Modeling of Anatomy, Electrophysiology and Tension Development in the Human Heart

Transcription

1 European Functional Cardiac Modeling Meeting Modeling of Anatomy, Electrophysiology and Tension Development in the Human Heart Dr.-Ing. Gunnar Seemann Overview Electrophysiology Tension development Anatomy 2

2 Anatomical Modeling Preprocessing Segmentation Visible Human Project National Library of Medicine Thin section photos 1800 (male) and 5000 (female) crosssectional digital images 1 mm (male) and 0.33 mm (female) distance between images 1280 x 2048 pixels per image 0.33 mm x 0.33 mm x 3 colors x 8 bit per pixel Filtering Classification Anatomical Models Cubic voxel representation 1 mm x 1 mm x 1 mm (male) and 0.33 mm x 0.33 mm x 0.33 mm (female) per voxel 70 tissue classes Orientation of muscle fibers 3 4

3 Visible Female Heart Visible Female Heart Additionally segmented atrial tissue classes right appendage left appendage PV PM CT: Crista Terminalis PM: Pectinate muscle PV: Pulmonary veins CT sinoatrial node Seemann et al Phil. Trans. Roy. Soc. in press 5 Individual MR Data and Model 6

4 Fiber Orientation in Cardiac Tissue Rat left ventricle Young et al., 1998, J. Micros. 192: Model 7 Atrial Cell Models Sinoatrial Node Courtemanche et al., 1998, Am. J. Physiol. 275(44): H3301-H321 dv m dt = 1 C m ( Ix I inter ) Atrial Cells 8

5 Ventricular Cell Models Priebe & Beuckelmann 1998 Circ Res. 82: Endo Mid Epi G.-R. Li et al Am. J. Physiol. 275: H369-H377 Seemann et al J Cardiovasc Electrophysiol. 14(S10):S219-S228 9 Heterogeneous Ventricle Model APD Endo APD Mid APD Epi V Rest Experiment 263±17 ms 376±31 ms 271±14 ms -81±3 mv Simulation 272 ms 343 ms 265 ms -80 mv Measurement Transmural ECG Simulation Shimizu et al Circ. 102: Seemann et al 2003 J Cardiovasc Electrophysiol. 14(10):S219-S228 10

6 Electromechanical Coupling Myosin Actin Bers 2002 Nature 415: Calcium binds to troponin C Shifting of tropomyosin opens myosin binding site of actin Interaction of actin and myosin Contraction of myofilaments 11 Tension Model A Actin M Myosin TM Tropomyosin T Troponin ATP Adenosintriphospate ADP Adenosindiphosphate Pi Phosphate λ Stress v Velocity! Weak Binding! Strong Binding Measurement Ca λ, XB T Simulation TCa TM TM off TM on A M F ADP λ, v, F A M F* ADP v v A M F M ADP v ATP v M A~M ATP ATP v v M ATP M ADP P i A M ADP P i A~M ADP P i Peterson et al AJP 260:H1013-H

7 Conduction: Bidomain Model (σ i Φ i ) = βi m (σ e Φ e ) = βi m V m = Φ i Φ e dv m dt = 1 C m ( Ix I inter ) Vm Transmembrane voltage Φ e Intracellular potential Φ i Extracellular potential σ i Intracellular conductivity σ e Extracellular conductivity Cm Membrane capacitance IX Ion current of type X Iinter Intercellular current β Surface/Volume ((σ e + σ i ) Φ e ) = (σ i V m ) ( dv m (σ i V m ) + (σ i Φ e ) = β C m + ) I x dt Elliptical PDE Parabolical PDE 13 Schematic Right Atrium SAN CT PM Atrium single cell simulation conduction velocity (m/s) measured simulated atrium 0,68 1,03 0,6 Crista Terminalis (CT) 1 1,2 1,18 1,2 Pectinate muscle (PM) 1,5 2 1,54 1,58 14

8 Atrial Simulation Measurement Feng et al.1998 Circ Res. 83: Simulation Activation times (ms) measured simulated Bachmann right atrium left atrium complete atrium Seemann et al Phil. Trans. Roy. Soc. in press 15 Simulation in the ventricular wall 16

9 Ventricular Electromechanics Transmembrane voltage Tension development Seemann et al LNCS FIMH: Electrophysiological heterogeneity is one mechanism to homogenize the mechanical process 17 Deformation with Spring Mass System 18

10 Pathological Modeling: Overview Atrial Flutter Atrial Fibrillation Atrial Electrophysiological Remodeling Ventricular Tachycardia Ventricular Fibrillation Mutations... Familial Atrial Fibrillation Long QT Syndromes Short QT Syndrome IKs Mutations IK1 Mutation 19 Ventricular Fibrillation Section of the Left Ventricle Seemann et al Biomedizinische Technik 48-1:

11 Mutation: Long QT Syndrome LQT1 LQT2 LQT3 Reduction of IKs Defect in gene KCNQ1 Reduction of IKr Defect in gene KCNH2 Late inactivation of INa Defect in gene SCN5A Shimizu et al.1998 Circ. 98: Shimizu et al.1997 Circ. 96: Seemann et al IEEE Computers in Cardiology 30: IK1 Mutation in ten Tusscher Model Epi AP Endo AP Mid AP 22

12 Mutation: IK1 Transmural ECG in heterogeneous ten Tusscher et al. Model 23 Other Research Activities Cellular Automaton for clinical studies Multi-channel ECG analysis Forward and inverse problem Optical mapping of electrical activity + tension and deformation mapping 24

13 Perspectives Further heterogeneities (apico-basal) Further Pathologies esp. arrhythmia Individual complete heart geometry Forward calculation on body model Detailed mechanics and blood flow Support of drug development Therapeutical applications 25