ICT-Bio 2006Report on Parallel Session 1

Multilevel Modelling and Simulation of Human Physiology and Disease Related Processes

‘The Virtual Physiological Human’

Rod Hose, Medical Physics, University of Sheffield

Speakers• Marco Viceconti Instituti Ortopedici Rizzoli

• Peter Hunter University of Auckland

• Catrin Bludszuweit-Philipp ASD

• Hans Gregerson University of Aalborg

• Nicholas Ayache INRIA

Overview

• What is the Virtual Physiological Human ?• Consistent messages from our speakers

– Illustration of concepts

• What we need• Impact• Consistent questions• Conclusion

© 2006 STEP Consortium

Virtual Physiological Human• Descriptive

– a framework within which observations made in the laboratories, in the hospitals, and in the field all over the world can be collected, catalogued, organised, shared and combined in any possible way.

• Integrative– a framework that allows experts to collaboratively analyse these

observations and develop scientific hypotheses that involve the knowledge of multiple scientific disciplines

• Predictive– a framework that makes possible to interconnect predictive models

defined at different scale, with different methods, and with different levels of detail, into systematic networks that provide concretisation to those systemic hypotheses, and make possible to verify their validity by comparison with other clinical or laboratory observations

Consistent Messages

• The VPH is a massive undertaking but it has enormous potential impact

• We are not alone…… IUPS Physiome…

• Multidisciplinary … and multicultural– Encompasses research themes traditionally supported by separate

communities: eg. DG Infso and DG Research……

• Heterogeneous models

• Multiscale: Space and Time– ‘There is no privileged level of causality’

Denis Noble, keynote address, ICT-Bio 2006

Consistent Messages

• Requires strong and robust infrastructure

• We are starting to see penetration into clinical and industrial application of elements of the VPH: all of our speakers had illustrations… and so did the keynote speaker in his opening address.

• We are learning fast: cycle time for new model generation is reducing as the infrastructure develops

The Challenge: spatial and temporal scales

The diversity of experimental models• bacterial models structural biology• murine models functional genomics• large animal models physiology• human clinical MRI, CT, etcRequires a hierarchy of inter-related models

pathwaymodels

ODEsstochastic

modelsPDEs

(continuum models)

gene reg.networks

MD/CG models

• 1 m person• 1 mm electrical length scale of cardiac tissue• 1 m cardiac sarcomere spacing• 1 nm pore diameter in a membrane protein

Space

109

• 109 s (70 yrs) human lifetime• 106 s (10 days) protein turnover• 103 s (1 hour) digest food• 1 s heart beat• 1 ms ion channel HH gating• 1 s Brownian motion

Time

1015

© 2006 STEP Consortium

Peritoneum

Prevertebralganglion

Sympathetic trunc

Nonspecific, slow gut afferents

Specific, fast peritoneal afferents

Silent gut afferents

Pain

Non-painful sensations

Vagal afferents

Extrinsic mechanosensitive nerve supply of the gut

© 2006 STEP Consortium

PET-CT Combining structural and functional

information

CT PET PET-CT

T Taxt, ER Gruner et al.

European Needs

• Specific advanced computational models of major physiological systems at the right scales

• Specific advanced image analysis and data assimilation methods to build patient-specific models

• Large databases with biomedical images and genetics

• Grid-enabled methods to exploit models on distributed databases with high computing power

Genome

Muscle tissueNerve tissueConnective tissueEpithelial tissue

Circulatory system Respiratory systemMusculo-skeletal systemSkin (integument)Digestive systemCentral nervous system Endocrine systemLymphoid systemMale reproductive system Female reproductive system Special sense organs

Organism (7)

OrganSystem(6)

Organ (5)

Tissue (4)

Cell (3)

Molecule (2)

Atom (1)

GenBankEMBL, DDBJ

TIGR

dbESTdSTS

PIR SwissProt

Prosite

PDBSCOPs

OMIN, Medline PubMed

SNPbase, …

DNA

RNA

Protein

Structure

TissueML

FieldML

C C

H H

H H

AnatML

CellML

www.cellml.org

Poul Nielsen

4. Physiome MLs, tools & databases

ConclusionThe Physiome project is about:• Models that capture patient-specific geometry (link to clinical imaging)• Multi-physics models based on biophysical mechanisms (can use power of physical constraints) • Multi-scale models that link to proteins, carbohydrates & lipids (can link to disease & drug action)

We need:• Open source software• Markup language standards for encoding models• Freely accessible model databases• Clinically driven applications• Industry partnerships

© 2006 STEP Consortium

VPH Impact• Economic

– Industry: reduced product cycle time, reduced risk, Pharmaceutical, medical device, automotive, aerospace, defence, sport/leisure, entertainment, ......

– Improved healthcare produces cost savings• Health

– Supports quantitative evidence-based medicine– Personalised healthcare

• Societal– Huge data resource to support epidemiological research– Reduces animal experimentation– Reduces ’reinvent the wheel syndrome– Increases public visibility of research investement

Personalized Physiological Human

• Coupling physiological models with biomedical images and signals

• raises fascinating scientific challenges• requires large scale effort (typ. European)

• Huge potential impact• towards more quantitative and predictive medicine

Visible Human Personalized Physiological Human

© Copyright ASD GmbH 2006

Simulations for medical devicesSimulations for medical devices

mimic reality closely

benefit treatment

reduce costs and time-to-market

understand needs and demands from industry and medical community:

Two main tasks for simulation experts:

give insights and motivations for use of modern technologies

© Copyright ASD GmbH 2006

Multilevel endovascular device analysisMultilevel endovascular device analysis

Haemodynamics

Vascular wallmechanics

Device designDevice mechanics

Biological responseThrombosis

Chemical processesDrug delivery

Genetics

Cardiovascularsystems

Patient-specificanatomies

Multilevelstent / coil analysis

Consistent Questions/Observations !• The VPH is a massive undertaking

– How will it be organised …. divided by organ ?– Will it be a snapshot in time ?– Will we try to include ‘everything’? … neurological

models , coupling to database information on genome and on molecular processes?

– How can we best exploit the huge quantity of ‘biological’ knowledge already generated?

– Will ‘it’ be open access, open source ?– Will ‘it’ be usable by non-experts ?