void TestAssigningModifiersToACellModel() throw(Exception)
{
boost::shared_ptr<ZeroStimulus> p_stimulus(new ZeroStimulus());
boost::shared_ptr<EulerIvpOdeSolver> p_solver(new EulerIvpOdeSolver);
CellShannon2004FromCellML* p_shannon = new CellShannon2004FromCellML(p_solver, p_stimulus);
TS_ASSERT_EQUALS(p_shannon->HasModifier("Alan"), false);
TS_ASSERT_THROWS_THIS(p_shannon->GetModifier("Alan"), "There is no modifier called Alan in this model.");
// Default modifier shouldn't do anything to the value inputted to calc()
TS_ASSERT_EQUALS(p_shannon->HasModifier("membrane_rapid_delayed_rectifier_potassium_current_conductance"), true);
TS_ASSERT_DELTA(p_shannon->GetModifier("membrane_rapid_delayed_rectifier_potassium_current_conductance")->Calc(123,0),123,1e-9);
// Make a new modifier
boost::shared_ptr<AbstractModifier> p_new_modifier(new FixedModifier(-90.0));
TS_ASSERT_THROWS_THIS(p_shannon->SetModifier("Alan",p_new_modifier), "There is no modifier called Alan in this model.");
// Assign it to the Shannon model
p_shannon->SetModifier("membrane_rapid_delayed_rectifier_potassium_current_conductance",p_new_modifier);
// We should now get a new answer to this.
TS_ASSERT_DELTA(p_shannon->GetModifier("membrane_rapid_delayed_rectifier_potassium_current_conductance")->Calc(0,0),-90,1e-9);
delete p_shannon;
}
// Run normally up to stretch-time, then apply stretch and
// run until stretch-off-time, then return to stretch=1
// and run until 1000ms.
void RunModelWithSacRecruitment(double stretch,
double stretchStartTime,
double stretchEndTime,
std::string directory,
std::string filePrefix,
bool clearDir)
{
boost::shared_ptr<SimpleStimulus> p_stimulus(new SimpleStimulus(
-3 /*magnitude*/,
3 /*duration*/,
10.0 /*start time*/));
boost::shared_ptr<EulerIvpOdeSolver> p_solver(new EulerIvpOdeSolver);
double time_step = 0.01;
HeartConfig::Instance()->SetOdePdeAndPrintingTimeSteps(time_step, time_step, 1.0);
CML_noble_varghese_kohl_noble_1998_basic_with_sac n98_with_sac(p_solver, p_stimulus);
OutputFileHandler handler(directory,clearDir);
out_stream p_file = handler.OpenOutputFile(filePrefix+".dat");
*p_file << 0 << " " << n98_with_sac.GetVoltage() << "\n";
double printing_dt = 1;
TimeStepper stepper(0, stretchStartTime, printing_dt);
while ( !stepper.IsTimeAtEnd() )
{
n98_with_sac.Compute(stepper.GetTime(), stepper.GetNextTime());
stepper.AdvanceOneTimeStep();
*p_file << stepper.GetTime() << " " << n98_with_sac.GetVoltage() << "\n";
}
n98_with_sac.SetStretch(stretch);
TimeStepper stepper2(stepper.GetTime(), stretchEndTime, printing_dt);
while ( !stepper2.IsTimeAtEnd() )
{
n98_with_sac.Compute(stepper2.GetTime(), stepper2.GetNextTime());
stepper2.AdvanceOneTimeStep();
*p_file << stepper2.GetTime() << " " << n98_with_sac.GetVoltage() << "\n";
}
n98_with_sac.SetStretch(1.0);
TimeStepper stepper3(stepper2.GetTime(), 1000, printing_dt);
while ( !stepper3.IsTimeAtEnd() )
{
n98_with_sac.Compute(stepper3.GetTime(), stepper3.GetNextTime());
stepper3.AdvanceOneTimeStep();
*p_file << stepper3.GetTime() << " " << n98_with_sac.GetVoltage() << "\n";
}
p_file->close();
}
void TestOdeSolverForFox2002WithRegularStimulus(void) throw (Exception)
{
clock_t ck_start, ck_end;
// Set stimulus
double magnitude = -80.0;
double duration = 1.0 ; // ms
double start = 50.0; // ms
double period = 500; // ms
boost::shared_ptr<RegularStimulus> p_stimulus(new RegularStimulus(magnitude, duration, period, start));
double end_time = 1000.0; //One second in milliseconds
HeartConfig::Instance()->SetOdeTimeStep(0.002); // 0.005 leads to NaNs.
boost::shared_ptr<EulerIvpOdeSolver> p_solver(new EulerIvpOdeSolver);
CellFoxModel2002FromCellML fox_ode_system(p_solver, p_stimulus);
// Solve and write to file
ck_start = clock();
RunOdeSolverWithIonicModel(&fox_ode_system,
end_time,
"FoxRegularStimLong",
500);
ck_end = clock();
double forward = (double)(ck_end - ck_start)/CLOCKS_PER_SEC;
CheckCellModelResults("FoxRegularStimLong");
// Solve using Backward Euler
HeartConfig::Instance()->SetOdeTimeStep(0.01);
CellFoxModel2002FromCellMLBackwardEuler backward_system(p_solver, p_stimulus);
ck_start = clock();
RunOdeSolverWithIonicModel(&backward_system,
end_time,
"BackwardFoxRegularStimLong",
100);
ck_end = clock();
double backward = (double)(ck_end - ck_start)/CLOCKS_PER_SEC;
CompareCellModelResults("FoxRegularStimLong", "BackwardFoxRegularStimLong", 0.15);
// Mainly for coverage, and to test consistency of GetIIonic
TS_ASSERT_DELTA(fox_ode_system.GetIIonic(),
backward_system.GetIIonic(),
1e-6);
std::cout << "Run times:\n\tForward: " << forward
<< "\n\tBackward: " << backward
<< std::endl;
}
void TestAccessingParametersWithoutModifiers() throw(Exception)
{
boost::shared_ptr<ZeroStimulus> p_stimulus(new ZeroStimulus());
boost::shared_ptr<EulerIvpOdeSolver> p_solver(new EulerIvpOdeSolver);
CellShannon2004FromCellML* p_shannon = new CellShannon2004FromCellML(p_solver, p_stimulus);
// We should now have all of the following methods available as an alternative to using 'modifiers'
TS_ASSERT_DELTA(p_shannon->GetParameter("membrane_fast_sodium_current_conductance"),16.0,1e-5);
TS_ASSERT_DELTA(p_shannon->GetParameter("membrane_L_type_calcium_current_conductance"),5.4e-4,1e-5);
TS_ASSERT_DELTA(p_shannon->GetParameter("membrane_rapid_delayed_rectifier_potassium_current_conductance"),0.03,1e-5);
TS_ASSERT_DELTA(p_shannon->GetParameter("membrane_slow_delayed_rectifier_potassium_current_conductance"),0.07,1e-5);
delete p_shannon;
}
void TestArchiving(void) throw(Exception)
{
//Archive
OutputFileHandler handler("archive", false);
handler.SetArchiveDirectory();
std::string archive_filename = ArchiveLocationInfo::GetProcessUniqueFilePath("GI.arch");
// Save
{
boost::shared_ptr<SimpleStimulus> p_stimulus(new SimpleStimulus(0.0,1.0,0.5));
boost::shared_ptr<EulerIvpOdeSolver> p_solver(new EulerIvpOdeSolver);
double time_step = 0.01;
HeartConfig::Instance()->SetOdePdeAndPrintingTimeSteps(time_step, time_step, time_step);
// icc and smc
AbstractCardiacCell* const p_smc = new CorriasBuistSMCModified(p_solver, p_stimulus);
AbstractCardiacCell* const p_icc = new CorriasBuistICCModified(p_solver, p_stimulus);
std::ofstream ofs(archive_filename.c_str());
boost::archive::text_oarchive output_arch(ofs);
output_arch << p_smc;
output_arch << p_icc;
delete p_smc;
delete p_icc;
}
// Load
{
std::ifstream ifs(archive_filename.c_str(), std::ios::binary);
boost::archive::text_iarchive input_arch(ifs);
AbstractCardiacCell* p_smc;
AbstractCardiacCell* p_icc;
input_arch >> p_smc;
input_arch >> p_icc;
TS_ASSERT_EQUALS( p_smc->GetNumberOfStateVariables(), 14U );
TS_ASSERT_EQUALS( p_icc->GetNumberOfStateVariables(), 18U );
delete p_smc;
delete p_icc;
}
}
void GenerateCells() throw (Exception)
{
// Do the conversions preserving generated sources
CellMLToSharedLibraryConverter converter(true);
std::string dirname = "TestGeneralizedRushLarsen";
std::string model = "LuoRudy1991";
boost::shared_ptr<AbstractIvpOdeSolver> p_solver;
boost::shared_ptr<ZeroStimulus> p_stimulus(new ZeroStimulus());
std::vector<std::string> args;
args.push_back("--grl1");
{ // No opt
// Copy CellML file into output dir
OutputFileHandler handler(dirname + "/normal");
FileFinder cellml_file("heart/src/odes/cellml/" + model + ".cellml", RelativeTo::ChasteSourceRoot);
FileFinder copied_file = handler.CopyFileTo(cellml_file);
// Create options file & convert
converter.CreateOptionsFile(handler, model, args);
DynamicCellModelLoaderPtr p_loader = converter.Convert(copied_file);
mpGeneralizedRushLarsenCell = dynamic_cast<AbstractCardiacCell*>(p_loader->CreateCell(p_solver, p_stimulus));
}
}
boost::shared_ptr<AbstractStimulusFunction> CreateStimulusForNode(Node<2>* pNode)
{
boost::shared_ptr<SimpleStimulus> p_stimulus ( new SimpleStimulus(-428000, 1.0, 0.1) );
return p_stimulus;
}
void TestHHModelAtSingularities()
{
/*
* Set stimulus
*/
double magnitude_stimulus = 0.0; // uA/cm2
double duration_stimulus = 0.; // ms
double start_stimulus = 0.0; // ms
boost::shared_ptr<SimpleStimulus> p_stimulus(new SimpleStimulus(
magnitude_stimulus,
duration_stimulus,
start_stimulus));
boost::shared_ptr<AbstractIvpOdeSolver> p_solver; // We don't actually need a solver
CellHodgkinHuxley1952FromCellML hh52_ode_system(p_solver, p_stimulus);
double v_singularity[2];
v_singularity[0]=-65;
v_singularity[1]=-50;
for (int i=0; i<2; i++)
{
std::vector<double> yleft;
//mVariableNames.push_back("V");
//mVariableUnits.push_back("mV");
yleft.push_back(v_singularity[i]+0.1);
//mVariableNames.push_back("n");
//mVariableUnits.push_back("");
yleft.push_back(0.325);
//mVariableNames.push_back("h");
//mVariableUnits.push_back("");
yleft.push_back(0.6);
//mVariableNames.push_back("m");
//mVariableUnits.push_back("");
yleft.push_back(0.05);
std::vector<double> rhsleft(yleft.size());
hh52_ode_system.EvaluateYDerivatives (0.0, yleft, rhsleft);
std::vector<double> yright;
//mVariableNames.push_back("V");
//mVariableUnits.push_back("mV");
yright.push_back(v_singularity[i]-0.1);
//mVariableNames.push_back("n");
//mVariableUnits.push_back("");
yright.push_back(0.325);
//mVariableNames.push_back("h");
//mVariableUnits.push_back("");
yright.push_back(0.6);
//mVariableNames.push_back("m");
//mVariableUnits.push_back("");
yright.push_back(0.05);
std::vector<double> rhsright(yright.size());
hh52_ode_system.EvaluateYDerivatives (0.0, yright, rhsright);
std::vector<double> y_at_singularity;
//mVariableNames.push_back("V");
//mVariableUnits.push_back("mV");
y_at_singularity.push_back(v_singularity[i]);
//mVariableNames.push_back("n");
//mVariableUnits.push_back("");
y_at_singularity.push_back(0.325);
//mVariableNames.push_back("h");
//mVariableUnits.push_back("");
y_at_singularity.push_back(0.6);
//mVariableNames.push_back("m");
//mVariableUnits.push_back("");
y_at_singularity.push_back(0.05);
std::vector<double> rhs_at_singularity(y_at_singularity.size());
hh52_ode_system.EvaluateYDerivatives (0.0, y_at_singularity, rhs_at_singularity);
for (int j=0; j<4; j++)
{
//std::cout << j << "\t" << rhsright[j] << "\t" << rhsleft[j] << "\t" << rhs_at_singularity[j] << std::endl;
TS_ASSERT_DELTA((rhsright[j]+rhsleft[j])/2, rhs_at_singularity[j], 0.1);
}
}
}
void TestTimingsWithAndWithoutJacobian() throw (Exception)
{
#ifdef CHASTE_CVODE
// Set up a default solver and a stimulus
boost::shared_ptr<AbstractIvpOdeSolver> p_solver;
boost::shared_ptr<AbstractStimulusFunction> p_stimulus(new RegularStimulus(-25,5,1000,1));
double simulation_duration = 10000; // This increased to 1e6 to give the timings shown on #1795.
double max_time_step = 1.0;
for (unsigned i=0; i<10; i++)
{
boost::shared_ptr<CvodeAdaptor> p_cvode_adaptor(new CvodeAdaptor()); // moving this outside the loop causes seg-faults!
p_cvode_adaptor->SetTolerances(1e-5, 1e-7); // Match AbstractCvodeCell
boost::shared_ptr<AbstractCardiacCell> p_cell_cvode_adaptor;
boost::shared_ptr<AbstractCvodeCell> p_cell_cvode;
switch (i)
{
case 0:
{
// Fox model
p_cell_cvode_adaptor.reset(new CellFoxModel2002FromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellFoxModel2002FromCellMLCvode(p_solver,p_stimulus));
break;
}
case 1:
{
// Shannon model
p_cell_cvode_adaptor.reset(new CellShannon2004FromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellShannon2004FromCellMLCvode(p_solver,p_stimulus));
break;
}
case 2:
{
// HH1952 model
p_cell_cvode_adaptor.reset(new CellHodgkinHuxley1952FromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellHodgkinHuxley1952FromCellMLCvode(p_solver,p_stimulus));
break;
}
case 3:
{
// Luo Rudy model
p_cell_cvode_adaptor.reset(new CellLuoRudy1991FromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellLuoRudy1991FromCellMLCvode(p_solver,p_stimulus));
break;
}
case 4:
{
// Mahajan model
p_cell_cvode_adaptor.reset(new CellMahajan2008FromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellMahajan2008FromCellMLCvode(p_solver,p_stimulus));
break;
}
case 5:
{
// Maleckar model
p_cell_cvode_adaptor.reset(new CellMaleckar2008FromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellMaleckar2008FromCellMLCvode(p_solver,p_stimulus));
break;
}
case 6:
{
// FaberRudy2000 model
p_cell_cvode_adaptor.reset(new CellFaberRudy2000FromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellFaberRudy2000FromCellMLCvode(p_solver,p_stimulus));
break;
}
case 7:
{
// DiFrancescoNoble1985 model
p_cell_cvode_adaptor.reset(new CellDiFrancescoNoble1985FromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellDiFrancescoNoble1985FromCellMLCvode(p_solver,p_stimulus));
break;
}
case 8:
{
// NobleVargheseKohlNoble1998a model
p_cell_cvode_adaptor.reset(new CellNobleVargheseKohlNoble1998aFromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellNobleVargheseKohlNoble1998aFromCellMLCvode(p_solver,p_stimulus));
break;
}
case 9:
{
// TenTusscher2006Epi model
p_cell_cvode_adaptor.reset(new CellTenTusscher2006EpiFromCellML(p_cvode_adaptor,p_stimulus));
p_cell_cvode.reset(new CellTenTusscher2006EpiFromCellMLCvode(p_solver,p_stimulus));
break;
}
default:
EXCEPTION("No model");
}
std::cout << p_cell_cvode_adaptor->GetSystemName() << ": " << p_cell_cvode_adaptor->GetNumberOfStateVariables() << " ODEs.\n";
// A standard CVODE adaptor solve
p_cvode_adaptor->SetMaxSteps(0xffffffff);
p_cell_cvode_adaptor->SetTimestep(max_time_step);
Timer::Reset();
p_cell_cvode_adaptor->SolveAndUpdateState(0, simulation_duration);
Timer::Print(" 1. CVODE adaptor (numeric Jacobian)");
// A standard native CVODE solve
p_cell_cvode->SetMaxSteps(0xffffffff);
p_cell_cvode->SetMaxTimestep(max_time_step);
p_cell_cvode->ForceUseOfNumericalJacobian(true);
TS_ASSERT(!p_cell_cvode->GetUseAnalyticJacobian());
Timer::Reset();
p_cell_cvode->SolveAndUpdateState(0, simulation_duration);
Timer::Print(" 2. CVODE native with Numeric Jacobian");
// A jacobian native CVODE solve
p_cell_cvode->ResetToInitialConditions();
p_cell_cvode->ForceUseOfNumericalJacobian(false);
TS_ASSERT(p_cell_cvode->GetUseAnalyticJacobian());
Timer::Reset();
p_cell_cvode->SolveAndUpdateState(0, simulation_duration);
Timer::Print(" 3. CVODE native with Analytic Jacobian");
}
#else
std::cout << "CVODE is not installed or Chaste hostconfig is not using it." << std::endl;
#endif
}
void TestLuoRudyGeneralizedRushLarsenMethod2()
{
EXIT_IF_PARALLEL;
HeartConfig::Instance()->SetOdeTimeStep(0.01);
GenerateCells2();
// Check the models really use Rush-Larsen
TS_ASSERT_EQUALS(Warnings::Instance()->GetNumWarnings(), 0u);
// Normal Luo-Rudy for comparison
boost::shared_ptr<HeunIvpOdeSolver> p_heun_solver(new HeunIvpOdeSolver());
CellLuoRudy1991FromCellML reference_model(p_heun_solver, mpGeneralizedRushLarsenCell->GetStimulusFunction());
// Check GetIIonic is identical
TS_ASSERT_DELTA(mpGeneralizedRushLarsenCell->GetIIonic(), reference_model.GetIIonic(), 1e-12);
// Test non-stimulated cell (using ComputeExceptVoltage)
mpGeneralizedRushLarsenCell->ComputeExceptVoltage(0.0, 1.0);
reference_model.ComputeExceptVoltage(0.0, 1.0);
TS_ASSERT_EQUALS(mpGeneralizedRushLarsenCell->GetNumberOfStateVariables(),
reference_model.GetNumberOfStateVariables());
for (unsigned i=0; i<reference_model.GetNumberOfStateVariables(); i++)
{
TS_ASSERT_DELTA(mpGeneralizedRushLarsenCell->rGetStateVariables()[i],
reference_model.rGetStateVariables()[i], 1e-6);
}
// Test stimulated cell (using Compute)
boost::shared_ptr<SimpleStimulus> p_stimulus(new SimpleStimulus(-25.5, 1.99, 0.0));
mpGeneralizedRushLarsenCell->ResetToInitialConditions();
mpGeneralizedRushLarsenCell->SetStimulusFunction(p_stimulus);
OdeSolution solutions_GRL2 = mpGeneralizedRushLarsenCell->Compute(0.0, 1.0, 0.01);
TS_ASSERT_EQUALS(solutions_GRL2.GetNumberOfTimeSteps(), 100u);
reference_model.ResetToInitialConditions();
reference_model.SetStimulusFunction(p_stimulus);
OdeSolution solutions_ref = reference_model.Compute(0.0, 1.0, 0.01);
for (unsigned i=0; i<reference_model.GetNumberOfStateVariables(); i++)
{
TS_ASSERT_DELTA(solutions_GRL2.rGetSolutions().back()[i],
solutions_ref.rGetSolutions().back()[i], 1e-2);
}
//Compare LuoRudy solution with general GRL2 solver solution (should match)
mpGeneralizedRushLarsenCell->ResetToInitialConditions();
boost::shared_ptr<ZeroStimulus> p_stimulus_zero(new ZeroStimulus());
mpGeneralizedRushLarsenCell->ResetToInitialConditions();
mpGeneralizedRushLarsenCell->SetStimulusFunction(p_stimulus_zero);
mpGeneralizedRushLarsenCell->SetTimestep(1e-3);
mpGeneralizedRushLarsenCell->SetVoltage(-30);
OdeSolution solutions_GRL2_stimulated_cell_order2 = mpGeneralizedRushLarsenCell->Compute(0.0, 1e-3);
boost::shared_ptr<GRL2IvpOdeSolver> p_grl2_solver(new GRL2IvpOdeSolver());
CellLuoRudy1991FromCellML reference_model_grl2(p_grl2_solver, mpGeneralizedRushLarsenCell->GetStimulusFunction());
// Compare with general GRL2 method
reference_model_grl2.ResetToInitialConditions();
reference_model_grl2.SetStimulusFunction(p_stimulus_zero);
reference_model_grl2.SetTimestep(1e-3);
reference_model_grl2.SetVoltage(-30);
OdeSolution ref_solution_grl2 = reference_model_grl2.Compute(0.0, 1e-3);
for (unsigned i=0; i<reference_model_grl2.GetNumberOfStateVariables(); i++)
{
double error1 = solutions_GRL2_stimulated_cell_order2.rGetSolutions().back()[i] - ref_solution_grl2.rGetSolutions().back()[i];
TS_ASSERT_DELTA(fabs(error1),0,5e-7);
}
// Free memory
delete mpGeneralizedRushLarsenCell;
// delete mpGeneralizedRushLarsenCellOpt;
}
void TestLuoRudyGeneralizedRushLarsenMethod()
{
EXIT_IF_PARALLEL;
HeartConfig::Instance()->SetOdeTimeStep(0.01);
GenerateCells();
// Check the models really use Rush-Larsen
TS_ASSERT_EQUALS(Warnings::Instance()->GetNumWarnings(), 0u);
// Some coverage
AbstractGeneralizedRushLarsenCardiacCell* p_grl_cell = dynamic_cast<AbstractGeneralizedRushLarsenCardiacCell*>(mpGeneralizedRushLarsenCell);
TS_ASSERT(p_grl_cell);
TS_ASSERT(!p_grl_cell->HasAnalyticJacobian());
TS_ASSERT(!p_grl_cell->GetUseAnalyticJacobian());
TS_ASSERT_THROWS_THIS(p_grl_cell->ForceUseOfNumericalJacobian(false),
"Using analytic Jacobian terms for generalised Rush-Larsen is not yet supported.");
TS_ASSERT_THROWS_NOTHING(p_grl_cell->ForceUseOfNumericalJacobian(true));
// Normal Luo-Rudy for comparison
boost::shared_ptr<HeunIvpOdeSolver> p_heun_solver(new HeunIvpOdeSolver());
CellLuoRudy1991FromCellML reference_model(p_heun_solver, mpGeneralizedRushLarsenCell->GetStimulusFunction());
// Check GetIIonic is identical
TS_ASSERT_DELTA(mpGeneralizedRushLarsenCell->GetIIonic(), reference_model.GetIIonic(), 1e-12);
// Test non-stimulated cell (using ComputeExceptVoltage)
mpGeneralizedRushLarsenCell->ComputeExceptVoltage(0.0, 1.0);
reference_model.ComputeExceptVoltage(0.0, 1.0);
TS_ASSERT_EQUALS(mpGeneralizedRushLarsenCell->GetNumberOfStateVariables(),
reference_model.GetNumberOfStateVariables());
for (unsigned i=0; i<reference_model.GetNumberOfStateVariables(); i++)
{
TS_ASSERT_DELTA(mpGeneralizedRushLarsenCell->rGetStateVariables()[i],
reference_model.rGetStateVariables()[i], 1e-6);
}
// Test stimulated cell (using Compute)
boost::shared_ptr<SimpleStimulus> p_stimulus(new SimpleStimulus(-25.5, 1.99, 0.0));
mpGeneralizedRushLarsenCell->ResetToInitialConditions();
mpGeneralizedRushLarsenCell->SetStimulusFunction(p_stimulus);
OdeSolution solutions_GRL1 = mpGeneralizedRushLarsenCell->Compute(0.0, 1.0, 0.01);
TS_ASSERT_EQUALS(solutions_GRL1.GetNumberOfTimeSteps(), 100u);
reference_model.ResetToInitialConditions();
reference_model.SetStimulusFunction(p_stimulus);
OdeSolution solutions_ref = reference_model.Compute(0.0, 1.0, 0.01);
for (unsigned i=0; i<reference_model.GetNumberOfStateVariables(); i++)
{
TS_ASSERT_DELTA(solutions_GRL1.rGetSolutions().back()[i],
solutions_ref.rGetSolutions().back()[i], 1e-2);
}
//Compare LuoRudy solution with general GRL1 solver solution (should match)
mpGeneralizedRushLarsenCell->ResetToInitialConditions();
boost::shared_ptr<ZeroStimulus> p_stimulus_zero(new ZeroStimulus());
mpGeneralizedRushLarsenCell->SetStimulusFunction(p_stimulus_zero);
mpGeneralizedRushLarsenCell->SetTimestep(1e-3);
mpGeneralizedRushLarsenCell->SetVoltage(-30);
OdeSolution solutions_GRL1_stimulated_cell_order1 = mpGeneralizedRushLarsenCell->Compute(0.0, 1e-3);
// Compare with SolveAndUpdateState for coverage
mpGeneralizedRushLarsenCell->ResetToInitialConditions();
mpGeneralizedRushLarsenCell->SetVoltage(-30);
mpGeneralizedRushLarsenCell->SolveAndUpdateState(0.0, 1e-3);
for (unsigned i=0; i<mpGeneralizedRushLarsenCell->GetNumberOfStateVariables(); i++)
{
TS_ASSERT_DELTA(mpGeneralizedRushLarsenCell->rGetStateVariables()[i],
solutions_GRL1_stimulated_cell_order1.rGetSolutions().back()[i], 1e-12);
}
// Compare with general GRL1 method
boost::shared_ptr<GRL1IvpOdeSolver> p_grl1_solver(new GRL1IvpOdeSolver());
CellLuoRudy1991FromCellML reference_model_grl1(p_grl1_solver, mpGeneralizedRushLarsenCell->GetStimulusFunction());
reference_model_grl1.ResetToInitialConditions();
reference_model_grl1.SetStimulusFunction(p_stimulus_zero);
reference_model_grl1.SetTimestep(1e-3);
reference_model_grl1.SetVoltage(-30);
OdeSolution ref_solution_grl1 = reference_model_grl1.Compute(0.0, 1e-3);
for (unsigned i=0; i<reference_model_grl1.GetNumberOfStateVariables(); i++)
{
double error1 = solutions_GRL1_stimulated_cell_order1.rGetSolutions().back()[i] - ref_solution_grl1.rGetSolutions().back()[i];
TS_ASSERT_DELTA(fabs(error1),0,5e-7);
}
// Test order of convergence (first-order method)
// Get two solutions with halved stepsize
mpGeneralizedRushLarsenCell->ResetToInitialConditions();
reference_model_grl1.SetStimulusFunction(p_stimulus_zero);
reference_model_grl1.SetVoltage(-30);
mpGeneralizedRushLarsenCell->SetTimestep(0.002);
solutions_GRL1_stimulated_cell_order1 = mpGeneralizedRushLarsenCell->Compute(0.0, 1.0);
mpGeneralizedRushLarsenCell->ResetToInitialConditions();
reference_model_grl1.SetStimulusFunction(p_stimulus_zero);
reference_model_grl1.SetVoltage(-30);
mpGeneralizedRushLarsenCell->SetTimestep(0.001);
OdeSolution solutions_GRL1_stimulated_cell_order2 = mpGeneralizedRushLarsenCell->Compute(0.0, 1.0);
// Get accurate solution to be used as reference solution
//boost::shared_ptr<HeunIvpOdeSolver> p_heun_solver(new HeunIvpOdeSolver());
reference_model.SetStimulusFunction(p_stimulus_zero);
reference_model.SetVoltage(-30);
reference_model.ResetToInitialConditions();
reference_model.SetTimestep(1e-6);
OdeSolution ref_solution = reference_model.Compute(0.0, 1.0);
for (unsigned i=0; i<reference_model.GetNumberOfStateVariables(); i++)
{
double error1 = solutions_GRL1_stimulated_cell_order1.rGetSolutions().back()[i] - ref_solution.rGetSolutions().back()[i];
double error2 = solutions_GRL1_stimulated_cell_order2.rGetSolutions().back()[i] - ref_solution.rGetSolutions().back()[i];
TS_ASSERT_DELTA(error1/error2, 2, 0.1);
}
// Free memory
delete mpGeneralizedRushLarsenCell;
// delete mpGeneralizedRushLarsenCellOpt;
}
void TestScaleFactorsMaleckar(void) throw (Exception)
{
double end_time =500;
boost::shared_ptr<RegularStimulus> p_stimulus(new RegularStimulus(-5.6,
6,
1000,
4.0));
boost::shared_ptr<EulerIvpOdeSolver> p_solver(new EulerIvpOdeSolver); //define the solver
HeartConfig::Instance()->SetOdeTimeStep(0.001);
CellMaleckar2008FromCellML atrial_ode_system(p_solver, p_stimulus);
const std::string control_file = "control";
const std::string first_set_file = "first_scale_factor_set";
const std::string second_set_file = "second_scale_factor_set";
const std::string AZD_file = "AZD_scale_factor_set";
OdeSolution control_solution;
OdeSolution first_scale_factor_set_solution;
OdeSolution second_scale_factor_set_solution;
OdeSolution AZD_scale_factor_set_solution;
double time_step=0.001;
double sampling_time=0.001;
std::vector<double> state_variables= atrial_ode_system.GetInitialConditions();
//default values
atrial_ode_system.SetParameter("ScaleFactorGks",1.0);
atrial_ode_system.SetParameter("ScaleFactorIto",1.0);
atrial_ode_system.SetParameter("ScaleFactorGkr",1.0);
atrial_ode_system.SetParameter("ScaleFactorGna",1.0);
atrial_ode_system.SetParameter("ScaleFactorAch",1e-24);
atrial_ode_system.SetParameter("ScaleFactorGNaK",1.0);
atrial_ode_system.SetParameter("ScaleFactorGNaCa",1.0);
atrial_ode_system.SetParameter("ScaleFactorGKur",1.0);
atrial_ode_system.SetParameter("ScaleFactorGK1",1.0);
atrial_ode_system.SetParameter("ScaleFactorGCaL",1.0);
atrial_ode_system.SetParameter("ScaleFactorAZD",0.0);
control_solution = p_solver->Solve(&atrial_ode_system, state_variables, 0, end_time, time_step, sampling_time);
control_solution.WriteToFile("TestIonicModels",
control_file,
"ms",//time units
100,//steps per row
false);/*true cleans the directory*/
//now apply the first scale factor set, decreases outward currents
atrial_ode_system.SetParameter("ScaleFactorGks",0.8);
atrial_ode_system.SetParameter("ScaleFactorIto",1.0);
atrial_ode_system.SetParameter("ScaleFactorGkr",0.9);
atrial_ode_system.SetParameter("ScaleFactorGna",1.0);
atrial_ode_system.SetParameter("ScaleFactorAch",1e-24);
atrial_ode_system.SetParameter("ScaleFactorGNaK",1.0);
atrial_ode_system.SetParameter("ScaleFactorGNaCa",1.0);
atrial_ode_system.SetParameter("ScaleFactorGKur",0.7);
atrial_ode_system.SetParameter("ScaleFactorGK1",0.6);
atrial_ode_system.SetParameter("ScaleFactorGCaL",1.0);
atrial_ode_system.SetParameter("ScaleFactorAZD",0.0);
state_variables= atrial_ode_system.GetInitialConditions();
first_scale_factor_set_solution = p_solver->Solve(&atrial_ode_system, state_variables, 0, end_time, time_step, sampling_time);
first_scale_factor_set_solution.WriteToFile("TestIonicModels",
first_set_file,
"ms",//time units
100,//steps per row
false);/*true cleans the directory*/
//now apply the secondscale factor set, this one increases inward currents
atrial_ode_system.SetParameter("ScaleFactorGks",1.0);
atrial_ode_system.SetParameter("ScaleFactorIto",1.0);
atrial_ode_system.SetParameter("ScaleFactorGkr",1.0);
atrial_ode_system.SetParameter("ScaleFactorGna",1.5);
atrial_ode_system.SetParameter("ScaleFactorAch",1e-24);
atrial_ode_system.SetParameter("ScaleFactorGNaK",1.0);
atrial_ode_system.SetParameter("ScaleFactorGNaCa",2.0);
atrial_ode_system.SetParameter("ScaleFactorGKur",1.0);
atrial_ode_system.SetParameter("ScaleFactorGK1",1.0);
atrial_ode_system.SetParameter("ScaleFactorGCaL",1.6);
atrial_ode_system.SetParameter("ScaleFactorAZD",0.0);
state_variables= atrial_ode_system.GetInitialConditions();
second_scale_factor_set_solution = p_solver->Solve(&atrial_ode_system, state_variables, 0, end_time, time_step, sampling_time);
second_scale_factor_set_solution.WriteToFile("TestIonicModels",
second_set_file,
"ms",//time units
100,//steps per row
false);/*true cleans the directory*/
//check the AZD scale factor (vs control)
atrial_ode_system.SetParameter("ScaleFactorGks",1.0);
atrial_ode_system.SetParameter("ScaleFactorIto",1.0);
atrial_ode_system.SetParameter("ScaleFactorGkr",1.0);
atrial_ode_system.SetParameter("ScaleFactorGna",1.0);
atrial_ode_system.SetParameter("ScaleFactorAch",1e-24);
atrial_ode_system.SetParameter("ScaleFactorGNaK",1.0);
atrial_ode_system.SetParameter("ScaleFactorGNaCa",1.0);
atrial_ode_system.SetParameter("ScaleFactorGKur",1.0);
atrial_ode_system.SetParameter("ScaleFactorGK1",1.0);
atrial_ode_system.SetParameter("ScaleFactorGCaL",1.0);
atrial_ode_system.SetParameter("ScaleFactorAZD",5.0);
AZD_scale_factor_set_solution = p_solver->Solve(&atrial_ode_system, state_variables, 0, end_time, time_step, sampling_time);
AZD_scale_factor_set_solution.WriteToFile("TestIonicModels",
AZD_file,
"ms",//time units
100,//steps per row
false);/*true cleans the directory*/
ColumnDataReader data_reader1("TestIonicModels", control_file);
std::vector<double> voltages1 = GetVoltages(data_reader1);
ColumnDataReader data_reader2("TestIonicModels", first_set_file);
std::vector<double> voltages2 = GetVoltages(data_reader2);
ColumnDataReader data_reader3("TestIonicModels", second_set_file);
std::vector<double> voltages3 = GetVoltages(data_reader3);
ColumnDataReader data_reader4("TestIonicModels", AZD_file);
std::vector<double> voltages4 = GetVoltages(data_reader4);
TS_ASSERT_EQUALS(voltages1.size(), voltages2.size());
TS_ASSERT_EQUALS(voltages2.size(), voltages3.size());
TS_ASSERT_EQUALS(voltages3.size(), voltages4.size());
//create the times vector
std::vector<double> times;
double k =0;
for (unsigned i=0; i<voltages2.size(); i++)
{
times.push_back(k);
k=k+0.1;
}
CellProperties cell_properties_control(voltages1, times);
CellProperties cell_properties_first(voltages2, times);
CellProperties cell_properties_second(voltages3, times);
CellProperties cell_properties_AZD(voltages4, times);
double control_APD = cell_properties_control.GetLastActionPotentialDuration(90);
double first_APD = cell_properties_first.GetLastActionPotentialDuration(90);
double second_APD = cell_properties_second.GetLastActionPotentialDuration(90);
double AZD_APD = cell_properties_AZD.GetLastActionPotentialDuration(90);
//test that the aps are actually longer than control (all interventions were meant to have that effect except the last one)
TS_ASSERT_LESS_THAN(control_APD, first_APD);
TS_ASSERT_LESS_THAN(control_APD, second_APD);
TS_ASSERT_LESS_THAN(AZD_APD, control_APD);
//leave some hardcoded value for testing
TS_ASSERT_DELTA(control_APD, 206.1278, 0.1);
TS_ASSERT_DELTA(first_APD, 403.8293, 0.1);
TS_ASSERT_DELTA(second_APD, 320.0195, 0.1);
TS_ASSERT_DELTA(AZD_APD , 187.8073, 0.1);
}
/**
* Here we test that the scale factors for the TT model do what they are expected to
* We check that they modify APD in a way that is expected.
*/
void TestScaleFactorsForTT06(void)
{
double simulation_end=500;/*end time, in milliseconds for this model*/
// Set the stimulus, the following values are appropriate for single cell simulations of this model.
double magnitude = -38.0; // pA/pF
double duration = 1.0; // ms
double start = 100; // ms
boost::shared_ptr<SimpleStimulus> p_stimulus(new SimpleStimulus(magnitude,
duration,
start));
boost::shared_ptr<EulerIvpOdeSolver> p_solver(new EulerIvpOdeSolver); //define the solver
HeartConfig::Instance()->SetOdeTimeStep(0.001);// with Forward Euler, this must be as small as 0.001.
const std::string control_file = "TT_epi";
const std::string mid_file = "TT_mid";
const std::string endo_file = "TT_endo";
const std::string LQT_file = "TT_LQT";
CellTenTusscher2006EpiFromCellML TT_model_epi(p_solver, p_stimulus);
TT_model_epi.SetParameter("ScaleFactorIto", 1.0);
TT_model_epi.SetParameter("ScaleFactorGkr", 1.0);
TT_model_epi.SetParameter("ScaleFactorGks", 1.0);
//run the model
RunOdeSolverWithIonicModel(&TT_model_epi,
simulation_end,
control_file,
100,
false);
CellTenTusscher2006EpiFromCellML TT_model_mid(p_solver, p_stimulus);
TT_model_mid.SetParameter("ScaleFactorIto", 1.0);
TT_model_mid.SetParameter("ScaleFactorGkr", 1.0);
TT_model_mid.SetParameter("ScaleFactorGks", 0.25);
RunOdeSolverWithIonicModel(&TT_model_mid,
simulation_end,
mid_file,
100,
false);
CellTenTusscher2006EpiFromCellML TT_model_endo(p_solver, p_stimulus);
TT_model_endo.SetParameter("ScaleFactorIto", 0.165);
TT_model_endo.SetParameter("ScaleFactorGkr", 1.0);
TT_model_endo.SetParameter("ScaleFactorGks", 0.66);
RunOdeSolverWithIonicModel(&TT_model_endo,
simulation_end,
endo_file,
100,
false);
CellTenTusscher2006EpiFromCellML TT_model_LQT(p_solver, p_stimulus);
TT_model_LQT.SetParameter("ScaleFactorIto", 1.0);
TT_model_LQT.SetParameter("ScaleFactorGkr", 0.0);
TT_model_LQT.SetParameter("ScaleFactorGks", 1.0);
RunOdeSolverWithIonicModel(&TT_model_LQT,
simulation_end,
LQT_file,
100,
false);
ColumnDataReader data_reader1("TestIonicModels", control_file);
std::vector<double> voltages1 = GetVoltages(data_reader1);
ColumnDataReader data_reader2("TestIonicModels", mid_file);
std::vector<double> voltages2 = GetVoltages(data_reader2);
ColumnDataReader data_reader3("TestIonicModels", endo_file);
std::vector<double> voltages3 = GetVoltages(data_reader3);
ColumnDataReader data_reader4("TestIonicModels", LQT_file);
std::vector<double> voltages4 = GetVoltages(data_reader4);
TS_ASSERT_EQUALS(voltages1.size(), voltages2.size());
TS_ASSERT_EQUALS(voltages2.size(), voltages3.size());
TS_ASSERT_EQUALS(voltages3.size(), voltages4.size());
//create the times vector
std::vector<double> times;
double k =0;
for (unsigned i=0; i<voltages2.size(); i++)
{
times.push_back(k);
k=k+0.1;
}
CellProperties cell_properties_control(voltages1, times);
CellProperties cell_properties_mid(voltages2, times);
CellProperties cell_properties_endo(voltages3, times);
CellProperties cell_properties_LQT(voltages4, times);
double control_APD = cell_properties_control.GetLastActionPotentialDuration(90);
double mid_APD = cell_properties_mid.GetLastActionPotentialDuration(90);
double endo_APD = cell_properties_endo.GetLastActionPotentialDuration(90);
double LQT_APD = cell_properties_LQT.GetLastActionPotentialDuration(90);
TS_ASSERT_DELTA(control_APD, 300.4789, 0.1);
TS_ASSERT_DELTA(mid_APD, 392.1871, 0.1);
TS_ASSERT_DELTA(endo_APD, 329.2048, 0.1);
TS_ASSERT_DELTA(LQT_APD , 347.8374, 0.1);
}
/**
* Here we test the scale factors methiods for the mahajan model.
* The idea is to set the scale factors for the 3 different cell types (epi, mid and endo)
* and check that the rsulting APD makes sense if compared to experiemntal results
*/
void TestScaleFactorsForMahajanModel(void) throw(Exception)
{
double end_time=300;
double time_step=0.01;
double sampling_time=time_step;
// Set stimulus
double magnitude_stimulus = -70.0; // pA/pF
double duration_stimulus = 1.0; // ms
double start_stimulus = 10.0; // ms
double period=1000;//here, this is ms
boost::shared_ptr<RegularStimulus> p_stimulus(new RegularStimulus(magnitude_stimulus,
duration_stimulus,
period,
start_stimulus));
boost::shared_ptr<EulerIvpOdeSolver> p_forward_solver(new EulerIvpOdeSolver); //define the solver
CellMahajan2008FromCellML forward_model(p_forward_solver, p_stimulus);
boost::shared_ptr<BackwardEulerIvpOdeSolver> p_backward_solver(new BackwardEulerIvpOdeSolver(
forward_model.GetNumberOfStateVariables()));
CellMahajan2008FromCellML epicardial_model(p_backward_solver, p_stimulus);
CellMahajan2008FromCellML endocardial_model(p_backward_solver, p_stimulus);
CellMahajan2008FromCellML midmyocardial_model(p_backward_solver, p_stimulus);
epicardial_model.SetParameter("ScaleFactorGks",1.0);
epicardial_model.SetParameter("ScaleFactorIto",1.0);
epicardial_model.SetParameter("ScaleFactorGkr",1.0);
midmyocardial_model.SetParameter("ScaleFactorGks",0.09);
midmyocardial_model.SetParameter("ScaleFactorIto",1.0);
midmyocardial_model.SetParameter("ScaleFactorGkr",1.0);
endocardial_model.SetParameter("ScaleFactorGks",0.86);
endocardial_model.SetParameter("ScaleFactorIto",0.2);
endocardial_model.SetParameter("ScaleFactorGkr",1.0);
std::vector<double> state_variables_epi = epicardial_model.GetInitialConditions();
std::vector<double> state_variables_endo = endocardial_model.GetInitialConditions();
std::vector<double> state_variables_mid = midmyocardial_model.GetInitialConditions();
const std::string mahajan_epi_file = "Mahajan_epi";
const std::string mahajan_mid_file = "Mahajan_mid";
const std::string mahajan_endo_file = "Mahajan_endo";
// Solve and write to file
OdeSolution epi_solution;
epi_solution = p_backward_solver->Solve(&epicardial_model, state_variables_epi, 0, end_time, time_step, sampling_time);
epi_solution.WriteToFile("TestIonicModels",
mahajan_epi_file,
"ms",//time units
100,//steps per row
false);/*true cleans the directory*/
OdeSolution mid_solution;
mid_solution = p_backward_solver->Solve(&midmyocardial_model, state_variables_mid, 0, end_time, time_step, sampling_time);
mid_solution.WriteToFile("TestIonicModels",
mahajan_mid_file,
"ms",//time units
100,//steps per row
false);/*true cleans the directory*/
OdeSolution endo_solution;
endo_solution = p_backward_solver->Solve(&endocardial_model, state_variables_endo, 0, end_time, time_step, sampling_time);
endo_solution.WriteToFile("TestIonicModels",
mahajan_endo_file,
"ms",//time units
100,//steps per row
false);/*true cleans the directory*/
ColumnDataReader data_reader_epi("TestIonicModels", mahajan_epi_file);
ColumnDataReader data_reader_mid("TestIonicModels", mahajan_mid_file);
ColumnDataReader data_reader_endo("TestIonicModels", mahajan_endo_file);
std::vector<double> times = data_reader_epi.GetValues("Time");
std::vector<double> v_endo = data_reader_endo.GetValues("membrane_voltage");
std::vector<double> v_epi = data_reader_epi.GetValues("membrane_voltage");
std::vector<double> v_mid = data_reader_mid.GetValues("membrane_voltage");
CellProperties cell_properties_endo(v_endo, times);
CellProperties cell_properties_epi(v_epi, times);
CellProperties cell_properties_mid(v_mid, times);
double epi_APD = cell_properties_epi.GetLastActionPotentialDuration(90);
double endo_APD = cell_properties_endo.GetLastActionPotentialDuration(90);
double mid_APD = cell_properties_mid.GetLastActionPotentialDuration(90);
// Check that percentage increase from epi to mid and endo (roughly*) matches results
// from McIntosh et al. Card Res, 45:397-409. 200 (Figure 1 and 2)
// *this is cardiac modelling after all...
TS_ASSERT_DELTA((mid_APD-epi_APD)*100/epi_APD, 48.6, 2); // new values because gtos and gtof were the wrong way round (in Mahajan paper - they copied and pasted from Shannon wrong!)
TS_ASSERT_DELTA((endo_APD-epi_APD)*100/epi_APD, 15.7, 2); // ""
}