Detection of acute nervous system injury with advanced diffusion-weighted MRI: a simulation and sensitivity analysis

• Published in: NMR in biomedicine 2015-11, Vol.28 (11), p.1489-1506
• Main Authors: Skinner, Nathan P., Kurpad, Shekar N., Schmit, Brian D., Budde, Matthew D.
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; axonal injury; beading; Computer Simulation; Diffuse Axonal Injury - pathology; diffusion kurtosis; diffusion tensor imaging; Diffusion Tensor Imaging - methods; double pulsed field gradient; Humans; Image Enhancement - methods; Image Interpretation, Computer-Assisted - methods; Models, Neurological; Models, Statistical; Reproducibility of Results; Sensitivity and Specificity
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.3405

Diffusion‐weighted imaging (DWI) is a powerful tool to investigate the microscopic structure of the central nervous system (CNS). Diffusion tensor imaging (DTI), a common model of the DWI signal, has a demonstrated sensitivity to detect microscopic changes as a result of injury or disease. However, DTI and other similar models have inherent limitations that reduce their specificity for certain pathological features, particularly in tissues with complex fiber arrangements. Methods such as double pulsed field gradient (dPFG) and q‐vector magic angle spinning (qMAS) have been proposed to specifically probe the underlying microscopic anisotropy without interference from the macroscopic tissue organization. This is particularly important for the study of acute injury, where abrupt changes in the microscopic morphology of axons and dendrites manifest as focal enlargements known as beading. The purpose of this work was to assess the relative sensitivity of DWI measures to beading in the context of macroscopic fiber organization and edema. Computational simulations of DWI experiments in normal and beaded axons demonstrated that, although DWI models can be highly specific for the simulated pathologies of beading and volume fraction changes in coherent fiber pathways, their sensitivity to a single idealized pathology is considerably reduced in crossing and dispersed fibers. However, dPFG and qMAS have a high sensitivity for beading, even in complex fiber tracts. Moreover, in tissues with coherent arrangements, such as the spinal cord or nerve fibers in which tract orientation is known a priori, a specific dPFG sequence variant decreases the effects of edema and improves specificity for beading. Collectively, the simulation results demonstrate that advanced DWI methods, particularly those which sample diffusion along multiple directions within a single acquisition, have improved sensitivity to acute axonal injury over conventional DTI metrics and hold promise for more informative clinical diagnostic use in CNS injury evaluation. Copyright © 2015 John Wiley & Sons, Ltd. Diffusion‐weighted imaging experiments were simulated in models of acute neuronal injury to test several analysis parameters. Diffusion models were tested in order to determine sensitivity to injury in a variety of fiber orientations. Although many models require coherent fiber tracts, some recently proposed techniques show improved sensitivity to injury regardless of tissue complexity. This can be sim