Computational Modeling
for the Health Care
Industry
Marc Horner, Ph.D.
ANSYS, Inc.
Evanston, IL
marc.horner@ansys.com
1
© 2011 ANSYS, Inc.
March 4, 2014
Agenda
• ANSYS overview
• Computational modeling in the
health care industry
• Regulatory support for
computational modeling
• Application areas
- Stent deployment to AAAs
- Blood pump biocompatibility
testing
- Ocular drug delivery
2
© 2011 ANSYS, Inc.
March 4, 2014
Products Overview
Leaders in the Field
Systems and Multiphysics
ANSYS Simplorer
ANSYS Workbench
ANSYS Engineering Knowledge Manager
3
ANSYS HPC
ANSYS DesignXplorer
Structural Mechanics
Fluid Dynamics
Electromagnetics
ANSYS Mechanical
ANSYS AUTODYN
ANSYS LS-DYNA
ANSYS nCode
ANSYS Acoustics
ANSYS FLUENT
ANSYS CFX
ANSYS POLYFLOW
ANSYS Icepak
ANSYS HFSS
ANSYS Maxwell
ANSYS Q3D
ANSYS Designer
© 2011 ANSYS, Inc.
March 4, 2014
Our Vision:
Simulation Driven Product Development
Detailed
Design
Simulation-Driven
Device Development
Concept
Physical
Prototype
Production
4
© 2011 ANSYS, Inc.
March 4, 2014
Our Focus
Focused
This is all we do.
Leading product technologies in all physics areas
Largest development team focused on simulation
Capable
2,000 employees - 60 locations, 40 countries
Trusted
96 of top 100 FORTUNE 500 industrials
ISO 9001 and NQA-1 certified
60 quarters of double digit growth
Up to 20% investment annually in R&D
Proven
Recognized as one of the world’s most innovative
and fastest-growing companies*
Largest simulation company in the world
Independent
Long-term financial stability
CAD agnostic
5
© 2011 ANSYS, Inc.
March 4, 2014
*BusinessWeek , FORTUNE
Computational Modeling - Inputs
Geometry
Fluids
Material
Properties
r = 1.05 g/cm3
 = 0.035 g/cm-s
Mechanical
6
© 2011 ANSYS, Inc.
March 4, 2014
Boundary Conditions
(Loads)
Computational Modeling - Outputs
Geometry
Fluids
Material
Properties
Boundary Conditions
(Loads)
Outputs
wall shear
pressure
r = 1.05 g/cm3
 = 0.035 g/cm-s
speed
Mechanical
7
© 2011 ANSYS, Inc.
March 4, 2014
Computational Modeling - Outputs
Geometry
Fluids
Material
Properties
Boundary Conditions
(Loads)
Outputs
wall shear
pressure
r = 1.05 g/cm3
 = 0.035 g/cm-s
speed
Mechanical
8
© 2011 ANSYS, Inc.
March 4, 2014
Top Healthcare Companies
Rely on ANSYS Simulation
9
© 2011 ANSYS, Inc.
March 4, 2014
Top Healthcare Companies
Rely on ANSYS Simulation
oxygenation
section inlet
blood
inlet
blood
outlet
Arterial/Plaque Stresses for Calcified (top)
and Cellular (low er) Plaque
pump
section
Drug eluting stent, species
distribution in the artery w all
* Horner et al., CVET (2010)
* Fill et al., ASAIO Journal (2008)
10
© 2011 ANSYS, Inc.
March 4, 2014
Top Healthcare Companies
Rely on ANSYS Simulation
Maxillofacial surgery modeling by TIMC-IMAG
(courtesy of TIMC-IMAG Laboratory, CNRS/UJF)
Sliding
Femurdistance
mesh
11
© 2011 ANSYS, Inc.
March 4, 2014
Von
Mises stress
Interpolated
Ym
in the prosthesis
Trabecular
Parametric
modeltensile
– 2 rotation
strain
parameters of the prosthesis
Top Healthcare Companies
Rely on ANSYS Simulation
tumor
Hyperthermia modeling
Patient with pacemaker
RF field in an MRI coil
12
© 2011 ANSYS, Inc.
March 4, 2014
Top Healthcare Companies
Rely on ANSYS Simulation
13
© 2011 ANSYS, Inc.
March 4, 2014
Top Healthcare Companies
Rely on ANSYS Simulation
Spray drying: particles paths
for two droplet diameters (Dp)
small Dp
large Dp
Turbulence dissipation
rate in a mixing tank
TWINCER Dry Powder Inhaler
EntrainedAir
airinlets
Classifier chambers
Drug capsule
14
© 2011 ANSYS, Inc.
March 4, 2014
Flow past
drug capsule
FDA Analysis of Product Recalls
from FDA Report “Understanding Barriers to Medical Device Quality”
16
“failures
product
and with
manufacturing
ANSYSintools
could design
have helped
1/3rd of
process
control
caused
than half of all
these
recalls
before more
they happened
product recalls”
© 2011 ANSYS, Inc.
March 4, 2014
Regulatory Update
Animal
Bench
Safety/Efficacy
Computational
19
© 2011 ANSYS, Inc.
March 4, 2014
Human
FDA Recommends Simulation
21
© 2011 ANSYS, Inc.
March 4, 2014
Simulation Lowers the Cost of Bringing
New Devices to Market
In the classic paradigm, there are three “legs” of the
stool for establishing device safety:
•
Bench testing
•
Animal studies
•
Clinical (human) trials
safety
$
Simulation is now perceived as a fourth leg that can
lower the cost of bringing a new device to market:
22
•
Expands our understanding of device performance
•
Cost of simulation is typically less than the other
three legs
© 2011 ANSYS, Inc.
March 4, 2014
safety
$
The FDA Speaks Our Language
OSEL Regulatory Support
23
© 2011 ANSYS, Inc.
March 4, 2014
Advancing Innovation
24
© 2011 ANSYS, Inc.
March 4, 2014
published October 2011
CDRH 2012 Strategic Priorities
Strategy 4.3. Strengthen Regulatory Science
CDRH will work collaboratively with our federal
government partners and external
constituencies to advance medical device
regulatory science.
Goal 4.3.1. By December 31, 2012, CDRH will
have in place mechanisms to enable
collaborative work between FDA, our federal
government partners and external
constituencies to advance medical device
regulatory science.
Goal 4.3.2. By September 30, 2012, CDRH will
expand computer modeling and simulation
efforts to support regulatory science.
25
© 2011 ANSYS, Inc.
March 4, 2014
document issued January 2012
The FDA Virtual Physiologic Patient
26
© 2011 ANSYS, Inc.
March 4, 2014
Guidance on Reporting
Methods for M&S*
Will provide reporting best practices for
computational modeling studies
Recent publication in J. Biomech. may provide
early insight
Sections:
27
2.1 Model Identification
2.4 Verification
2.2 Model structure
2.5 Validation
2.3 Simulation structure
2.6 Availability
© 2011 ANSYS, Inc.
March 4, 2014
* draft released January 2014
ASME V&V40 Standard on Computational
Modeling of Medical Devices
The required level of validation is determined
by the influence of the model on the decision
being made and the consequences of being
wrong.
28
© 2011 ANSYS, Inc.
March 4, 2014
FDA Sponsored Conferences in 2013
29
© 2011 ANSYS, Inc.
March 4, 2014
Publicly Available FDA Presentations
Highlighting Computational Modeling
30
© 2011 ANSYS, Inc.
March 4, 2014
BLOOD PUMP BIOCOMPATIBILITY TESTING
52
© 2011 ANSYS, Inc.
March 4, 2014
Introduction
Ension, Inc. is a medical device R&D firm located
near Pittsburgh, PA.
Ension is developing a pediatric cardiopulmonary
assist system (pCAS) under contract from the
National Institutes of Health to address shortcomings associated with current implementations
of extracorporeal membrane oxygenation
(ECMO).
53
© 2011 ANSYS, Inc.
March 4, 2014
ExtraCorporeal Membrane Oxygenation (ECMO)
54
© 2011 ANSYS, Inc.
March 4, 2014
Current state
55
© 2011 ANSYS, Inc.
March 4, 2014
Ension Cardiopulmonary Assist System
(pCAS)
Simplify and
miniaturize
• Integrate pumping
and mass exchange
• Locate pumpoxygenator close to
patient allowing
parent to hold child
The Ension pCAS will minimize priming volumes, decrease
the need for system anticoagulation, and provide improved
ergonomics allowing improved parent-child bonding
56
© 2011 ANSYS, Inc.
March 4, 2014
Integrated Design
57
© 2011 ANSYS, Inc.
March 4, 2014
Prototype fabrication &
experimental validation
Pump impeller and housing
• Acrylic
• 4 axis CNC mill
Oxygenator
• Polypropylene HFMs
• Acrylic tubing & molded end caps
• Modified tubing connectors
• Polyurethane potting
In vitro experiments
• anti-coagulated bovine blood
• temperature 37ºC
• hematocrit 36%
• 1 hour duration
59
© 2011 ANSYS, Inc.
March 4, 2014
Discrete modeling and optimization of
pCAS components
• Pump Mesh
– hybrid mesh
– eight fluid sub-domains
– 1.7M cell mesh
• Oxygenator Mesh
– three fluid sub-domains
– hexahedral bundle,
tetrahedral inlet/outlet
– 1.3M cell mesh
60
© 2011 ANSYS, Inc.
March 4, 2014
Computational Simulation Details
Working fluid: blood
• UDF calculated blood properties as a function of hematocrit, pH and
temperature
– Density ~ 1050 kg/m3
– Viscosity ~ 0.0035 Pa·s
For the pump:
•
•
•
•
Standard κ-ε turbulence model
Impeller rotation modeled using multiple reference frame approach (MRF)
Flow rate applied at the inlet
No-slip at all solid-fluid interfaces
For the oxygenator:
• Porous media model used in the fiber zone
• Flow rate applied at the inlet
• No-slip at all solid-fluid interfaces
61
© 2011 ANSYS, Inc.
March 4, 2014
63
© 2011 ANSYS, Inc.
March 4, 2014
Hemolysis prediction
Hemolysis is a function of shear stress (t ) and exposure time (t).
The hemolysis index (HI) is the percentage of hemoglobin released into
the plasma phase. Experimental research1,2 has yielded the
following relation for HI:
The HI relation is implemented as a postprocessing step applied to a converged flow
solution. Steps to calculating HI are:
1. A particle injection is defined at the pump inlet.
2. A subroutine calculates HI along particle
trajectories.
3. Accumulated HI is reported for tracked particles
which reach the pump outlet.
64
© 2011 ANSYS, Inc.
March 4, 2014
1
Goubergrits et al., Art. Organs, 28 2004
2
Giersiepen, Doctoral Thesis, 1988
Hemolysis Results
65
© 2011 ANSYS, Inc.
March 4, 2014
Acknowledgments
• Ension, Inc. – Mark Gartner, Brian Fill, Dr. Greg
Johnson, Jason Miller, Jeff Speakman, Sarah Wright
This work was supported by Pediatric Circulatory
Support Contract No. HHSN268200449189C
71
© 2011 ANSYS, Inc.
March 4, 2014
OCULAR DRUG DELIVERY
72
© 2011 ANSYS, Inc.
March 4, 2014
Validated Animal Models
human
rabbit
Validated animal models can:
- reduce animal testing requirements
- help us to understand what will happen in humans
73
© 2011 ANSYS, Inc.
March 4, 2014
* Whitcomb et al. ARVO 2012
ANSYS Eye Models
human eye
74
© 2011 ANSYS, Inc.
March 4, 2014
rabbit eye
ANSYS Eye Models
- Computational Grid
human eye
75
© 2011 ANSYS, Inc.
March 4, 2014
rabbit eye
The ANSYS Human Eye
ciliary muscle
iris
lens
sclera
choroid
cornea
retina
vitreous
humor
aq.
humor
trabecular
meshwork
ciliary body
76
© 2011 ANSYS, Inc.
March 4, 2014
Model Overview
Assumptions:
- Axisymmetric geometry
- Constant thickness for tissues, e.g. retina
- Homogeneous material properties for each tissue
- Scalar (drug) transport equation is sequentially
coupled to the flow field
Physics Modeled:
1.
Aqueous humour flow:
2.
Buoyancy:
- Energy equation
3.
Drug delivery
mass flux
- Navier-Stokes + porous media equations
- Scalar transport equations, incl. partitioning
- Weibull model for drug dissolution/release
time
78
© 2011 ANSYS, Inc.
March 4, 2014
Modeling in Workbench
Base Geometry
(could be
parameterized)
Create Mesh
Aqueous Humour
and Thermal
Modeling
79
© 2011 ANSYS, Inc.
March 4, 2014
Drug Delivery
Modeling
Velocity Vectors in the Human Eye
- Effect of Buoyancy
Without buoyancy
80
© 2011 ANSYS, Inc.
March 4, 2014
With buoyancy
Velocity Vectors in the Human Eye
- Effect of Buoyancy
Without buoyancy
81
© 2011 ANSYS, Inc.
March 4, 2014
With buoyancy
Particle Tracks for the Human Eye
- Effect of Buoyancy
without buoyancy
83
© 2011 ANSYS, Inc.
March 4, 2014
with buoyancy
Velocity Vectors on the Symmetry Plane
- with Buoyancy
Human eye
85
© 2011 ANSYS, Inc.
March 4, 2014
Rabbit eye
Pressure Contours on the Symmetry Plane
- with Buoyancy
Human eye
Rabbit eye
IOP “tuned” via trabecular meshwork resistance
87
© 2011 ANSYS, Inc.
March 4, 2014
Drug Delivery from a Bolus
- Human Eye
88
© 2011 ANSYS, Inc.
March 4, 2014
4 weeks
8 weeks
12 weeks
16 weeks
Drug Delivery from a Bolus
- Human Eye
89
© 2011 ANSYS, Inc.
March 4, 2014
Drug Particle Modeling
90
© 2011 ANSYS, Inc.
March 4, 2014
Missel et al, Pharm Res (2010)
Drug Particle Model Results
91
© 2011 ANSYS, Inc.
March 4, 2014
Missel et al, Pharm Res (2010)
steady to
instantaneous
time-scales
ex vivo to in vivo
(courtesy of Wyeth USA)
single to multi-physics
idealized to
patient-specific
small to
large length
scales
103
© 2011 ANSYS, Inc.
March 4, 2014