Abstract

PurposeTo identify optimal pulsed gradient spin‐echo (PGSE) and oscillating gradient spin‐echo (OGSE) sequence settings for maximizing sensitivity to axon diameter in idealized and practical conditions.MethodsSimulations on a simple two‐compartment white matter model (with nonpermeable cylinders) are used to investigate a wide space of clinically plausible PGSE and OGSE sequence parameters with trapezoidal diffusion gradient waveforms. Signal sensitivity is measured as a derivative of the signal with respect to axon diameter. Models of parallel and dispersed fibers are investigated separately to represent idealized and practical conditions.ResultsSimulations show that, for the simple case of gradients perfectly perpendicular to straight parallel fibers, PGSE always gives maximum sensitivity. However, in real‐world scenarios where fibers have unknown and dispersed orientation, low‐frequency OGSE provides higher sensitivity. Maximum sensitivity results show that on current clinical scanners (G max = 60 mT/m, signal to noise ratio (SNR) = 20) axon diameters below 6 µm are indistinguishable from zero. Scanners with stronger gradient systems such as the Massachusetts General Hospital (MGH) Connectom scanner (G max = 300 mT/m) can extend this sensitivity limit down to 2–3 µm, probing a much greater proportion of the underlying axon diameter distribution.ConclusionLow‐frequency OGSE provides additional sensitivity to PGSE in practical situations. OGSE is particularly advantageous for systems with high performance gradients. Magn Reson Med 75:688–700, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Highlights

  • IntroductionAxon diameter statistics provide information about the function and performance of white matter pathways

  • We find that when gradients are perfectly perpendicular to the fibers, maximum sensitivity is always achieved for N 1⁄4 1, maximum possible d and some G that depends on axon diameter a

  • More complex models increase the difficulty of locating most sensitive sequence parameters and could potentially influence some of the results presented here, e.g., membranes with permeable walls could create an increase in signal loss for sequences with large b-value, oscillating gradient spin-echo (OGSE) sequences with N > 1 would have further advantage over pulsed gradient spin-echo (PGSE) sequences

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Summary

Introduction

Axon diameter statistics provide information about the function and performance of white matter pathways. Published online 25 March 2015 in Wiley Online Library (wileyonlinelibrary.com). VC 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

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