Dissertation Proposal

Modernization of the Mock
Circulatory Loop
Advanced physical modeling, high performance
hardware, and incorporation of anatomical geometry
Charles E. Taylor
12/1/2012
VCU BME: Artificial Heart Laboratory
Dissertation Proposal
Charles Edward Taylor
Table of Contents
ABSTRACT ...................................................................................................................................................................... 3
PROJECT NARRATIVE ................................................................................................................................................... 4
FACILITIES AND OTHER RESOURCES ........................................................................................................................ 5
COMPUTATIONAL RESOURCES ......................................................................................................................................... 5
PROTOTYPING SUPPORT ................................................................................................................................................. 5
INVESTIGATOR SUPPORT ................................................................................................................................................. 6
EQUIPMENT .................................................................................................................................................................... 7
SPECIFIC AIMS ............................................................................................................................................................... 8
RESEARCH STRATEGY ................................................................................................................................................. 9
A
B
C
SIGNIFICANCE ....................................................................................................................................................... 9
INNOVATION ........................................................................................................................................................ 11
APPROACH .......................................................................................................................................................... 12
Overview of the personnel and approach ............................................................................................................... 12
Preliminary studies supporting approach ............................................................................................................... 13
Aim 1: Develop computational plant models with process control logic. ................................................................ 15
Experimental Approach ........................................................................................................................................................ 16
Validation, evaluation, and benchmarks ............................................................................................................................... 17
Potential problems and alternate strategies ......................................................................................................................... 17
Aim 2: Deploy a fully automated mock circulatory loop .......................................................................................... 17

Aim 3: Integrate critical anatomical geometries; left atrium and ascending aorta. ................................................. 19
BIBLIOGRAPHY AND REFERENCES CITED .............................................................................................................. 21

RESOURCE SHARING PLAN ....................................................................................................................................... 25
DATA SHARING PLAN .................................................................................................................................................... 25
SOFTWARE SHARING PLAN ............................................................................................................................................ 25
Proprietary and Confidential
Abstract
Page 2 of 25
Abstract
A systemic mock circulatory loop plays a pivotal role as the in vitro assessment tool for left heart medical
devices. The standard design employed by many research groups dates to the early 1970's, and lacks the
acuity needed for the advanced device designs currently being explored. The necessity to update the
architecture of this in vitro tool has become apparent as the historical design fails to deliver the performance
needed to simulate conditions and events that have been clinically identified as challenges for future device
designs. In order to appropriately deliver the testing solution needed, a comprehensive evaluation of the
functionality demanded must be understood. The resulting system is a fully automated systemic mock
circulatory loop, inclusive of anatomical geometries at critical flow sections, and accompanying software tools
to execute precise investigations of cardiac device performance.
Delivering this complete testing solution will be achieved through three research aims: (1) Utilization of
advanced physical modeling tools to develop a high fidelity computational model of the in vitro system. This
model will enable control design of the logic that will govern the in vitro actuators, allow experimental settings
to be evaluated prior to execution in the mock circulatory loop, and determination of system settings that
replicate clinical patient data. (2) Deployment of a fully automated mock circulatory loop that allows for runtime
control of all the settings needed to appropriately construct the conditions of interest. It is essential that the
system is able to change set point on the fly; simulation of cardiovascular dynamics and event sequences
require this functionality. The robustness of an automated system with incorporated closed loop control logic
yields a mock circulatory loop with excellent reproducibility, which is essential for effective device evaluation.
(3) Incorporating anatomical geometry at the critical device interfaces; ascending aorta and left atrium. These
anatomies represent complex shapes; the flows present in these sections are complex and greatly affect
device performance. Increasing the fidelity of the local flow fields at these interfaces delivers a more accurate
representation of the device performance in vivo.
The expanded research capabilities of these combined tools will enable investigations of complex
cardiovascular events and conditions previously unachievable. In addition to the findings and device design
implications of those efforts, research in the biomedical engineering benefits from (a) the applied practice of
using cutting edge physical modeling tools and control design methods for computational tool development of
multi domain systems, (b) an in vitro testing solution that reflects advancements in cardiac device research,
and (c) focusing a highly proprietary field towards established public databases.
This work is being developed under Gerald E. Miller, whose expertise and history in the field of cardiac
devices will be an invaluable resource in the direction and dissemination of this work. Completion of work in
his Artificial Heart Laboratory grants access to cutting edge research tools and facilities that will be crucial in
the execution of the research aims of this proposed work.
Abstract
Page 3 of 25
Project Narrative
Automation of mock circulatory loop analysis increases the investigative capabilities of cardiac assist
technology assessment enabling clinical challenges that are currently not being simulated to be overcome.
Producing an analogous in silico model enables the predetermination of mechanical settings that match clinical
data, assisting this transition from the clinic to the bench testing environment. Incorporating anatomical
geometries at the critical interfaces to the devices increases the acuity of the simulation, enabling more
accurate assessments of performance and efficacy.
Project Narrative
Page 4 of 25
Facilities and Other Resources

Virginia Commonwealth University has provided an excellent site for development during the preliminary
investigations, and will continue to deliver the resources for this projects completion. The institution has
extensive support for the electronics design, mechanical prototyping and software development necessary for
the automated process control of the mock circulatory loop. The development space currently housing the
preliminary designs is suitable for the project execution; floor space and facilities resources have been
established. As part of this projects alternate strategy, external service providers have been identified and are
presented to communicate the appropriate contingency planning contained in this proposal. Collaborations
with key software and hardware vendors have allowed cutting edge products and technologies to be
implemented in this current project. With this strong system of internal resources, external service vendors,
and collaboration the execution of the current project is aptly supported through the Artificial Heart Laboratory
at VCU.
Computational Resources
The physical modeling software validated in the preliminary designs and targeted for the project will be
developed in The MathWorks (Natick, MA) Matlab and Simulink environments. A close collaboration with
this company has allowed the laboratory to readily deploy some of the current products used in the
construction of the computational models. As many of these products are cutting edge, and have minimal
application precedent in biomedical engineering, the interest by The MathWorks to have successful
installations is high. Support for these products has been well maintained, and the preliminary work has shown
their success. Current product development, and future release timing, has been communicated by The
MathWorks to ensure that this project takes advantage of the latest functionality.
Data archival and presentation tools are provided free of charge by Microsoft through the Microsoft
Developer Network Academic Alliance (MSDNAA). These server and databases packages allow for the
content generated by this project to be appropriately managed and accessed. The Artificial Heart Laboratory
currently runs a SharePoint Server on a Windows Server platform with SQL Server database tools. This
deployment allows for all content pertaining to this project to be web accessible with appropriate security
measures in place for access restriction. It will serve as the repository that will be opened to collaborators, and
certain content of this project made available to the public, per the data sharing plan.
The Biomedical Engineering department at VCU has research groups currently developing anatomical
models for other projects. The proximity of these groups to this investigator allows for adequate technical
support during the model construction process. Sharing of advancements in model construction techniques
has been discussed, with support by the advanced users in those groups pledged to this project. With a large
medical facility at VCU, there is a wide availability of consultants for assessing the anatomical features of the
models.
The programming support within the engineering community at VCU provides sufficient resources for
troubleshooting unforeseen software challenges. Drs. Bai and Pawluk of the Biomedical Engineering faculty
provide programming expertise in close proximity to the research facilities of the Artificial Heart Laboratory.
Assistance with the microcontroller programming and embedded electronics interfacing will be sourced from
Zachary Dziczkowski, a graduate student in Computer Science and Engineering, with who a collaborative
agreement is in place for this support. Further embedded electronics support can be solicited from faculty in
the Computer Science and Engineering department, who reside in the two adjoining engineering buildings on
the VCU campus.
Prototyping Support
The support of the School of Engineering at VCU allows access to a robust machine shop. All the
fabrication in the preliminary designs was completed with this resource. Outsourcing of coatings necessary for
the material compatibility has been orchestrated through the machine shop personnel and their industry
contacts. Industry proven personnel administer the shop, and have been a valuable resource in design
assessment. This laboratory has been a significant contributor to the Engineering School's machine shop, with
instruction given by the investigator on cutting edge CNC programming products and fabrication of anatomical
structures. The machine shop capabilities and information sharing will continue to be an integral part to the
success in the mechanical systems development in this project. In the event that a design cannot be
Page 5 of 25
manufactured with this facility, Khem Precision Machining (Richmond, VA) will be contracted to fabricate the
parts.
The Artificial Heart Laboratory has developed its electronics prototyping resources to the extent that it can
fabricate its own circuit boards in house from raw materials. The capabilities allow for trace isolation on copper
clad boards, tinning, surface mount reflow, hot air rework, and soldering. These functions enable circuit boards
to be produced for a fraction of the price external resources charge. In the event that there is a design that
cannot be manufactured with this equipment, Advanced Circuits (Aurora, CO) will be used as a contract
service to supply the boards.
Support for the electronics design is available through the faculty in the Biomedical Engineering
department. Drs. Wetzel and Fei provide tremendous expertise when consultation on electrical circuit design
is required. Their combined knowledge of high and low wattage designs will be useful during this projects work
on actuation and sensor signal conditioning, respectively. Outside of these intradepartmental resources, the
department of Electrical Engineering's faculty has many individuals that can provide consultation on the issues
this project may encounter.
Investigator Support
The investigator for this project is currently funded as a Research Assistant, which allows the full dedication
of his time to this project. There are no major obligations outside of the work contained in this proposal. Minor
obligations include Laboratory Manager duties with respect to safety inspections and personnel management.
Currently, there are no undergraduate researchers directly reporting to this investigator. A second year
doctoral student is on hand to assist with some of the aims of this proposal.
Training: Skill development has been supported by the Artificial Heart Laboratory in the form of
product training courses that have been attended by the investigator. Attendance of future training
courses should not be necessary at this point in time. Support to attend application training can be
arranged if necessary. Departmental interaction with the aforementioned faculty supporting the
different facets of this project also enables cross-training to occur. Coursework and lecture series
complement the educational resources available for research skill development.
Mentoring: The mentor to this investigator, Dr. Miller, has an established record of cardiovascular
research. His expertise in the area of mock circulatory loops and medical devices provide an
invaluable resource for this investigator. Consultation on system features and research field gaps
will aid in positioning this projects work as a cutting edge simulation platform for cardiovascular
device assessment. Having good rapport with most of the Biomedical Engineering faculty, this
investigator has a broad base for career development counseling and leadership advice.
Facilities and Administration Support: The facilities of the Artificial Heart Laboratory have been
sufficiently outfitted, with no foreseen issues. Administrative support through the Biomedical
Engineering department has been exceptional. Supplies purchases have been streamlined to allow
for next day delivery to be achieved from preferred vendors. The research to date in this laboratory
has benefited greatly from this administrative support.
Development and support resources available to this investigator through the Biomedical Engineering
department at VCU are extraordinary. Their presence will be invaluable through the execution of this projects
aims, and will be integral to the development of this investigators research capability.
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Equipment
As discussed in the Facilities section, the resources available to this investigator at VCU are exceptional.
Much of the work contained in this proposal is to be developed from raw materials, integrated circuit
components, and code generation tools. The enumeration of the critical hardware and software packages
used to complete the aims of this proposal are presented as follows:
Computational resources: Two 3.0 GHz Core 2-Duo Windows XP 32-bit machines with 4GB of RAM,
240GB hard drives and Radeon workstation graphics cards. The two stations are used for software
programming and CAD work. Five Pentium 4 Windows XP 32-bit machines with 4GB of RAM. These systems
are used for data acquisition, prototyping, and data servers. One Dell T2200 workstation with Quad Core
3.0GHz i7 Pentium Windows XP 32-bit, 4GB of RAM and Nvidia Quadro 2000 with CUDA 2.0 GPU support.
This system is tasked with PIV control, PIV processing, and GPU processing.
Software Resources: SolidWorks Professional licenses that include the Motion, Simulation, and Flow
Simulation packages. MasterCAM for SolidWorks provides the machine code generation for the CNC work.
The MathWorks toolboxes central to the completion of this proposed work are: Simulink Coder, Matlab Coder,
Embedded Coder, Control Design Toolbox, Parameter Estimation Toolbox, Optimization Toolbox, and Fixed
Point Toolbox. National Instruments LabVIEW with the Real-Time Module allows for robust data acquisition
solutions.
Electronics: Electronics prototyping equipment in the form of an Agilent 10MHz oscilloscope and an HP
signal generator are currently owned by the laboratory. National Instruments PXI hardware with embedded
controller and data acquisition hardware allow for accurate data sampling and real-time signal processing to be
achieved. An assortment of integrated circuits, passive components, and microcontrollers has been compiled
in the laboratory to enable embedded electronics research to be appropriately supported. High performance
pressure sensors (Entran EPX model) and accurate flow meters (Transonic T100) utilized by the laboratory
ensure that effective measurement technologies are employed for the in vitro system.
Fabrication resources: The laboratory has acquired a T-Tech PCB mill that is capable of isolating surface
mount footprints and comes with isolation routing software. A Haas 3-axis CNC, Stratasys FDM rapid
prototyping machine, lathe, Prototrac enabled milling station, welding station, and an assortment of tooling
yields a well endowed machine shop available 5 days a week through the school of engineering. Additional
usage can be contracted through the school of engineering for $20/hour.
Equipment
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Specific Aims
Mock circulatory loops are employed in ventricular assist device, total artificial hearts, and prosthetic valve
evaluation as in vitro analogues of the cardiovascular system. These systems function as both basic research
tools for design development and preclinical evaluation units for safety verification. The design of the mock
circulatory loops in use now has not deviated much from their initial embodiments of the 1970's; fluid tanks with
variable air spaces and manual valves. As the technology of the implantable devices has seen major
innovations, the in vitro assessment tools should reflect this development and provide a more advanced testing
solution.
This project proposes a high performance mock circulatory loop, inclusive of critical anatomical geometries,
and accompanying computational tools for a state of the art solution to cardiac device assessment. A
combination of novel hardware and application of industrial software solutions will be used to produce a system
with a level of functionality that is currently not available in the field, allowing for previously unachievable
simulations to be performed. The knowledge of the team in the areas of device prototyping, embedded system
programming, and medical device research ensure the deliverables of this project will be realized through the
following aims:
Aim 1: Develop computational plant models of the mock circulatory loop inclusive of process
control logic
Challenge: Develop an in silico physical system model that is capable of accurately simulating an
analogous in vitro platform; it must also include the monitoring algorithms and control logic governing the
actuators.
Approach: Utilize commercially available physical modeling tools to rapidly develop the computational
models. Parameter estimation functions and control design tools will be used to tune the model components to
experimental performance data and develop the appropriate controller methods, respectively.
Impact: Utilization of industrial engineering tools in developing these computational resources, and
executing the control design, illustrates an application of this software technique not widely applied in this field.
Aim 2: Deploy a fully automated mock circulatory loop
Challenge: Fabricate an in vitro embodiment of the computational model that represents the performance
bandwidth and control acuity seen in silico.
Approach: Construct the following subsystems of the mock circulatory loop: ventricular simulator, arterial
compliance chamber, peripheral resistor, and pulmonary simulator. Utilize commercial code translation
products to deploy the computational control elements onto the embedded control systems hardware.
Impact: This system will provide a robust testing platform with functionality that is currently not available in
this field; nonlinear arterial compliance and change of all controlled set points in runtime.
Aim 3: Integrate critical anatomical geometries; left atrium and ascending aortic root.
Challenge: Incorporate the anatomical geometry of the left atrium and the ascending aortic root, which
need to be based off a publicly available patent data set.
Approach: Extract the geometry from the Visible Human Project, process the results into a model capable
of fabrication, engineer the interfaces to the mock circulatory loop, and produce the in vitro pieces.
Impact: Inclusion of these anatomically correct sections develops the local flow field characteristics that
have been shown to have significant impact on device performance.
This integrated multi scale research tool approach provides an investigator with the (a) in silico tools that
allow for effective experimental design, (b) in vitro performance that enables a wide range of cardiovascular
parameters to be simulated, and (c) accurate local flow conditions in the regions of the devices being
evaluated. These deliverables provide the functionality that has been in increasing demand as the need for
experimental acuity has risen.
Principle Personnel
Charles Taylor, VCU Artificial Heart Laboratory: Design, development and deployment of the mock
circulatory system and computational tools. Gerald Miller, VCU Artificial Heart Laboratory: Advisor of project
design goals and consultant on applied research stemming from the deliverables.
Specific Aims
Page 8 of 25
Research Strategy
A
Significance
Translational medicine and human health impact are the hallmarks of funding packages granted through
the NIH. Advanced in vitro methods for left ventricular assist device and prosthetic valve assessments have
been identified as catalysts for more successful device designs, resulting in better clinical outcomes [1].
Research groups that have implantable device projects employ mock circulatory loops as their means for
evaluation, but mainly rely on traditional designs. Steady state cardiovascular conditions and highly idealized
simulation of cardiovascular system function has been the mainstay of device assessment in these traditional
systems [2]. Clinical studies have shown that current limitations in quality of life with implanted patients arise
from changes in cardiovascular conditions (e.g. postural changes, sudden exertion) [3]. It is necessary to test
the emerging technologies against the challenging conditions witnessed in the clinic in order to address these
issues.
Translating these physiological conditions into an early stage in vitro environment necessitates a reflective
analog of the cardiovascular system. This analog must have the functional capacity to have runtime parameter
control, recursiveness, and flow field similarity at the interfaces to the devices being tested. Although the
cardiovascular system can be functionally represented in a lumped parameter model, embodied as a mock
circulatory loop, the capability of executing changes in the parameters without stopping the system is key for
constructing complex events [4]. Additionally, simulating dynamics enables the analysis at a multitude of
stationary settings in a battery testing method; this could screen a device against a large set of conditions each
representative of a target patient population. The second point of functionality, recursiveness, is integral to the
closed loop circulation of the cardiovascular system. Designing the appropriate system to correctly provide the
recursive response can be challenging; it has many dependencies and is highly dynamic. Inclusion of
anatomical geometries at interfaces of the mock circulatory loop and the devices being tested is crucial. The
accuracy of these local flow fields have been shown to have a strong effect on heart valve function and pump
efficiencies[5,6]. The investigator of this proposal has made advances in the deployment of a mock circulatory
loop design, through the revision of critical subsystems, which address the functionality necessitated for an in
vitro cardiovascular system model. Continued efforts on the remaining elements of this model are crucial to
providing this field with the appropriate investigational capability.
Robust in vitro testing has been identified by regulatory agencies, and governing scientific bodies, as
integral to the safety assessment of devices in this field [7]. This investigator has identified key software
designs and completed hardware developments that satisfy these agency initiatives and provide the requisite
testing solution. Experimental condition design tools based on software packages being used for system
modeling are readily adaptable to satisfying this proposed work. Use of PhysioBank patient databases as in
vitro condition sources connects this work with current clinical efforts, and can only be achieved with updating
the current mock circulatory loop technology [8]. Applying Visible Human Project data as the basis for
anatomical models continues the effort to utilize pre-existing government databases, which enables the
comparative analysis by other researchers [9]. The strategies chosen by this investigator highlight the value of
using currently funded databases and commercial engineering tools to produce high functioning investigational
tools and establish design paths for continued development in this field.
Applying these strategies to the development of a new mock circulatory loop model addresses the
limitations of presently implemented systems. The restrictions of current models fall primarily in the insufficient
automation and anatomical irrelevancy of the systems. This investigator proposes that developing a robust
experimental system, with supporting computational tools, would advance research in this field through the
following:
Illustrate the application of sophisticated physical modeling software in the construction of

mock circulatory loop computational models (Aim 1). Computational models have been
developed concurrently with mock circulatory loops by other groups [10,11]. However, the acuity of
these models has not provided the fidelity that is required for constructing precision control systems
or design of experiments with dynamic conditions. The construction of a model through a method
that is not based on hydraulic first principles (e.g. adaptation of electrical modeling packages) is
typically the culprit of poor performance [12]. Physical modeling packages that are built for the
systems they are representing (hydraulic, mechanical, etc.) produce exceptional performance in
these models [13,14]. The goal of translating the application of these modeling methods into
Research Strategy
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Figure C.1: Diagram of the objectives and how the work

is encompassed by the respective aims. In silico work is
grouped in the upper half of the illustration, with the in
vitro analogues for each presented in the lower half.
Computational model work on the subsystems
representing the elements of the mock circulatory loop is
delivered by Aim 1 (red outline). Fabrication of the
hardware and incorporating the subsystems into a mock
circulatory loop is presented in Aim 2 (blue outline). The
development of the anatomical CAD models and
production of the in vitro pieces is presented in Aim 3
(green outline).
biomedical engineering, specifically the medical device field, has large ramifications in the design
efficiency by adopters of these tools.
Application of embedded control techniques to solve current limitations in mock circulatory

loop performance (Aim 2). Control of particular mock circulatory loop parameters has not been
successfully implemented by other groups in this field. Attempts at controlling arterial compliance
with traditional sensors and hardware have not been effective, until implementation of a novel
control strategy was deployed by this investigator [15]. Inertial effects within the system are another
area of difficulty for many designs, especially when trying to correctly model the cardiovascular
recursiveness [16]. The commercial applications utilized in efficiently constructing the embedded
control systems and novel hardware has been of particular interest to the in vitro groups of this field.
Free anatomical CAD model development path with low cost fabrication method (Aim 3).
Development of anatomical structures for investigations is a resource intensive task; dataset
acquisition, cost of modeling software, and cost of model fabrication [17]. This proposal seeks to
illustrate a method for utilizing the Visible Human Project data in the construction of anatomical
CAD models through open source software. The fabrication method chosen for these models
requires resources typically available to engineering groups; a CNC mill as opposed to stereo
lithography (SLA) systems. The basis of this work on a publicly available dataset seeks to cut the
cost of model development and homogenize the models used by research groups.
Automated mock circulatory loop, including anatomical sections, with accompanying

experimental design software for accurate investigation of cardiac devices. Supplying this
field with a robust and accurate testing system enables many of the pressing clinical concerns to be
effectively investigated. Advancing the state of preclinical evaluation tools will have a sizeable
impact on the investigational quality and technological advancement of the devices developed with
this platform. This project not only proposes this completed system, but publication of the
workflows (Figure C.1) applied in the achievement of this objective may enhance research
capabilities in this field through the following:
Aim 1: Modeling process for constructing the plant model of the mock circulatory loop can be
extended to device computational models. Ventricular assist device and total artificial heart
developers working with multi-domain modeling will greatly benefit from the deliverables of this
project. Providing this field with these cutting edge methods accelerates development efforts on
other funded projects currently burdened with the computational modeling of these complex
systems.
Aim 2: Embedded control systems have an increasing role in device development in this field.
Introducing development tools that assist in the translation of complex control architecture onto the
target hardware is beneficial to many groups still utilizing manual coding techniques. Implementing
code generation tools that were developed for regulated environments addresses future compliance
issues with the FDA in this area [18]. Increasing the code deployment throughput synergizes the
research return for the device projects and streamlines the development process.
Research Strategy
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Aim 3: Anatomical geometry inclusion is crucial to many biomedical engineering projects. The use
of cryoslice data in this project and open source software are novel, with a broad spectrum of
applications in this field. The promotion of this data source, and software packages, will hopefully
enable research that was previously cost prohibitive without these resources.
This proposal promotes the solutions an automated mock circulatory loop will provide, but it also
illustrates multiple design tools that have significant implications on applied biomedical research.
This modernization of design tools is crucial to successfully implementing high fidelity testing tools
and technological development of devices in this field.
Public dissemination of methods, architecture, and resulting data. The utilization of public
datasets for both the anatomical geometry (Visible Human Project) and conditions (PhysioBank)
were deliberately chosen so that other researchers could apply the work of this proposal more
easily. In following this open source data model, contact has been made with the administrators of
both databases to procure resources for data publication (see letters of support). Publishing the
simulated event data (in silico and in vitro) in the PhysioBank, delivers on one of the missions of this
database being a repository for cardiovascular conditions data. Submission of the anatomical CAD
files to the Visible Human Project seeks to establish a forum in this database for geometries that
are based on the imaging data. These data sharing initiatives are crucial to this investigators vision
of common data sources in this field and higher utilization of previously funded repositories.
The deployment of the automated mock circulatory loop, and inclusion of the anatomical sections, is crucial
to the advancement of this platform as a modern approach to device assessment. The broader implication of
this work lies in the methods and data sources employed. Accelerating development with these approaches
has the ability to impact a wide range of research. Enabling this research base with these cutting edge
methods has the potential to increase the momentum in other funded projects and accelerate progress towards
the public health solutions they are pursuing.
Innovation
With the functionality of current mock circulatory loop designs failing to successfully translate the clinical
performance challenges to the in vitro setting, a modernization of this testing solution was needed. Applying
advanced physical modeling software to this field proved to be a novel approach in satisfying the high fidelity
requirement, and quick development timeline, for a computational model. This modeling approach allowed for
model elements, based on their respective first principles, to be integrated across physical domains and
incorporated with the control logic. Utilizing embedded code generation tools, the computational models
control logic sections were implemented on the embedded processors of the mock circulatory loop. This
seamless model-to-code approach is a cutting edge technique translated to this area of research [19,20].
Automation principles applied to the mock circulatory loop have also proven to be novel for this field.
Measurement and control of all runtime parameters has resulted in novel functionality in this design. Control of
arterial compliance in runtime was found to be a first for this research field, and enables a large range of
simulation capabilities previously seen as unobtainable [21]. The success with arterial compliance is
exemplary of the advances a total automation perspective brings to the mock circulatory loop; cardiovascular
dynamics simulations can be conducted and nonlinear compliance can be modeled.
Implementation of public databases for both the conditions design and anatomical geometry is an
innovative means of homogenizing the basis for device evaluation. Data mining the PhysioBank resources for
challenging and exemplary conditions delivers a basis for the resulting experimental design [22]. This resource
continues to offer new datasets, which feeds the experimental capacity of the investigational tools connected to
it. Taking advantage of the cryoslice data in the Visible Human Project delivers a unique solution to the high
resolution requirements of modeling soft tissue. Creating a contributable database for extracted geometry
based on this dataset expands the offering this source provides. Implementing these models in a physical
form within the automated mock circulatory loop builds on the experimental data that is attributable to these
open source geometries; this assists other research groups by providing validation datasets to their in silico
results based on this anatomy.
Research Strategy
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Figure C.2: Gantt chart illustrating the dependencies of this project and the relative timeline.
Approach
Overview of the personnel and approach

The production of an automated mock circulatory loop was postulated during previous investigations where
gaps present in the existing testing solutions limited the fidelity of the simulations[2325]. The aims of this
proposal were constructed from the identified performance requirements needed to satisfy current ISO
certifications for medical devices and desired features that would meet future demands of this system [2628].
Datasets obtained in one aim may initiate work in another, resulting in a staggered progression through the
stated objectives (Figure C.2). Although innovation tasks are reserved for the PI, support work during the
implementation process will be partially subsidized by the staff of the Artificial Heart Laboratory and its
collaborators. The dissection of the personnel and approach is discussed here.
Project leadership and system development: The PI, Charles Taylor, will be the project manager for the
work contained in this proposal. His previous industry experience in designing high throughput ADME profiling
systems has endowed him with the technological experience and design management skills needed for
successful completion of this work [2931]. Application of his knowledge and leadership has resulted in
successful research projects in the Artificial Heart Laboratory, 3 primary authorships of peer-reviewed journal
articles on advancements made to mock circulatory loop design, and 14 conference presentations on material
supporting this proposed work. The success of this project lies in Mr. Taylor's expertise in automated testing
systems and the management skills he will apply in its execution.
Programming work: The PI will be responsible for development of code for this project. Preimplementation debugging and testing routines might be delegated to lab support personnel to enable the
investigator to pursue other objectives of this project. Training on the embedded code generation tools was
identified by the PI as necessary for successful implementation of those methods; education on the software,
with no consultancy on the application, was provided through commercial training resources. Collaboration
with a Computer Science investigator has been established for embedded hardware programming support.
System fabrication work: Production of the system components will be performed by the PI. His
experience in custom fabrication and prototyping techniques enables these components to be produced for a
fraction of the outsourced price. Utilizing CAD/CAM packages and having prior knowledge of CNC systems,
the PI will be able to effectively produce the elements of the system that would be challenging and costly to
contract for production (e.g. anatomical sections). In-laboratory development of electronic prototypes has
accelerated the production of embedded control solutions, and positions this lab as a desirable collaborator
within the institution. Coordination of fabrication resources (e.g. machine shop rental) and training of Artificial
Heart Laboratory personnel on fabrication methods will assist the production of the components needed for this
system.
Anatomical model work: Development of the anatomical models will be coordinated by the PI and
executed as part of a team effort by the members of the Artificial Heart Laboratory. As this is a new capability
in this laboratory, it is the interest of all personnel to be involved in this project aim. The PI will make the
decision on the software package to use, once all options have been explored. The guidance on the geometry
extraction and model construction practices will be of his design. Preparation of the model for fabrication will
be the responsibility of the PI, due to his background in prototype construction.
Timeline: Preliminary mock circulatory loop design encompassed by Aim 1 will be pursued first.
Prototypes and characterization of the mock circulatory loop subsystems outlined Aim 2 will be developed next.
Design of control logic and full computational models will be completed in the next phase as part of Aim 1. The
completion of Aim 2 will result in the application of the control designs and deployment of the mock circulatory
loop. Aim 3 will be pursued at intervals through previous phases, with targeted implementation of the models
coming after completion of the automated mock circulatory loop. The final stage is producing datasets from
the system, disseminating the work, and coordinating database contributions.
Research Strategy
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Figure C.3: Annotated picture of modified

Harvard Apparatus Pulsatile Blood Pump:
manual stroke volume knob (1), manual
pumping controls (2), manual/auto switch
(3), diastole/systole out (4), USB port (5).
Figure C.4: Illustration of percent systole change and control.
Preliminary studies supporting approach

Groundwork for this project proposal was initiated to test the viability of the development techniques and to
provide proofs of concept for certain hardware designs. The discussion of these preliminary research results
are presented as case studies and illustrate how the aims of this proposal will be completed.
Peripheral resistor design and characterization: The method of applying a physical modeling package
to the characterization of a piece of mock circulatory loop hardware was recently published [32]. This method
illustrated the application of parameter estimation techniques in deducing the constitutive equation values for a
custom device from experimental data. This method was applied to a flow control valve with a variable area
orifice as the control mechanism. A custom design was pursued due to large operating bandwidth and
automated precision needed for the intended investigations; the operating requirements were not satisfied with
commercially available products [33]. The ability to elucidate the discharge coefficient and critical Reynolds
number assisted in refining the accuracy of the valve's computational model [34,35]. The MathWorks software
environment was chosen as the modeling platform due to the well supported physical modeling libraries and
parameter estimation tools. The computational model for the valve was constructed with the Simscape
physical modeling toolbox using the pre-existing hydraulic library blocks. The Parameter Estimation Toolbox's
least squares algorithm was used for the determination of the computational model values by fitting to
experimental data. The work on characterizing the peripheral resistor was first in the development process as
this was seen as the easiest mechanism to model and test the parameter estimation process. The success of
this method illustrates a workflow capable of developing high fidelity computational models from in vitro
components, which is a critical aim of this proposal.
Automation of the Harvard Apparatus Pulsatile Blood Pump: The ability to implement embedded
control on a subsystem using logic developed in a computational model was validated and published as the
work on the automation of the Harvard Apparatus Pulsatile Blood Pump, with the finished product shown in
Figure C.3 [36]. Utilizing the methods employed on the previously mentioned peripheral resistor work, a
complete computational plant model of the Harvard pump was developed. This was constructed via parameter
estimation from experimental data collected in studies that targeted characterization of the different domains of
this pump; electrical, mechanical, and hydraulic. The driveline of the system was modeled in SolidWorks and
imported as a rigid body system into Simulink via the SimMechanics Link [37,38]. This enabled an accurate
depiction of the driveline to be represented without the investment of time to develop the equations for the
linkage dynamics.
Interfacing the multi-domain aspects of this model was also proven with the
electromechanical motor to driveline to hydraulic pump head network.
With this accurate computational representation of the system, an accurately tuned algorithm was
developed for process control of this pump. Control design and optimization tools were employed to build and
tune the logic governing the pump operation. Ultimately, a feed-forward PI control topology was implemented
to produce exceptional pump performance. This resulted in a pumping mechanism that greatly exceeds the
manufacturers stated performance and effectively maintains set points for pumping values (Figure C.6).
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Figure C.5: Compliance chamber

design: pneumatic lines (1),
displacement
sensor
(2),
pneumatic pressure sensor (3),
bleed port (4), hydraulic pressure
sensor (5), hydraulic chamber (6),
membrane
(7),
pneumatic Figure C.6: Runtime compliance change and control illustration. The
chamber (8), fastening hardware initial discrepancy in the computational model is due to the initial
conditions prescribed.
(9), rail mount (10).
Development of the communication scheme that would be applied to the other subsystems in the mock
circulatory loop was part of this preliminary work. The use of USB interfaces for the microcontroller
communication yields a modern connectivity approach that is easily scalable for future designs; large
communication bandwidth and ubiquitous connector interface. The communication drivers that were
developed for this pump controller were designed to be translated easily to other subsystems.
The efforts in this published work embody the perspective of this proposal's strategy and the workflows
designed to achieve its aims. The methods employed are cutting edge in physical plant modeling and control
design. The success of this formative work substantiates these methods as the appropriate path for achieving
the performance necessitated and efficient investment of effort by the investigator.
Implementation of a Novel Compliance Control Chamber: The real-time control of arterial compliance
had not been effectively achieved in this field. Previous attempts have been based on open loop control of the
arterial compliance with no established means of changing the compliance and effectively measuring the new
setting [15,39,40]. Establishing this capability was integral to the targeted simulation of cardiovascular
dynamics where the arterial compliance plays a role in severe pathological events and injury states [21]. This
functionality also enables battery testing devices through a multitude of conditions without stopping the flow of
the system.
Building on the principals of the peripheral resistor and Harvard pump automation, work on a novel arterial
compliance chamber design (Figure C.5) with accompanying controller was completed [41]. Development and
control of this device employed the same system characterization through parameter estimation, computational
model construction, and control design methods previously discussed with the peripheral resistor. The novelty
of this design was the application of well known membrane solid mechanics [4244]. Utilizing a laser
displacement sensor with 3 micron resolution, the center deflection of a highly distensible circular membrane
could be accurately resolved into the volume displacement. Using this membrane as a barrier between the
hydraulic system of the mock circulatory loop and a closed pneumatic chamber, the volume expansion of the
mock loop could be accurately controlled. This control is achieved via air pressure regulation of the pneumatic
chamber that consequently governs the expansion of the membrane for a particular hydraulic pressure.
Utilizing the computational model for this device, a process controller was developed with exceptional results of
runtime arterial compliance measurement and set point change (Figure C.6). A novel aspect of the control
design is the capability to maintain compliance on a set pressure-volume curve. This enables investigations of
nonlinear compliance effects in vitro; a well-known tissue mechanics fact with no mock circulatory loop
application to date [45].
The design deployed illustrates this investigators capability of developing novel solutions to obtain
previously unachieved testing performance. The success of the work entailed in this publication falls on the
workflow illustrated in the previous preliminary work and its capability of enabling rapid development of novel
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A
C

D
Figure C.7: Stages of the aortic root model: ITK-SNAP trace (A), lofted model (B), machined prototype with
particle flow (C), PIV data from tilting disc valve study using prototype (D).
solutions. With this critical investigation of arterial compliance control methods complete, the aim of this
proposal in producing a robust mock circulatory system is further supported.
Fabrication of the ascending aortic root from Visible Human Project Cryoslice data: Anatomical
sections that interface with the devices being assessed in the mock circulatory loop must be accurately
depicted, as their geometry has considerable impact on the local flow fields governing device performance
[46,47]. Inclusion of these geometries in mock circulatory loop designs has become standard practice, with
both rigid and flexible models being included by various groups [48,49]. Incorporating these anatomical
features into the flow path of the current mock circulatory loop has been the subject of a continuing line of
presentation spearheaded by this investigator.
The unique approach to development of these models has been the open source nature of the model
construction process. Utilizing a public image dataset, and constructing the model with free software, enables
the results generated by this group to be more easily compared to other conclusions reached from this public
data. The lack of publicly available high resolution MRI or CT data resulted in a novel approach of using cryoslice data to extract the aortic geometry. The Visible Human Project, through the National Library of Medicine,
provides a comprehensive set of cryo-slice images with square voxel dimensions of 0.3 mm. ITK-SNAP[50]
was used to extract the aortic lumen boundary and construct an STL file of the results (Figure C.7A).
Processing of this STL file was achieved through the use of Blender for smoothing and facet reduction [51,52].
The model was imported into SolidWorks to construct a lofted model (Figure C.7B), which facilitates the
fabrication [53].
The ascending aorta was initially constructed to test the feasibility of prototype manufacturing through
subtractive fabrication. This method was investigated for its ability to produce PIV capable prototypes with
excellent optical clarity, which can be an issue with 3D printing methods(e.g. SLA) [17] . This approach is also
a commercial technique for producing complex geometries in molds, which would become useful for
distensible models that would need to be cast [54]. The success of this method was realized with an
ascending aorta section machined from acrylic (Figure C.7C), and connected to the mock circulatory loop, to
evaluate a tilting disc valve (Figure C.7D) [55]. Completion of this preliminary prototype concluded a large
effort to develop an anatomical model construction process that maintained high spatial resolution and that
was open source based. The latter continues the efforts of this PI in connecting the work of this proposal with
other funded initiatives, and basing research results on data that is publicly available.
Aim 1: Develop computational plant models with process control logic.

In order to appropriately utilize the potential of the mock circulatory loop, a computational model of the
entire system will be constructed using physical modeling software (see Figure C.8). This computational
model will be used with parameter estimation tools to determine system settings that reproduce chosen clinical
blood pressure waveforms.
The preliminary work describes a well formed technique of applying the Simscape physical modeling tools
to the computational modeling efforts of this proposal. Expanding this work to encompass the entire mock
circulatory loop, with governing logic, will present modeling challenges not previously encountered. The
preliminary work was subsystem focused, with the initial conditions and boundary conditions being specific to
those isolated investigations. Adaptation of these subsystem models will need to be performed, as they cannot
be simply connected.
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Resistance SetPoints
1
SetPoint File
Compliance SetPoints
Harvard Pump SetPoints
Pulmonary Simulator SetPoints
Inputs
Ouputs
SetPoints
Inputs
PS Controls
PS Sensors
PS Controller
Ouputs
SetPoints
Inputs
HP Controls
HP Sensors
HP Controller
PS Inlet
PS Outlet
Pulmonary Simulator [PS]
Ouputs
SetPoints
Inputs
CC Controls
CC Sensors
Compliance Controller
HP Inlet
HP Outlet
Harvard Pump [HP]
Ouputs
SetPoints
PR Controls
PR Sensors
ResistanceController
CC Inlet
CC Outlet
Compliance Chamber [CC]
PR Inlet
PR Outlet
Peripheral Resistor [PR]
Figure C.8: Simulink model of the mock circulatory loop. System settings are imported from the workspace
and parsed to their respective subsystem controllers (upper left). The controller blocks (green with drop
shadow) represent the logic governing the performance of the connected physical models.
Experimental Approach
Computational modeling techniques typically employed for modeling mock circulatory loops have involved
the application of electrical analogs in the form of Windkessel models [11,56,57]. This method of modeling
makes large assumptions when used for hydraulic systems and is limited when incorporating active controls for
system elements. The utilization of physical modeling packages based on the first principles that are being
modeled enables the computational model to simulate the nuisances of those particular domains. Effects of
local resistances, discharge coefficients, and connection height differences can be incorporated using these
physical modeling tools. The perspective of these modeling packages is such that the computational model
should be reflective of the in vitro system; whereas the Windkessel approach models the cardiovascular
system and the mock circulatory loop is an approximation to the in silico model. The governing principle of the
modeling approach taken here is that the performance of the computational model is its ability to replicate
physiological waveforms and match the in vitro behavior. Accurately modeling the mechanisms of the in vitro
system satisfies the latter, with the former being delivered by appropriate design of those mechanisms to
deliver the waveforms desired.
1. Constructing a venous reservoir model completes the needed elements of a systemic mock
circulatory loop typically employed [58]. The reservoir design involves a decoupled return line to prevent
perturbations from being delivered to the pump. This type of hydraulic design is not reflected in the Simscape
libraries, which requires that this particular modeling element be custom programmed [59]. This will involve
identifying the constitutive equations for a hydraulic tank with a free surface that is not pressure controlled.
The governing equations will be modified to account for the flow contribution of the return line, but not the
pressure. Coding this custom hydraulic element is possible, and will produce a Simscape modeling element
that is capable of being incorporated with the rest of the physical model.
2. Design a pulmonary simulator that allows for appropriate simulation of the supply to the left atrium.
This model should include a mechanism for pressure development (e.g. pump model) and control of the
pressure as a function of flow delivered[60]. The inlet to this simulator will be the venous reservoir tank and
the outlet will be connected to the Harvard pump inlet. Model elements of this subsystem should be based on
real hardware performance values, to assist in the translation of this system to the in vitro setting.
3. Calculating the initial conditions to connect the subsystems will involve the identification of the
steady state no flow operating point of the system, and correcting the subsystem parameters. This will involve
applying hydraulic principles of column height and utilization of the membrane deformation data from the
arterial compliance chamber investigations. A steady state low flow (~1 lpm) initial condition will also be
determined to assist the model execution time, as starting the model from a no flow state comes at a large
computational cost due to the inertial terms in the hydraulic elements. The accurate determination of these
initial conditions is crucial to ensuring the model will execute with the various subsystems connected, as well
as expediting the initialization computations.
4. Construct a full mock circulatory loop model from the subsystems discussed in the preliminary data
and the venous reservoir model. This comprehensive model should couple the performance of the validated
subsystem models and include simulated sensor data from points in the mock circulatory [61]. This
embodiment strives to reproduce the interaction of all the elements present in the in vitro system; all physical
domains and interfacing elements. This becomes the full model standard from which computational
optimizations can be made.
5. Accelerate execution speed of model through the use of code packaging tools, solver choices, and
simulation methods. Optimization tools exist to reduce code execution time by eliminating redundancies and
developing transfer functions for eligible code segments[62,63]. Choice of numerical methods for solving the
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system of equations associated with the physical modeling networks has a large impact on simulation time.
Tuning the rules governing the solution convergence and step size can produce performance benefits.
Utilizing a fixed step solver can be tested to see if there is a performance gain by reducing small steps taken
by variable step solvers. Utilization of local solvers for the physical networks, and a discrete execution for the
logic blocks, has the best acceleration capability for this model. An xPC target approach can also be
investigated to deliver a real time model execution rate [64]. The need for solvers in the physical modeling
networks limits the acceleration capabilities of the total model; software tools to expedite the solver process are
limited.
6. Develop parameter estimation tools for settings determination using the total mock circulatory loop
model. The computational model should be tuned to match a physiological pressure waveform, providing the
settings needed for reproduction of that data in vitro. The source of the waveforms to be matched has been
identified as the following PhysioBank databases containing blood pressure data: MIMIC, MIMIC II, and
MGH/MF [8,65]. A graphical user interface will be developed to identify the waveform of interest in the
database, apply parameter estimation of the model to determine the settings needed to replicate that
waveform, and export those settings to a file that can be used as a simulation list for the mock circulatory loop.
Connectivity to the PhysioBank ATM interface will be explored, as this interface is easy to use and
reprogramming this functionality is not efficient. The Parameter Estimation Toolbox will be used for settings
determination, due to its excellent performance in the preliminary investigations.
Validation, evaluation, and benchmarks
The success of the computational model will be evaluated against two factors; ability to replicate the in vitro
system performance and the parameter estimation performance in elucidating settings for PhysioBank
conditions simulation. The primary goal is to position this computational model as a bridge between the clinical
conditions of interest to be simulated and the mock circulatory loop experimental design. Secondary is the
models execution speed and the development of a multi-tiered approach to accelerating the execution of the
primary goal. Accuracy: A Large Scale Trust-Region-Reflective Non Linear Least Squares method will be
used as the assessment of waveform similarity during model fitting to patient data; this maintains consistency
with the previous parameter estimation work [6668]. A normalized cost function based on sum of squared
errors (SSE), will be used to assess the final similarity of the data:
Equation 1
The cost function must be normalized to the number of discrete samples (n) used in the residuals (r)
determination to account for the difference in beat periods for different heart rates. The threshold of 10 was
developed during the preliminary work, and was found to produce acceptable results. Speed: The execution
speed of the computational models should be greater than a real time simulation in the mock circulatory loop.
A desired acceleration would be a 1:10, or larger, computational:experimental execution time ratio for a
simulation. Timer methods within the Matlab environment will be used to assess the simulation performance.
Potential problems and alternate strategies
Full physical model execution speed cannot be accelerated. Investigation into model simplifications
will be pursued; torque and pressure sources in place of mechanical and pneumatic systems [69]. Conversion
to state-space models will be investigated if the simplified physical models are not sufficient in accelerating the
computation time [70].
Parameter estimation converges on multiple solutions. In the event that the parameter estimation
tools do not provide singular values for the settings associated with a particular waveform, reduction of the
variables being estimated will become necessary. This will be achieved through time domain estimations of
heart rate by periodicity calculations and percent systole through waveform inflection methods [71,72]. The
remaining variables will be determined through the parameter estimation routine.
Aim 2: Deploy a fully automated mock circulatory loop

An in vitro testing platform is crucial for the investigation of devices destined for in vivo use. The testing
system used for assessment of cardiac assist devices and prosthetic valves is the mock circulatory loop. The
embodiment this design discussed in this proposal is a lumped parameter design targeted at simulating the
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Figure C.9: Control dashboard for the mock circulatory

loop. The fields in the upper left denote the conditions list
file to run and the data output file. Sensor traces to the left
are used for in process monitoring. The panels to the right
interface to subsystems and show conditions progress.
Figure C.10: Mock circulatory loop currently

deployed: Harvard Pump (1), aortic root
model (2), compliance chamber (3), resistor
(4), venous reservoir (5), pulmonary simulator
(6), PIV camera (7), PIV laser rail (8).
systemic circulation, specifically the conditions in the ascending aorta. The perspective of this work is the
automation of the subsystems tasked with controlling each of these lumped parameters.
Producing the mock circulatory loop will be achieved through fabricating standalone subsystems and
integrating them with a host controller. The subsystems deployment will involve design development, custom
fabrication, and controller programming. A host controller will be developed to conduct the subsystems
through the simulations of interest, and will act as a data repository during the acquisitions. Data handling
solutions will be developed to ensure that experimental data is collected and stored efficiently [73].
The preliminary work on the peripheral resistor, arterial compliance chamber, and Harvard Apparatus pump
illustrate the success of this investigator in producing the requisite testing subsystems. The design choices in
these preliminary models took into account this final vision of integration, and were designed to be controlled
by a host system. The distributed control approach was chosen for its robustness and the offloading
computational power from a host system. Robustness of this design lies in the ability for a failed process
control to have minimal impact on the rest of the system, with the host controller able to identify this failure and
safely shutdown the system. The controller frequencies chosen to achieve the high performance of this
system come at a computational cost, and exceed the capabilities of a Microsoft Windows based control
system [74,75]. Distributing these high frequency tasks to embedded processors allows the host controller to
have minimal computational overhead during experiments, which may be desirable if this mock loop controller
is tasked with other running other investigational software (e.g. PIV programs).
1. Develop host controller that will coordinate the subsystems by communicating desired set points
selected by the user on a GUI interface or through the execution of a conditions file list. This host controller
should also be able to integrate read back data from the subsystems with other sensor data being collected
from the mock circulatory loop. The output of this host controller program should be in a format that is easily
stored and manipulated. National Instruments LabVIEW programming environment will be utilized for its ease
in creating GUIs (Figure C.9) and the well developed interfaces with data acquisition hardware currently owned
by this laboratory. This environment also enables the host controller to be easily scaled to high performance
Real-Time Operating Systems (RTOS) in the event a Windows based acquisition is not capable of handling the
requirements of this application.
2. Integrate subsystems into a full systemic mock circulatory loop. This system embodiment will be
comprised of the elements discussed in the preliminary data (peripheral resistor, arterial compliance chamber,
automated Harvard Apparatus pump) and a venous reservoir (Figure C.10). The construction of an
appropriate support scaffold and installing of conduit connections will be performed; a mechanical breadboard
approach to the mounting and quick disconnect connections will be employed to ease future alterations.
Ascending aortic condition simulation will be realized with this system version [76].
3. Fabricate the pulmonary simulator to appropriately construct the inlet conditions of the left ventricular
simulator. This simulator will draw from the venous reservoir and deliver the appropriate pressure head, based
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on a flow delivered algorithm, replicating pulmonary output impedance. The hardware targeted for this
subsystem is a pressure sensor downstream of a centrifugal pump and a level sensor in the venous reservoir
feeding the pump; shown as element 6 in Figure C.10.
4. Install pressure and flow sensors between subsystems. Distributed pressure sensors and flow
sensors along conduits in the system will be used for experimental performance evaluation: simulated arterial
pressure, pulse wave velocity, measured cardiac output, and measured peripheral resistance. These sensors
will be connected to the host controller via signal conditioning electronics and data acquisition hardware.
5. Implement a data storage solution that is capable of handling large acquisition times characteristic of
ISO-14708 standards; 30 days in length [27]. The file structure envisioned is time oriented segmentation; a
multi day investigation would result in sequential data files. Binary format and NI proprietary Technical Data
Management Solution (TDMS) file format will be the initial capture file formats investigated. The data will have
to be converted into the PhysioNet file format, with the appropriate channel names tagged, per the data
sharing plan outlined in this proposal. This will allow for the PhysioBank ATM interface to be used for data
visualization. Internal data storage redundancy will involve using a WebDAV server for online file storage with
LZW compression of the files.
The validation of this in vitro system will come from its ability to produce physiologically accurate
waveforms that were predicted by the computational model. Performance analysis will be conducted to ensure
that the operating bandwidth of the system matches the specified design; limits tested with the isolated
subsystems should be reflected in the complete mock circulatory loop. Reproducibility analysis will be
performed to ensure that the system can accurately maintain set points to produce highly similar pressure
waveforms. Accuracy: The cost function analysis (Equation 1) used in the computational to experimental
analysis (Aim 1) will be used for reproducibility verification; the threshold of <5 will be used. Stability: The
system will be operated at set point limits to ensure safe and stable operating at those extremes. Battery
testing will be conducted to ensure transitions through multiple set points do not make the system unstable.
Inter-controller interference would be eliminated by increasing the conduit length between the
subsystems or introducing local resistances at connections. If this does not solve the issue, then
programmatic decoupling methods will have to be introduced.
Host controller communication bandwidth is consumed. Although the USB communication bandwidth
is 10Mbps, changes to the amount of data being streamed from the may cause a bottleneck in the USB
controller. Data buffer solutions will be expanded to deal with this issue. A subsequent technique would be to
migrate to a higher speed USB controller.
Aim 3: Integrate critical anatomical geometries; left atrium and ascending aorta.
Incorporating anatomical geometries at device interfaces to the mock circulatory loop is critical in
simulating the complex flow fields shown to have significant effect on device efficacy and performance. For the
purposes of left heart devices, the anatomy of the left atrium, left ventricle and aorta must be represented in
the in vitro system. Respectively, these anatomies cannot be approximated with straight conduits, cylindrical
piston chambers, and curved conduits. This investigator aims to address these classical approximations, and
the errors resulting from them, by incorporating sufficient representations of this crucial anatomy in the mock
circulatory loop.
The preliminary work by this investigator to create an ascending aorta section was successful, and has
shown to be an effective means of evaluating tilting disc outlet flow fields (Figure C.7D). This preliminary work
represents outlet geometry; the future work will focus on the inlet geometry of the left atrium, which should
have a large effect on device performance [6,77]. The development of a left ventricle model is not being
pursued in this proposed work, as it necessitates a prototyping method that would produce a distensible
model[78]. The incorporation of the left atrium and ascending aorta is seen as sufficient for this stage of the
mock circulatory loop development.
Anatomical models that successfully represent the in vivo tissue geometry must be derived from accurately
extracted boundaries, and fabricated through methods that are capable of maintaining this accuracy. The
additional requirements of prosthetic device configurability and PIV compatibility add constraints to the
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fabrication method and material choice. The preliminary work substantiated swept CAD model design based
on traced cryo-slice data, and machining the lumen from acrylic to achieve the aforementioned design
requirements. Applying this method to the left atrium is seen as a viable means of delivering a model of this
anatomy. This subtractive machining yields a smooth surface with a clear wall that requires minimal polishing
prior to imaging, as opposed to SLA models with their crosshatched wall construction. The structural integrity
of this machined model is also superior to deposition models, which is critical when considering the handling to
gain access to the prosthetic valves being tested [79,80].
1. Construct left atrium computer model from the Visible Human Project female cryo slice data. ITKSNAP will be used to trace the boundary of the left atrium from the mitral valve plane to the ostias of the
various interfacing vessels. Geometry past the ostia will not be considered, as this extends the model beyond
what is considered to be sufficient at this stage. Blender will be used to refine the results of the ITK-SNAP
tracing; smoothing of the mesh and facet reduction will be performed. The processed mesh will be imported to
SolidWorks for development of the swept model. This swept model allows for smooth surface machining and
reduces the computational effort of working with this geometry in the CAD packages. Interfaces will be
designed to appropriately connect the fabricated model to the mock circulatory loop and allow for different
mitral valves to be inserted for analysis.
2. Fabrication of the left atrium model from cast acrylic. The swept model will be processed into a split
part design to allow for the machining of separate interfacing pieces. MasterCAM for SolidWorks will be used
to program the machine paths. The same machining technique from the preliminary work on the ascending
aorta will be applied to this model; rough cut material removal, waterline finishing passes, and scallop finishing
passes. The model pieces will be adhered at the part lines to construct the full left atrium. Subsequent
machining of the interfacial geometry will be performed to allow for mock loop connection and prosthetic mitral
valve placement.
3. Incorporate left atrium model in mock circulatory loop. Connection of the model to the mock
circulatory loop will be achieved through the designed connections for the mitral valve interface and the
pulmonary veins. Scaffolding will have to be engineered to adequately support the model on the deck, which
should also allow for the PIV system to gain access to the investigation space.
Successful fabrication of the left atrium model, with subsequent imaging of left atrial flow patterns by PIV,
will validate the completion of this proposed aim. Assessment of this model will be taken from a functional to
performance perspective. Adequate hermetic seals will be validated through hydraulic pressure tests when
connected to the mock circulatory loops; this will test not only the connection seals but the part line seal. It is
critical that this model holds its hermetic seals for a range of -150 to 250 mmHg gauge pressure; this is the
range of pressures that could exist upstream of the Harvard Apparatus pump [81]. Accuracy: Model will be
verified to have similar boundaries to that of the lumen in the cryo slice data. Post machining CMM will be
used to verify the machining paths, and could be used to validate against the original cryo slice geometry for
full workflow verification. Performance: Acquisition of images that clearly depict particle movement in the flow
will validate the PIV compatibility of the model. Assessment will be performed with a 40:60 (weight)
glycerine:water solution, which will result in slight distortion due to the refractive index mismatch [82]. Only
clarity of the model is being assessed, as refractive index matching is not needed to ensure PIV compatibility.
Left atrium ostias cannot be machined with a single part line due to the limitations of the CNC method.
Part line choice will be investigated, as another plane of dissection could provide the appropriate access by the
mill. Multiple part lines will also be considered. Subsequent outsourcing of the work to a shop with 5-axis mill
capabilities will result if the in-house equipment limitations cannot be overcome.
Left atrium cannot be machined by a split part design. The model will be fabricated in ABS plastic
using the in house deposition printing equipment. PIV windows machined from acrylic will be inserted into the
printed model to satisfy the imaging requirements. Utilization of SLA technology could be applied if the window
method is deemed insufficient and research funds support this decision. Limitations in structural integrity will
have to be entertained if deposition models are used, with possible engineering solutions needed to prevent
material failure due to use.
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Bibliography and References Cited

[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
Neal M. L., and Kerckhoffs R., 2010, Current progress in patient-specific modeling, Brief Bioinform,
11(1), pp. 111126.
Patient Simulator and Training Center (Mock Circulation Tank); Users Manual [Online]. Available:
http://www.perfusion.ws/Syncardia/TAH-t%20Training%20Center%20User%20Manual.pdf.
[Accessed:
16-Dec-2012].
Iaizzo P. A., 2009, Handbook of cardiac anatomy, physiology, and devices, Springer, New York, NY.
Yubing S., Patricia L., and Rodney H., Review of Zero-D and 1-D Models of Blood Flow in the
Cardiovascular System, BioMedical Engineering OnLine, 10.
Kar B., Delgado III R. M., Frazier O., Gregoric I. D., Harting M. T., Wadia Y., Myers T. J., Moser R. D.,
and Freund J., 2005, The effect of LVAD aortic outflow-graft placement on hemodynamics and flow:
Implantation technique and computer flow modeling, Texas Heart Institute Journal, 32(3), p. 294.
Long Q., Merrifield R., Yang G. Z., Kilner P. J., Firmin D. N., and Xu X. Y., 2003, The influence of inflow
boundary conditions on intra left ventricle flow predictions., Journal of biomechanical engineering,
125(6), p. 922.
Patel S. M., Allaire P. E., Wood H. G., Throckmorton A. L., Tribble C. G., and Olsen D. B., 2005,
Methods of failure and reliability assessment for mechanical heart pumps, Artificial organs, 29(1), pp.
1525.
Moody G. B., Mark R. G., and Goldberger A. L., 2011, PhysioNet: Physiologic signals, time series and
related open source software for basic, clinical, and applied research, Proceedings of the 33rd Annual
International Conference of the IEEE EMBS, Boston, Massachusetts, pp. 83278330.
Ackerman M. J., 1998, The visible human project, Proceedings of the IEEE, 86(3), pp. 504511.
Liu Y., 2003, Design Of A Performance Test Loop For An Artificial Heart Pump, Masters Thesis,
University of Virginia, Charlottesvill, VA USA.
Timms D. L., Gregory S. D., Greatrex N. A., Pearcy M. J., Fraser J. F., and Steinseifer U., 2011, A
Compact Mock Circulation Loop for the In Vitro Testing of Cardiovascular Devices, Artificial Organs,
35(4), pp. 384391.
Hsu P. L., Cheng S. J., Saumarez R. C., Dawes W. N., and McMahon R. A., 2008, An extended
computational model of the circulatory system for designing ventricular assist devices, ASAIO Journal,
54(6), p. 594.
Lvine J., and Mllhaupt P., eds., 2010, Advances in the theory of control, signals and systems with
physical modeling, Springer, Berlin.
Johansson P., and Andersson B., 2008, Comparison of simulation programs for supercapacitor
modelling, Masters Thesis, Chalmers University of Technology, Gothenberg, Sweden.
Gregory S. D., 2009, Simulation and development of a mock circulation loop with variable compliance,
Masters Thesis, Queensland University of Technology, Brisbane, Australia.
Pantalos G. M., Koenig S. C., Gillars K. J., Giridharan G. A., and Ewert D. L., 2004, Characterization of
an Adult Mock Circulation for Testing Cardiac Support Devices, ASAIO Journal, 50(1), pp. 3746.
De Zlicourt D., Pekkan K., Kitajima H., Frakes D., and Yoganathan A. P., 2005, Single-Step
Stereolithography of Complex Anatomical Models for Optical Flow Measurements, Journal of
Biomechanical Engineering, 127(1), p. 204.
Kornecki A., and Zalewski J., 2009, Certification of software for real-time safety-critical systems: state of
the art, Innovations in Systems and Software Engineering, 5(2), pp. 149161.
Severa O., and Cech M., 2012, REX - Rapid development tool for automation and robotics, 2012
IEEE/ASME International Conference on Mechatronics and Embedded Systems and Applications
(MESA), pp. 184 189.
Loire J., and Neelakantam A. K. R., 2011, Development of a Steer-By-Wire application in
MATLAB/Simulink, Masters Thesis, Chalmers University of Technology, Gothenberg, Sweden.
Li J. K.-J., and Zhu Y., 1994, Arterial Compliance and Its Pressure Dependence in Hypertension and
Vasodilation, Angiology, 45(2), pp. 113117.
Panwar N. S., Kelly G. S., Taylor C. E., and Miller G. E., 2012, Search Engine of Physiological
Conditions in the PhysioBank Database., Podium presentation at the Virginia Academy of Science 90th
Annual Meeting, Norfolk, VA.
Manning K. B., and Miller G. E., 1999, Shaft/Shaft-Seal Interface Characteristics of a Multiple Disk
Centrifugal Blood Pump, Artificial Organs, 23(6), pp. 552558.
Page 21 of 25
[24] Thatte S. M., 2006, In Vitro Flow Visualization Study of the Interface Between Outflow Graft of
Ventricular Assist Device and Aorta, Dissertation, Virginia Commonwealth University, Richmond, VA
USA.
[25] Walker A., 2010, In Vitro Evaluation of Mechanical Heart Valve Performance Using a Novel Test
Chamber in an Automated Mock Circulatory Loop, Masters Thesis, Virginia Commonwealth University,
Richmond, VA USA.
[26] International Organization for Standardization, 1987, Centrifugal, mixed flow and axial pumps - Code for
hydraulic performance tests - Precision class, ISO 5198.
[27] International Organization for Standardization, 2010, Implants for surgery - Active implantable medical
devices, Part 5: Circulatory support Devices, ISO 14708-5.
[28] International Organization for Standardization, 2005, Cardiovascular implants Cardiac valve
prostheses, ISO 5840.
[29] Taylor C. E., Rourick R. A., and Walsh J. P., 2007, High Throughput Solubility Analysis; a Tailored
Approach to Supporting Drug Discovery Efforts, Poster presentation at the American Association of
Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition, San Diego, CA.
[30] Taylor C. E., Rourick R. A., and Walsh J. P., 2007, A Modular Chemical and Photo-Stability Chamber
Purpose-Built for an LC/MS-Enabled Liquid Handler, Poster presentation at the American Association of
Pharmaceutical Scientists (AAPS) Annual Meeting and Exposition, San Diego, CA.
[31] Taylor C. E., Yang Q., Walsh J. P., and Rourick R. A., 2007, An Automated Dynamic BioAnalytical
Sample Preparation Routine for Integration with Liquid Handlers, Poster presentation at the Chemical
and Pharmaceutical Structure Analysis (CPSA) Conference, Langhorne, PA.
[32] Taylor C. E., and Miller G. E., 2012, Implementation of an automated peripheral resistance device in a
mock circulatory loop with characterization of performance values using Simulink Simscape and
Parameter Estimation., Journal of Medical Devices, 6(4), p. 045001.
[33] Wilmer W. Nichols, 2011, McDonalds blood flow in arteries: theoretical, experimental and clinical
principles., Hodder Arnold, London.
[34] Watton J., 2009, Fundamentals of fluid power control, Cambridge University Press, Cambridge UK;;New
York.
[35] Liptk B., 2006, Instrument engineers handbook, CRC Taylor & Francis, Boca Raton Fla. [u.a.].
[36] Taylor C. E., Dziczkowski Z. W., and Miller G. E., 2012, Automation of the Harvard Apparatus Pulsatile
Blood Pump, Journal of Medical Devices, 6(4), p. 045002.
[37] Jamali P., and Shirazi K. H., 2012, Robot Manipulators: Modeling, Simulation and Optimal Multi-Variable
Control, Applied Mechanics and Materials, 232, pp. 383387.
[38] Zarghani N. H., 2009, Modeling and simulation of an active robotic device for flexible needle insertion,
Master, National University of Singapore, Singapore.
[39] Liu Y., Allaire P., Wood H., and Olsen D., 2005, Design and initial testing of a mock human circulatory
loop for left ventricular assist device performance testing, Artificial Organs, 29(4), pp. 341345.
[40] Liu Y., Allaire P., Wu Y., Wood H., and Olsen D., 2006, Construction of an Artificial Heart Pump
Performance Test System, Cardiovascular Engineering, 6(4), pp. 151158.
[41] Taylor C. E., and Miller G. E., 2012, Mock Circulatory Loop Compliance Chamber Employing a Novel
Real-Time Control Process, Journal of Medical Devices, 6(4), p. 045003.
[42] Ugural A., 1999, Stresses in plates and shells, WCB/McGraw Hill, Boston.
[43] Reddy J., 1999, Theory and analysis of elastic plates, Taylor & Francis, Philadelphia PA.
[44] Reddy J. N., Huang C. L., and Singh I. R., 1981, Large deflections and large amplitude vibrations of
axisymmetric circular plates, Int. J. Numer. Meth. Engng., 17(4), pp. 527541.
[45] Fung Y. C., 1993, Biomechanics: Mechanical Properties of Living Tissues, Springer-Verlag, New York.
[46] Pekkan K., Zelicourt D. de, Ge L., Sotiropoulos F., Frakes D., Fogel M. A., and Yoganathan A. P., 2005,
Physics-Driven CFD Modeling of Complex Anatomical Cardiovascular Flows - A TCPC Case Study,
Annals of Biomedical Engineering, 33(3), pp. 284300.
[47] Dasi L. P., Simon H. A., Sucosky P., and Yoganathan A. P., 2009, FLUID MECHANICS OF ARTIFICIAL
HEART VALVES, Clinical and Experimental Pharmacology and Physiology, 36(2), pp. 225237.
[48] Desai M., Ahmed M., Darbyshire A., You Z., Hamilton G., and Seifalian A. M., 2011, An Aortic Model for
the Physiological Assessment of Endovascular Stent-Grafts, Annals of Vascular Surgery, 25(4), pp. 530
537.
Page 22 of 25
[49] Minakawa M., Fukuda I., Yamazaki J., Fukui K., Yanaoka H., and Inamura T., 2007, Effect of cannula
shape on aortic wall and flow turbulence: hydrodynamic study during extracorporeal circulation in mock
thoracic aorta, Artificial organs, 31(12), pp. 880886.
[50] Yushkevich P. A., Piven J., Hazlett H. C., Smith R. G., Ho S., Gee J. C., and Gerig G., 2006, Userguided 3D active contour segmentation of anatomical structures: significantly improved efficiency and
reliability, Neuroimage, 31(3), pp. 11161128.
[51] 2012, Blender, Blender.org [Online]. Available: http://www.blender.org/. [Accessed: 14-Dec-2012].
[52] Mojica-Santiago J. A., Villongco C. A., Krummen D. E., Frank L. R., and McCulloch A. D., 2011,
Reconstructing Patient-Specific Models of the Dyssynchronous Failing Heart using CT and DTMR
Images, Proceeding of the Biomedical Engineering Society Annual Meeting, Hartford, CT.
[53] Gorder R., 2010, Mass Transport and Shear Stress within the Carotid Artery Bifurcation: A Study of Flow
E ects on Atherosclerosis, Masters Thesis, University of Washington, Seattle, WA.
[54] Lasemi A., Xue D., and Gu P., 2010, Recent development in CNC machining of freeform surfaces: A
state-of-the-art review, Computer-Aided Design, 42(7), pp. 641654.
[55] Taylor C. E., Kelly G. S., Warren S. J., and Miller G. E., 2012, Aortic model developed from Visible
Human Project data integrated with a fully automated mock circulatory loop., Poster presentation at the
Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS), San
Diego, CA.
[56] Ferrari G., Kozarski M., Zieliski K., Fresiello L., Molfetta A., Grczyska K., Pako K. J., and Darowski
M., 2011, A modular computational circulatory model applicable to VAD testing and training, Journal of
Artificial Organs, 15(1), pp. 3243.
[57] Wu Y., Allaire P., Tao G., and Olsen D., 2005, Modeling, estimation and control of cardiovascular
systems with a left ventricular assist device, American Control Conference, 2005. Proceedings of the
2005, pp. 38413846.
[58] Pantalos G. M., Koenig S. C., Gillars K. J., and Ewert D. L., 2002, Mock circulatory system for testing
cardiovascular devices, Engineering in Medicine and Biology, 2002. 24th Annual Conference and the
Annual Fall Meeting of the Biomedical Engineering Society EMBS/BMES Conference, 2002. Proceedings
of the Second Joint, IEEE, pp. 1597 1598 vol.2.
[59] Enocksson S., 2011, Modeling in MathWorks Simscape by building a model of an automatic gearbox,
Uppsala University.
[60] Tann D., Bertrand E., Kadem L., Pibarot P., and Rieu R., 2009, Assessment of left heart and
pulmonary circulation flow dynamics by a new pulsed mock circulatory system, Experiments in Fluids,
48(5), pp. 837850.
[61] Taylor C. E., and Miller G. E., 2011, A Fully Automated Mock Loop With Corresponding Simulink
Simscape Model Connected to PhysioBank Data., Poster presentation at the Biomedical Engineering
Society 2011 Annual Meeting, Hartford, CT.
[62] The MathWorks, 2010, Simscape 3.0 Users Guide, The MathWorks, Natick, MA.
[63] The MathWorks, Simulink 7.0 Users Guide, The MathWorks, Natick, MA.
[64] Egel T., 2009, Real time simulation using non-causal physical models, SAE Technical Paper, pp. 01
1021.
[65] Saeed M., Lieu C., Raber G., and Mark R. G., 2002, MIMIC II: a massive temporal ICU patient database
to support research in intelligent patient monitoring, Computers in Cardiology, 2002, pp. 641644.
[66] Branch M. A., Coleman T. F., and Li Y., 1999, A subspace, interior, and conjugate gradient method for
large-scale bound-constrained minimization problems, SIAM Journal on Scientific Computing, 21(1), pp.
123.
[67] More J. J., and Sorensen D. C., 1983, Computing a Trust Region Step, Society for Industrial and
Applied Mathematics. SIAM Journal on Scientific and Statistical Computing, 4(3), p. 20.
[68] Byrd R. H., Schnabel R. B., and Shultz G. A., 1988, Approximate solution of the trust region problem by
minimization over two-dimensional subspaces, Mathematical Programming, 40-40(1-3), pp. 247263.
[69] Wellstead P. E., 1979, Introduction to physical system modelling, Academic Press London.
[70] Williams R. L., and Lawrence D. A., 2007, Linear State-Space Control Systems, John Wiley & Sons.
[71] Zong W., Heldt T., Moody G. B., and Mark R. G., 2003, An open-source algorithm to detect onset of
arterial blood pressure pulses, Proceedings of the Computers in Cardiology Conference, pp. 259 262.
[72] Li B. N., Dong M. C., and Vai M. I., 2010, On an automatic delineator for arterial blood pressure
waveforms, Biomedical Signal Processing and Control, 5(1), pp. 7681.
Page 23 of 25
[73] Farley M., 2004, Storage Networking Fundamentals: An Introduction to Storage Devices, Subsystems,
Applications, Management, and File Systems (Cisco Press Fundamentals), Cisco Press.
[74] Mosterman P. J., Prabhu S., and Erkkinen T., 2011, An industrial embedded control system design
process., Proceedings of the Canadian Engineering Education Association.
[75] Santo S., 2001, Embedded battle royal [embedded operating systems], Spectrum, IEEE, 38(12), pp.
3641.
[76] Taylor C. E., Kelly G. S., Warren S. J., and Miller G. E., 2012, Simulation of cardiovascular conditions
and critical events in a fully automated mock circulatory loop., Poster presentation at the American
Society of Artificial Internal Organs (ASAIO) Annual Meeting, San Francisco, CA.
[77] Yoganathan A. P., He Z., and Casey Jones S., 2004, Fluid Mechanics of Heart Valves, Annual Review
of Biomedical Engineering, 6(1), pp. 331362.
[78] Gregory S., Timms D., Pearcy M. J., and Tansley G., 2009, A naturally shaped silicone ventricle
evaluated in a mock circulation loop: A preliminary study, Journal of Medical Engineering & Technology,
33(3), pp. 185191.
[79] Chua C. K., Leong K. F., and Lim C. C. S., 2010, Rapid Prototyping: Principles and Applications, World
Scientific, Singapore.
[80] Noorani R., 2006, Rapid Prototyping - Principles and Applications, John Wiley & Sons.
[81] Dorsi J. M., 1990, Testing a multiple disk pump for use as an artificial ventricle., Thesis, Texas A&M
University, College Station, TX.
[82] Geoghegan P. H., Buchmann N. A., Spence C. J. T., Moore S., and Jermy M., 2012, Fabrication of rigid
and flexible refractive-index-matched flow phantoms for flow visualisation and optical flow
measurements, Experiments in Fluids, 52(5), pp. 13311347.
Page 24 of 25
Resource Sharing Plan

The initiative of modernizing mock circulatory loop technology for the benefit of this research field requires
that critical portions of this work become publicly available. Appropriate dissemination through literature and
presentation does not fully endow the research field in a way that is consistent with this investigators vision for
adoption of these methods. Publishing the relevant data and software tools in a publicly accessible forum is
the final goal of this project.
Data Sharing Plan

Publication of simulated events and conditions, both in silico and in vitro, will be published as raw data.
Use of SharePoint resources currently in use by the laboratory will serve as the content provider medium; this
will enable web access of the data as zipped files. Incorporation of this data into PhysioNet will be pursued,
due to their well developed archiving and data visualization tools. If the data is not accepted into that
database, per their data review policy, adaptation of their online viewing tools to display data outside their
system will be tested. Ultimately, the public accessibility of this data is desired to enable comparative research
and promote particular experimental sequences as paradigms for device assessment.
Open access to the anatomical models is also desired to continue the Visible Human Project's initiative of
providing free anatomical imaging datasets to non-commercial researchers. By starting a repository of CAD
models developed from this data, it enables other research groups to be unburdened with obtaining this
models. With groups adopting this models, homogenization of the anatomy will benefit comparative analysis of
the resulting data sets. The repository will be contained on the SharePoint site. The model data submitted to
the site will be accepted based on its adherence to an SOP on the method developed by this investigator. This
will ensure some uniformity in the model quality. The National Library of Medicine has been approached to
include a link to this repository on its website, to assist in advertising this academic resource.
Software Sharing Plan

Publication of the mock circulatory loop computational model is desired in a code protected format. This
will enable others to conduct investigations with this model, while maintaining the ownership of its architecture.
Further publication of compiled parameter estimation code will be investigated. This has been a requested
offering by other researchers. It promotes the experimental design approach developed by this project; using
clinical waveforms as conditions sources for mock circulatory loop investigations.
SharePoint resources for the publication of these software packages will be used. Other code publication
resources do not allow for inclusion of support resources and adequate presentation of the material contained.
It is also the interest of this laboratory to maintain control of the dissemination of this code, with the flexibility to
make changes to the availability and type of content provided.
Resource Sharing Plan
Page 25 of 25

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Modernization of the Mock

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Aim 2: Deploy a fully automated mock circulatory loop .......................................................................................... 17

BIBLIOGRAPHY AND REFERENCES CITED .............................................................................................................. 21

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Facilities and Other Resources

Facilities and Other Resources

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Proprietary and Confidential

Facilities and Other Resources

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Illustrate the application of sophisticated physical modeling software in the construction of

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Figure C.1: Diagram of the objectives and how the work

Application of embedded control techniques to solve current limitations in mock circulatory

Automated mock circulatory loop, including anatomical sections, with accompanying

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Overview of the personnel and approach

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Figure C.3: Annotated picture of modified

Charles Edward Taylor

Figure C.4: Illustration of percent systole change and control.

Preliminary studies supporting approach

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Figure C.5: Compliance chamber

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Aim 1: Develop computational plant models with process control logic.

Proprietary and Confidential

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Pulmonary Simulator [PS]

Harvard Pump [HP]

Compliance Chamber [CC]

Peripheral Resistor [PR]

VCU BME: Artificial Heart Laboratory

Charles Edward Taylor

Aim 2: Deploy a fully automated mock circulatory loop

VCU BME: Artificial Heart Laboratory