title: PGSE, OGSE, and sensitivity to axon diameter in diffusion MRI: Insight from a simulation study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Low-frequency OGSE provides additional sensitivity to PGSE in practical situations. OGSE is particularly advantageous for systems with high performance gradients.
authors: Department of Computer Science and Centre for Medical Image Computing, University College London (UCL), London, UK.
authors: Ivana
authors: I
authors: Drobnjak
authors: Department of Computer Science and Centre for Medical Image Computing, University College London (UCL), London, UK.
authors: Hui
authors: H
authors: Zhang
authors: Department of Computer Science and Centre for Medical Image Computing, University College London (UCL), London, UK.
authors: Andrada
authors: A
authors: Ianuş
authors: Department of Computer Science and Centre for Medical Image Computing, University College London (UCL), London, UK.
authors: Enrico
authors: E
authors: Kaden
authors: Department of Computer Science and Centre for Medical Image Computing, University College London (UCL), London, UK.
authors: Daniel C
authors: DC
authors: Alexander
mesh_terms: D001369:Axons / Q000648:ultrastructure*; D003198:Computer Simulation; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D019047:Phantoms, Imaging; D012680:Sensitivity and Specificity; D066127:White Matter / Q000033:anatomy & histology*
keywords: axon diameter; diffusion gradients; diffusion imaging; oscillating gradient spin-echo; pulsed gradient spin-echo