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Structural identifiability analysis of a cardiovascular system model

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(1)

Structural(iden-fiability(analysis(

of(a(cardiovascular(system(model(

A.#Pironet,(P.C.(Dauby,(J.G.(Chase,(

(2)

• 

To(be(clinically(relevant,(mathema-cal(models(

have(to(be(made(pa-ent.specific.(

(3)

• 

To(be(clinically(relevant,(mathema-cal(models(

have(to(be(made(pa-ent.specific.(

• 

Can#we#find#a#measurement#set#which#allows#

to#iden-fy#all#model#parameters?(

Introduc-on(

(4)

• 

To(be(clinically(relevant,(mathema-cal(models(

have(to(be(made(pa-ent.specific.(

• 

Can#we#find#a#measurement#set#which#allows#

to#iden-fy#all#model#parameters?#

• 

Structural(iden-fiability(analysis.(

Introduc-on(

(5)

• 

To(be(clinically(relevant,(mathema-cal(models(

have(to(be(made(pa-ent.specific.(

• 

Can#we#find#a#measurement#set#which#allows#

to#iden-fy#all#model#parameters?#

• 

Structural(iden-fiability(analysis.(

• 

Goal:(inves-gate(structural(iden-fiability(of(

the(sixEchamber(CVS(model(from(a(clinically(

available(measurement(set.(

Introduc-on(

(6)

SixEchamber(CV(system(model(

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(7)

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(8)

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(19)

Con-nuity(equa-on:

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(20)

Iden-fiability(of(the(CV(system(model(

Right&

ventricle& Pulmonary&artery&

Pulmonary& vein& Le4& ventricle& Aorta& Vena&cava& erv( elv( Ppa( Ppu( Pao( Pvc( SV(=(∫((Q(dt(0(T(

(21)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((r(PvcR(–(Prv)( tc( Qpv(=((r(PrvR(–(Ppa)( pv( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0(

During(the(whole(cardiac(cycle(

(22)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Qsys(=((PaoR(–(Pvc( sys( .( .( .( .( .( .( T( 0(

During(the(whole(cardiac(cycle(

(23)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Qsys(=((PaoR(–(Pvc( sys( .( .( .( .( .( .( T( 0( ∫((Qsys(dt(=(( ∫(((Pao(–(Pvc)(dt( Rsys( T( 0( T( 0(

During(the(whole(cardiac(cycle(

(24)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Qsys(=((PaoR(–(Pvc( sys( .( .( .( .( .( .( T( 0( SV(=(( ∫(((Pao(–(Pvc)(dt( Rsys( T( 0(

During(the(whole(cardiac(cycle(

(25)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Qsys(=((PaoR(–(Pvc( sys( .( .( .( .( .( .( T( 0( Rsys(=(( ∫(((Pao(–(Pvc)(dt( SV( T( 0(

During(the(whole(cardiac(cycle(

(26)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((r(PvcR(–(Prv)( tc( Qpv(=((r(PrvR(–(Ppa)( pv( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0(

During(the(whole(cardiac(cycle(

(27)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((r(PvcR(–(Prv)( tc( Qpv(=((r(PrvR(–(Ppa)( pv( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0(

During(the(whole(cardiac(cycle(

(28)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((r(PvcR(–(Prv)( tc( Qpv(=((r(PrvR(–(Ppa)( pv( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( T( 0(

During(the(whole(cardiac(cycle(

(29)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((r(PvcR(–(Prv)( tc( Qpv(=((r(PrvR(–(Ppa)( pv( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0(

During(the(whole(cardiac(cycle(

(30)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((r(PvcR(–(Prv)( tc( Qpv(=((r(PrvR(–(Ppa)( pv( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0(

During(the(whole(cardiac(cycle(

(31)

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(32)

Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((r(PvcR(–(Prv)( tc( Qpv(=((r(PrvR(–(Ppa)( pv( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0(

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(33)

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(34)

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(36)

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(37)

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(38)

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(39)

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(40)

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(41)

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(42)

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(43)

During(cardiac(ejec-on:(P

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(44)

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pa( Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((Pvc(R–(Prv( tc( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0( Pvc(=(Evc( .( .( Pao(–(Pvc( Rsys( –( Rtc( Pvc(–(Prv( Qpv(=(0((

(68)

During(cardiac(filling:(P

vc

(>(P

rv(

and(P

rv

(<(P

pa( Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((Pvc(R–(Prv( tc( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0( Pvc(=(Evc( .( .( Pao(–(Pvc( Rsys( –( Pvc(–(Prv( Rtc( Pvc(=(Evc(.( R sys( –( Rtc( P.(ao(–(P.(vc( P.(vc(–(P.(rv( ..( Qpv(=(0((

(69)

During(cardiac(filling:(P

vc

(>(P

rv(

and(P

rv

(<(P

pa( Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=(Qtc(–(Qpv( Vpa(=(Qpv(–(Qpul( Vpu(=(Qpul(–(Qmt( SBV(=(Vlv(+(Vao(+(Vvc(+(Vrv(+(Vpa(+(Vpu( SV(=(∫((Q(dt( ( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((Pvc(R–(Prv( tc( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0( Pvc(=(Evc( .( .( Pao(–(Pvc( Rsys( –( Pvc(–(Prv( Rtc( Pvc(=(Evc(.( R sys( –( Rtc( P.(ao(–(P.(vc( P.(vc(–(P.(rv( ..( Prv(=(Erv((erv((Vrv(+(Erv((erv((Vrv( ( .( .( .( Qpv(=(0(( .( .( .( .(

(70)

During(cardiac(filling:(P

vc

(>(P

rv(

and(P

rv

(<(P

pa( Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( Vvc(=(Qsys(–(Qtc( Vrv(=( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( Pvc(=(Evc((Vvc( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((Pvc(R–(Prv( tc( Qpul(=((PpaR(–(Ppu( pul( .( .( .( .( .( .( .( .( .( .( .( .( .( .( T( 0( Pvc(=(Evc( .( .( Pao(–(Pvc( Rsys( –( Pvc(–(Prv( Rtc( Pvc(=(Evc(.( R sys( –( Rtc( P.(ao(–(P.(vc( P.(vc(–(P.(rv( ..( Prv(=(Erv((erv((Vrv(+(Erv((erv((Vrv( ( .( .( .( Qpv(=(0(( Pvc(–(Prv( Rtc( .( .( .( .(

(71)

During(cardiac(filling:(P

vc

(>(P

rv(

and(P

rv

(<(P

pa( Vlv(=(Qmt(–(Qav( Vao(=(Qav(–(Qsys( ( Vrv(=( Ppu(=(Epu((Vpu( Plv(=(Elv((elv((Vlv( Pao(=(Eao((Vao( ( Prv(=(Erv((erv((Vrv( Ppa(=(Epa((Vpa( Qmt(=((r(PpuR(–(Plv)( mt( Qav(=((r(PlvR(–(Pao)( av( Qsys(=((PaoR(–(Pvc( sys( Qtc(=((Pvc(R–(Prv( tc( Qpul(=((PpaR(–(Ppu( pul( .( .( ( .( .( .( .( .( .( .( .( T( 0( Pvc(=(Evc( .( .( Pao(–(Pvc( Rsys( –( Pvc(–(Prv( Rtc( Pvc(=(Evc(.( R sys( –( Rtc( P.(ao(–(P.(vc( P.(vc(–(P.(rv( ..( Prv(=(Erv((erv((Vrv(+(Erv((erv((Vrv( ( .( .( .( Pvc(–(Prv( Rtc( .( .( .( .(

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