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A four-compartment multiscale model of fluid and drug distribution in vascular tumours

A four-compartment multiscale model of fluid and drug distribution in vascular tumours
A four-compartment multiscale model of fluid and drug distribution in vascular tumours

It is vital to elucidate the subtle relationship between vascular network structure and mass transport to predict and improve the efficacy of anti-cancer treatments. In this paper, mathematical homogenization is used to derive a new multiscale continuum model of blood and chemotherapy transport in the arteriole, capillary and venule networks, and interstitium of a vascular tumour. This model and framework enables information at a range of vascular hierarchies to be fed into an effective description on the length scale of the tumour. The model is explored in a case study of a simple geometry representative of a tumour in a dorsal skinfold geometry setup. Specifically, we explore the role of vascular network architecture in influencing fluid and drug perfusion on the length scale of the chamber. A single parameter, P, is identified that relates tumour-scale fluid perfusion to the permeability and density of the capillary bed. By fixing the topological and physiological properties of the arteriole and venule networks, an optimal value for P is identified which maximises tumor fluid transport and is thus hypothesized to benefit chemotherapy delivery. We calculate the values for P for eight explicit network structures; in each case vascular intervention by either decreasing the permeability, or increasing the density, of the capillary network would increase fluid perfusion through the cancerous tissue. Chemotherapy delivery via either a single injection or constant perfusion in a idealised, two-dimensional tumour, representative of an in vivo testing setup, is compared; single injection is consistently more successful compared to constant perfusion, and the model outputs predict when to deliver a second dose. These results highlight the potential of computational modelling to elucidate the link between vascular architecture and fluid, drug distribution in tumours.

mathematical modelling, homogenization, vasculature, cancer, chemotherapy
2040-7947
Shipley, R.J.
308c05c9-31d1-43c9-bc88-710fb06f9586
Sweeney, P.W.
6cca0461-e802-42cd-9e03-c516ccf890fe
Chapman, S.J.
2fb8f0b2-56ab-4ac7-8518-35abf1047cf9
Roose, T.
3581ab5b-71e1-4897-8d88-59f13f3bccfe
Shipley, R.J.
308c05c9-31d1-43c9-bc88-710fb06f9586
Sweeney, P.W.
6cca0461-e802-42cd-9e03-c516ccf890fe
Chapman, S.J.
2fb8f0b2-56ab-4ac7-8518-35abf1047cf9
Roose, T.
3581ab5b-71e1-4897-8d88-59f13f3bccfe

Shipley, R.J., Sweeney, P.W., Chapman, S.J. and Roose, T. (2020) A four-compartment multiscale model of fluid and drug distribution in vascular tumours. International Journal for Numerical Methods in Biomedical Engineering, [e3315]. (doi:10.1002/cnm.3315).

Record type: Article

Abstract

It is vital to elucidate the subtle relationship between vascular network structure and mass transport to predict and improve the efficacy of anti-cancer treatments. In this paper, mathematical homogenization is used to derive a new multiscale continuum model of blood and chemotherapy transport in the arteriole, capillary and venule networks, and interstitium of a vascular tumour. This model and framework enables information at a range of vascular hierarchies to be fed into an effective description on the length scale of the tumour. The model is explored in a case study of a simple geometry representative of a tumour in a dorsal skinfold geometry setup. Specifically, we explore the role of vascular network architecture in influencing fluid and drug perfusion on the length scale of the chamber. A single parameter, P, is identified that relates tumour-scale fluid perfusion to the permeability and density of the capillary bed. By fixing the topological and physiological properties of the arteriole and venule networks, an optimal value for P is identified which maximises tumor fluid transport and is thus hypothesized to benefit chemotherapy delivery. We calculate the values for P for eight explicit network structures; in each case vascular intervention by either decreasing the permeability, or increasing the density, of the capillary network would increase fluid perfusion through the cancerous tissue. Chemotherapy delivery via either a single injection or constant perfusion in a idealised, two-dimensional tumour, representative of an in vivo testing setup, is compared; single injection is consistently more successful compared to constant perfusion, and the model outputs predict when to deliver a second dose. These results highlight the potential of computational modelling to elucidate the link between vascular architecture and fluid, drug distribution in tumours.

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ShipleyChapmanRoose-REVISED - Accepted Manuscript
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More information

Accepted/In Press date: 17 January 2020
e-pub ahead of print date: 7 February 2020
Keywords: mathematical modelling, homogenization, vasculature, cancer, chemotherapy

Identifiers

Local EPrints ID: 438541
URI: http://eprints.soton.ac.uk/id/eprint/438541
ISSN: 2040-7947
PURE UUID: c1231a9f-59f1-431b-911e-c494c65c4d9d
ORCID for T. Roose: ORCID iD orcid.org/0000-0001-8710-1063

Catalogue record

Date deposited: 16 Mar 2020 17:30
Last modified: 17 Jan 2021 05:01

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