In vivo measurement of axon diameter distribution in the corpus callosum of rat brain

Abstract

Here, we present the first in vivo non-invasive measurement of the axon diameter distribution in the rat corpus callosum. Previously, this measurement was only possible using invasive histological methods. The axon diameter, along with other physical properties, such as the intra-axonal resistance, membrane resistance and capacitance etc. helps determine many important functional properties of nerves, such as their conduction velocity. In this work, we provide a novel magnetic resonance imaging method called AxCaliber, which can resolve the distinct signatures of trapped water molecules diffusing within axons as well as water molecules diffusing freely within the extra-axonal space. Using a series of diffusion weighted magnetic resonance imaging brain scans, we can reliably infer both the distribution of axon diameters and the volume fraction of these axons within each white matter voxel. We were able to verify the known microstructural variation along the corpus callosum of the rat from the anterior (genu) to posterior (splenium) regions. AxCaliber yields a narrow distribution centered approximately 1 microm in the genu and splenium and much broader distributions centered approximately 3 microm in the body of the corpus callosum. The axon diameter distribution found by AxCaliber is generally broader than those usually obtained by histology. One factor contributing to this difference is the significant tissue shrinkage that results from histological preparation. To that end, AxCaliber might provide a better estimate of the in vivo morphology of white matter. Being a magnetic resonance imaging based methodology, AxCaliber has the potential to be used in human scanners for morphological studies of white matter in normal and abnormal development, and white matter related diseases.

Microstructural parameter estimation in vivo using diffusion MRI and structured prior information

“…Refs. 4 and 25). We denote the isotropic volume fraction with f i and the restricted volume fraction with f r , subject to $0\le f_{\mathrm{normali}}+f_{\mathrm{normalr}}\le 1$.…”

Studying neuroanatomy using MRI

“…The composite hindered and restricted water diffusion (CHARMED) model 139 replaced the sticks with cylindrical fibers of fixed diameter and modeled the extra-axonal space using a tensor. AxCaliber 140 further added a distribution of axon diameters and included a compartment to represent stationary/glial cell water 141 . Modified versions of the above models were used in 142 to provide a model for white matter diffusion that was relatively simple and yet complex enough to probe axonal density and diameter.…”

In-Vivo Estimates of Axonal Characteristics Using Optimized Diffusion MRI Protocols for Single Fibre Orientation

“…This avoids the need for high angular resolution, which potentially dramatically reduces the number of required measurements. As in [2,3], we constrain most measurements in the protocol to have gradient direction perpendicular to the fibre bundles, but we include one measurement in the parallel direction for the estimation of diffusivity along the axons. We extend the algorithm to optimize M different PGSE settings and include Ω = diag{w 1 , · · · , w M } with M m=1 w m = 1 in the optimisation of Eq.…”

“…The method is validated in in-vitro optic and sciatic nerve samples and estimated parameters show good correlation with corresponding histology. Barazany et al [3] applies the AxCalibre approach to image axon size distributions in the corpus callosum of live rat brain. However, scan times are long and the high 7T magnetic field and maximum gradient strength (400 mT/m) are impossible to achieve on a live human scanners, that typically operate at 1.5-3T and can achieve maximum gradient strength between 30-60 mT/m.…”

“…To attain the reduction we discard the requirement for orientational invariance and focus on structures with known fibre orientation such as the corpus callosum similar to earlier studies [2,3]. We modify the existing protocol optimization framework [5] to incorporate this a-priori information about fibre organisation and define single fibre (SF) protocols that measure only the diffusion signal perpendicular and parallel to the known fibre orientation.…”