Assessing the Precision of Magnetic Resonance Imaging Axon Diameter Inferences using Oscillating Gradient Spin Echo Pulse Sequences in a 15 T System

Abstract

Previous research has linked numerous neurological disorders post-mortem to abnormalities in axon distribution and integrity within white matter tracts. Therefore, it is of high interest to investigate methods that will eventually be able to measure axon diameters in white matter tracts in vivo. Diffusion Magnetic Resonance Imaging is a method with the potential to infer microstructure in vivo using temporal diffusion spectroscopy. Temporal diffusion spectroscopy, when used with certain pulse sequences, such as Oscillating Gradient Spin Echo, can be used to infer micron-scale axon diameters. The most common geometric model used to fit the diffusion signals assumes that axons are long, parallel, straight, cylinders, where only the transverse intra-axonal diffusion coefficient is sensitive to the cylinder’s inner diameter. However, previous research has demonstrated that this geometric model tends to overestimate the intra-axonal diameter of axonal fibers. Due to recent advances in hardware, high-gradient strengths can be used to achieve shorter diffusion times and probe smaller restriction sizes than previously possible. To calibrate temporal diffusion spectroscopy with Oscillating Gradient Spin Echo pulse sequences in this project ex vivo mouse brains were imaged, and the genu substructure of the corpus callosum was analyzed. The images were collected using a 15.2 T Bruker NMR system located at the Vanderbilt University of Institute of Imaging Science. Data were collected in two experiments; first an initial calibration experiment was performed to test the proposed parameters. Then a second experiment was conducted to validate the inferred magnetic resonance axon diameters using transmission electron microscopy in a sample of 6 mice (3 male, 3 female)."I would like to acknowledge the financial support provided by the Natural Sciences and Engineering Research Council of Canada (NSERC) and Research Manitoba."Master of Science in Bioscience, Technology and Public Polic