Abstract

Recent advances in diffusion-weighted MRI provide "restricted diffusion signal fraction" and restricting pore size estimates. Materials based on co-electrospun oriented hollow cylinders have been introduced to provide validation for such methods. This study extends this work, exploring accuracy and repeatability using an extended acquisition on a 300 mT/m gradient human MRI scanner, in substrates closely mimicking tissue, that is, non-circular cross-sections, intra-voxel fiber crossing, intra-voxel distributions of pore-sizes, and smaller pore-sizes overall. In a single-blind experiment, diffusion-weighted data were collected from a biomimetic phantom on a 3T Connectom system using multiple gradient directions/diffusion times. Repeated scans established short-term and long-term repeatability. The total scan time (54 min) matched similar protocols used in human studies. The number of distinct fiber populations was estimated using spherical deconvolution, and median pore size estimated through the combination of CHARMED and AxCaliber3D framework. Diffusion-based estimates were compared with measurements derived from scanning electron microscopy. The phantom contained substrates with different orientations, fiber configurations, and pore size distributions. Irrespective of one or two populations within the voxel, the pore-size estimates (~5 μm) and orientation-estimates showed excellent agreement with the median values of pore-size derived from scanning electron microscope and phantom configuration. Measurement repeatability depended on substrate complexity, with lower values seen in samples containing crossing-fibers. Sample-level repeatability was found to be good. While no phantom mimics tissue completely, this study takes a step closer to validating diffusion microstructure measurements for use in vivo by demonstrating the ability to quantify microgeometry in relatively complex configurations.

Highlights

  • Obtaining reliable quantitative tissue microstructure information using non-i­nvasive MRI has long been a holy grail in microstructural MRI.[1,2] Improvements in gradient hardware[3,4] give increased sensitivity to smaller water displacements, and higher signal-t­o-­noise ratio (SNR) per unit time, while improvements in modeling[2] can potentially yield higher specificity to compartment-s­pecific properties

  • For example, the former is taken as an indicator of “axon density,” while the latter is taken as an indicator of axon diameter, one of the major factors influencing the speed of action potentials.[8,9]

  • This single-­blind study used a 3T Connectom human MRI scanner, advanced modeling, and a co-e­lectrospun hollow PCL-­polysiloxane-­ based surfactant (PSi) microfiber phantom to establish the reliability of microfiber diameter estimates in a scan time < 1 h

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Summary

Funding information

EPSRC, Grant/Award Number: EP/ M029778/1; Wolfson Foundation; Wellcome Trust, Grant/Award Number: 096646/Z/11/Z and 104943/Z/14/Z; Biomedical Research Centre (BRC); University of Manchester; University College London; Shanghai Municipal Science and Technology Major Project: 2018SHZDZX01; ZJ Lab; Shanghai Center for Brain Science and Brain-­ Inspired Technology; Ministry of Science and Technology (MOST), Grant/Award Number: MOST 110-­2321-­B-­010-­004, MOST 110-­2321-­B-­010-­007, MOST 110-­2634-­F-­010-­001 and MOST 108-­2321-­ B-­010-­010-­MY2. This study extends this work, exploring accuracy and repeatability using an extended acquisition on a 300 mT/m gradient human MRI scanner, in substrates closely mimicking tissue, that is, non-­circular cross-­sections, intra-­voxel fiber crossing, intra-­voxel distributions of pore-­sizes, and smaller pore-­sizes overall. Diffusion-­based estimates were compared with measurements derived from scanning electron microscopy. Results: The phantom contained substrates with different orientations, fiber configurations, and pore size distributions. | 1515 voxel, the pore-­size estimates (~5 μm) and orientation-e­stimates showed excellent agreement with the median values of pore-­size derived from scanning electron microscope and phantom configuration. Conclusion: While no phantom mimics tissue completely, this study takes a step closer to validating diffusion microstructure measurements for use in vivo by demonstrating the ability to quantify microgeometry in relatively complex configurations. KEYWORDS crossing fiber, diameter, diffusion MRI, electron microscopy, microstructure, phantom

| INTRODUCTION
| METHODS
| RESULTS
| DISCUSSION
| Limitations of the study and future directions
Findings
CONFLICT OF INTEREST
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