Feng-Lei Zhou

Biomimetic phantom for the validation of diffusion magnetic resonance imaging

A range of advanced diffusion MRI (dMRI) techniques are currently in development which characterize the orientation of white matter fibers using diffusion tensor imaging (DTI). There is a need for a physical phantom with microstructural features of the brains white matter to help validate these methods.

Coaxially electrospun axon-mimicking fibers for diffusion magnetic resonance imaging.

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.

Biomimetic Phantom for Cardiac Diffusion MRI

Diffusion magnetic resonance imaging (MRI) is increasingly used to characterize cardiac tissue microstructure, necessitating the use of physiologically relevant phantoms for methods development. Existing phantoms are generally simplistic and mostly simulate diffusion in the brain. Thus, there is a need for phantoms mimicking diffusion in cardiac tissue.

Preparation and characterization of polycaprolactone microspheres by electrospraying

ABSTRACT The ability to reproducibly produce and effectively collect electrosprayed polymeric microspheres with controlled morphology and size in bulk form is challenging. In this study, microparticles were produced by electrospraying polycaprolactone (PCL) of various molecular weights and solution concentrations in chloroform, and by collecting materials on different substrates. The resultant PCL microparticles were characterized by optical and electron microscopy to investigate the effect of molecular weight, solution concentration, applied voltage, working distance, and flow rate on their morphology and size. The work demonstrates the key role of a moderate molecular weight and/or solution concentration in the formation of spherical PCL particles via an electrospraying process. Increasing the applied voltage was found to produce smaller and more uniform PCL microparticles. There was a relatively low increase in the particle average size with an increase in the working distance and flow rate. Four types of substrates were adopted to collect electrosprayed PCL particles: a glass slide, aluminium foil, liquid bath, and copper wire. Unlike 2D bulk structures collected on the other substrates, a 3D tubular structure of microspheres was formed on the copper wire which could find application in the construction of 3D tumor mimics.

Diffusion tensor MRI phantom exhibits anomalous diffusion

This paper reports diffusion weighted MRI measurements of cyclohexane in a novel diffusion tensor MRI phantom composed of hollow coaxial electrospun fibers (average diameter 10.2 μm). Recent studies of the phantom demonstrated its potential as a calibration standard at low b values (less than 1000 s/mm<;sup>2<;/sup>) for mean diffusivity and fractional anisotropy. In this paper, we extend the characterization of cyclohexane diffusion in this heterogeneous, anisotropic material to high b values (up to 5000 s/mm<;sup>2<;/sup>), where the apparent diffusive motion of the cyclohexane exhibits anomalous behavior (i.e., the molecular mean squared displacement increases with time raised to the fractional power 2α/β). Diffusion tensor MRI was performed at 9.4 T using an Agilent imaging scanner and the data fit to a fractional order Mittag-Leffler (generalized exponential) decay model. Diffusion along the fibers was found to be Gaussian (2α/β=l), while diffusion across the fibers was sub-diffusive (2α/β<;l). Fiber tract reconstruction of the data was consistent with scanning electron micrograph images of the material. These studies suggest that this phantom material may be used to calibrate MR systems in both the normal (Gaussian) and anomalous diffusion regimes.

Axon mimicking hydrophilic hollow polycaprolactone microfibres for diffusion magnetic resonance imaging

Highly hydrophilic hollow polycaprolactone (PCL) microfibres were developed as building elements to create tissue-mimicking test objects (phantoms) for validation of diffusion magnetic resonance imaging (MRI). These microfibres were fabricated by the co-electrospinning of PCL-polysiloxane-based surfactant (PSi) mixture as shell and polyethylene oxide as core. The addition of PSi had a significant effect on the size of resultant electrospun fibres and the formation of hollow microfibres. The presence of PSi in both co-electrospun PCL microfibre surface and cross-section, revealed by X-ray energy dispersive spectroscopy (EDX), enabled water to wet these fibres completely (i.e., zero contact angle) and remained active for up to 12 months after immersing in water. PCL and PCL-PSi fibres with uniaxial orientation were constructed into water-filled phantoms. MR measurement revealed that water molecules diffuse anisotropically in the PCL-PSi phantom. Co-electrospun hollow PCL-PSi microfibres have desirable hydrophilic properties for the construction of a new generation of tissue-mimicking dMRI phantoms.

Hollow polycaprolactone microspheres with/without single surface hole by co-electrospraying

We describe the co-electrospraying of hollow microspheres from a polycaprolactone (PCL) shell solution and various core solutions including water, cyclohexane, poly(ethylene oxide) (PEO), and polyethylene glycol (PEG), using different collectors. The morphologies of the resultant microspheres were characterized by scanning electron microscopy (SEM), confocal microscopy, and nano-X-ray computed tomography (nano-XCT). The core/shell solution miscibility played an important role in the co-electrospraying process and the formation of microsphere structures. Spherical particles were more likely to be produced from miscible combinations of core/shell solutions than from immiscible ones. Hollow PCL microspheres with a single hole in their surfaces were produced when an ethanol bath was used as the collector. The mechanism by which the core/shell structure is transformed into single-hole hollow microspheres is proposed to be primarily based on the evaporation through the shell and extraction by ethanol of the core solution and is described in detail. Additionally, we present a 3D macroscopic tubular structure composed of hollow PCL microspheres, directly assembled on a copper wire collector during co-electrospraying. SEM and nano-XCT confirm that microspheres in the 3D bulk structure remain hollow.

A biomimetic tumour tissue phantom for validating diffusion-weighted MRI measurements

To develop a biomimetic tumor tissue phantom which more closely reflects water diffusion in biological tissue than previously used phantoms, and to evaluate the stability of the phantom and its potential as a tool for validating diffusion‐weighted (DW) MRI measurements.

Co-electrospun Brain Mimetic Hollow Microfibres Fibres for Diffusion Magnetic Resonance Imaging

Diffusion magnetic resonance imaging (dMRI) provides a non-invasive tool to explore biological tissues, including brain with its highly organised hierarchical fibrous structures. An MR phantom is a test object with known size and material for the calibration of MR scanners and the validation of image processing algorithms. Despite extensive research on the development of brain-mimicking phantoms, there are significant problems with using the existing phantoms for dMRI. This chapter is designed to lead the reader through the development of brain-mimetic phantoms for application in dMRI. Our starting point is a brief introduction to the dMRI technique and phantoms previously developed to mimic brain tissues. The second section focuses on the preparation and characterization of novel physical phantoms composed of co-electrospun hollow microfibres. Finally, the evaluation of the developed co-electrospun phantoms is presented in the third section.

Stability and reproducibility of co-electrospun brain-mimicking phantoms for quality assurance of diffusion MRI sequences

ABSTRACT Grey and white matter mimicking phantoms are important for assessing variations in diffusion MR measures at a single time point and over an extended period of time. This work investigates the stability of brain‐mimicking microfibre phantoms and reproducibility of their MR derived diffusion parameters. The microfibres were produced by co‐electrospinning and characterized by scanning electron microscopy (SEM). Grey matter and white matter phantoms were constructed from random and aligned microfibres, respectively. MR data were acquired from these phantoms over a period of 33 months. SEM images revealed that only small changes in fibre microstructure occurred over 30 months. The coefficient of variation in MR measurements across all time‐points was between 1.6% and 3.4% for MD across all phantoms and FA in white matter phantoms. This was within the limits expected for intra‐scanner variability, thereby confirming phantom stability over 33 months. These specialised diffusion phantoms may be used in a clinical environment for intra and inter‐site quality assurance purposes, and for validation of quantitative diffusion biomarkers. HIGHLIGHTSGrey and white matter mimicking phantoms showed mean diffusivity and fractional anisotropy values typical of tissue.Diffusion measures for the phantoms were stable over 33 months.The porosity of the phantoms was observed to be stable over 30 months.The phantoms may be used for QA purposes in a clinical environment and for validation of quantitative diffusion biomarkers.