Mechanistic modelling of dynamic MRI data predicts that tumour heterogeneity decreases therapeutic response.

British Journal of Cancer
R VenkatasubramanianN S Forbes

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) contains crucial information about tumour heterogeneity and the transport limitations that reduce drug efficacy. Mathematical modelling of drug delivery and cellular responsiveness based on underutilised DCE-MRI data has the unique potential to predict therapeutic responsiveness for individual patients. To interpret DCE-MRI data, we created a modelling framework that operates over multiple time and length scales and incorporates intracellular metabolism, nutrient and drug diffusion, trans-vascular permeability, and angiogenesis. The computational methodology was used to analyse DCE-MR images collected from eight breast cancer patients at Baystate Medical Center in Springfield, MA. Computer simulations showed that trans-vascular transport was correlated with tumour aggressiveness because increased vessel growth and permeability provided more nutrients for cell proliferation. Model simulations also indicate that vessel density minimally affects tissue growth and drug response, and nutrient availability promotes growth. Finally, the simulations indicate that increased transport heterogeneity is coupled with increased tumour growth and poor drug response. Mathematical m...Continue Reading

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Citations

Feb 8, 2014·Integrative Biology : Quantitative Biosciences From Nano to Macro·Rachel W KasinskasNeil S Forbes
Mar 31, 2015·Expert Opinion on Drug Metabolism & Toxicology·Hen Popilski, David Stepensky
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Oct 27, 2017·Journal of Theoretical Biology·Dan E GanzNeil S Forbes

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