Ultrahigh field imaging of myelin disease models: Toward specific markers of myelin integrity?

Abstract

Specific magnetic resonance imaging (MRI) markers of myelin are critical for the evaluation and development of regenerative therapies for demyelinating diseases. Several MRI methods have been developed for myelin imaging, based either on acquisition schemes or on mathematical modeling of the signal. They generally showed good sensitivity but validation for specificity toward myelin is still warranted to allow a reliable interpretation in an in vivo complex pathological environment. Experimental models of dys−/demyelination are characterized by various levels of myelin disorders, axonal damage, gliosis and inflammation, and offer the opportunity for powerful correlative studies between imaging metrics and histology. Here, we review how ultrahigh field MRI markers have been correlated with histology in these models and provide insights into the trends for future developments of MRI tools in human myelin diseases. To this end, we present the biophysical basis of the main MRI methods for myelin imaging based on T 1 , T 2 , water diffusion, and magnetization transfer signal, the characteristics of animal models used and the outcomes of histological validations. To date such studies are limited, and demonstrate partial correlations with immunohistochemical and electron microscopy measures of myelin.These MRI metrics also often correlate with axons, glial, or inflammatory cells in models where axonal degeneration or inflammation occur as potential confounding factors. Therefore, the MRI markers' specificity for myelin is still perfectible and future developments should improve mathematical modeling of the MR signal based on more complex systems or provide multimodal approaches to better disentangle the biological processes underlying the MRI metrics. K E Y W O R D Shistological correlation, MRI markers, multiple sclerosis, myelin, specificity

An interactive meta-analysis of MRI biomarkers of myelin

“…These results included 50 review articles. From the 50 review articles, six were selected as relevant for both the topics of myelin and related MRI-histology comparisons ( Cohen-Adad, 2018 ; Laule and Moore, 2018 ; Laule et al, 2007 ; MacKay and Laule, 2016 ; Petiet et al, 2019 ; Turner, 2019 ). After the assessment, 58 original research studies were considered eligible, as shown in Appendix 1—table 1 (in the appendix) and Figure S2.…”

“…Despite being the most realistic approach, this comparison involves several methodological choices, from the specific technique used as a reference to the quantitative measure used to describe the relationship between MRI and histology. So far, a long list of studies have looked at MRI-histology comparisons ( Cohen-Adad, 2018 ; Laule and Moore, 2018 ; MacKay and Laule, 2016 ; Petiet et al, 2019 ), each of them focusing on a specific pathology and a few MRI measures.…”

An interactive meta-analysis of MRI biomarkers of myelin

“…These results included 50 review articles. From the 50 review articles, six were selected as relevant for both the topics of myelin and related MRI-histology comparisons (Cohen-Adad, 2018; Laule & Moore, 2018; Laule et al, 2007; A. L. MacKay & Laule, 2016; Petiet et al, 2019; Turner, 2019). After the assessment, 58 original research studies were considered eligible, as shown in Table A1 (in the appendix) and Figure S2.…”

“…Despite being the most realistic approach, this comparison involves several methodological choices, from the specific technique used as a reference to the quantitative measure used to describe the relationship between MRI and histology. So far, a long list of studies have looked at MRI-histology comparisons (Cohen-Adad, 2018; Laule & Moore, 2018; A. L. MacKay & Laule, 2016; Petiet et al, 2019), each of them focusing on a specific pathology and a few MRI measures.…”

The R1-weighted connectome: complementing brain networks with a myelin-sensitive measure

“…The use of qMRI metrics to weight the connectome could have important implications for many applications. qMRI offers several techniques that are sensitive to myelin (Laule et al, 2007;Petiet et al, 2019), such as magnetization transfer, myelin water imaging, or relaxometry (for a complete list see (Heath et al, 2018)). Additionally, these techniques could be used to estimate the conduction velocity and conduction delays, and to incorporate these metrics as weights in the connectome.…”