Determinants of anisotropic water diffusion in nerves

Abstract

We report NMR diffusion measurements of water in three central nervous system models, namely the nonmyelinated olfactory, and the myelinated trigeminal and optic nerves of the spotted and long-nosed garfish. A similar degree of anisotropy of the average diffusion coefficients (DNMR) is observed for all three freshly excised nerve types (DNMR(parallel)/DNMR-(perpendicular) is 3.6 +/- 1.2, 3.2 +/- 0.9, and 2.6 +/- 0.4 for the olfactory, trigeminal, and optic nerves, respectively). The anisotropy of DNMR for the nonmyelinated olfactory nerve argues strongly that myelin is not a necessary determinant of diffusional anisotropy in ordered axonal systems (even though it may contribute when present). Garfish nerves treated with vinblastine, in order to depolymerize microtubules and inhibit fast axonal transport, also exhibit diffusional anisotropy (DNMR(parallel)/DNMR(perpendicular) is 2.6 +/- 0.4, 2.8 +/- 0.8, and 2.2 +/- 0.7 for the olfactory, trigeminal, and optic nerves, respectively) thus excluding a significant role for microtubules and fast axonal transport in that observed anisotropy.

Diffusion‐tensor MRI: theory, experimental design and data analysis – a technical review

“…In the central nervous system (CNS), diffusion anisotropy is not simply caused by myelin in white matter, since several studies have shown that, even before myelin is deposited, diffusion anisotropy can be measured using MRI. [93][94][95][96] Thus, despite the fact that increases in myelin are temporally correlated with increases in diffusion anisotropy, structures other than the myelin sheath must be contributing to diffusion anisotropy. 97 This is an important point, because there is a common misconception that the degree of diffusion anisotropy can be used as a quantitative measure or 'stain' of myelin content, when in reality no such simple relationship exists.…”

A review of diffusion tensor imaging studies in schizophrenia

“…(Parenthetically, this restricted mobility of water is described as anisotropic, whereas unrestricted mobility of water, such as would be observed for cerebrospinal fluid, is described as iso-tropic.) And, while myelination is not essential for diffusion anisotropy of nerves, see for example studies of nonmyelinated garfish olfactory nerves (Beaulieu and Allen, 1994) and studies of neonate brains prior to the appearance of myelin (Huppi et al, 1998), tightly packed multiple myelin membranes accompanying axons are generally assumed to be the major barrier to diffusion in myelinated fiber tracts. Moreover, the tissue properties of white matter fiber tracts, including the density of the fibers, the average fiber diameter, the thickness of the myelin sheaths, and the directionality (or coherence) of the fibers in each voxel, all affect the diffusion of water molecules, and thus, in turn, provide useful information about white matter fiber tract organization.…”

Mapping somatosensory connectivity in adult mice using diffusion MRI tractography and super-resolution track density imaging

“…These findings would not result from connectivity between adjacent layer IV barrels (Feldmeyer, 2012) and, although there is evidence to suggest a higher concentration of myelin within the septal area compared to barrel hollows (Barrera et al, 2012), myelin is not essential for anisotropic diffusion in nerve fibres, with evidence of minor amounts of anisotropy in rodent and piglet cortex (Hoehn-Berlage et al, 1999;Mori et al, 2001;Thornton et al, 1997). In fact, anisotropy from un-myelinated nerves in garfish (Beaulieu and Allen, 1994), rodent (Seo et al, 1999), zebrafish (Ullmann et al, 2013) and human fetal brain (Tucciarone et al, 2009) suggest the radial alignment of microstructure including cell membranes is a sufficient barrier to diffusion to result in anisotropic diffusivity. In addition, complex biological architecture may influence the degree of anisotropy, including axon thickness, density and extracellular space (Beaulieu, 2002).…”