.08% for T1, MTR, MTsat and MTV when quantified over all WM, while the standard-deviation across subjects was 70.5ms, 1.34%, 0.20% and 2.44%. Even though particular WM regions did exhibit significant differences, these differences were on the same order as test-retest errors. No significant difference was found between age groups for all metrics. Conclusion While T1-based metrics (T1 and MTV) exhibited better reliability than MT-based measurements (MTR and MTsat), the observed differences between subjects or WM regions were comparable to (and often smaller than) the MDC. This makes it difficult to determine if observed changes are due to variations in myelin content, or simply due to measurement error. Measurement error remains a challenge in spinal cord myelin imaging, but this study provides statistical guidelines to standardize the field and make it possible to conduct large-scale multi-center studies.

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Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations

January Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations Simon Le vy 1 2 3 4 Marie-Claude Guertin 0 1 4 Ali Khatibi 1 2 4 Aviv Mezer 1 4 Kristina Martinu 1 2 4 Jen-I Chen 1 2 4 Nikola Stikov 1 3 4 Pierre Rainville 1 2 4 Julien Cohen-Adad 1 3 4 0 Montreal Health Innovations Coordinating Center (MHICC), Montreal Heart Institute , Montreal, QC , Canada , 4 Psychology Department, Bilkent University , Ankara , Turkey , 5 Interdisciplinary program in Neuroscience, Bilkent University , Ankara , Turkey , 6 National Magnetic Resonance Research Center (UMRAM), Bilkent University , Ankara , Turkey , 7 The Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem , Jerusalem , Israel , 8 Department of Stomatology, Faculty of Dentistry, Universit e de Montr eÂal , Montreal, QC , Canada , 9 Montreal Heart Institute , Montreal, QC , Canada 1 Current address: Centre d'Exploration M eÂtabolique par Re sonance Magn eÂtique (CEMEREM), AP-HM, H oÃpital de la Timone, Poà le d'imagerie meÂdicale , Marseille , France 2 Centre de Recherche de l'Institut Universitaire de Ge riatrie de Montre al (CRIUGM) , Montr eÂal, QC , Canada 3 0 Functional Neuroimaging Unit, CRIUGM, Universite de Montre al , Montreal, QC , Canada 4 Editor: Fernando de Castro, Instituto Cajal-CSIC , SPAIN Volume (MTV). - Data Availability Statement: The current Quebec law on the protection of private data prevents us from sharing all the MRI datasets this work is based on, even though they are de-identified, because they contain potentially sensitive information. This restriction has been imposed by the ethical review board of the Research Center of Montreal University Geriatric Institute (Comite mixte d'eÂthique de la recherche du RNQ, approval number CMER-RNQ_14-15-010). To contact the research ethics board of the RNQ, please refer to Purpose Methods To implement a statistical framework for assessing the precision of several quantitative MRI metrics sensitive to myelin in the human spinal cord: T1, Magnetization Transfer Ratio (MTR), saturation imposed by an off-resonance pulse (MTsat) and Macromolecular Tissue Thirty-three healthy subjects within two age groups (young, elderly) were scanned at 3T. Among them, 16 underwent the protocol twice to assess repeatability. Statistical reliability indexes such as the Minimal Detectable Change (MDC) were compared across metrics quantified within different cervical levels and white matter (WM) sub-regions. The differences between pathways and age groups were quantified and interpreted in context of the test-retest repeatability of the measurements. Results The MDC was respectively 105.7ms, 2.77%, 0.37% and 4.08% for T1, MTR, MTsat and MTV when quantified over all WM, while the standard-deviation across subjects was 70.5ms, 1.34%, 0.20% and 2.44%. Even though particular WM regions did exhibit significant differences, these differences were on the same order as test-retest errors. No significant difference was found between age groups for all metrics. Mrs Karima Bekhiti (phone: +1 514 527-9565 #3223; email: . ca). Notwithstanding this limitation, we are willing to share the MRI data from four members of the lab, from which we have obtained explicit approval. Furthermore, we are also sharing the processing scripts used in this work, which will enable other researchers to re-run the analyses on the shared datasets. The data and scripts have now been uploaded to https://osf.io/ezmrj/. Funding: This study was funded by the Canada Research Chair in Quantitative Magnetic Resonance Imaging (JCA), the Canadian Institutes of Health Research [CIHR FDN-143263] (JCA), the Canadian Institutes of Health Research [CIHR MOP-130341] (JCA and PR), the Fonds de Recherche du QueÂbecÐSante [FRQS-28826] (JCA), the Fonds de Recherche du QueÂbecÐ Nature et Technologies [2015-PR-182754] (JCA), the Natural Sciences and Engineering Research Council of Canada [NSERC-435897-2013] (JCA), the Natural Sciences and Engineering Research Council of Canada [NSERC 2016-06774] (NS), the Quebec BioImaging Network (JCA) and the Montreal Heart Institute Foundation (NS). Those funds were used for MRI data acquisition, computer and software resources and authors' funding. Competing interests: The authors have declared that no competing interests exist. Conclusion While T1-based metrics (T1 and MTV) exhibited better reliability than MT-based measurements (MTR and MTsat), the observed differences between subjects or WM regions were comparable to (and often smaller than) the MDC. This makes it difficult to determine if observed changes are due to variations in myelin content, or simply due to measurement error. Measurement error remains a challenge in spinal cord myelin imaging, but this study provides statistical guidelines to standardize the field and make it possible to conduct largescale multi-center studies. (...truncated)


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Simon Lévy, Marie-Claude Guertin, Ali Khatibi, Aviv Mezer, Kristina Martinu, Jen-I Chen, Nikola Stikov, Pierre Rainville, Julien Cohen-Adad. Test-retest reliability of myelin imaging in the human spinal cord: Measurement errors versus region- and aging-induced variations, PLOS ONE, 2018, Volume 13, Issue 1, DOI: 10.1371/journal.pone.0189944