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.
Highlights
Solid tumours are characterised by an abnormal microenvironment that distinguishes them from healthy tissue and reduces drug delivery to the cancerous tissue
We investigate the impact of varying the properties of the capillary bed on fluid perfusion in a case study of a simplified geometry representative of a dorsal skinfold chamber, by solving the fluid transport Equations (21) and (22) using the finite element package COMSOL Multiphysics
To test the impact of varying P on fluid perfusion in the capillaries and interstitium, we evaluate the flux of fluid in the capillaries and interstitium that travels from region 1 into region 2, Qc
Summary
Solid tumours are characterised by an abnormal microenvironment that distinguishes them from healthy tissue and reduces drug delivery to the cancerous tissue This is a consequence of numerous factors that include a poorly organised vascular architecture, irregular blood flow, and the compression of blood and lymphatic vessels by cancer cells.[1] The. Int J Numer Meth Biomed Engng. One approach is to employ continuum models in which imaging data are used to deduce functional properties relevant to blood and mass transport.[4,5,6,7] The mathematical process of homogenisation[8] is one candidate for developing these continuum models, as it enables spatial heterogeneities at different scales to be transformed into a tractable tissue-scale model. This homogenisation approach enabled the influence of exact particle shape on hydraulic permeability to be determined
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: International journal for numerical methods in biomedical engineering
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
