summers imeko 2011

Progress on Measurement in

Biology & Medicine:

Multiscale Systems Engineering

Ron Summers

Dept Electronic & Electrical Engineering, Loughborough University, UK

R.Summers@lboro.ac.uk

http://www-staff.lboro.ac.uk/~lsrs1

Outline

• Introduction to the Team

• Multiscale Modelling

Anatomic Level of Analysis

Cellular Level of Analysis

Protein Level of Analysis

Genome Level of Analysis

• Future Work

International Team

Multiscale Modelling

Context

Engineering Dimension

“…multiscale modelling is the field of solving

physical problems which have important

features at multiple scales, particularly

multiple spatial and (or) temporal scales”.

Wikipedia, accessed 2010

Scales of Measurement

Hunter P, Robbins P, Noble D (2002) The IUPS human physiome project. Eur J Physiol 445 1-9

Medical Dimension

• Why is it important to better understand

congenital heart defects ?

• What is the Tetralogy of Fallot from an

anatomical standpoint ?

• Which embryological processes are

involved in the formation of the Tetralogy

of Fallot ?

Why is it important to know more about the congenital

heart defect and particularly about the Tetralogy of Fallot ?

The prevalence of congenital heart defects,

the most common congenital anomaly

observed in newborns, has been reported to

be 5-10 per 1000 births

10% of the childhood mortality

Tetralogy of Fallot is the most common form

of cyanotic congenital heart disease.

It affects 9%-15% of all infants and children

with congenital heart disease (CHD) which

represents 55%-70% of all cyanotic

congenital malformations

We need to improve our knowledge about

this abnormality

Multiscale Modelling

Anatomic Level

Aorta

Pulmonary artery

Right

Ventricle

Anterior view Posterior view

Anatomy of the Normal Human Heart

Tetralogy of Fallot

Pulmonary Stenosis

Ventricular Septal Defect by

malalignment

Dextroposition of the Aorta

(aortic overriding)

Right ventricular hypertrophy

desaturation

Muscular

Septum

Membranous

Septum

Nature

Normal Anatomic Development

Multiscale Modelling

Cellular Level

Scales of Measurement

Hunter P, Robbins P, Noble D (2002) The IUPS human physiome project. Eur J Physiol 445 1-9

Epithelial to Mesenchymal Transition

Notch Delta

EMT Simulations

In vitro EMT

Wildtype Notch1 BMP2

L. Luna-zurita et al. “Integration of a Notch-dependent mesenchymal gene

program and Bmp2-driven cell invasiveness regulates murine cardiac

valve formation,” The Journal of Clinical Investigation, vol. 120, 2010.

Multiscale Modelling

Protein Level

Multiscale Modelling

Genome Level

Which embryological processes are involved

in the formation of the Tetralogy of Fallot ?

Scale of tissue and cells

Which embryological processes are involved in the

formation of the Tetralogy of Fallot ? Scale of gene regulation

Future Work

A lot of work remains…

• Information Issues • Scale-linking

• Biological Networks

• Methodological Issues • Multiscale Model Process

• Multiscale Model Validation

• Multiscale Visualization

• Software Issues • Multiscale Software Programming

• Patho-physiological Issues • Anatomic Definition of Tetralogy of Fallot

Thank you for your

attention

Optical Physiological Tomography: Concepts

Comprises biomedical photonics, microelectronics engineering, systems engineering, applied signal and image processing, and multiscale modelling/simulation

Fast Fast

digital digital

CameraCamera

USBUSB

MicroMicro--

electronicselectronics

Oxyg

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level

O2%

Oxyg

en

level

H i g h

Low

Frequency

6 – 9 HzW

avelength

(400 –900nm

)

MultiMulti--

wavelengthwavelength

illuminatorilluminator

Electronic sub system

Photonics sub system

Biophotonics Imaging System