Coaxially Electrospun Axon-Mimicking Fibers for Diffusion Magnetic Resonance Imaging Feng-Lei Zhou, †,‡ Penny L. Hubbard, †,§ Stephen J. Eichhorn, ∥ and Geoffrey J.M. Parker* ,†,§ † Centre for Imaging Sciences, Manchester Academic Health Science Centre, § Biomedical Imaging Institute, and ‡ Materials Science Centre, School of Materials, The University of Manchester, Manchester M13 9PT, United Kingdom ∥ Physics, College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter EX4 4QF, United Kingdom ABSTRACT: The study of brain structure and connectivity using diffusion magnetic resonance imaging (dMRI) has recently gained substantial interest. However, the use of dMRI still faces major challenges because of the lack of standard materials for validation. The present work reports on brain tissue-mimetic materials composed of hollow microfibers for application as a standard material in dMRI. These hollow fibers were fabricated via a simple and one-step coaxial electrospining (co-ES) process. Poly(ε- caprolactone) (PCL) and polyethylene oxide (PEO) were employed as shell and core materials, respectively, to achieve the most stable co-ES process. These co-ES hollow PCL fibers have different inner diameters, which mainly depend on the flow rate of the core solution and have the potential to cover the size range of the brain tissue we aimed to mimic. Co-ES aligned hollow PCL fibers were characterized using optical and electron microscopy and tested as brain white matter mimics on a high-field magnetic resonance imaging (MRI) scanner. To the best of our knowledge, this is the first time that co-ES hollow fibers have been successfully used as a tissue mimic or phantom in diffusion MRI. The results of the present study provide evidence that this phantom can mimic the dMRI behavior of cellular barriers imposed by axonal cell membranes and myelin; the measured diffusivity is compatible with that of in vivo biological tissues. Together these results suggest the potential use of co-ES hollow microfibers as tissue-mimicking phantoms in the field of medical imaging. KEYWORDS: coaxial electrospinning, hollow fibers, diffusion magnetic resonance imaging, phantom ■ INTRODUCTION Brain structure and internal connectivity are areas of substantial past and current research activity. Diffusion magnetic resonance imaging (dMRI) provides a noninvasive tool to explore brain tissue by the measurements of the passive diffusion of tissue water among the cellular structures, the classic example being the anisotropic diffusion observed within white matter. 1 Brain white matter consists of highly ordered bundles at the molecular (filaments), microscopic (axons), and macroscopic (tracts) length scales, with orientationally coherent structure often persisting for more than the MRI voxel length scale (∼2 mm). This tissue, with its highly organized hierarchical structures, leads to an orientationally anisotropic fibrous arrangement in vivo, both in animals and in humans. MRI tissue mimics or phantoms for neurological use have to date proved to be a promising, but limited, tool for calibration and validation of dMRI methods, such as tractography and microstructure measurement. 2,3 These phantoms aim to approximate the cellular structure of tissues (micrometers) and the long-range connections within the brain (centimeters). It is advantageous to have a phantom that exhibits the same or similar properties (“cell” size, “tract” structure, “membrane” permeability, etc.) to human and/or animal tissue, but there are significant problems with using the existing phantoms for brain dMRI. 4 Examples of existing phantom materials are natural plant materials (e.g., asparagus stems), animal tissues, (e.g., excised pig and rat spinal cord) as well as other animal nerve structures (e.g., garfish or lobster nerves), all of which have been used as biological phantoms. 5−9 The exact microstructure and diffusion characteristics of these materials are however generally not a close match to in vivo human tissue, and they are inherently uncontrollable in experimental use and change on excision and preservation and during storage. They are therefore poor choices for calibration purposes, although an MRI compatible viable isolated tissue maintenance chamber, which allows white matter tissue to be kept in a viable in vivo state for many hours, could enable animal tissues to perform better as phantoms. 10 Synthetic phantoms, which aim to mimic axons and fiber bundles, such as those made from glass or plastic capillary and textile filament fibers, have been proposed to overcome these issues. 9,11−14 However, the rigidity of glass capillaries and the large diameters of plastic capillaries impose limits to the macroscopic and microscopic geometry of phantom design. None of the available textile filament fibers are hollow, and all existing synthetic options have very low and fixed membrane Received: September 7, 2012 Accepted: November 7, 2012 Published: November 7, 2012 Research Article www.acsami.org © 2012 American Chemical Society 6311 dx.doi.org/10.1021/am301919s | ACS Appl. Mater. Interfaces 2012, 4, 6311−6316