Experimental studies of g-ratio MRI in ex vivo mouse brain

&NA; This study aimed to experimentally evaluate a previously proposed MRI method for mapping axonal g‐ratio (ratio of axon diameters, measured to the inner and outer boundary of myelin). MRI and electron microscopy were used to study excised and fixed brains of control mice and three mouse models of abnormal white matter. The results showed that g‐ratio measured with MRI correlated with histological measures of myelinated axon g‐ratio, but with a bias that is likely due to the presence of non‐myelinated axons. The results also pointed to cases where the MRI g‐ratio model simplifies to be primarily a function of total myelin content. Graphical abstract Figure. No caption available.

[1]  K Suzuki,et al.  TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. , 2001, Nature neuroscience.

[2]  M. Rydmark,et al.  Axon diameter and myelin sheath thickness in nerve fibres of the ventral spinal root of the seventh lumbar nerve of the adult and developing cat. , 1983, Journal of anatomy.

[3]  Robert P. Carson,et al.  Deletion of Rictor in neural progenitor cells reveals contributions of mTORC2 signaling to tuberous sclerosis complex. , 2013, Human molecular genetics.

[4]  Julien Cohen-Adad,et al.  Promise and pitfalls of g-ratio estimation with MRI , 2017, NeuroImage.

[5]  Hans Lassmann,et al.  Cellular Damage and Repair in Multiple Sclerosis , 2004 .

[6]  Kathryn L. West,et al.  Evaluation of diffusion kurtosis imaging in ex vivo hypomyelinated mouse brains , 2016, NeuroImage.

[7]  Alex L. MacKay,et al.  Quantitative interpretation of NMR relaxation data , 1989 .

[8]  Kathryn L. West,et al.  Myelin volume fraction imaging with MRI , 2016, NeuroImage.

[9]  F. Dick,et al.  Whole-Brain In-vivo Measurements of the Axonal G-Ratio in a Group of 37 Healthy Volunteers , 2015, Front. Neurosci..

[10]  F. Kruggel,et al.  Quantitative mapping of the per‐axon diffusion coefficients in brain white matter , 2015, Magnetic resonance in medicine.

[11]  Julien Cohen-Adad,et al.  In vivo histology of the myelin g-ratio with magnetic resonance imaging , 2015, NeuroImage.

[12]  David H Rowitch,et al.  Oligodendrocyte PTEN is required for myelin and axonal integrity, not remyelination , 2010, Annals of neurology.

[13]  Ran Tao,et al.  Myelin, myelin-related disorders, and psychosis , 2015, Schizophrenia Research.

[14]  C. Laule,et al.  Myelin water imaging in multiple sclerosis: quantitative correlations with histopathology , 2006, Multiple sclerosis.

[15]  G. Bartzokis.  Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease , 2004, Neurobiology of Aging.

[16]  Andrew L. Alexander,et al.  Mapping an index of the myelin g-ratio in infants using magnetic resonance imaging , 2016, NeuroImage.

[17]  W. Rushton.  A theory of the effects of fibre size in medullated nerve , 1951, The Journal of physiology.

[18]  Kathryn L. West,et al.  Hypomyelination following deletion of Tsc2 in oligodendrocyte precursors , 2015, Annals of clinical and translational neurology.

[19]  G A Johnson,et al.  Diffusion‐weighted MR microscopy with fast spin‐echo , 1993, Magnetic resonance in medicine.

[20]  J. Thiessen,et al.  Quantitative MRI and ultrastructural examination of the cuprizone mouse model of demyelination , 2013, NMR in biomedicine.

[21]  Brian A. Wandell,et al.  Bound pool fractions complement diffusion measures to describe white matter micro and macrostructure , 2011, NeuroImage.

[22]  K Suzuki,et al.  Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre , 2001, Neuropathology and applied neurobiology.

[23]  A. MacKay,et al.  Magnetic resonance imaging of myelin , 2007, Neurotherapeutics.

[24]  G. B. Pike,et al.  MRI‐based myelin water imaging: A technical review , 2015, Magnetic resonance in medicine.

[25]  Jean-Philippe Thirion,et al.  Image matching as a diffusion process: an analogy with Maxwell's demons , 1998, Medical Image Anal..

[26]  C. Hildebrand,et al.  Changing relation between onset of myelination and axon diameter range in developing feline white matter , 1982, Journal of the Neurological Sciences.

[27]  T. Chomiak,et al.  What Is the Optimal Value of the g-Ratio for Myelinated Fibers in the Rat CNS? A Theoretical Approach , 2009, PloS one.

[28]  J. Helpern,et al.  MRI quantification of non‐Gaussian water diffusion by kurtosis analysis , 2010, NMR in biomedicine.

[29]  Joseph A. Helpern,et al.  White matter characterization with diffusional kurtosis imaging , 2011, NeuroImage.

[30]  Talma Hendler,et al.  Abnormal white matter integrity in young children with autism , 2011, Human brain mapping.

[31]  Daniel C. Alexander,et al.  Multi-compartment microscopic diffusion imaging , 2016, NeuroImage.

[32]  D. Selkoe.  Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[33]  Kathryn L. West,et al.  A revised model for estimating g-ratio from MRI , 2016, NeuroImage.

[34]  Jean-Philippe Thiran,et al.  Accelerated Microstructure Imaging via Convex Optimization (AMICO) from diffusion MRI data , 2015, NeuroImage.

[35]  Matteo Mancini,et al.  Introducing axonal myelination in connectomics: A preliminary analysis of g-ratio distribution in healthy subjects , 2018, NeuroImage.

[36]  Tim B. Dyrby,et al.  Orientationally invariant indices of axon diameter and density from diffusion MRI , 2010, NeuroImage.

[37]  J. Hennig.  Multiecho imaging sequences with low refocusing flip angles , 1988 .

[38]  B. Ardekani,et al.  Estimation of tensors and tensor‐derived measures in diffusional kurtosis imaging , 2011, Magnetic resonance in medicine.

[39]  Robert P. Carson,et al.  Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin , 2012, Neurobiology of Disease.

[40]  J. Julien,et al.  Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Daniel C. Alexander,et al.  NODDI: Practical in vivo neurite orientation dispersion and density imaging of the human brain , 2012, NeuroImage.

[42]  Jelle Veraart,et al.  In vivo quantification of demyelination and recovery using compartment-specific diffusion MRI metrics validated by electron microscopy , 2016, NeuroImage.

[43]  E. Bullmore,et al.  Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: The orbitofronto-striatal model revisited , 2008, Neuroscience & Biobehavioral Reviews.

[44]  M. Horsfield,et al.  Optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging , 1999, Magnetic resonance in medicine.

[45]  Alex J. de Crespigny,et al.  An approach to high resolution diffusion tensor imaging in fixed primate brain , 2007, NeuroImage.

[46]  M. A. Matthews,et al.  A quantitative study of morphological changes accompanying the initiation and progress of myelin production in the dorsal funiculus of the rat spinal cord , 1971, The Journal of comparative neurology.

[47]  Craig K. Jones,et al.  Applications of stimulated echo correction to multicomponent T2 analysis , 2012, Magnetic resonance in medicine.