Owen11CellPopulationGenerator.cpp

/*

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#include "Owen11CellPopulationGenerator.hpp"
#include "BaseUnits.hpp"
#include "CancerCellMutationState.hpp"
#include "StalkCellMutationState.hpp"
#include "Cell.hpp"
#include "DefaultCellProliferativeType.hpp"
#include "Owen2011OxygenBasedCellCycleModel.hpp"
#include "VesselNetworkCellPopulationInteractor.hpp"
#include "CellLabelWriter.hpp"
#include "CellMutationStatesWriter.hpp"
#include "CellProliferativePhasesCountWriter.hpp"
#include "CellProliferativeTypesWriter.hpp"
#include "CellProliferativePhasesWriter.hpp"
#include "CellsGenerator.hpp"
#include "PottsMesh.hpp"
#include "Exception.hpp"
#include "Owen11CaUpdateRule.hpp"
#include "Owen11CaBasedDivisionRule.hpp"
#include "Owen11Parameters.hpp"
#include "Secomb04Parameters.hpp"
#include "GenericParameters.hpp"
#include "BaseUnits.hpp"
#include "RandomNumberGenerator.hpp"

template<unsigned DIM>
Owen11CellPopulationGenerator<DIM>::Owen11CellPopulationGenerator() :
    mpVesselNetwork(),
    mpRegularGrid(),
    mpPottsMeshGenerator(),
    mpCancerCellMutationState(boost::shared_ptr<CancerCellMutationState>(new CancerCellMutationState)),
    mpNormalCellMutationState(),
    mpStalkCellMutationState(boost::shared_ptr<StalkCellMutationState>(new StalkCellMutationState)),
    mReferenceLength(BaseUnits::Instance()->GetReferenceLengthScale()),
    mTumourRadius(0.0*unit::metres),
    mCellPopulationReferenceLength(BaseUnits::Instance()->GetReferenceLengthScale())
{

}

template<unsigned DIM>
boost::shared_ptr<Owen11CellPopulationGenerator<DIM> > Owen11CellPopulationGenerator<DIM>::Create()
{
    MAKE_PTR(Owen11CellPopulationGenerator<DIM>, pSelf);
    return pSelf;
}

template<unsigned DIM>
Owen11CellPopulationGenerator<DIM>::~Owen11CellPopulationGenerator()
{

}

template<unsigned DIM>
void Owen11CellPopulationGenerator<DIM>::SetVesselNetwork(boost::shared_ptr<VesselNetwork<DIM> > pNetwork)
{
    mpVesselNetwork = pNetwork;
}

template<unsigned DIM>
void Owen11CellPopulationGenerator<DIM>::SetRegularGrid(boost::shared_ptr<RegularGrid<DIM> > pGrid)
{
    mpRegularGrid = pGrid;
}

template<unsigned DIM>
void Owen11CellPopulationGenerator<DIM>::SetReferenceLengthScale(units::quantity<unit::length> lengthScale)
{
    mReferenceLength = lengthScale;
}

template<unsigned DIM>
void Owen11CellPopulationGenerator<DIM>::SetTumourRadius(units::quantity<unit::length> tumourRadius)
{
    mTumourRadius = tumourRadius;
}

template<unsigned DIM>
boost::shared_ptr<CaBasedCellPopulation<DIM> > Owen11CellPopulationGenerator<DIM>::Update()
{
    if(!mpRegularGrid)
    {
        EXCEPTION("A regular grid is required to set of the cell population");
    }

    unsigned extents_z = 1;
    if(DIM==3)
    {
        extents_z = mpRegularGrid->GetExtents()[2];
    }

    mpPottsMeshGenerator = boost::shared_ptr<PottsMeshGenerator<DIM> >(new PottsMeshGenerator<DIM>(mpRegularGrid->GetExtents()[0], 0, 0,
                                                                                                   mpRegularGrid->GetExtents()[1], 0, 0,
                                                                                                   extents_z, 0, 0));

    PottsMesh<DIM>* p_mesh = mpPottsMeshGenerator->GetMesh();

    // There is a bug in Chaste causing index out of bounds for large grid spacing. It may be better to use a scaling here
    // so grid spacing is always one.
    if(DIM==2)
    {
        p_mesh->Scale(mpRegularGrid->GetSpacing()/mCellPopulationReferenceLength,
                mpRegularGrid->GetSpacing()/mCellPopulationReferenceLength);
    }
    else
    {
        p_mesh->Scale(mpRegularGrid->GetSpacing()/mCellPopulationReferenceLength,
                mpRegularGrid->GetSpacing()/mCellPopulationReferenceLength,
                mpRegularGrid->GetSpacing()/mCellPopulationReferenceLength);
    }

    std::vector<unsigned> location_indices;
    for (unsigned index=0; index < p_mesh->GetNumNodes(); index++)
    {
        location_indices.push_back(index);
    }

    // Fill the grid with cells
    std::vector<CellPtr> cells;
    MAKE_PTR(DefaultCellProliferativeType, p_diff_type);
    CellsGenerator<Owen2011OxygenBasedCellCycleModel, DIM> cells_generator;

//    MAKE_PTR(StemCellProliferativeType, p_stem_type);
//
//    double oxygen_concentration = 30.0;
//    for (unsigned i = 0; i < location_indices.size(); i++)
//    {
//        // Assign an oxygen based cell cycle model, which requires a dimension to be set.
//        Owen2011OxygenBasedCellCycleModel* const p_model = new Owen2011OxygenBasedCellCycleModel;
//        p_model->SetDimension(2);
//        CellPtr p_cell(new Cell(p_state, p_model));
//        p_cell->SetCellProliferativeType(p_stem_type);
//        p_cell->SetApoptosisTime(30);
//        cells.push_back(p_cell);
//        p_cell->GetCellData()->SetItem("oxygen", oxygen_concentration);
//    }

    //            // Create a tumour cells in a cylinder in the middle of the domain
    //            boost::shared_ptr<Part<3> > p_tumour_cell_region = GetInitialTumourCellRegion();
    //            std::vector<unsigned> location_indices = p_tumour_cell_region->GetContainingGridIndices(num_x, num_y, num_z, spacing);
    //
    //            std::vector<Node<3>*> nodes;
    //            for(unsigned idx=0; idx<location_indices.size(); idx++)
    //            {
    //                c_vector<double, 3> location = Grid::GetLocationOf1dIndex(location_indices[idx], num_x, num_y, spacing);
    //                nodes.push_back(new Node<3>(idx, location, false));
    //            }
    //            NodesOnlyMesh<3> mesh;
    //            mesh.ConstructNodesWithoutMesh(nodes, 1.5 * spacing);
    //            std::vector<CellPtr> cells;
    //            CellsGenerator<SimpleOxygenBasedCellCycleModel, 3> cells_generator;
    //            cells_generator.GenerateBasic(cells, mesh.GetNumNodes());
    //            NodeBasedCellPopulation<3> cell_population(mesh, cells);
    //            cell_population.SetAbsoluteMovementThreshold(2.0 * spacing);
    //            cell_population.AddCellWriter<CellLabelWriter>();

    cells_generator.GenerateBasicRandom(cells, p_mesh->GetNumNodes(), p_diff_type);
    boost::shared_ptr<CaBasedCellPopulation<DIM> > p_cell_population =
            boost::shared_ptr<CaBasedCellPopulation<DIM> >(new CaBasedCellPopulation<DIM> (*p_mesh, cells, location_indices, 2));

    // Label stalk cells if the is a vessel network
    if(mpVesselNetwork)
    {
        VesselNetworkCellPopulationInteractor<DIM> interactor = VesselNetworkCellPopulationInteractor<DIM>();
        interactor.SetVesselNetwork(mpVesselNetwork);
        interactor.PartitionNetworkOverCells(*p_cell_population, mCellPopulationReferenceLength);
//        interactor.LabelVesselsInCellPopulation(*p_cell_population, mpStalkCellMutationState, mpStalkCellMutationState);
    }

    // Set up tumour cells in the centre of the domain
    if(DIM==2)
    {
        DimensionalChastePoint<DIM> origin(double(mpRegularGrid->GetExtents()[0])*mpRegularGrid->GetSpacing()/(2.0*mReferenceLength),
                                         double(mpRegularGrid->GetExtents()[1])*mpRegularGrid->GetSpacing()/(2.0*mReferenceLength),
                                         0.0, mReferenceLength);
        boost::shared_ptr<Part<DIM> > p_sub_domain = Part<DIM>::Create();
        boost::shared_ptr<Polygon<DIM> > circle = p_sub_domain->AddCircle(mTumourRadius, origin);
        for (unsigned ind = 0; ind < p_mesh->GetNumNodes(); ind++)
        {
            if (p_sub_domain->IsPointInPart(DimensionalChastePoint<DIM>(p_mesh->GetNode(ind)->rGetLocation(), mCellPopulationReferenceLength)))
            {
                p_cell_population->GetCellUsingLocationIndex(ind)->SetMutationState(mpCancerCellMutationState);
            }
        }
    }
    else
    {
        double dimensionless_spacing = mpRegularGrid->GetSpacing()/mReferenceLength;
        c_vector<double, DIM> dimensionless_origin = mpRegularGrid->GetOrigin().GetLocation(mReferenceLength);

        DimensionalChastePoint<DIM> origin(double(mpRegularGrid->GetExtents()[0])*dimensionless_spacing/2.0 + dimensionless_origin[0],
                                         double(mpRegularGrid->GetExtents()[1])*dimensionless_spacing/2.0 + dimensionless_origin[0],
                                         double(mpRegularGrid->GetExtents()[2])*dimensionless_spacing/2.0 + dimensionless_origin[0],
                                         mReferenceLength);

        for(unsigned idx=0; idx<mpRegularGrid->GetNumberOfPoints(); idx++)
        {
            units::quantity<unit::length> distance = mpRegularGrid->GetLocationOf1dIndex(idx).GetDistance(origin);
            if(distance<=mTumourRadius)
            {
                p_cell_population->GetCellUsingLocationIndex(idx)->SetMutationState(mpCancerCellMutationState);
            }
        }
    }

    // Set up the cell cycle model . Note that Cell Based Chaste does not use dimensional analysis so we need to be careful with units.
    units::quantity<unit::pressure> initial_oxygen_tension(30.0*unit::mmHg);
    units::quantity<unit::solubility>  solubility = Secomb04Parameters::mpOxygenVolumetricSolubility->GetValue("Owen11CellPopulationGenerator") *
            GenericParameters::mpGasConcentrationAtStp->GetValue("Owen11CellPopulationGenerator");
    units::quantity<unit::concentration>  initial_oxygen_concentration = initial_oxygen_tension*solubility;

    std::list<CellPtr> cells_updated = p_cell_population->rGetCells();
    std::list<CellPtr>::iterator it;
    for (it = cells_updated.begin(); it != cells_updated.end(); ++it)
    {
        (*it)->GetCellData()->SetItem("Phi", 0.99*RandomNumberGenerator::Instance()->ranf());
        (*it)->GetCellData()->SetItem("oxygen", initial_oxygen_concentration/BaseUnits::Instance()->GetReferenceConcentrationScale());
        (*it)->GetCellData()->SetItem("VEGF", 0.0);
        (*it)->GetCellData()->SetItem("p53", 0.0);
        (*it)->GetCellData()->SetItem("Number_of_cancerous_neighbours", 0.0);
        (*it)->GetCellData()->SetItem("Number_of_normal_neighbours", 0.0);
//        (*it)->SetApoptosisTime(24); //hours
    }

    // Specify an update rule
    MAKE_PTR(Owen11CaUpdateRule<DIM>, p_update_rule);
    p_update_rule->SetVesselNetwork(mpVesselNetwork);
    p_update_rule->SetRegularGrid(mpRegularGrid);

    MAKE_PTR(Owen11CaBasedDivisionRule<DIM>, p_division_rule);
    p_division_rule->SetVesselNetwork(mpVesselNetwork);
    p_division_rule->SetRegularGrid(mpRegularGrid);

    p_cell_population->RemoveAllUpdateRules();
    p_cell_population->AddUpdateRule(p_update_rule);
    p_cell_population->SetCaBasedDivisionRule(p_division_rule);

    return p_cell_population;
}

//template class Owen11CellPopulationGenerator<1> ;
template class Owen11CellPopulationGenerator<2> ;
template class Owen11CellPopulationGenerator<3> ;