title: AxonPacking: An Open-Source Software to Simulate Arrangements of Axons in White Matter.
abstract: HIGHLIGHTSAxonPacking: Open-source software for simulating white matter microstructure.Validation on a theoretical disk packing problem.Reproducible and stable for various densities and diameter distributions.Can be used to study interplay between myelin/fiber density and restricted fraction. Quantitative Magnetic Resonance Imaging (MRI) can provide parameters that describe white matter microstructure, such as the fiber volume fraction (FVF), the myelin volume fraction (MVF) or the axon volume fraction (AVF) via the fraction of restricted water (fr). While already being used for clinical application, the complex interplay between these parameters requires thorough validation via simulations. These simulations required a realistic, controlled and adaptable model of the white matter axons with the surrounding myelin sheath. While there already exist useful algorithms to perform this task, none of them combine optimisation of axon packing, presence of myelin sheath and availability as free and open source software. Here, we introduce a novel disk packing algorithm that addresses these issues. The performance of the algorithm is tested in term of reproducibility over 50 runs, resulting density, and stability over iterations. This tool was then used to derive multiple values of FVF and to study the impact of this parameter onfrand MVF in light of the known microstructure based on histology sample. The standard deviation of the axon density over runs was lower than 10-3and the expected hexagonal packing for monodisperse disks was obtained with a density close to the optimal density (obtained: 0.892, theoretical: 0.907). Using an FVF ranging within [0.58, 0.82] and a mean inter-axon gap ranging within [0.1, 1.1] μm, MVF ranged within [0.32, 0.44] andfrranged within [0.39, 0.71], which is consistent with the histology. The proposed algorithm is implemented in the open-source software AxonPacking (https://github.com/neuropoly/axonpacking) and can be useful for validating diffusion models as well as for enabling researchers to study the interplay between microstructure parameters when evaluating qMRI methods.
authors.affiliation: NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique MontrealMontreal, QC, Canada; Signal Processing Department, École Centrale de NantesNantes, France.
authors.forename: Tom
authors.initials: T
authors.lastname: Mingasson
authors.affiliation: NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal Montreal, QC, Canada.
authors.forename: Tanguy
authors.initials: T
authors.lastname: Duval
authors.affiliation: NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique MontrealMontreal, QC, Canada; Department of Biomedical Engineering, Montreal Heart Institute, University of MontrealMontreal, QC, Canada.
authors.forename: Nikola
authors.initials: N
authors.lastname: Stikov
authors.affiliation: NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique MontrealMontreal, QC, Canada; Functional Neuroimaging Unit, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Université de MontréalMontreal, QC, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Cohen-Adad
keywords: axon density; disks packing; fraction restricted; microstructure; myelin volume; quantitative MRI; white matter