Abstract
Recent years have seen an increased understanding of the importance of myelination in healthy brain function and neuropsychiatric diseases. Non-invasive microstructural magnetic resonance imaging (MRI) holds the potential to expand and translate these insights to basic and clinical human research, but the sensitivity and specificity of different MR markers to myelination is a subject of debate. To consolidate current knowledge on the topic, we perform a systematic review and meta-analysis of studies that validate microstructural imaging by combining it with myelin histology. We find meta-analytic evidence for correlations between various myelin histology metrics and markers from different MRI modalities, including fractional anisotropy, radial diffusivity, macromolecular pool, magnetization transfer ratio, susceptibility and longitudinal relaxation rate, but not mean diffusivity. Meta-analytic correlation effect sizes range widely, between R2 = 0.26 and R2 = 0.82. However, formal comparisons between MRI-based myelin markers are limited by methodological variability, inconsistent reporting and potential for publication bias, thus preventing the establishment of a single most sensitive strategy to measure myelin with MRI. To facilitate further progress, we provide a detailed characterisation of the evaluated studies as an online resource. We also share a set of 12 recommendations for future studies validating putative MR-based myelin markers and deploying them in vivo in humans.
Highlights
Myelin is crucial for healthy brain function
We find that validation studies have a median sample size of 13 (Fig. 3A), comparable to the median of the most cited fMRI studies during the period of publication included in our meta-analysis (12), but below current median sample size (20) (Szucs and Ioannidis, 2020)
In the studies we examined, relaxometry metrics such as R1 are more commonly validated with within-subject designs, which means it is unclear whether they would be able to pick up between-subject variability in myelination in the general population
Summary
Myelin is crucial for healthy brain function. Recent studies have highlighted the possibility that myelination may undergo subtle increases and decreases in adulthood, in response to neuronal activity or experience (Sampaio-Baptista et al, 2013; Sinclair et al, 2017), and that these changes may be crucial for learning and memory formation (Mckenzie et al, 2014; Pan et al, 2020; Steadman et al, 2020). When myelin is damaged or lost (demyelination), neural communication is affected. Robust in vivo markers to assess myelination could enable diagnosis and treatment monitoring for a wide range of conditions, as well as more detailed study of healthy brain function in humans
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