Axcaliber: A method for measuring axon diameter distribution from diffusion MRI

The diameter of a myelinated nerve axon is directly proportional to its conduction velocity, so the axon diameter distribution helps determine the channel capacity of nervous transmission along fascicles in the central (CNS) and peripheral nervous systems (PNS). Previously, this histological information could only be obtained using invasive tissue biopsies. Here we propose a new NMR‐based approach that employs a model of water diffusion within “restricted” cylindrical axons to estimate their diameter distribution within a nerve bundle. This approach can be combined with MRI to furnish an estimate of the axon diameter distribution within each voxel. This method is validated by comparing the diameter distributions measured using the NMR and histological techniques on sciatic and optic nerve tissue specimens. The axon diameter distribution measured in each voxel of porcine spinal cord using MRI and using histological methods were similar. Applications are expected in longitudinal studies designed to follow nerve growth in normal and abnormal development, as well as in diagnosing disorders and diseases affecting specific populations of axons in the CNS and PNS. Magn Reson Med 59:1347–1354, 2008. © 2008 Wiley‐Liss, Inc.

[1]  J. Hursh.  THE PROPERTIES OF GROWING NERVE FIBERS , 1939 .

[2]  J. E. Tanner,et al.  Spin diffusion measurements : spin echoes in the presence of a time-dependent field gradient , 1965 .

[3]  K. J. Packer,et al.  Pulsed NMR studies of restricted diffusion. I. Droplet size distributions in emulsions , 1972 .

[4]  R. A. Davidoff.  From Neuron to Brain , 1977, Neurology.

[5]  S. Waxman.  Determinants of conduction velocity in myelinated nerve fibers , 1980, Muscle & nerve.

[6]  J. M. Ritchie,et al.  On the relation between fibre diameter and conduction velocity in myelinated nerve fibres , 1982, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[7]  P. Callaghan,et al.  Diffusion of fat and water in cheese as studied by pulsed field gradient nuclear magnetic resonance , 1983 .

[8]  M. Alexander,et al.  Principles of Neural Science , 1981 .

[9]  J. Tsuruda,et al.  Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. , 1990, Radiology.

[10]  W. Raub.  From the National Institutes of Health. , 1990, JAMA.

[11]  D. Cory,et al.  Measurement of translational displacement probabilities by NMR: An indicator of compartmentation , 1990, Magnetic resonance in medicine.

[12]  K. J. Packer,et al.  Rapid determination of water droplet size distributions by PFG-NMR , 1990 .

[13]  P. Callaghan,et al.  Diffraction-like effects in NMR diffusion studies of fluids in porous solids , 1991, Nature.

[14]  H. Pfeifer.  Principles of Nuclear Magnetic Resonance Microscopy , 1992 .

[15]  C. Beaulieu,et al.  Determinants of anisotropic water diffusion in nerves , 1994, Magnetic resonance in medicine.

[16]  P. Basser,et al.  MR diffusion tensor spectroscopy and imaging. , 1994, Biophysical journal.

[17]  P. Basser.  Inferring microstructural features and the physiological state of tissues from diffusion‐weighted images , 1995, NMR in biomedicine.

[18]  David S. Martin,et al.  Diffusion and Perfusion Magnetic Resonance Imaging: Applications to Functional MRI , 1996 .

[19]  P. Basser,et al.  Toward a quantitative assessment of diffusion anisotropy , 1996, Magnetic resonance in medicine.

[20]  P. Basser,et al.  Diffusion tensor MR imaging of the human brain. , 1996, Radiology.

[21]  S Arndt,et al.  An MRI study of the corpus callosum in autism. , 1997, The American journal of psychiatry.

[22]  P. Basser,et al.  A simplified method to measure the diffusion tensor from seven MR images , 1998, Magnetic resonance in medicine.

[23]  I. Bone,et al.  ‘The Axon–Structure, function and Pathophysiology’ , 1998, Spinal Cord.

[24]  P. V. van Zijl,et al.  Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging , 1999, Annals of neurology.

[25]  M. Raichle,et al.  Tracking neuronal fiber pathways in the living human brain. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Y. Cohen,et al.  Displacement imaging of spinal cord using q‐space diffusion‐weighted MRI , 2000, Magnetic resonance in medicine.

[27]  P. Basser,et al.  In vivo fiber tractography using DT‐MRI data , 2000, Magnetic resonance in medicine.

[28]  Sinisa Pajevic,et al.  Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: Application to white matter fiber tract mapping in the human brain , 1999, Magnetic resonance in medicine.

[29]  S Cluskey,et al.  Mechanisms of neurodegeneration in amyotrophic lateral sclerosis , 2001, Molecular pathology : MP.

[30]  Derek K. Jones,et al.  Virtual in Vivo Interactive Dissection of White Matter Fasciculi in the Human Brain , 2002, NeuroImage.

[31]  T. Hendler,et al.  High b‐value q‐space analyzed diffusion‐weighted MRI: Application to multiple sclerosis , 2002, Magnetic resonance in medicine.

[32]  Derek K. Jones,et al.  Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review , 2002 .

[33]  M. Johns,et al.  Measurement of emulsion droplet sizes using PFG NMR and regularization methods. , 2003, Journal of colloid and interface science.

[34]  P. Basser,et al.  New modeling and experimental framework to characterize hindered and restricted water diffusion in brain white matter , 2004, Magnetic resonance in medicine.

[35]  S. Allpress,et al.  Sensory nerve pathology in amyotrophic lateral sclerosis , 2004, Acta Neuropathologica.

[36]  P. Salinas,et al.  Retrograde signalling at the synapse: a role for Wnt proteins. , 2005, Biochemical Society transactions.

[37]  Yaniv Assaf,et al.  Composite hindered and restricted model of diffusion (CHARMED) MR imaging of the human brain , 2005, NeuroImage.

[38]  Y. Yovel,et al.  AxCaliber – A Method to Measure the Axon Diameter Distribution and Density in Neuronal Tissues , 2005 .

[39]  S. Wakana,et al.  MRI Atlas of Human White Matter , 2005 .

[40]  P. Szeszko,et al.  MRI atlas of human white matter , 2006 .

[41]  On the Relation between the Conduction-rate , the Fibre-diameter and the Internodal Distance of the Medullated Nerve Fibre , 2007 .

[42]  Yaniv Assaf,et al.  Virtual definition of neuronal tissue by cluster analysis of multi-parametric imaging (virtual-dot-com imaging) , 2007, NeuroImage.