ASN Neuro

Measuring Myelin Integrity: Coming of Age in Preclinical and Clinical Arenas

By the turn of the twentieth century, major questions about cell form and function in the peripheral nervous system (PNS) and central nervous system (CNS) were moving beyond simple considerations of cell size and morphology to structure and function. One such consideration was the relationship between the axonal projections of medium and large peripheral neurons and the birefringent wrapping of medullated nerves (myelinated axons).

Early anecdotal observations by the H.H. Donaldson and E. Dunn laboratories at the University of Chicago suggested this relationship approximated a proportional ratio of cross-sectional axon-to-myelin areas. In 1905 H.H. Donaldson and G.W. Hoke demonstrated this proportionality with a study that is arguably the most extensive morphological analysis of the axon-myelin relation performed to date: 27 species from all five myelinating vertebrate classes spanning 400 million years of evolution. Concurrently, J. Erlanger and H.S. Gasser at Washington University were taking advantage of early advances in electronics to measure voltage and electric current in bull frog PNS. They probed the activity of mixed nerves and characterized compound action potentials in terms of myelinated and nonmyelinated axon structure.

The amalgamation of findings from multiple laboratories through the mid-twentieth century led to increased understanding of and interest in predicting the mechanism of nerve action in terms of electrical and chemical structure and morphology. Ruston’s 1951 summary of the field was a significant step forward and remains influential even today. His theoretical insights into myelinated axon form and function and the significance of myelin g ratio analysis corroborated the observations by Donaldson & Hoke, but refuted those of other major studies in which experimental and interpretational shortcomings had found their way into g ratio analyses. And despite several efforts to correct those issues in the last half century, the artifacts have largely persisted. Concomitantly, advances in measurement technologies such as neuroimaging and volumetric electron microscopy have provided new details of internode structure.

The objectives of articles in the current Collection include the development of more accurate g ratio analyses and alternatives and to highlight the increasing relevance of g ratios in clinical neuroimaging where non-invasive measurement of axon-myelin interactions are critical to understanding and treating behavioral and degenerative diseases.

To achieve these objectives, sharply focused primary or review articles should address any of the following subtopics under physiological conditions or disease states:

• Mathematical and computational approaches to g ratio and alternate methodological analyses (including all necessary statistical/mathematical proofs).
• Automated and semi-automated approaches to measuring g ratios and alternatives from microscopy, neuroimaging and other technologies, paying particular attention to eliminating technical shortcomings of past studies including insufficient measurement resolution and inadequate statistical models.
• Analysis across a wide range of vertebrate species to determine if the constancy of the axon-myelin relationship found in the PNS also holds for the CNS.
• Characterization of the nuances of internodal structure as well as novel genes, genetic variants that regulate structure and function.
• Application of g ratio methodologies to connectomics, disease and associations with neural function and behavior.

Submission Instructions:

All manuscripts submitted to this Article Collection will undergo full peer-review; the Guest Advisor will not be handling submitted articles. Please review the journal’s aims and scope and author instructions prior to submission.

Please submit your manuscript through Taylor & Francis's Submission Portal.

During the first step of the submission process (under the "Manuscript Details" heading), you will find the question "Are you submitting your paper for a specific special issue or article collection?" Click the radio button for "Yes".

Next, you will be prompted to select the "Special Issue or Article Collection name" from the dropdown menu. Choose "Measuring Myelin Integrity" from the list. This will ensure that your manuscript is considered for inclusion.

The manuscript submission deadline is 1 November 2026.

If you have any questions about this Article Collection, please contact Krista Thom at [email protected].

Guest Advisors:

Prof. Alexander Gow is a molecular/cell neuroscientist interested in generating and analyzing mouse models of neurodegenerative diseases including multiple sclerosis, leukodystrophies and neuropsychiatric disorders. Prof. Gow uses a multidisciplinary systems approach involving transgene/knockout/knockin technologies, molecular/cell biology, fluorescence and electron microscopy, behavior, auditory evoked potentials, electrophysiology, computational modelling, and AAV gene delivery.

Prof. Mariana Lazar is an investigator with extensive expertise in MRI methods and their applications to the study of the brain microstructure and connectivity in both healthy population and psychiatric disorders. Recently she has pursued a multimodal imaging approach that has extended her area of expertise to myelin and magnetization transfer imaging, relaxometry and iron imaging, and magnetic resonance spectroscopy imaging. An area of particular interest for her lab is understanding abnormal myelin changes during both development and aging, including in psychotic disorders and Alzheimer’s disease and related disorders.

Prof. Nikola Stikov is a researcher at the Montreal Heart Institute, and co-director of NeuroPoly, the Neuroimaging Research Laboratory at École Polytechnique, University of Montreal. His research runs the gamut of quantitative magnetic resonance imaging, from basic issues of standardization and accuracy, to biophysical modelling, microstructural imaging and clinical applications.