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.
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