On the microstructural origin of brain white matter hydraulic permeability
File(s)
Accepted version
Author(s)
Vidotto, Marco
Bernardini, Andrea
Trovatelli, Marco
De Momi, Elena
Dini, Daniele
Type
Journal Article
Abstract
Brain microstructure plays a key role in driving the transport of drug molecules directly administered to the brain tissue, as in Convection-Enhanced Delivery procedures. The proposed research analyzes the hydraulic permeability of two white matter (WM) areas (corpus callosum and fornix) whose three-dimensional microstructure was reconstructed starting from the acquisition of electron microscopy images. We cut the two volumes with 20 equally spaced planes distributed along two perpendicular directions, and, on each plane, we computed the corresponding permeability vector. Then, we considered that the WM structure is mainly composed of elongated and parallel axons, and, using a principal component analysis, we defined two principal directions, parallel and perpendicular, with respect to the axons’ main direction. The latter were used to define a reference frame onto which the permeability vectors were projected to finally obtain the permeability along the parallel and perpendicular directions. The results show a statistically significant difference between parallel and perpendicular permeability, with a ratio of about two in both the WM structures analyzed, thus demonstrating their anisotropic behavior. Moreover, we find a significant difference between permeability in corpus callosum and fornix, which suggests that the WM heterogeneity should also be considered when modeling drug transport in the brain. Our findings, which demonstrate and quantify the anisotropic and heterogeneous character of the WM, represent a fundamental contribution not only for drug-delivery modeling, but also for shedding light on the interstitial transport mechanisms in the extracellular space.
Date Issued
2021-09-07
Date Acceptance
2021-07-26
Citation
Proceedings of the National Academy of Sciences of USA, 2021, 118 (36)
ISSN
0027-8424
Publisher
National Academy of Sciences
Journal / Book Title
Proceedings of the National Academy of Sciences of USA
Volume
118
Issue
36
Copyright Statement
© 2021 PNAS, for non-commercial use only. Please see licence: https://www.pnas.org/site/aboutpnas/licenses.xhtmlPublished under the PNAS license.
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Commission of the European Communities
Grant Number
EP/N025954/1
688279
Publication Status
Published
Article Number
ARTN e2105328118
Date Publish Online
2021-09-03