Generation of realistic white matter substrates with controllable morphology for diffusion MRI simulations

Abstract

Numerical phantoms have played a key role in the development of diffusion MRI (dMRI) techniques seeking to estimate features of the microscopic structure of tissue by providing a ground truth for simulation experiments against which we can validate and compare techniques. One common limitation of numerical phantoms which represent white matter (WM) is that they oversimplify the true complex morphology of the tissue which has been revealed through ex vivo studies. It is important to try to generate WM numerical phantoms that capture this realistic complexity in order to understand how it impacts the dMRI signal. This thesis presents work towards improving the realism of WM numerical phantoms by generating fibres mimicking natural fibre genesis. A novel phantom generator is presented which was developed over two works, resulting in Contextual Fibre Growth (ConFiG). ConFiG grows fibres one-by-one, following simple rules motivated by real axonal guidance mechanisms. These simple rules enable ConFiG to generate phantoms with tuneable microstructural features by growing fibres while attempting to meet morphological targets such as user-specified density and orientation distribution. We compare ConFiG to the state-of-the-art approach based on packing fibres together by generating phantoms in a range of fibre configurations including crossing fibre bundles and orientation dispersion. Results demonstrate that ConFiG produces phantoms with up to 20% higher densities than the state-of-the-art, particularly in complex configurations with crossing fibres. We additionally show that the microstructural morphology of ConFiG phantoms is comparable to real tissue, producing diameter and orientation distributions close to electron microscopy estimates from real tissue as well as capturing complex fibre cross sections. ConFiG is applied to investigate the intra-axonal diffusivity and probe assumptions in a family of dMRI modelling techniques based on spherical deconvolution (SD), demonstrating that the microscopic variations in fibres’ shapes affects the diffusion within axons. This leads to variations in the per-fibre signal contrary to the assumptions inherent in SD which may have a knock-on effect in popular techniques such as tractography

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