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
The subtle relationship between vascular network structure and mass transport is vital to predict and improve the efficacy of anticancer treatments. Here, mathematical homogenisation is used to derive a new multiscale continuum model of blood and chemotherapy transport in the vasculature and interstitium of a vascular tumour. This 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 behaviour is explored through a demonstrative case study of a simplified representation of a dorsal skinfold chamber, to examine 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 tumour fluid transport and is thus hypothesised 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. Chemotherapeutic strategies are compared and indicate that single injection is consistently more successful compared with constant perfusion, and the model predicts optimal timing of a second dose. These results highlight the potential of computational modelling to elucidate the link between vascular architecture and fluid, drug distribution in tumours.
cancer, chemotherapy, homogenization, mathematical modelling, vasculature
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
March 2020
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, 36 (3), [e3315].
(doi:10.1002/cnm.3315).
Abstract
The subtle relationship between vascular network structure and mass transport is vital to predict and improve the efficacy of anticancer treatments. Here, mathematical homogenisation is used to derive a new multiscale continuum model of blood and chemotherapy transport in the vasculature and interstitium of a vascular tumour. This 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 behaviour is explored through a demonstrative case study of a simplified representation of a dorsal skinfold chamber, to examine 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 tumour fluid transport and is thus hypothesised 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. Chemotherapeutic strategies are compared and indicate that single injection is consistently more successful compared with constant perfusion, and the model predicts optimal timing of 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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Shipley_et_al-2020-International_Journal_for_Numerical_Methods_in_Biomedical_Engineering
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More information
Accepted/In Press date: 17 January 2020
e-pub ahead of print date: 7 February 2020
Published date: March 2020
Additional Information:
© 2020 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.
Keywords:
cancer, chemotherapy, homogenization, mathematical modelling, vasculature
Identifiers
Local EPrints ID: 438541
URI: http://eprints.soton.ac.uk/id/eprint/438541
ISSN: 2040-7947
PURE UUID: c1231a9f-59f1-431b-911e-c494c65c4d9d
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Date deposited: 16 Mar 2020 17:30
Last modified: 17 Mar 2024 05:15
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Author:
R.J. Shipley
Author:
P.W. Sweeney
Author:
S.J. Chapman
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