© 2011 ANSYS, Inc. March 4, 2014 1

Computational Modeling for the Health Care

Industry

Marc Horner, Ph.D.

ANSYS, Inc.

Evanston, IL

marc.horner@ansys.com

© 2011 ANSYS, Inc. March 4, 2014 2

• 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

Agenda

© 2011 ANSYS, Inc. March 4, 2014 3

Fluid Dynamics Structural Mechanics

ANSYS Simplorer

ANSYS Engineering Knowledge Manager

ANSYS HPC ANSYS Workbench

Electromagnetics

ANSYS DesignXplorer

Systems and Multiphysics

ANSYS FLUENT

ANSYS CFX

ANSYS POLYFLOW

ANSYS Icepak

ANSYS HFSS

ANSYS Maxwell

ANSYS Q3D

ANSYS Designer

ANSYS Mechanical

ANSYS AUTODYN

ANSYS LS-DYNA

ANSYS nCode

ANSYS Acoustics

Products Overview Leaders in the Field

© 2011 ANSYS, Inc. March 4, 2014 4

Our Vision: Simulation Driven Product Development

Concept Physical

Prototype

Production

Simulation-Driven Device Development

Detailed

Design

© 2011 ANSYS, Inc. March 4, 2014 5

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

*BusinessWeek , FORTUNE

Our Focus

© 2011 ANSYS, Inc. March 4, 2014 6

Computational Modeling - Inputs

r = 1.05 g/cm3

= 0.035 g/cm-s

Geometry Material

Properties

Boundary Conditions

(Loads)

Fluids

Mechanical

© 2011 ANSYS, Inc. March 4, 2014 7

Computational Modeling - Outputs

r = 1.05 g/cm3

= 0.035 g/cm-s

Geometry Material

Properties

Boundary Conditions

(Loads)

speed

wall shear pressure

Outputs

Fluids

Mechanical

© 2011 ANSYS, Inc. March 4, 2014 8

Computational Modeling - Outputs

r = 1.05 g/cm3

= 0.035 g/cm-s

Geometry Material

Properties

Boundary Conditions

(Loads)

speed

wall shear pressure

Outputs

Fluids

Mechanical

© 2011 ANSYS, Inc. March 4, 2014 9

Top Healthcare Companies Rely on ANSYS Simulation

© 2011 ANSYS, Inc. March 4, 2014 10

Top Healthcare Companies Rely on ANSYS Simulation

pump section

oxygenation section inlet

blood inlet

blood outlet

* Fill et al., ASAIO Journal (2008)

Drug eluting stent, species distribution in the artery w all

* Horner et al., CVET (2010)

Arterial/Plaque Stresses for Calcif ied (top) and Cellular (low er) Plaque

© 2011 ANSYS, Inc. March 4, 2014 11

Top Healthcare Companies Rely on ANSYS Simulation

Maxillofacial surgery modeling by TIMC-IMAG

(courtesy of TIMC-IMAG Laboratory, CNRS/UJF)

Femur mesh Interpolated Ym Parametric model – 2 rotation parameters of the prosthesis

Sliding distance Von Mises stress in the prosthesis

Trabecular tensile strain

© 2011 ANSYS, Inc. March 4, 2014 12

Top Healthcare Companies Rely on ANSYS Simulation

tumor

Hyperthermia modeling

RF field in an MRI coil

Patient with pacemaker

© 2011 ANSYS, Inc. March 4, 2014 13

Top Healthcare Companies Rely on ANSYS Simulation

© 2011 ANSYS, Inc. March 4, 2014 14

Top Healthcare Companies Rely on ANSYS Simulation

Turbulence dissipation rate in a mixing tank

small Dp

Spray drying: particles paths for two droplet diameters (Dp)

large Dp

Drug capsule

Classifier chambers Air inlets

TWINCER Dry Powder Inhaler

Flow past drug capsule

Entrained air

© 2011 ANSYS, Inc. March 4, 2014 16

FDA Analysis of Product Recalls from FDA Report “Understanding Barriers to Medical Device Quality”

“failures in product design and manufacturing

process control caused more than half of all product recalls”

ANSYS tools could have helped with 1/3rd of these recalls before they happened

© 2011 ANSYS, Inc. March 4, 2014 19

Regulatory Update

Animal Bench

Computational Human

Safety/Efficacy

© 2011 ANSYS, Inc. March 4, 2014 21

FDA Recommends Simulation

© 2011 ANSYS, Inc. March 4, 2014 22

In the classic paradigm, there are three “legs” of the stool for establishing device safety:

• Bench testing

• Animal studies

• Clinical (human) trials

Simulation is now perceived as a fourth leg that can lower the cost of bringing a new device to market:

• Expands our understanding of device performance

• Cost of simulation is typically less than the other three legs

Simulation Lowers the Cost of Bringing New Devices to Market

safety

$

safety

$

© 2011 ANSYS, Inc. March 4, 2014 23

OSEL Regulatory Support

The FDA Speaks Our Language

© 2011 ANSYS, Inc. March 4, 2014 24

Advancing Innovation

published October 2011

© 2011 ANSYS, Inc. March 4, 2014 25

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.

CDRH 2012 Strategic Priorities

document issued January 2012

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The FDA Virtual Physiologic Patient

© 2011 ANSYS, Inc. March 4, 2014 27

Will provide reporting best practices for computational modeling studies

Recent publication in J. Biomech. may provide early insight

Sections:

Guidance on Reporting Methods for M&S*

2.4 Verification

2.5 Validation

2.6 Availability

* draft released January 2014

2.1 Model Identification

2.2 Model structure

2.3 Simulation structure

© 2011 ANSYS, Inc. March 4, 2014 28

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.

© 2011 ANSYS, Inc. March 4, 2014 29

FDA Sponsored Conferences in 2013

© 2011 ANSYS, Inc. March 4, 2014 30

Publicly Available FDA Presentations Highlighting Computational Modeling

© 2011 ANSYS, Inc. March 4, 2014 52

BLOOD PUMP BIOCOMPATIBILITY TESTING

© 2011 ANSYS, Inc. March 4, 2014 53

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 short-

comings associated with current implementations

of extracorporeal membrane oxygenation

(ECMO).

© 2011 ANSYS, Inc. March 4, 2014 54

ExtraCorporeal Membrane Oxygenation (ECMO)

© 2011 ANSYS, Inc. March 4, 2014 55

Current state

© 2011 ANSYS, Inc. March 4, 2014 56

Ension Cardiopulmonary Assist System (pCAS)

Simplify and miniaturize

• Integrate pumping and mass exchange

• Locate pump-oxygenator 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

© 2011 ANSYS, Inc. March 4, 2014 57

Integrated Design

© 2011 ANSYS, Inc. March 4, 2014 59

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

© 2011 ANSYS, Inc. March 4, 2014 60

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

© 2011 ANSYS, Inc. March 4, 2014 61

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

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© 2011 ANSYS, Inc. March 4, 2014 64

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:

1 Goubergrits et al., Art. Organs, 28 2004

2 Giersiepen, Doctoral Thesis, 1988

The HI relation is implemented as a post- processing 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.

© 2011 ANSYS, Inc. March 4, 2014 65

Hemolysis Results

© 2011 ANSYS, Inc. March 4, 2014 71

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

© 2011 ANSYS, Inc. March 4, 2014 72

OCULAR DRUG DELIVERY

© 2011 ANSYS, Inc. March 4, 2014 73

Validated Animal Models

rab

bit

h

um

an

* Whitcomb et al. ARVO 2012

Validated animal models can: - reduce animal testing requirements - help us to understand what will happen in humans

© 2011 ANSYS, Inc. March 4, 2014 74

ANSYS Eye Models

human eye rabbit eye

© 2011 ANSYS, Inc. March 4, 2014 75

ANSYS Eye Models - Computational Grid

human eye rabbit eye

© 2011 ANSYS, Inc. March 4, 2014 76

The ANSYS Human Eye

sclera

choroid

retina vitreous humor

cornea

iris

aq. humor

lens

trabecular meshwork

ciliary muscle

ciliary body

© 2011 ANSYS, Inc. March 4, 2014 78

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:

- Navier-Stokes + porous media equations

2. Buoyancy:

- Energy equation

3. Drug delivery

- Scalar transport equations, incl. partitioning

- Weibull model for drug dissolution/release time

mas

s fl

ux

© 2011 ANSYS, Inc. March 4, 2014 79

Modeling in Workbench

Aqueous Humour and Thermal

Modeling Drug Delivery Modeling

Base Geometry (could be

parameterized) Create Mesh

© 2011 ANSYS, Inc. March 4, 2014 80

Velocity Vectors in the Human Eye - Effect of Buoyancy

Without buoyancy With buoyancy

© 2011 ANSYS, Inc. March 4, 2014 81

Velocity Vectors in the Human Eye - Effect of Buoyancy

Without buoyancy With buoyancy

© 2011 ANSYS, Inc. March 4, 2014 83

Particle Tracks for the Human Eye - Effect of Buoyancy

without buoyancy with buoyancy

© 2011 ANSYS, Inc. March 4, 2014 85

Velocity Vectors on the Symmetry Plane - with Buoyancy

Human eye Rabbit eye

© 2011 ANSYS, Inc. March 4, 2014 87

Pressure Contours on the Symmetry Plane - with Buoyancy

Human eye Rabbit eye

IOP “tuned” via trabecular meshwork resistance

© 2011 ANSYS, Inc. March 4, 2014 88

Drug Delivery from a Bolus - Human Eye

4 weeks 8 weeks

12 weeks 16 weeks

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Drug Delivery from a Bolus - Human Eye

© 2011 ANSYS, Inc. March 4, 2014 90

Drug Particle Modeling

Missel et al, Pharm Res (2010)

© 2011 ANSYS, Inc. March 4, 2014 91

Drug Particle Model Results

Missel et al, Pharm Res (2010)

© 2011 ANSYS, Inc. March 4, 2014 103

small to large length

scales

idealized to patient-specific

steady to instantaneous

time-scales ex vivo to in vivo

single to multi-physics (courtesy of Wyeth USA)