Assessing the accuracy of using oscillating gradient spin echo sequences with AxCaliber to infer micron-sized axon diameters

Current magnetic resonance imaging (MRI) axon diameter measurements rely on the pulsed gradient spin-echo sequence, which is unable to provide diffusion times short enough to measure small axon diameters. This study combines the AxCaliber axon diameter fitting method with data generated from Monte Carlo simulations of oscillating gradient spin-echo sequences (OGSE) to infer micron-sized axon diameters, in order to determine the feasibility of using MRI to infer smaller axon diameters in brain tissue. Monte Carlo computer simulation data were synthesized from tissue geometries of cylinders of different diameters using a range of gradient frequencies in the cosine OGSE sequence . Data were fitted to the AxCaliber method modified to allow the new pulse sequence. Intra- and extra-axonal water were studied separately and together. The simulations revealed the extra-axonal model to be problematic. Rather than change the model, we found that restricting the range of gradient frequencies such that the measured apparent diffusion coefficient was constant over that range resulted in more accurate fitted diameters. Thus a careful selection of frequency ranges is needed for the AxCaliber method to correctly model extra-axonal water, or adaptations to the method are needed. This restriction helped reduce the necessary gradient strengths for measurements that could be performed with parameters feasible for a Bruker BG6 gradient set. For these experiments, the simulations inferred diameters as small as 0.5 μm on square-packed and randomly packed cylinders. The accuracy of the inferred diameters was found to be dependent on the signal-to-noise ratio (SNR), with smaller diameters more affected by noise, although all diameter distributions were distinguishable from one another for all SNRs tested. The results of this study indicate the feasibility of using MRI with OGSE on preclinical scanners to infer small axon diameters.