Kakkar, Lebina Shrestha;
(2017)
Axon diameter mapping using diffusion MRI.
Doctoral thesis , UCL (University College London).
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Abstract
Axon diameter plays a key role in the function and performance of nerve pathways of the central and peripheral nervous system. Therefore, there is a growing interest in imaging axon diameter non-invasively. One such technique is using diffusion MRI. The purpose of this thesis is to test the feasibility of axon diameter imaging using diffusion MRI. This thesis provides for the first time a thorough experimental framework for evaluation and comparison of diffusion MR sequences, specifically two promising sequences: SDE and OGSE. The thesis involves designing a phantom to determine intrinsic sensitivity of the diffusion sequences to axon diameters. Additional experiments involving an ex vivo monkey brain and a viable rat sciatic nerve are carried out. The comparison of OGSE and SDE sequences across all different experiments demonstrate that OGSE is better than SDE. Diameter estimates of the optimal sequences are compared to the ground truth and the accuracy are found to depend on the gradient strength and SNR. For clinical scanners (G=62 mT/m and SNR>20), diameters of 5 μm are below the resolution limit. At G=300 mT/m and SNR=20, the resolution limit is 2.5 μm within an ex vivo monkey brain, causing overestimated diameters; however, an excellent prediction of the low-high-low diameter trend across the corpus callosum is observed. For G=800 mT/m and SNR=10, the resolution limit is at 2.5-3 μm for a viable rat sciatic nerve and excellent histology match is obtained. This thesis demonstrates that axon diameter imaging using diffusion MRI is possible in the nervous system. The small axons of the central nervous system require strong gradients, which are increasingly becoming more available, and peripheral nervous system have axons that are large enough to be imaged at clinical gradient strengths. This, therefore, opens up possibilities of using axon diameters as biomarkers for neurodegenerative diseases and peripheral nerve regeneration studies.
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