Towards in vivo g-ratio mapping using MRI: Unifying myelin and diffusion imaging

BACKGROUND The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease. NEW METHOD This is the second review on the topic of g-ratio mapping using MRI. RESULTS This review summarizes the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches. COMPARISON WITH EXISTING METHODS Using simulations based on recently published data, this review reveals caveats to the state-of-the-art calibration methods that have been used for in vivo g-ratio mapping. It highlights the need to estimate both the slope and offset of the relationship between these MRI-based markers and the true myelin volume fraction if we are really to achieve the goal of precise, high sensitivity g-ratio mapping in vivo. Other challenges discussed in this review further evidence the need for gold standard measurements of human brain tissue from ex vivo histology. CONCLUSIONS We conclude that the quest to find the most appropriate MRI biomarkers to enable in vivo g-ratio mapping is ongoing, with the full potential of many novel techniques yet to be investigated.