Abstract
Objective. The use of diffusion magnetic resonance imaging (dMRI) opens the door to characterizing brain microstructure because water diffusion is anisotropic in axonal fibres in brain white matter and is sensitive to tissue microstructural changes. As dMRI becomes more sophisticated and microstructurally informative, it has become increasingly important to use a reference object (usually called an imaging phantom) for validation of dMRI. This study aims to develop axon-mimicking physical phantoms from biocopolymers and assess their feasibility for validating dMRI measurements. Approach. We employed a simple and one-step method—coaxial electrospinning—to prepare axon-mimicking hollow microfibres from polycaprolactone-b-polyethylene glycol (PCL-b-PEG) and poly(D, L-lactide-co-glycolic) acid (PLGA), and used them as building elements to create axon-mimicking phantoms. Electrospinning was firstly conducted using two types of PCL-b-PEG and two types of PLGA with different molecular weights in various solvents, with different polymer concentrations, for determining their spinnability. Polymer/solvent concentration combinations with good fibre spinnability were used as the shell material in the following co-electrospinning process in which the polyethylene oxide polymer was used as the core material. Following the microstructural characterization of both electrospun and co-electrospun fibres using optical and electron microscopy, two prototype phantoms were constructed from co-electrospun anisotropic hollow microfibres after inserting them into water-filled test tubes. Main results. Hollow microfibres that mimic the axon microstructure were successfully prepared from the appropriate core and shell material combinations. dMRI measurements of two phantoms on a 7 tesla (T) pre-clinical scanner revealed that diffusivity and anisotropy measurements are in the range of brain white matter. Significance. This feasibility study showed that co-electrospun PCL-b-PEG and PLGA microfibre-based axon-mimicking phantoms could be used in the validation of dMRI methods which seek to characterize white matter microstructure.
Highlights
Soft tissues such as human brain white matter and cardiac muscle exhibit a preferred microstructural orientation, with axonal fibres of 0.16-9 μm [1] and cardiac myocytes of 10-25 μm [2] in diameter.Diffusion magnetic resonance imaging has become a non-invasive tool to characterise such microstructure, due to the fact that water diffusion is anisotropic in these fibrous tissues and is sensitive to tissue microstructural changes [3]
The present work primarily reported the microstructures of copolymer fibres via electrospinning and co-electrospinning, and water diffusion behaviour in hollow microfibres, but wettability and physico-chemical properties of copolymers as reported in previous studies [18, 25] are important for the resultant fibre phantoms
As with the PCL-b-Poly(ethylene glycol) (PEG) copolymer, these results demonstrate that both PLGA-I and II can be processed into smooth and uniform fibres using appropriate solvent systems
Summary
Soft tissues such as human brain white matter and cardiac muscle exhibit a preferred microstructural orientation, with axonal fibres of 0.16-9 μm [1] and cardiac myocytes of 10-25 μm [2] in diameter. Diffusion magnetic resonance imaging (dMRI) has become a non-invasive tool to characterise such microstructure, due to the fact that water diffusion is anisotropic in these fibrous tissues and is sensitive to tissue microstructural changes [3]. Physical phantoms have been widely used for validation of dMRI Ac. AUTHOR SUBMITTED MANUSCRIPT - BB-102476.R2. Melt-spun hollow microfibres [5, 6] and 3D printed fibres [7] have shown potential for use in the construction of axon-mimicking MR phantoms. Melt-spun hollow polypropylene (PP) fibres have ~12 μm inner diameter and are mono-dispersed [5], whereas fused deposition modelling (FDM) 3D printed fibres have a thickness of
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