The quest for measuring myelin with MRI – An interactive meta-analysis of quantitative comparisons with histology

Matteo Mancini; Agah Karakuzu; Thomas Nichols; Julien Cohen-Adad; Mara Cercignani; Nikola Stikov

doi:10.1101/2020.07.13.200972

Abstract

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 Statement

The authors have declared no competing interest.

Footnotes

Links to interactive figures and PRISMA checklist have been added.
https://neurolibre.github.io/myelin-meta-analysis

Abbreviations and mathematical symbols

AD: axial diffusivity
AK: axial kurtosis
AWF: axonal water fraction
FA: fraction anisotropy
ihMTR: inhomogeneous magnetization transfer ratio
k_fm: free water-macromolecular exchange rate
k_mf: macromolecular-free water exchange rate
M0m: macromolecular pool magnetization fraction
MD: mean diffusivity
MK: mean kurtosis
MPF: macromolecular pool fraction
MT: magnetization transfer
MTR: magnetization transfer ratio
MTR-UTE: magnetization transfer ratio (using ultra-short echo time)
MTV: macromolecular tissue volume
MVF-MT: myelin volume fraction (estimated from MT)
MVF-T2: myelin volume fraction (estimated from T2)
MWF: myelin water fraction
PD: proton density
PN: peripheral nerve
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
QSM: quantitative susceptibility mapping
R1f: free water pool longitudinal relaxation rate
R2*: apparent transverse relaxation rate
RAFF: relaxation along a fictitious field
RD: radial diffusivity
RD-DBSI: radial diffusivity (from diffusion basis spectrum imaging)
RDe: extra-cellular compartment radial diffusivity
RK: radial kurtosis
rSPF: relative semi-solid proton fraction
SC: spinal cord
T1: longitudinal relaxation time
T1p: adiabatic longitudinal relaxation time
T1sat: longitudinal relaxation time under magnetization transfer irradiation
T2: transverse relaxation time
T2f: free water pool transverse relaxation time
T2int: transverse relaxation intermediate component
T2m: macromolecular pool transverse relaxation rate
T2p: adiabatic transverse relaxation time

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