Multi-scale modelling using Chaste: the PreDiCT project
Alberto Corrias Computing Laboratory , Oxford University
Oxford, 24th March 2009
The preDiCT project: prediction of Drug CardioToxicity
University of Oxford (UK) Aureus Pharma (France) Centro di Ricerca Sviluppo e Studi Superiori in Sardegna, CRS4 (Italy) Fujitsu Laboratories Europe (UK) Glaxo SmithKline (UK) Novartis (Switzerland) F. Hoffman-La Roche (Switzerland) Szegedi Todomanyegyetem (Hungary) Universidad Politecnica de Valencia (Spain)
A European joint effort between academia and industry:
To provide an efficient computational framework for the study of possible adverse side effects in the early stages of drug development.
Multi-scale approach
Cell model(s)
Whole organ models
Ionic currents
From Cordeiro et al. (1998)
Bernabeu et al. 2008
ECG
Case study 1 : Purkinje-myocardial interface
Case study 2 : ECG simulations
Huelsing D, Spitzer K and Pollard A. AJP 2000
Case study 1 : Purkinje-Myocardial interface
Motivation and final aim: investigate the electrotonic interactions at Purkinje-myocardial interface
with realistic cell models in realistic anatomical geometries.
Case study 1 : Purkinje-Myocardial interface
3 mm 3 mm
0.75 mm
Noble Di Francesco cell
Mahajan-Shiferaw cell
A simplified situation simulating a Purkinje fibre that excites myocardial tissue.
Stimulation only at Purkinje nodes
Case study 1 : Purkinje-Myocardial interface
Activation of myocardium by a Purkinje fibre
Activation Repolarisation
Case study 1 : Purkinje-Myocardial interface
Case study 2 : ECG forward problem
Image from Malmivuo & Plonsey. “Bioelectromagnetism”. Oxford University Press, 1995
Case study 2 : ECG forward problemH
eart
reg
ion
Bat
h
Case study 2 : ECG forward problem
A simplified situation simulating a (small) cut ellipsoid with Faber-Rudy cell modelin a (small) volume control.
Cross section
Stimulation of the apex of the heart
Case study 2 : ECG forward problem
Heart activation (Vm) Surface potentials (Φe)
Case study 2 : ECG forward problem
Cellular action potentials
ECG
(at the pink spot)
Control
HERG blockExtracellular/bath potentials (Φe)
Thank you for your attention!