Abstract
Diffusion‐weighted MRI is an important tool for in vivo and non‐invasive axon morphometry. The ActiveAx technique utilises an optimised acquisition protocol to infer orientationally invariant indices of axon diameter and density by fitting a model of white matter to the acquired data. In this study, we investigated the factors that influence the sensitivity to small‐diameter axons, namely the gradient strength of the acquisition protocol and the model fitting routine. Diffusion‐weighted ex. vivo images of the mouse brain were acquired using 16.4‐T MRI with high (G max of 300 mT/m) and ultra‐high (G max of 1350 mT/m) gradient strength acquisitions. The estimated axon diameter indices of the mid‐sagittal corpus callosum were validated using electron microscopy. In addition, a dictionary‐based fitting routine was employed and evaluated. Axon diameter indices were closer to electron microscopy measures when higher gradient strengths were employed. Despite the improvement, estimated axon diameter indices (a lower bound of ~ 1.8 μm) remained higher than the measurements obtained using electron microscopy (~1.2 μm). We further observed that limitations of pulsed gradient spin echo (PGSE) acquisition sequences and axonal dispersion could also influence the sensitivity with which axon diameter indices could be estimated. Our results highlight the influence of acquisition protocol, tissue model and model fitting, in addition to gradient strength, on advanced microstructural diffusion‐weighted imaging techniques. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.
Highlights
Advances in diffusion-weighted MRI over the past 19 years have provided in vivo non-invasive estimates of axon morphometry [1,2,3,4,5,6,7,8]
Measures of axon diameter from electron microscopy (EM) were higher than those reported in a previous study [38], in which shrinkage artefacts caused by tissue preparation affected the results
We report the non-invasive measurement of the axon diameter index in the mouse corpus callosum from a diffusion-weighted MRI acquisition with ultra-high gradient strength, and validate the measurement against EM data
Summary
Advances in diffusion-weighted MRI over the past 19 years have provided in vivo non-invasive estimates of axon morphometry [1,2,3,4,5,6,7,8]. Yang School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia summary statistic of the axon diameter distribution, using acquisition protocols that are feasible for in vivo human imaging [3]. This technique models the geometry of tissue microstructure and fits the model to diffusion-weighted measurements of different encoding properties (e.g. duration, directions and strengths). The model assumes that the signal attenuation during the diffusion-encoding gradient originates from the sum of water displacements in different tissue media, such as intra- and extraaxonal spaces. Yang Faculty of Information Engineering, Southwest University of Science and Technology, Mianyang, China
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