PT - JOURNAL ARTICLE AU - Matteo Mancini AU - Agah Karakuzu AU - Thomas Nichols AU - Julien Cohen-Adad AU - Mara Cercignani AU - Nikola Stikov TI - The quest for measuring myelin with MRI – An interactive meta-analysis of quantitative comparisons with histology AID - 10.1101/2020.07.13.200972 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.07.13.200972 4099 - http://biorxiv.org/content/early/2020/07/26/2020.07.13.200972.short 4100 - http://biorxiv.org/content/early/2020/07/26/2020.07.13.200972.full AB - Several MRI measures have been proposed as in vivo biomarkers of myelin content, each with a concrete application ranging from plasticity to pathology. Despite the broad availability of these myelin-sensitive MRI modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable one for quantifying myelin is still ongoing.In this study, we performed a systematic review of published quantitative validation studies, and used meta-analysis tools to clarify how different these measures are when compared to the underlying histology, controlling for the study sample size and using interactive visualization tools (https://neurolibre.github.io/myelin-meta-analysis). A first qualitative selection of 58 studies proposed 35 different measures to characterize myelin content. However, a quantitative analysis showed that most of these measures have a limited coefficient of determination and provide little information to inform future studies, because of the large prediction intervals and high heterogeneity. These results indicate that most measures are statistically equivalent regarding their relationship with histology and that future work should take inter-study variability into consideration.Competing Interest StatementThe authors have declared no competing interest.ADaxial diffusivityAKaxial kurtosisAWFaxonal water fractionFAfraction anisotropyihMTRinhomogeneous magnetization transfer ratiok_fmfree water-macromolecular exchange ratek_mfmacromolecular-free water exchange rateM0mmacromolecular pool magnetization fractionMDmean diffusivityMKmean kurtosisMPFmacromolecular pool fractionMTmagnetization transferMTRmagnetization transfer ratioMTR-UTEmagnetization transfer ratio (using ultra-short echo time)MTVmacromolecular tissue volumeMVF-MTmyelin volume fraction (estimated from MT)MVF-T2myelin volume fraction (estimated from T2)MWFmyelin water fractionPDproton densityPNperipheral nervePRISMAPreferred Reporting Items for Systematic Reviews and Meta-AnalysesQSMquantitative susceptibility mappingR1ffree water pool longitudinal relaxation rateR2*apparent transverse relaxation rateRAFFrelaxation along a fictitious fieldRDradial diffusivityRD-DBSIradial diffusivity (from diffusion basis spectrum imaging)RDeextra-cellular compartment radial diffusivityRKradial kurtosisrSPFrelative semi-solid proton fractionSCspinal cordT1longitudinal relaxation timeT1padiabatic longitudinal relaxation timeT1satlongitudinal relaxation time under magnetization transfer irradiationT2transverse relaxation timeT2ffree water pool transverse relaxation timeT2inttransverse relaxation intermediate componentT2mmacromolecular pool transverse relaxation rateT2padiabatic transverse relaxation time