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@article{Vidotto:2021:10.1073/pnas.2105328118,
author = {Vidotto, M and Bernardini, A and Trovatelli, M and De, Momi E and Dini, D},
doi = {10.1073/pnas.2105328118},
journal = {Proceedings of the National Academy of Sciences of USA},
title = {On the microstructural origin of brain white matter hydraulic permeability},
url = {http://dx.doi.org/10.1073/pnas.2105328118},
volume = {118},
year = {2021}
}
TY - JOUR
AB - 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.
AU - Vidotto,M
AU - Bernardini,A
AU - Trovatelli,M
AU - De,Momi E
AU - Dini,D
DO - 10.1073/pnas.2105328118
PY - 2021///
SN - 0027-8424
TI - On the microstructural origin of brain white matter hydraulic permeability
T2 - Proceedings of the National Academy of Sciences of USA
UR - http://dx.doi.org/10.1073/pnas.2105328118
UR - http://hdl.handle.net/10044/1/91449
VL - 118
ER -