An Optimum Principle Predicts the Distribution of Axon Diameters in Normal White Matter

Pajevic, Sinisa; Basser, Peter J.

doi:10.1371/journal.pone.0054095

Cited by 18 publications

(19 citation statements)

References 31 publications

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“…Previous MRI-based methods used a gamma function to model the ADD (Assaf et al, 2008; Barazany et al, 2009). More recent attempts to derive the parametric form of the ADD used biomechanical (Gov, 2009) or neurophysiological (Pajevic and Basser, 2013) principles, based on minimizing energy consumption or optimizing information transmission, respectively. These new distributions are based on principles of optimization that the nervous system is implicitly assumed to follow.…”

Section: Discussionmentioning

confidence: 99%

White matter microstructure from nonparametric axon diameter distribution mapping

et al. 2016

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We report the development of a double diffusion encoding (DDE) MRI method to estimate and map the axon diameter distribution (ADD) within an imaging volume. A variety of biological processes, ranging from development to disease and trauma, may lead to changes in the ADD in the central and peripheral nervous systems. Unlike previously proposed methods, this ADD experimental design and estimation framework employs a more general, nonparametric approach, without a priori assumptions about the underlying form of the ADD, making it suitable to analyze abnormal tissue. In the current study, this framework was used on an ex vivo ferret spinal cord, while emphasizing the way in which the ADD can be weighted by either the number or the volume of the axons. The different weightings, which result in different spatial contrasts, were considered throughout this work. DDE data were analyzed to derive spatially resolved maps of average axon diameter, ADD variance, and extra-axonal volume fraction, along with a novel sub-micron restricted structures map. The morphological information contained in these maps was then used to segment white matter into distinct domains by using a proposed k-means clustering algorithm with spatial contiguity and left–right symmetry constraints, resulting in identifiable white matter tracks. The method was validated by comparing histological measures to the estimated ADDs using a quantitative similarity metric, resulting in good agreement. With further acquisition acceleration and experimental parameters adjustments, this ADD estimation framework could be first used preclinically, and eventually clinically, enabling a wide range of neuroimaging applications for improved understanding of neurodegenerative pathologies and assessing microstructural changes resulting from trauma.

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Section: Discussionmentioning

confidence: 99%

White matter microstructure from nonparametric axon diameter distribution mapping

et al. 2016

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“…Unlike what we observed in vivo , mibolerone did not influence the axon-diameter distributions in sympathetic neurons. Since axon-diameter distribution within nerve fascicles is influenced by the anatomical constraints, namely a fixed number of fibers in an available volume (Pajevic and Basser, 2013), it is possible that the lack of such a constraint influenced the distribution of axon diameter in neurons developing in the low-density culture.…”

Section: Discussionmentioning

confidence: 99%

Axon diameter and axonal transport: In vivo and in vitro effects of androgens

et al. 2015

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Testosterone is a sex hormone involved in brain maturation via multiple molecular mechanisms. Previous human studies described age-related changes in the overall volume and morphological properties of white matter during male puberty. Based on this work, we have proposed that testosterone may induce an increase of radial growth and, possibly, modulate axonal transport. In order to determine whether this is the case we have used two different experimental approaches. With electron microscopy, we have evaluated sex differences in the structural properties of axons in the corpus callosum (splenium) of young rats, and tested consequences of castration carried out after weaning. Then we examined in vitro the effect of the non-aromatizable androgen Mibolerone on the structure and bidirectional transport of wheat-germ agglutinin vesicles in the axons of cultured sympathetic neurons. With electron microscopy, we found robust sex differences in axonal diameter (males>females) and g ratio (males>females). Removal of endogenous testosterone by castration was associated with lower axon diameter and lower g ratio in castrated (vs. intact) males. In vitro, Mibolerone influenced the axonal transport in a time- and dose-dependent manner, and increased the axon caliber as compared with vehicle-treated neurons. These findings are consistent with the role of testosterone in shaping the axon by regulating its radial growth, as predicted by the initial human studies.

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“…19 different physical aspects of the brain compared to peripheral nerves (Chomiak and Hu, 2009;Pajevic and Basser, 2013). Indeed, it is important to be careful with computing the conduction velocity: as shown in a computational work (Pajevic et al, 2014), small changes in its value can have profound effects on neural activity in terms of synchrony and signal…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Introducing axonal myelination in connectomics: A preliminary analysis of g-ratio distribution in healthy subjects

et al. 2018

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Please cite this article as: Mancini, M., Giulietti, G., Dowell, N., Spanò, B., Harrison, N., Bozzali, M., Cercignani, M., Introducing axonal myelination in connectomics: A preliminary analysis of g-ratio distribution in healthy subjects, NeuroImage (2017), doi: 10.1016/j.neuroimage.2017.09.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Introducing axonal myelination in connectomics: a preliminary analysis of g-ratio distribution in healthy subjects Matteo M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT2 AbstractMicrostructural imaging and connectomics are two research areas that hold great potential for investigating brain structure and function. Combining these two approaches can lead to a better and more complete characterization of the brain as a network. The aim of this work is characterizing the connectome from a novel perspective using the myelination measure given by the g-ratio. The g-ratio is the ratio of the inner to the outer diameters of a myelinated axon, whose aggregated value can now be estimated in vivo using MRI. In two different datasets of healthy subjects, we reconstructed the structural connectome and then used the g-ratio estimated from diffusion and magnetization transfer data to characterise the network structure. Significant characteristics of g-ratio weighted graphs emerged. First, the g-ratio distribution across the edges of the graph did not show the power-law distribution observed using the number of streamlines as a weight. Second, connections involving regions related to motor and sensory functions were the highest in myelin content. We also observed significant differences in terms of the hub structure and the rich-club organization suggesting that connections involving hub regions present higher myelination than peripheral connections.Taken together, these findings offer a characterization of g-ratio distribution across the connectome in healthy subjects and lay the foundations for further investigating plasticity and pathology using a similar approach.

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An Optimum Principle Predicts the Distribution of Axon Diameters in Normal White Matter

Cited by 18 publications

References 31 publications

White matter microstructure from nonparametric axon diameter distribution mapping

White matter microstructure from nonparametric axon diameter distribution mapping

Axon diameter and axonal transport: In vivo and in vitro effects of androgens

Introducing axonal myelination in connectomics: A preliminary analysis of g-ratio distribution in healthy subjects

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