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!