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An interactive meta-analysis of MRI biomarkers of myelin

Mancini, Matteo, Karakuzu, Agah, Cohen-Adad, Julien, Cercignani, Mara, Nichols, Thomas E, Stikov, Nikola·2020·eLife
DOI 10.7554/elife.61523PMC PMC7647401

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Abstract

Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analyzed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization ( https://neurolibre.github.io/myelin-meta-analysis ). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology.

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Figure 1. Sankey diagram representing the screening procedure (PRISMA flow chart provided in the appendix). To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/01/selection.html#figure-1.
Figure 1. Sankey diagram representing the screening procedure (PRISMA flow chart provided in the appendix). To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/01/selection.html#figure-1.CC BY · PubMed Central
Figure 2. Bubble chart of R2 values between a given MRI measure and histology for each study across MRI measures, with the area proportional to the number of samples. To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/02/closer_look.html#figure-3.
Figure 2. Bubble chart of R2 values between a given MRI measure and histology for each study across MRI measures, with the area proportional to the number of samples. To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/02/closer_look.html#figure-3.CC BY · PubMed Central
Figure 3. Treemap chart of the studies considered for the meta-analysis, organized by MRI measure. The color of each box represents the reported R2 value while the size box is proportional to the sample size. To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/02/closer_look.html#figure-4.
Figure 3. Treemap chart of the studies considered for the meta-analysis, organized by MRI measure. The color of each box represents the reported R2 value while the size box is proportional to the sample size. To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/02/closer_look.html#figure-4.CC BY · PubMed Central
Figure 4. Forest plots showing the R2 values reported by the studies and estimated from the mixed-effect model for each measure. The hourglasses and the dotted lines in the mixed-effect model outcomes represent the prediction intervals. To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/03/meta_analysis.html#figure-5.
Figure 4. Forest plots showing the R2 values reported by the studies and estimated from the mixed-effect model for each measure. The hourglasses and the dotted lines in the mixed-effect model outcomes represent the prediction intervals. To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/03/meta_analysis.html#figure-5.CC BY · PubMed Central
Figure 5. Results from the repeated measures meta-regression, displayed in terms of z-scores (left) and p-values (right) for each pairwise comparison across all the MRI measures. In the z-score heatmap, each element refers to the comparison between the measure on the x axis with the one on the y axis. For example, MPF and FA (z-score = 7.14; p-value<0.0001) are statistically different, while MPF and T1 (z-score = 2.51; p-value=0.43) are not statistically different. To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/03/meta_analysis.html#figure-6.
Figure 5. Results from the repeated measures meta-regression, displayed in terms of z-scores (left) and p-values (right) for each pairwise comparison across all the MRI measures. In the z-score heatmap, each element refers to the comparison between the measure on the x axis with the one on the y axis. For example, MPF and FA (z-score = 7.14; p-value<0.0001) are statistically different, while MPF and T1 (z-score = 2.51; p-value=0.43) are not statistically different. To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/03/meta_analysis.html#figure-6.CC BY · PubMed Central
Figure 6. Experimental conditions and methodological choices influencing the R2 values (top: reference techniques; middle: pathology model; bottom: tissue types). To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/04/other_factors.html#figure-7.
Figure 6. Experimental conditions and methodological choices influencing the R2 values (top: reference techniques; middle: pathology model; bottom: tissue types). To see the interactive figure: https://neurolibre.github.io/myelin-meta-analysis/04/other_factors.html#figure-7.CC BY · PubMed Central
Appendix 1—figure 1. PRISMA flowchart for the meta-analysis.
Appendix 1—figure 1. PRISMA flowchart for the meta-analysis.CC BY · PubMed Central

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Authors
Mancini, M., Karakuzu, A., Cohen-Adad, J., Cercignani, M., Nichols, T. E., & Stikov, N.
Affiliations
  • Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom
  • NeuroPoly Lab, Polytechnique Montreal, Montreal, Canada
  • Wellcome Centre for Integrative Neuroimaging (WIN FMRIB), University of Oxford, Oxford, United Kingdom
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2020-10-21
Volume
9
ISSN
2050-084X
DOI
10.7554/elife.61523
PMC
PMC7647401
Cited by
168
References
8
Language
en
Licence
Funders
  • Wellcome Trust (213722/Z/18/Z)
  • National Institutes of Health (R01MH096906)

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