Human Body Modeling with ANSYS Software. Marc Horner, Ph.D. Technical Lead, Healthcare ANSYS, Inc.



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Human Body Modeling with ANSYS Software Marc Horner, Ph.D. Technical Lead, Healthcare ANSYS, Inc. 1

Overview This talk is motivated by the following observations: 1. Our understanding, and thus our ability to mathematically describe, the human body is to the point where one can assemble human body models as boundary conditions for biomedical simulations. 2. Improvements in ease of use and stability of multiphysics modeling tools. 3. Computational capabilities are continually increasing. 2

Types of Human Body Models Human Body Modeling CFD, FEA, and emag models coupled to lumped parameter representations of the human body CARDIOVASCULAR MUSCULOSKELETAL DRUG DELIVERY EMAG Parametric System Level DOE for HBM Fully automated process Application areas: Coronary stents Peripheral stents Artificial organs Application areas: Orthopaedic implants Exercise equipment Application areas: Transdermal Inhalers Oral Intrathecal Application areas: Medical imaging Cardiology Drug delivery Cancer treatments 3

Types of Human Body Models Human Body Modeling CFD, FEA, and emag models coupled to lumped parameter representations of the human body CARDIOVASCULAR MUSCULOSKELETAL DRUG DELIVERY EMAG Parametric System Level DOE for HBM Fully automated process Application areas: Coronary stents Peripheral stents Artificial organs Application areas: Orthopaedic implants Exercise equipment Application areas: Transdermal Inhalers Oral Intrathecal Application areas: Medical imaging Cardiology Drug delivery Cancer treatments 4

Idealized Blood Flow Material properties Can typically assume density and viscosity at average hematocrit and high shear. = 1.05 g/cm 3 = 0.035 g/cm-s Inflow conditions Literature a good source for inflow data* 5 Geometry Resting Condition Q tot = 6.8 L/min, 75 bpm** Exercising Condition Q tot = 12.8 L/min, 117 bpm** * Stevens et al., Math Biosciences (2003) ** Murgo et al., Circ Res (2003)

Patient Specific Blood Flow Material properties Can take a blood sample and measure the patients hematocrit, protein content, etc. vs H* vs ** Inflow conditions Taken from on-line measurements*** 6 Geometry (courtesy Materialise Inc.) * Hinghofer-Szalkay,?? (1986) ** Cho & Kensey, Biorheology (1991) *** Huntsman et al., Circulation (1983)

My Flow Patterns speed pressure 7 wall shear

Outflow Conditions For Aortic Flows One complicating factor in aortic flow modeling is the application of accurate outflow boundary conditions. Specialized conditions are required because the flow split at a bifurcation is controlled by downstream organ demand, not the bifurcation geometry. Without a specialized condition, an analyst will not have a proper understanding of the baseline flow patterns and how an implanted device affects those patterns. Flow Rate Reqs for Human Organ Circuits 1 +5.5 L/min -0.3 L/min -0.8 L/min -1.1 L/min -1.1 L/min -2.2 L/min 8 1 Rhodes & Tanner, Med Physiology (1995)

Modeling Options for Outflow BCs Create a detailed geometric model of the entire cardiovascular system, extending from the heart to the capillaries. The problems with this approach are obvious: Large geometric model required to capture full geometric details Accuracy of the geometry will be at question, esp. below 0.5 mm 9 * Image from Texas Heart Institute web-site

Modeling Options for Outflow BCs Create a detailed geometric model of the entire cardiovascular system, extending from the heart to the capillaries. The problems with this approach are obvious: Large geometric model required to capture full geometric details Accuracy of the geometry will be at question, esp. below 0.5 mm Use a lumped parameter approach to alleviate the need for detailed geometry at all length scales. The image to the right is an electrical circuit model of the human circulatory system, extending from the heart to the small arteries. Each box contains a lumped parameter representation of an artery section. Electrical Circuit Model of the Human Cardiovascular System* 10 * Westerhof et al., J Biomech (1969)

Lumped Parameter Model Details The circuit on the lower left can be used to model the flow rate and pressure losses in each artery section. This circuit is referred to as a 3 element Windkessel. inertance term accounts for inertial effects (primarily in the large arteries) resistance term accounts for downstream flow resistance (primarily in the capillary beds) R R D C compliance term accounts for artery expansion/contraction (primarily in the large arteries) 11

The Westerhof Circuit in Simplorer 12

Impedance Comparison Westerhof Model Simplorer Model (Inverted L Network) Ansoft LLC 500.00 total input imedance magnitude AC Curve Info mag(1/e1.i) 400.00 300.00 mag(1/e1.i) 200.00 100.00 0.00 0.00 2.00 4.00 6.00 8.00 10.00 12.00 Ansoft LLC total input imedance phase 25.00 Curve Info -ang_deg(e1.i) [deg] 0.00-25.00-50.00 AC -ang_deg(e1.i) -75.00 0.00 2.00 4.00 6.00 8.00 10.00 12.00 F [khz] 13

Insert FLUENT into the Simplorer HBM 14

Validation Flow Past a Symmetric Bifurcation The Windkessel boundary condition was applied to an idealized representation of the abdominal aorta. Transient values for the inlet flow rate and outlet pressures were culled from a literature source*. The geometry and boundary conditions were symmetric in this case. As seen in the figure on the right, there was excellent agreement between published and computational results for the outlet pressure. Q in Iliac RCR parameters R D = 3.22 mm Hg-s/cc R = 0.55 mm Hg-s/cc C = 0.001 cc/mm Hg P out Outlet pressure from SI[mplorerr compared well with the results of Taylor 15 * Wan et al. (preprint)

A Non Symmetric Case velocity 16 pressure

Types of Human Body Models Human Body Modeling CFD, FEA, and emag models coupled to lumped parameter representations of the human body CARDIOVASCULAR MUSCULOSKELETAL DRUG DELIVERY EMAG Parametric System Level DOE for HBM Fully automated process Application areas: Coronary stents Peripheral stents Artificial organs Application areas: Orthopaedic implants Exercise equipment Application areas: Transdermal Inhalers Oral Intrathecal Application areas: Medical imaging Cardiology Drug delivery Cancer treatments 17

Anybody for Implant Loads AnyBody: Determine spine kinematics ANSYS: FEM analysis of a spine implant based on the spine kinematics AnyBody provides a detailed description of the loads and joint forces occurring in the human body in daily activity. ANSYS Mechanical can import loads from Anybody, providing critical information for testing orthopaedic implants and the like. 18

Orthopaedic Workflow Activities of daily living Medical images Musculoskeletal Simulation Optimization CAD/Mesh Finite Element Analysis 19 FEA loads for activities of daily living

Functional Patient Specific Modeling Activities of daily living Patient information Boundary conditions FE-model 20

Unique Open Body Model Library 21

Daily Activity Analysis 22

Dynamic Physiologic Loads 23

In vivo validation Hip forces Thielen et al. 2009 24

A Hip Simulator 25 video from: http://edp.tkk.fi/en/research/tribology/research_projects/biotribology/

Slide Track Patterns - Slide tracks represent the relative motion of the ball and cup waveforms whole head patterns flattened patterns Slide tracks on the head are determined by mounting pens to fixed points on the cup and vice versa for slide tracks on the cup. 26 Upper fig: Calonius and Saikko, Acta Polytechnica (2003) Lower fig: Calonius and Saikko, J Biomech (2002)

Variation in Slide Track Patterns 27

Model Inputs Geometry Femur and implant provided in STL format Acetabular cup was created in ANSYS Mechanical d head = 20 mm d cup = 22 mm Initial STL geometry Kinematic joint conditions provided by AnyBody: Implant and cup assembly Angle in Degrees 23 13 3-7 2.84 3.84 4.84-17 -27 Time (S) Walking HipAbduction HipFlexion HipExternalRot ation 140 120 100 80 60 40 20 0-20 0 0.5 1 Cycling Flexion Abduction Ext. Rotation 28

Implementation Geometry Head, cup (rigid), and stem Material properties Default material properties used for all parts Boundary Conditions Angular data entered as displacement BC s for the cup in tabular format Solver ANSYS Mechanical 12.1 transient solver Rigid flexible contact maintained between the head and the cup Post processing Slide tracks are calculated using an APDL script which is inserted as a command object stem cup head 29

Creating Slide Tracks using APDL Choose location of the pen Get the node number for the pen location Track the node during the transient cycle Report (x,y,z) vs time for the node at the end of simulation Use point locations to create keypoints Join keypoints to form a spline Display the spline with initial geometry to see the slide tracks 30

Slide Tracks on the Cup Walking Profile Side of cup Top of cup 31

Slide Tracks on the Cup Cycling Profile Side of cup Top of cup 32

Slide Tracks on the Cup Walking Forces Force vs time data 3500 3000 2500 29 2000 1500 1000 500 0-500 50 64 87 69 2 2.2 2.4 2.6 2.8 3 3.2-1000 -1500 MediolateralForce AnteroPosteriorForce ProximoDistalForce 33 Slide track with time-step locations

Slide Tracks on the Cup Walking Forces Force vs time data 3500 3000 2500 147 2000 1500 1000 500 0-500 168 182 205 187 2 2.2 2.4 2.6 2.8 3 3.2-1000 -1500 MediolateralForce AnteroPosteriorForce ProximoDistalForce 34 Slide track with time-step locations

Slide Tracks on the Cup Kinematics Side of cup Top of cup 35

Wear Calculation Archard s Law defines the effect of sliding distance (v) and contact pressure ( ) on the per cycle wear depth (w): Which can be approximated as: where, k w is the wear coef. (which is material and surface dependent) = 1.066E 6 is the contact stress, and S is the sliding distance w(, ) k (,, t) v(,, t) dt w cycle cycle k w S 36

Cumulative Wear (after 1 cycle) walking cycling wear depth reported in (mm) 37

Validation Clinical Data Hall et al (Proc Instn Mech Engrs, 1998) measured wear of UHMWPE acetabular components retrieved from 200 patients. 38

Types of Human Body Models Human Body Modeling CFD, FEA, and emag models coupled to lumped parameter representations of the human body CARDIOVASCULAR MUSCULOSKELETAL DRUG DELIVERY EMAG Parametric System Level DOE for HBM Fully automated process Application areas: Coronary stents Peripheral stents Artificial organs Application areas: Orthopaedic implants Exercise equipment Application areas: Transdermal Inhalers Oral Intrathecal Application areas: Medical imaging Cardiology Drug delivery Cancer treatments 39

Pharmacokinetic (PK) Modeling PK models utilize a compartmentalized approach to model drug distribution in the body over time. The compartments represent organs and other drug depots. PK models simulate drug/chemical: Absorption Distribution Metabolism Excretion 40 Coupling the PK model to the drug delivery model enables the designer to further refine the delivery system to work together with the human body, understand dependence on patient variability, disease state, etc.

Transdermal Delivery Model The system consists of a cylindrical patch applied to the skin. The drug reservoir (in the patch) contains a mixture of drug and permeation enhancer. Diffusion is the only mode of transport out of the patch and through the skin. The far boundary of the skin is the inlet to the microcirculation, which acts as a drug sink. Two boundary conditions are tested at the far wall: 1. zero flux condition which assumes the plasma is an infinite sink 2. PK condition to account for drug build up in plasma microcirculation patch skin 41

Transdermal Model Details Axisymmetry is assumed Drug and enhancer are modeled as user defined scalars in FLUENT A transient diffusion equation models transport through the skin and patch: c t i, where i = drug, permeation enhancer D c i i r = 0.9 cm patch skin r = 0.925 cm 50.8 m 50.8 m The interfacial conditions at the patch skin interface are continuity of flux and a partitioning (jump) condition: D i, patch ci, patch Di, skin ci, skin c drug, skin / c drug, patch K, where K is the partition coefficient 42

Transdermal Model Details Formulation Effects The permeation enhancer increases the drug flux through the skin. The level of enhancement is typically a function of the local enhancer concentration. Two typical situations are: D drug,skin = D drug,0 + *C pe K drug,skin = K drug,0 + *C pe increasing increasing The permeation enhancer increases the diffusivity of drug in the skin The permeation enhancer increases drug solubility in the skin 43

Validation Case Fentanyl Patch, No PK Model Rim et al. examined the effect of enhancement type on drug flux. These plots compare FLUENT results to their experimental and computational results. Comparison of drug flux through lower boundary of epidermis. Initial concentration of drug and enhancer 0.06, 0.04(gm cm 3 ). dt=100, ncells=58400, µ=1.8e 4, η=0.0 2.5 Comparison of drug flux through lower boundary of epidermis. Initial concentration of drug and enhancer 0.06, 0.04(gm cm 3 ). dt=100, ncells=58400, µ=0.0, η=19.0 2.5 Drug Flux (µg cm 2 hr 1 ) 2.0 1.5 1.0 0.5 0.0 simulation experiment reference 0 10 20 30 40 50 60 Drug Flux (µg cm 2 hr 1 ) 2.0 1.5 1.0 0.5 0.0 simulation experiment reference 0 10 20 30 40 50 60 Time (hr) Time (hr) flux when D drug =f(c enhancer ) flux when K = f(c drug ) 44 Reference: Rim et al., Annals of BME, (2005)

CFD Model PK Model Pharmacokinetic (PK) Analysis of a Fentanyl Patch MOTIVATION: Understand/optimize patch performance by including the physiologic processing of drug. Patch model extensions: BC between epidermis and dermal vasculature: c D P [ c l, t) f C ( t)] z u p ( The ODE s for the three compartment PK model are: dc dt [ c l, t) plasma: well-perfused compartment: poorly perfused compartment: [ k k p el 21 k C 2 12 2 ( k 13 ( t) k ] C 31 C 3 p ( t) 3 f u ( t) C p ( t)] dc2 dt k12c p( t) / 2 k21c2 ( t) dc3 dt k13c p ( t) / 3 k31c3( t) 45

CFD Model PK Model Pharmacokinetic (PK) Analysis of a Fentanyl Patch MOTIVATION: Understand/optimize patch performance by including the physiologic processing of drug. Patch model extensions: BC between epidermis and dermal vasculature: c D P [ c l, t) f C ( t)] z u p ( The ODE s for the three compartment PK model are: dc dt [ c l, t) plasma: well-perfused compartment: poorly perfused compartment: [ k k p el 21 k C 2 12 2 ( k 13 ( t) k ] C 31 C 3 p ( t) 3 f u ( t) C p ( t)] dc2 dt k12c p( t) / 2 k21c2 ( t) dc3 dt k13c p ( t) / 3 k31c3( t) 46

Types of Human Body Models Human Body Modeling CFD, FEA, and emag models coupled to lumped parameter representations of the human body CARDIOVASCULAR MUSCULOSKELETAL DRUG DELIVERY EMAG Parametric System Level DOE for HBM Fully automated process Application areas: Coronary stents Peripheral stents Artificial organs Application areas: Orthopaedic implants Exercise equipment Application areas: Transdermal Inhalers Oral Intrathecal Application areas: Medical imaging Cardiology Drug delivery Cancer treatments 47

HFSS Workbench Link for Modeling Cancer Treatment Hyperthermia cancer treatment used to accelerate effects of chemotherapy RF power applied to tumor using phased array antenna Eight strip dipole antennas connected in parallel pairs and printed on inner surface of cylindrical plastic shell HFSS Model of Patient with Phased Array Applicator on Lower Leg MRI Cross Section of Lower Leg with Tumor (Courtesy Duke University Medical Center) 48

HFSS Model of RF Phased Array Applicator Device operates at 138 MHz Element excitations optimized to concentrate power inside tumor Electric Field Magnitude with Optimized Array Weights HFSS Model of RF Phased Array Applicator HFSS Model of Applicator on Leg Tumor (shown in green) 49 Local Specific Absorption Rate (SAR) with Optimized Array Weights

Transient Thermal Analysis in ANSYS Workbench 50 Geometry in ANSYS Workbench Electromagnetic power is a function of time 28 W used to reach desired temperature and 9 W to maintain temperature Transient analysis used to determine temperature rise inside tumor Reaches 47 C in 6 minutes and is maintained there for 14 minutes Results of Transient Thermal Analysis (max/min temperature in the tumor) Results of Transient Thermal Analysis

Closing Remarks Coupling detailed simulations to lumped parameter models can provide more rigorous prediction of device performance. 51

Closing Remarks Coupling detailed simulations to lumped parameter models can provide more rigorous prediction of device performance. V&V is possible. 2.5, µ, η P out Drug Flux (µg cm 2 hr 1 ) 2.0 1.5 1.0 0.5 0.0 simulation experiment reference 0 10 20 30 40 50 60 52 Time (hr)

Closing Remarks ANSYS provides flexible and open solutions that can be adapted to solve even the most challenging problems facing the biomedical engineers of today. The ANSYS vision for this industry includes collaborating with other software vendors to enable one way and/or cosimulation with the highest fidelity models available. 53