Simulation of haemodynamic flow in head and neck cancer chemotherapy
© Rhode et al; licensee BioMed Central Ltd. 2011
Received: 24 October 2011
Accepted: 2 December 2011
Published: 2 December 2011
In recent years, intra arterial chemotherapy has become an important component in head and neck cancer treatment. However, therapy success can vary significantly and consistent treatment guidelines are missing. The purpose of this study was to create a computer simulation of the chemical agent injection in the head and neck arteries to investigate the distribution and concentration of the chemical.
Realistic three dimensional patient specific geometry was created from image scan data. Pulsatile blood flow, turbulence, the chemical agent injection via a catheter, and the mixture between blood and the chemical were then simulated through the arterial network by computational fluid dynamics software.
The results show a consistent chemical distribution throughout all the arteries and this is ineffective. In addition, due to high wall shear stress and turbulence at the inner bifurcation wall, serious complications during the treatment could occur, for instance haemolysis or thrombosis.
The modelled catheter position is insufficient to provide a high chemical agent concentration in the desired tumour feeding artery, which is vital for therapy success.
Keywordspatient specific model blood flow dynamics non-Newtonian chemotherapy multiphase model
In head and neck cancer treatment and particularly in oral cancer treatment, surgery or radiotherapy alone or radiotherapy in combination with chemotherapy is generally administered. All modalities can lead to significant problems with swallowing and speech with consequent reduction in life quality. The general aim in cancer treatment is to approach maximum tumour control with minimum related side effects. In recent years, chemotherapy has become more relevant and is now an important treatment component in combined modality approaches, several studies in this subject are summarized in [, p. 127]. Studies, using concurrent chemoradiation in comparison with radiation alone, are commonly randomized trials, which vary in radiation dose, fractionation schedule, and administered chemotherapy. The dosage scheme, which is usually given in mass per body surface area (mg/m2), as well as the administration method of the chemical is vital for the prognosis.
Using intra-arterial infusion improved the success of treatment. This is because of the arteries that supply specific tissue, detailed in [2, 3]. This technique allows the supply of much higher chemical agent concentration directly to the tumour than intra-venous infusion. The latter, distributes the chemical agent throughout the whole body and causes increased side effects. Because of the patient specific artery geometry and resultant haemodynamics, there is no method that always leads to success, and this is discussed in . The knowledge about the chemical agent concentration in blood and the technique by which the tumours were infused is vital for therapy success . The aim is to supply a high application rate of chemical in a specified target region inside the arterial network.
Advances in computational methods and three-dimensional imaging techniques allow improved understanding of haemodynamic flow in the cardiovascular network. Computational fluid dynamics (CFD) solves differential equations of fluid flows numerically and is an excellent technique for analysing and displaying blood flow in the head and neck arterial network. In contrast to previous studies [6–9], using two or three-dimensional ideal geometry, this project deals with real geometry obtained from image-scan segmentation of a patient [10–14].
Simulation of patient specific two-component flow, using various injection positions and parameters, for instance the mass flow rate of the chemical agent, should deepen the knowledge of chemical agent distribution in the artery network, which is the aim of this study. If an accurate computer simulation is achievable in a sufficiently short time, patient specific computation would provide the basis of comparing the effect of several treatment methods and parameters prior to therapy. A two-component transient CFD model can assist medical scientists to select the most appropriate treatment strategy.
Considering the pulsatile character of blood flow, a transient CFD model is required. The model is reduced to the interesting region of the common carotid artery (CCA) bifurcation, the lingual artery (LA), facial artery (FA) and superior thyroid artery (STA) branch, including two-component flow. In particular the CFD model comprises the two liquids blood (continuous component or primary phase) and the chemical agent cisplatin (dispersed component or secondary phase). Cisplatin is injected via a catheter into the arterial blood flow. Due to this, the catheter has to be considered as thin pipe inside the CCA, because the catheter walls cause wall friction and influence the haemodynamic flow pattern.
Short before the common carotid bifurcation.
Internal carotid artery at the height of the superior thyroid branch.
Inside the lingual artery.
It was decided to compute the first injection position, because the catheter can be modelled as straight ideal pipe, shown in Figure 1(a). Small pipe geometry creation using few voxels is complicated in Scanip™. Hence, it is impossible to model the catheter entirely including the inner wall in such small dimensions. A catheter outer wall diameter of approximately 1.2 mm (this is 30% larger than the real catheter) and tolerable wall smoothness was achieved with the CAD primitive generation tools in Scanip™. An additional volume at the top end of the catheter was created to obtain a catheter-blood interface in the following mesh import in Gambit™ . Using the split face tool in Gambit™, this interface was divided by a circle of 0.6 mm diameter and an ideal circular face for the catheter outflow boundary condition was obtained. This face is slightly smaller than the real catheter inner diameter. Since the catheter inner wall is not considered in the model, it was decided to neglect the cisplatin flow inside the catheter entirely and the catheter volume remains unmeshed. Otherwise recirculation would occur inside the catheter near the catheter-blood interface. Additionally the steady ideal pipe flow of cisplatin inside the catheter is entirely solvable with analytical equations.
The mesh consists of hexahedron elements in the vessel core and tetrahedron elements adjacent to walls. A mesh independence test was done in a previous steady simulation on the highest blood flow rate of CCA using wall y+ and pressure gradient adaption . Due to just slightly monitor data changes after the mesh adaption, the initial mesh of counting 224,115 cells was taken.
The most appropriate data for the CCA inlet is given in  obtained from older volunteers and shown with the solid line in Figure 3(b). However, it can be expected that because of the stress during chemotherapy, the heart rate should be higher than the reported 65 beats per minute in this source. Additionally, the study was made with healthy volunteers. Hence, it is not known how a catheter will affect the reported rate of flow range. These two inlet conditions are converted into a mass flux boundary in the Fluent™ simulation. In particular a transient table for the CCA and a constant value for cisplatin is used. The volume fraction of the dispersed phase cisplatin was set to 100% at the cisplatin inlet and 0% at the CCA inlet.
The Newtonian material model was used for cisplatin with properties of water, ρ = 998.2 kg/m3and μ = 0.001003 Pa s.
After testing one initial cycle using 100 time steps, the transient simulation proceeded in batch mode using 200 equal distant time steps for one additional cycle. Double precision, first order discretization and the pressure based segregated PISO solver including skewness and neighbour correction of one, were used with a convergence criteria of 1 · 10-7 for the cisplatin volume fraction residual. All other settings remained at Fluent™ default values. Data for each 10 th time step was saved. The computing time required approximately four days, shared by three parallel processors.
3 Results and discussion
Furthermore, in consequence of the frontal orientated cisplatin inlet stream towards the CCA bifurcation wall, the wall shear stress shows a peak (≈ 80 Pa) in this region, presented in Figure 4(c) and 4(d) for systole and diastole, respectively. This level of high wall shear stress can potentially cause acute vascular endothelial changes as it was found in  that the acute yield stress is approximately 37.9 Pa.
Due to the toxic properties of cisplatin, this catheter outflow position can cause several complications, such as local inflammation and neurological complications, for instance headache and facial paresis, .
The distribution and concentration of the chemical agent cisplatin have been investigated in a realistic three dimensional patient specific geometry of human head and neck arteries. The used injection position gives an ineffective cisplatin division. This means that the chemical agent is distributed in all arteries and not in one specific tumour feeding artery, a fact of great importance. High wall shear stress and turbulence near the CCA bifurcation inner walls can cause serious harm, for instance acute vascular endothelial changes or haemolysis. It should be expected that an injection position in the core of the artery further downstream would reduce this high exposure. The time continuous cisplatin inlet condition seems to be ineffective during diastole, when upstream recirculation in the CCA mainly occurs. It should be investigated if a time dependent injection during the advantageous systole would lead to an equal cycle averaged cisplatin concentration with reduced side effects caused by the catheter inflow.
In blood flow CFD simulation using multiphase models, neither mass flow nor velocity outlets are practicable, due to required outlet data for each phase. This data is unknown a priori for the secondary phase cisplatin and is the aim of this simulation. An assumed flow rate weighting was used in this model based on measured data for the two main outlets ICA and ECA. It is assumed that the general blood flow division remains unchanged in comparison with measured data of healthy volunteers in the normal state. An injection position further downstream in a side branch of the ECA would probably change the blood flow division. An alternative proper methodology would be to use the pressure inlet and outlet boundary conditions, that require only the volume fraction of the secondary phase at the inlets, and adjust the pressure to a correct level. However, time dependent pressure functions for each model boundary were not available and are difficult to assess for small arteries, such as the LA and FA. The implementation of an arterial one dimensional model seams to be the superior way for future CFD simulations dealt with in [26–31].
List of abbreviations used
- APA :
ascending pharyngeal artery
- BCA :
- CAD :
computer aided design
- CCA :
common carotid artery
- CFD :
computational fluid dynamics
- CT :
- ECA :
external carotid artery
- FA :
- ICA :
internal carotid artery
- LA :
- PISO :
pressure implicit with splitting of operators
- RSA :
right subclavian artery
- SST :
shear stress transport
- STA :
superior thyroid artery
- VA :
We acknowledge support by Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of Karlsruhe Institute of Technology.
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