An interactive meta-analysis of MRI biomarkers of myelin

  1. Matteo Mancini  Is a corresponding author
  2. Agah Karakuzu
  3. Julien Cohen-Adad
  4. Mara Cercignani
  5. Thomas E Nichols
  6. Nikola Stikov
  1. Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, United Kingdom
  2. NeuroPoly Lab, Polytechnique Montreal, Canada
  3. CUBRIC, Cardiff University, United Kingdom
  4. Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Canada
  5. Neuroimaging Laboratory, Fondazione Santa Lucia, Italy
  6. Wellcome Centre for Integrative Neuroimaging (WIN FMRIB), University of Oxford, United Kingdom
  7. Big Data Institute, University of Oxford, United Kingdom
  8. Montreal Heart Institute, Université de Montréal, Canada
7 figures, 2 tables and 4 additional files


Sankey diagram representing the screening procedure (PRISMA flow chart provided in the appendix).
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.
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:

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:

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:

Experimental conditions and methodological choices influencing the R2 values (top: reference techniques; middle: pathology model; bottom: tissue types).
Appendix 1—figure 1
PRISMA flowchart for the meta-analysis.


Table 1
Results from the mixed-effect models: for each measure we reported the number of studies, the estimate and standard error of the overall R2 distribution, the τ2 and the I2.
MeasureNumber of studiesEstimateStandard errorTau2I2
Appendix 1—table 1
Selected studies for qualitative analysis.
StudyMRI measure(s)Histology/microscopy measureTissueConditionFocus
Schmierer et al., 2004T1, MTRHistology - LFBHumanMultiple sclerosisBrain
Odrobina et al., 2005T1, T2, T2int, MWF, M0m, MTRMicroscopy - Myelin fractionAnimal - RatDemyelination - TelluriumPN
Pun et al., 2005T1, T2int, MWFMicroscopy - Myelin fractionAnimal - RatDemyelination - TelluriumPN
Laule et al., 2006MWFHistology - LFBHumanMultiple sclerosisBrain
Schmierer et al., 2007aT1, MTR, MPF, T2mHistology - LFBHumanMultiple sclerosisBrain
Schmierer et al., 2007bFA, MDHistology - LFBHumanMultiple sclerosisBrain
Jito et al., 2008FAMicroscopy - Myelin sheath areaAnimal - MouseHealthyBrain
Kozlowski et al., 2008MWF, FA, AD, RD, MDImmunohistochemistry - MBPAnimal - RatInjury - Dorsal columnar transectionSC
Laule et al., 2008MWFHistology - LFBHumanMultiple sclerosisBrain
Schmierer et al., 2008T1, T2, MTR, MPF, MD, FA, AD, RDHistology - LFBHumanMultiple sclerosisBrain
Wu et al., 2008T2Histology - LFBAnimal - MouseDemyelination - CuprizoneBrain
Zaaraoui et al., 2008MTRImmunohistochemistry - MBPAnimal - MouseDemyelination - CuprizoneBrain
Takagi et al., 2009FA, ADEM - Myelin thicknessAnimal - RatDegeneration - Contusive injuryPN
Wang et al., 2009FA, RDHistology - LFBAnimal - RatIschemia - Induced hypoxiaBrain
Zhang et al., 2009RDHistology - LFBAnimal - RatInjury - Dorsal columnar transectionSC
Schmierer et al., 2010MTR, T2Histology - LFBHumanMultiple sclerosisBrain
Fatemi et al., 2011MTRImmunohistochemistry - MBPAnimal - MouseIschemia - Induced hypoxiaBrain
Laule et al., 2011MWFImmunohistochemistry - MBPHumanMultiple sclerosisBrain
Underhill et al., 2011MPFHistology - LFBAnimal - MouseHealthyBrain
Chandran et al., 2012FA, RDImmunohistochemistry - MBPAnimal - MouseDemyelination - CuprizoneBrain
Tardif et al., 2012T1, T2, MTR, PDImmunohistochemistry - MBPHumanMultiple sclerosisBrain
Fjær et al., 2013MTRImmunohistochemistry - PLPAnimal - MouseDemyelination - CuprizoneBrain
Harkins et al., 2013MWF, MPFMicroscopy - Myelin fractionAnimal - RatEdema - HexacloropheneSC
Janve et al., 2013MPF, R1a, k_ba, FA, RD, MD, ADHistology - LFBAnimal - RatDemyelination - LipopolysaccharideBrain
Thiessen et al., 2013MPF, R1f, k_fm, k_mf, T2f, T2m, MD, RD, AD, FA, T1, T2EM - Myelin thicknessAnimal - MouseDemyelination - CuprizoneBrain
Kozlowski et al., 2014MWFImmunohistochemistry - MBPAnimal - RatInjury - Dorsal columnar transectionSC
Wang et al., 2014RD, RD-DBSIImmunohistochemistry - MBPAnimal - MouseDemyelination - Autoimmune encephalomyelitisSC
Fjær et al., 2015MTRImmunohistochemistry - PLPAnimal - MouseDemyelination - Autoimmune encephalomyelitisBrain
Seehaus et al., 2015FA, RD, MDHistology - SilverHumanHealthyBrain
Turati et al., 2015MPFImmunohistochemistry - MBPAnimal - MouseDemyelination - CuprizoneBrain
Wang et al., 2015RD-DBSIHistology - LFBHumanMultiple sclerosisSC
Aojula et al., 2016FA, AD, RD, MDImmunohistochemistry - MBPAnimal - RatHydrocephalusBrain
Hakkarainen et al., 2016T1, T2, MTR, T1p, T2p, RAFFHistology - Gold chlorideAnimal - RatHealthyBrain
Jelescu et al., 2016RD, RK, AWF, Rde, T2, MTREM - Myelin fractionAnimal - MouseDemyelination - CuprizoneBrain
Kelm et al., 2016MD, RD, MK, RK, AWFEM - Myelin fractionAnimal - MouseDemyelination - KnockoutBrain
Reeves et al., 2016T1, T2Immunohistochemistry - MBPHumanEpilepsyBrain
Tu et al., 2016FA, AD, RD, MD, MTRImmunohistochemistry - MBPAnimal - RatTraumatic brain injuryBrain
Chang et al., 2017FA, AD, RD, MDImmunohistochemistry - MBPAnimal - MouseHealthyBrain
Chen et al., 2017MWFEM - Myelin fractionAnimal - RatInjury - Dorsal columnar transectionSC
Khodanovich et al., 2017MPFHistology - LFBAnimal - MouseDemyelination - CuprizoneBrain
Lehto et al., 2017aRAFF, MTR, T1sat, FA, MD, AD, RDHistology - Gold chlorideAnimal - RatDemyelination - LipopolysaccharideBrain
Lehto et al., 2017bMTRHistology - Gold chlorideAnimal - RatTraumatic brain injuryBrain
van Tilborg et al., 2018FAImmunohistochemistry - MBPAnimal - RatWhite matter injuryBrain
Beckmann et al., 2018MTRHistology - LFBAnimal - MouseDemyelination - CuprizoneBrain
Berman et al., 2018MTVEM - Myelin fractionAnimal - MouseDemyelination - KnockoutBrain
Hametner et al., 2018R2*, T1, QSMHistology - LFBHumanVascular diseasesBrain
Praet et al., 2018MK, RK, AK, FA, MD, RD, ADImmunohistochemistry - MBPAnimal - MouseAmyloidosisBrain
Wendel et al., 2018FA, AD, RD, MDImmunohistochemistry - MBPAnimal - MouseTraumatic brain injuryBrain
West et al., 2018MPF, MWF, MVF-T2, MVF-MTEM - Myelin fractionAnimal - MouseDemyelination - KnockoutBrain
Yano et al., 2018FA, RD, MDImmunohistochemistry - PLPAnimal - MouseDemyelination - CuprizoneBrain
Abe et al., 2019FA, RD, ADMicroscopy - Myelin thicknessAnimal - MouseOptogenetic stimulationBrain
Duhamel et al., 2019ihMTR, MTRMicroscopy - FluorescenceAnimal - MouseHealthyBrain
Khodanovich et al., 2019MPFImmunohistochemistry - MBPAnimal - MouseDemyelination - CuprizoneBrain
Mollink et al., 2019FAImmunohistochemistry - MBPHumanAmyotrophic lateral sclerosisBrain
Peters et al., 2019FA, MDHistology - LFBHumanTuberous sclerosis complexBrain
Pol et al., 2019QSM, FA, MDHistology - SolochromeAnimal - MouseHealthyBrain
Soustelle et al., 2019MPF, RD, MWF, rSPFImmunohistochemistry - MBPAnimal - MouseDemyelination - CuprizoneBrain
Guglielmetti et al., 2020MTR, MTR-UTEImmunohistochemistry - MBPAnimal - MouseHealthyBrain

Additional files

Source code 1

A Jupyter notebook in ipynb format containing the Python code used to process the data, run the analyses and generate all the figures.

In order to execute the notebook, the Python (3.7) and R (3.6) interpreters are required, as well as the R packages metafor (2.4) and multcomp (1.4), and the following Python packages: numpy (1.18.4); pandas (0.25.3); plotly (4.8.1); rpy2 (3.3.4); xlrd (1.2.0). The notebook assumes that the spreadsheet is in the same path as the notebook itself. More details are provided here: (Mancini, 2020; copy archived at swh:1:rev:17ca8673c9e15c54ad0b814248b69232b63c3a38).
Source data 1

A spreadsheet in xlsx format containing all the data and details collected for the studies considered in this systematic review.
Supplementary file 1

A multimedia file in HTML format containing an interactive version of the figures in this manuscript plus additional ones.
Transparent reporting form

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  1. Matteo Mancini
  2. Agah Karakuzu
  3. Julien Cohen-Adad
  4. Mara Cercignani
  5. Thomas E Nichols
  6. Nikola Stikov
An interactive meta-analysis of MRI biomarkers of myelin
eLife 9:e61523.