1. Infusion Mechanisms in Brain White Matter and Their Dependence on Microstructure: An Experimental Study of Hydraulic Permeability
- Author
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Joseph M. Sherwood, Maria Teresa Mongelli, Daniele Dini, Elena De Momi, Marco Vidotto, Darryl R. Overby, Andrea Bernardini, Asad Jamal, Michael Madekurozwa, Ferdinando Rodriguez y Baena, Engineering & Physical Science Research Council (EPSRC), Commission of the European Communities, and Royal Academy Of Engineering
- Subjects
Materials science ,ovine brain tissue ,0206 medical engineering ,Biomedical Engineering ,02 engineering and technology ,Permeability ,White matter ,Drug Delivery Systems ,0903 Biomedical Engineering ,Hydraulic conductivity ,Brain White Matter ,0801 Artificial Intelligence and Image Processing ,medicine ,Animals ,Hydraulic machinery ,Anisotropy ,Sheep ,Convection-enhanced delivery ,directionality of axons ,Brain ,Microstructure ,020601 biomedical engineering ,White Matter ,Biological materials ,0906 Electrical and Electronic Engineering ,Permeability (earth sciences) ,medicine.anatomical_structure ,hydraulic permeability ,infusion-based flow ,Biomedical engineering - 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, also demonstrating 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.
- Published
- 2021
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