To 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.Methods:
Simulations 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.Results:
Simulations 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 (Gmax = 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 (Gmax = 300 mT/m) can extend this sensitivity limit down to 2–3 μm, probing a much greater proportion of the underlying axon diameter distribution.Conclusion:
Low-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 Wiley Periodicals, Inc.