Estimating Blood Flow TO: FROM: DATE: SUBJECT: 1 Professor Andreas Linninger / Chih-Yang Hsu Ossama Anis December 2, 2014 Class Project Dear Prof. Linninger and Chih-Yang Hsu, The following report will discuss the approach taken in the estimation of blood flow in a vascular network. I have clearly stated the purpose and significance of this project. Figures have been generated to simulate the relationship between concentration, pressure, and blood flow. Known and unknown variables have been established along with boundary conditions. Three equations that are applied to these variables allow one to gain the unknown in the problem. The Conservation, Hagen-Poiseuille, and the species transport equations are utilized in this problem. Thank you, Ossama Anis Estimating Blood Flow 2 ESTIMATING BLOOD FLOW IN THE CEREBRAL VASCULATURE Ossama Anis* University of Illinois at Chicago* oanis2@uic.edu December 2014 This report is produced under the supervision of BIOE310 lecturer Prof. Linninger. Abstract One of the leading causes of death in the United States is cerebrovascular disease. The condition of a person’s blood vessels determines how prone one is to a vascular disease. Hemodynamics studies the movement of blood through vessels or vascular systems. To properly assess the symptoms of these diseases, extensive knowledge in hemodynamics is a necessity. Imaging techniques allow physicians to observe blood flow and perform surgeries simultaneously. However, this technique only allows physicians to determine blood flow and vessel health by observing the change in image intensity. The significance of this project is to use dynamic image signals to estimate blood flow in cerebral blood vessels. In doing so, some information is discovered to help determine the impact of blood flow on different aspects of vascular health. Furthermore, this study may help improve the quality of healthcare provided to patients with vascular disease. Simulations are used to predict blood flow and dye transport. The known variables are initial concentration, time, resistance, and pressure boundary conditions whereas the unknowns consist of blood flow, pressures, and concentration profiles. Then, a comparison can be made between the simulated dye concentration profiles and the parameter estimation model, where flow rates are unknown. Estimated flow rates will be produced using least square error approach via the known concentration profiles. If the flow rates obtained are correct, the concentration profile dynamics will be the same. 1. Introduction Vascular disease is one of the most common forms of death that occurs in the United States. Cerebrovascular disease, along with diseases of the heart and arteries, is one type of vascular disease. When observing arteries, the diameter of the vessels is of great concern. Plaque can accumulate along the walls of the artery, thereby shrinking its diameter. Stenosis, which is the narrowing of a vessel, can cause a disruption in the blood flow or even close off the vessel. A narrow or blocked artery located in the brain can lead to a stroke. A buildup of plaque can result in damaging the arterial wall which, in turn, can lead to blood clots. Pieces of plaque can also breakoff into the bloodstream and get stuck in smaller branches of the vasculature. Plaque can also decrease or stop blood flow completely by building up in a certain place in the artery. When something of this sort occurs in the brain, certain parts of the brain will not receive the blood that they need due to a significant decrease in blood flow. The Circle of Willis, as seen in Figure 1, is a group of arteries that are the main suppliers of blood [1]. If these become clogged, severe damage can occur. The Circle of Willis consists of the basilar and internal carotid arteries, both of which are inflowing. The basilar artery branches off into the posterior cerebral artery, thus supplying blood to the back of the brain. The internal carotid artery flows into the anterior and middle cerebral arteries supplying the front part of the brain. Furthermore, these elongate out to both sides of the brain, consisting of the right and left sides of the anterior cerebral, middle cerebral, and posterior cerebral arteries. All of these deliver blood to certain parts of the brain and, if clogged, can cause serious damage. The flows and pressures differ in direction and magnitude in each vessel as depicted in Figure 3. To enhance current procedures concerning vascular health, simulations are created to demonstrate blood flow. The data gathered from the observation of blood flow can be interpreted into potentially valuable information. This should help to improve the measures taken when dealing with hemodynamics and health. Estimating Blood Flow 3 (b) will be comprised of the solutions to the set of equations as denoted in the matrix equation. π΄π₯ = π (3) Boundary conditions of the system must be known in order to solve for pressures and flows. Solving for (x) will conclude values for each pressure and flow contained within the system. The last equation utilized was the species transport equation, which represents the difference in concentration with respect time. Figure 1. The Circle of Willis is a network of arteries that supply blood to the brain [5]. π 2. Methods There are various things to be cautious about when estimating blood flow through a network of cerebral blood vessels. To determine blood flow, there are many crucial concepts to consider. Conservation law explains how a measureable property in an isolated physical system does not vary as the system progresses. This is represented in the conservation equation which represents the flow going in the system being equal to the flow going out of the system as shown in equation 1. ∑ πΉπΌπ = ∑ πΉππ’π‘ (1) In this circumstance, the blood flow entering a node is equal to the blood flow exiting that node. Conservation balances will be applied to each face, which represents a vessel or connections between each node. Pressure values will be assigned to each node while flows are assigned to each face. Once the conservation balances are derived, constitutive equations may be formulated using the Hagen-Poiseuille law as shown below. βπ = πΌπΉ; πΌ = 8ππΏ ππ 4 (2) In fluid dynamics, this law declares that the change in pressure is equal to the flow rate between the two nodes multiplied by the resistance. The pressures coming in and out of the system as well as the viscosity of the blood must be established in order to consider the two concepts mentioned above. Both conservation and constitutive equations will be put into a matrix (A), while the vector (x) consists of all the pressures at each node and the flows in between them. The vector ππΆ = πΉπΌπ πΆπΌπ − πΉππ’π‘ πΆππ’π‘ + πΌππ ππ‘ (4) Diameters and lengths of the vessels are known and needed in order to determine the volume of each vessel. Once volumes and viscosities have been established, it will be used to calculate the concentration profiles at each node. These observations allow us to approximate volumetric flow rates, pressure drops, and other steady-state properties at each vessel in the network. Utilizing the fundamental concepts described above allows one to determine the concentration profiles in each node. Implicit Euler methods are applied to observe the difference in concentration with respect to time. After simulation of concentrations, one can use these representations to interpret the flow. Simulating with different boundary conditions will provide altered concentrations and, in turn, yield various residuals. This way can be tedious and allows for alternative methods to be of use. Integral approximation, a method that will be discussed and elaborated on upon further reading, may work more efficiently and can be utilized as a source of validation. These methods have been done on a simple bifurcated network and the results coincide. This can be applied to any specific network, such as the Circle of Willis in this case, to determine the blood flow specific to that system. 3. Results In Figure 3, the Circle of Willis is displayed in a basic format that represents the network. This diagram has been broken down and labeled at each pressure point and flow terminal. The direction of the flows are observed either flowing in or out of the node. The communicating arteries consist of a bidirectional flow that can supply blood to either side of the brain in case of insufficient flow. This diagram can easily be used to derive a matrix for both faces and nodes, by utilizing Estimating Blood Flow 4 conservation and constitutive laws which will, in turn, determine flows and pressures in this network. The inputs in this network will be the left and right internal carotid arteries, along with the two vertebral arteries that join to become the basilar artery. The outputs are the left and right middle cerebral arteries, anterior cerebral arteries, and posterior cerebral arteries. The equations have been formulated and implemented with a simple bifurcated network before advancing on to a more complicated model such as the Circle of Willis. From conducting this simulation, the results obtained allowed for the comparison of different aspects within the network. The Circle of Willis is observed after dye was injected. The observations determined that there was an initial increase in concentration, then peaked to Figure 2. The simple bifurcated network with three flows connecting the four pressure points. Assume the network is injected with dye at pressure point one (P1). a maximum, followed by a decrease. As observed in Figure 4, the concentration is initially very high because the time begins when injection of dye occurs. Once the dye completely exits the vessel, the concentration profile will be zero. Figure 4 also depicts that various initial pressures only changes the duration of the concentration profiles. Various initial pressures were applied in order to compare their residuals, displayed in Figure 5. The results conclude that if there is a higher pressure coming into the network, the concentration profiles will be shorter in duration. Simulating with different initial pressures and comparing their residuals will allow for interpretation of flows. Figure 3. Illustrates a network of the Circle of Willis. This diagram displays pressure points and the directions of the flows throughout the system. Estimating Blood Flow 5 Concentration Profiles (pIn = 75) 1 0.9 0.9 0.8 0.8 0.7 0.7 Concentrations Concentrations Control for Concentration Profiles (pIn = 100) 1 0.6 0.5 0.4 0.6 0.5 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0 0 0.05 0.1 0.15 0.2 Time 0.25 0.3 0.35 0 0.4 0 0.05 0.1 1 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.5 0.4 0.2 0.1 0.1 0.1 0.15 0.2 Time 0.25 0.3 0.35 0 0.4 0 0.05 0.1 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.5 0.4 0.2 0.1 0.1 0.15 0.2 Time 0.25 0.25 0.3 0.35 0.4 0.3 0.35 0.4 0.4 0.3 0.1 0.2 Time 0.5 0.2 0.05 0.15 0.6 0.3 0 0.4 Concentration Profiles (pIn = 200) 1 Concentrations Concentrations Concentration Profiles (pIn = 175) 1 0 0.35 0.4 0.3 0.05 0.3 0.5 0.2 0 0.25 0.6 0.3 0 0.2 Time Concentration Profiles (pIn = 150) 1 Concentrations Concentrations Concentration Profiles (pIn = 125) 0.15 0.3 0.35 0.4 0 0 0.05 0.1 0.15 0.2 Time 0.25 Figure 4. The graphs above display the concentration of dye injected into a network with various initial pressures applied. Each graph represents the dye concentration profiles with respect to time. It is easy to depict that a higher inlet pressure will result in a shorter duration of the concentration profile throughout the system. Estimating Blood Flow 6 Concentration Profiles with Noise (10 dB) Pressures and Corresponding Residuals (10 dB) 40 1 0.9 35 0.8 30 0.6 Residuals Concentrations 0.7 0.5 0.4 25 0.3 20 0.2 0.1 0 0 0.05 0.1 0.15 0.2 Time 0.25 0.3 0.35 15 60 0.4 80 Concentration Profiles with Noise (20 dB) 100 120 140 Pressure (mmHg) 160 180 200 180 200 180 200 Pressures and Corresponding Residuals (20 dB) 18 1 16 0.8 14 0.7 12 0.6 Residuals Concentrations 0.9 0.5 10 8 0.4 6 0.3 4 0.2 2 0.1 0 0 0.05 0.1 0.15 0.2 Time 0.25 0.3 0.35 0 60 0.4 80 Concentration Profiles with Noise (30 dB) 100 120 140 Pressure (mmHg) 160 Pressures and Corresponding Residuals (30 dB) 1 16 0.9 14 0.8 12 10 0.6 Residuals Concentrations 0.7 0.5 0.4 8 6 0.3 4 0.2 2 0.1 0 0 0.05 0.1 0.15 0.2 Time 0.25 0.3 0.35 0.4 0 60 80 100 120 140 Pressure (mmHg) 160 Figure 6. The graphs on the left represent the concentration of dye with respect to time, injected into the Circle of Willis, with an initial pressure of 100 mmHg. Noise is taken into account and corresponding signal-to-noise ratios (SNR) are calculated in decibels. The higher the SNR, the less noise there is interrupting the signal. The graphs on the right validate that noise and residuals are directly proportional. The more noise contained within the signal, the larger the residual will be. Estimating Blood Flow 7 potentially life-threatening. The medical world can benefit from this correlation by using it to find efficient drug delivery systems. Hemodynamics is a very crucial concept that, if understood completely, could be a very valuable tool. If correlations can be confirmed between blood flow and other health concepts, these types of simulations would prove to be useful. These correlations still need to be explored and could possibly consist of preventative measures for strokes. Furthermore, if these simulations could mirror actual patient’s brains, the benefits would be exponential. Pressures and Corresponding Residuals 15 Residuals 10 5 6. Intellectual Property 0 60 80 100 120 140 Pressure (mmHg) 160 180 200 Figure 5. Displayed above are the residuals corresponding to various boundary conditions. The residual is zero when the inlet pressure is 100 mmHg. 4. Discussion Blood flow rates can be estimated using a few different methods. One of these methods includes the use of inversing data. The least-squares approach or matrix pseudo-inverse is utilized to determine flow rates from experimentally gained concentration profiles. Integration of the concentration profiles is necessary, therefore, it is logical to suggest the trapezoidal method. Although it is an easy procedure to carry out, it brings with it numerical and experimental error. Limitations include aerodynamic properties of the blood flow along with the fact that inlet pressures into the internal carotid and vertebral arteries may not be the same. Biological and physiological data and some modeling procedures provided to you from Dr. Linninger’s lab are subject to IRB review procedures and Intellectual property procedures. Therefore, the use of these data and procedures are limited to the coursework only. Publications need to be approved and require joint authorship with staff of Dr. Linninger’s lab. 7. References 1. Bhara, A., D. Espino Barros Perez. Collateral Blood Flow in Diseased State. Chicago: University of Illinois at Chicago, Bioengineering Department. 2. Hsu, C., & A. Linninger. Modeling the Whole Brain Vascular Network for Hemodynamics Computation. Chicago: Laboratory for Product and Process Design. 2014. 3. Kulkarni, K. Mathematical Modeling, Problem Inversion and Design of Distributed Chemical and Biological Systems. Chicago. (2008) 4. McEneaney, J., & M. Dytso. Simulation of Capillary Blood Flow Rates after Occlusion and Vasodilation of Left Cerebral Arteries. Chicago. 5. ""Brainstem Circle of Willis"" Brain Anatomy. WordPress, 2014. Web. 27 Nov. 2014. <http://brainanatomy.tk/tag/brainstem-circle-ofwillis>. 5. Conclusion In conducting these simulations, it has been found that estimating blood flow in the cerebral vasculature is, indeed, possible. Pressures and flows can be determined for each vessel by taking the correct measures. Concentration profiles can then be determined using fundamental concepts, such as the Euler method. We can infer blood flow rates from the concentration profiles by creating simulations with different boundary conditions and comparing their residuals or by integral approximation. With this knowledge, it is inferred that the initial pressure of the dye injected is relative to the blood flow rate. This concept can be applied to real-life situations that are