Infusion mechanisms in brain white matter and its dependence of microstructure: an experimental study of hydraulic permeability
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Published version
Author(s)
Type
Journal Article
Abstract
Objective: Hydraulic permeability is a topic of deep interest in biological materials because of its important role in a range of drug delivery-based therapies. The strong dependence of permeability on the geometry and topology of pore structure and the lack of detailed knowledge of these parameters in the case of brain tissue makes the study more challenging. Although theoretical models have been developed for hydraulic permeability, there is limited consensus on the validity of existing experimental evidence to complement these models. In the present study, we measure the permeability of white matter (WM) of fresh ovine brain tissue considering the localised heterogeneities in the medium using an infusion based experimental set up, iPerfusion. We measure the flow across different parts of the WM in response to applied pressures for a sample of specific dimensions and calculate the permeability from directly measured parameters. Furthermore, we directly probe the effect of anisotropy of the tissue on permeability by considering the directionality of tissue on the obtained values. Additionally, we investigate whether WM hydraulic permeability changes with post-mortem time. To our knowledge, this is the first report of experimental measurements of the localised WM permeability, showing the effect of axon directionality on permeability. This work provides a significant contribution to the successful development of intra-tumoural infusion-based technologies, such as convection-enhanced delivery (CED), which are based on the delivery of drugs directly by injection under positive pressure into the brain.
Date Issued
2021-04-01
Date Acceptance
2020-09-03
Citation
IEEE Transactions on Biomedical Engineering, 2021, 68 (4), pp.1229-1237
ISSN
0018-9294
Publisher
Institute of Electrical and Electronics Engineers
Start Page
1229
End Page
1237
Journal / Book Title
IEEE Transactions on Biomedical Engineering
Volume
68
Issue
4
Copyright Statement
© 2020 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/
License URL
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Commission of the European Communities
Engineering & Physical Science Research Council (EPSRC)
Royal Academy Of Engineering
Grant Number
EP/N025954/1
688279
EP/J010499/1
BMPF_P67271
Subjects
0801 Artificial Intelligence and Image Processing
0903 Biomedical Engineering
0906 Electrical and Electronic Engineering
Biomedical Engineering
Publication Status
Published
Date Publish Online
2020-09-15