Johns Hopkins University Applied Physics Laboratory

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Johns Hopkins University Applied Physics
Laboratory
A Collaborative Modeling and Simulation
Environment for Space Biomedical Research 2003
European Simulation Interoperability
Workshop Stockholm, Sweden June 16-19, 2003
James E. Coolahan, Ph.D. James.Coolahan_at_jhuapl.e
du 1 240-228-5155 The Johns Hopkins
University Applied Physics Laboratory 11100 Johns
Hopkins Road Laurel, MD USA 20723-6099
The work presented herein was supported by the
National Aeronautics and Space Administration
(NASA) through the National Space Biomedical
Research Institute (NSBRI) under NASA Cooperative
Agreement NCC9-58.
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Presentation Outline

• Background
• Space Biomedicine Issues
• The National Space Biomedical Research Institute
  (NSBRI)
• Physiological Modeling
• Initial NSBRI Collaborative Simulations
• The Cardiovascular - Ventricular System (CVVS)
  Federation
• The Human Exercise Federation
• Collaborative Environment Concepts
• Collaborative Environment Definition
• Elements of Collaborative Environments
• A Collaborative Environment for Space Biomedical
  Research
• Characteristics of the NSBRI MS Community
• Concept for an NSBRI MS Collaborative Environment

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A Systems Perspective for Human Function in
Long-Duration Spaceflight

• Threats
• Radiation
• Coronal mass ejections
• Cosmic rays
• Airborne particulates
• Pathogens
• Airborne
• Waterborne
• Foodborne
• Wounds
• Decompression

Spacecraft Natural Environment Temperature Humidit
y Barometric pressure Atmospheric
composition Ambient light Microgravity
The Human Body in Confined Spaceflight in
Microgravity
Psychosocial factors
Neurovestibular adaptation
Circadian rhythms
Immunology / hematology
Cardiovascular alterations
Nutrition
Other Issues Biomass (food) production Waste
management Air quality maintenance
Muscle atrophy
Countermeasures Shielding Exercise Artificial
gravity Pharmacology (Smart) medical care
Bone loss
The System
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NASA Human Space Life SciencesCritical Path
Roadmap

• Approach to risk mitigation
• Identify, understand, and manage the risks
• Prevent or reduce effects to acceptable levels to
  ensure crew safety, health, and performance
  during and after space flight
• Beginning in 1998, identified 55 risks and 250
  critical questions in 9 categories (e.g., bone
  loss, cardiovascular alterations, human behavior
  and performance, etc.)
• Characterized risks as severe (type I), very
  serious (type II), and serious (type III)
• Examples of risks
• Occurrence of serious cardiac dysrhythmias (type
  II)
• Impaired cardiovascular response to exercise
  stress (type III)
• Loss of skeletal muscle mass, strength, and/or
  endurance (type II)
• More Information available at http//criticalpath
  .jsc.nasa.gov

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The National Space Biomedical Research Institute
(NSBRI)
Organization Consortium of 12 institutions,
founded in 1997, funded by NASA
Primary Mission Objective To ensure safe and
productive human exploration and development of
space beyond Earth orbit See http//www.nsbri.org
for more information

• Research Teams
• Bone Loss
• Cardiovascular Alterations
• Human Performance Factors, Sleep and
  Chronobiology
• Immunology, Infection and Hematology
• Muscle Alterations and Atrophy
• Neurobehavioral and Psychosocial Factors
• Neurovestibular Adaptation
• Nutrition, Physical Fitness, and Rehabilitation
• Radiation Effects
• Smart Medical Systems
• Technology Development
• New research area in FY 2001

• Consortium Members
• Baylor College of Medicine (lead)
• Brookhaven National Laboratory
• Harvard Medical School
• The Johns Hopkins University School of Medicine
  and Applied Physics Laboratory
• Massachusetts Institute of Technology
• Morehouse School of Medicine
• Mount Sinai School of Medicine
• Rice University
• Texas AM University
• University of Arkansas for Medical Sciences
• University of Pennsylvania Health System
• University of Washington
• Added to consortium in 1999

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Comparison of MS Levels Military Simulation vs.
Physiological Modeling
Levels of Aggregation
Military Simulation
Physiological Modeling
PATRIOT-centric example
Cardiac-centric example
Human
Whole body
91 Gulf War
Cardio-vascular
System
Air defense
Organ
Missile intercept
Heart
Cell
Myocyte
Terminal guidance
Ca
Molecule
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Cardiovascular - Ventricular System (CVVS)
Federation Approach

• Principal risk area addressed occurrence of
  serious cardiac dysrhythmias
• Objective model responses of cardiovascular
  system variables (heart rate, blood pressure,
  etc.) following hypothetical cardiac electrical
  state changes
• Approach federate an existing system-level
  cardiovascular model with a more detailed
  simulator of ventricular electrical-mechanical
  activity
• Research Cardiovascular Simulator (RCVSIM)
• Major components
• Lumped parameter model of pulsatile heart and
  circulation
• Short-term regulatory system model
• Electrical circuit analogs of mechanical system
  components
• Charge analogous to blood volume
• Current analogous to blood flow rate
• Voltage analogous to pressure
• Hybrid Cellular Automata (HCA) Heart Model
• Each ventricle modeled by a 700 x 700 array
• Each grid arranged into 10 cm x 3.18 cm cylinder

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Cardiovascular - Ventricular System (CVVS)
Federation Block Diagram
Adapted from 02S-SIW-012, Integrating Cardiac and
Cardiovascular Simulations Using the HLA
Input Data File
LeftVentricle Federate
700 x 700 Array Vector Potential
Differences 700 Radii of Concentric Rings
Capacitance dCdt
EDC, ESC Intraventricular Pressure
Research CardioVascularSIMulator
ECG Federate
EDC, ESC Intraventricular Pressure
700 x 700 Array Vector Potential
Differences 700 Radii of Concentric Rings
Capacitance dCdt
Right Ventricle Federate
Input Data File
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CVVS Federation ExecutionHemodynamics During
Ventricular Tachycardia
Simulated Electrocardiogram
Adapted from 02S-SIW-012, Integrating Cardiac and
Cardiovascular Simulations Using the HLA
Arterial Pressure Left Ventricle Pressure
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Rationale for the Human Exercise Federation

• Exercise is a multiple-system countermeasure
  employed regularly in all long-duration space
  missions to reduce
• orthostatic intolerance upon return from
  microgravity
• muscle atrophy
• bone loss
• Multiple exercise countermeasures are / have been
  used
• cycle ergometer
• treadmill
• resistive exercise device
• Astronauts on the International Space Station
  (ISS) exercise an average of 2.5 hours per day, 6
  days per week
• Given ISS maintenance requirements, every hour
  spent exercising is an hour not available for
  mission tasks (aggravated by reduced crew size)
• If exercise methods and effects in microgravity
  can be better understood and modeled, in the
  future, less exercise time may be required to
  produce needed benefits

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Human Exercise Federation Approach

• NSBRI convened Exercise Workshop in August, 2002
• Small interdisciplinary research team formed to
  move concept forward
• Settled on first step of producing simulation of
  cycle ergometer exercise protocol used by U.S.
  astronauts since Skylab in 1970s
• 5 minutes of rest
• 5 minutes at a work level corresponding to 25 of
  each astronaut's preflight VO2,max
• 5 minutes at 50 VO2,max
• 5 minutes at 75 VO2,max
• 5 minutes recovery
• Key elements of the Human Exercise Federation
• Streamlined version of CVVS Federation
• Blood flow federate (based on work done at MIT)
• Whole-body lactate metabolism model (Case Western
  Reserve University)
• Skeletal muscle energetics model (University of
  Washington)

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NSBRI Human Exercise Federation
Ergometer Federate
Work in Progress

• Height (m)
• Training Factor

Respiratory Federate
Minute Ventilation (L/min)
Combined Lactate Metabolism and Muscle Energetics
Federate

• Muscle Mass (kg)

Instantaneous Lung Volume (L)
Respiration Rate (Hz) Tidal Volume (L)
O2 CO2 Partial Arterial Pressures (mmHg)

• O2 Uptake (L/min)
• CO2 Output (L/min)
• Blood Lactate Conc
• Muscle Lactate Conc

Sympathetic Activator Federate
Work Rate (watts)
Target Blood Pressure (mmHg)

• Cardiac Output (L/min)
• Arterial Resistance (PRU)
• Venous Resistance (PRU)
• Mean Arterial Pressure (mmHg)
• Mean Venous Pressure (mmHg)

• Blood Flows (Splanchnic, Muscle, Other) (L/min)

Research Cardiovascular Simulator (RCVSIM)
Federate
Local Blood Flow Regulator Federate
Pedal Rate (RPM)
Total Peripheral Resistance (PRU) Delta
Blood Volume (ml)
Heart Rate (bpm) Blood Pressure (mmHg)
Stroke Volume (L)

• All cycle ergometer output data

Data Collection Federate
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Modeling and SimulationCollaborative Environment
Concepts

• An MS-focused collaborative environment
  definition
• an enduring collection of subject matter experts
  (SMEs) supported by interoperable tools and data
  bases, authoritative information resources, and
  product/process models that are focused on a
  common domain or set of problems
• Examples of in-process MS collaborative
  environments in the U.S. Department of Defense
• Joint Strike Fighter (JSF) program
• U.S. Army Future Combat Systems (FCS) program

Source A Roadmap for Simulation Based
Acquisition Report of the Joint Simulation
Based Acquisition Task Force, December 1998
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Elements of aCollaborative Environment (CE)
Purpose

• A defined purpose for which the CE is intended to
  be used
• The involvement of subject matter experts (SMEs)
  from all functional disciplines that are
  stakeholders in the domain or set of problems
  upon which the CE is focused
• Availability of a set of interoperable models,
  simulations, tools, and data appropriate to the
  domain or problem set
• Systems to enable electronic collaboration over a
  distance for exchange of information, access to
  authoritative data, and execution of simulations
• A systems architecture framework for the CE
• An agreed upon set of standards, rules, and local
  conventions, to which all CE users and components
  adhere
• An agreed upon set of processes for configuration
  management and for Verification, Validation, and
  Accreditation (VVA)
• Coordinated policy, planning, and investment
  strategies to ensure continuing support of the CE

People
Tools
Standards
Processes
Adapted from 00S-SIW-113, SBA Collaborative
Environment Concepts for Mission and Product Areas
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Some Characteristics of the NSBRI Bioastronautics
Core Modeling Effort

• Effort needs to produce near-term
  countermeasures for long-duration human
  spaceflight
• Subject matter domain crosses many areas of
  physiological function
• There are legacy simulations of value
• Simulations exist across all levels of the
  physiological simulation pyramid
• Researchers are spread across several NSBRI teams
• Researchers are spread throughout the U.S.

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A Potential Way Ahead for an NSBRIBioastronautics
MS Collaborative Environment
Users, Tools, and Resources Will Be Physically
Distributed
Authorized NSBRI Users
Tools Layer
Translators
Local inputs
Resources Layer
NSBRI Bioinformatics Resource Repository
NASA Life Sciences Data Archive
Other archives (future)
NSBRI Data Archive
NSBRI Archived MS Results
NSBRI MS Documentation
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Acknowledgments

• JHU/APL Collaborators / Contributors
• Andrew B. Feldman, Ph.D.
• Robert R. Lutz
• Sean P. Murphy
• Randy Saunders
• Joseph G. Kovalchik, Ph.D.
• Additional Human Exercise Federation
  Collaborators / Contributors
• Roger G. Mark, M.D., Ph.D., Massachusetts
  Institute of Technology
• Martin J. Kushmerick, M.D., Ph.D., University of
  Washington
• Marco E. Cabrera, Ph.D., Case Western Reserve
  University
• Ramakrishna Mukkamala, Ph.D., Michigan State
  University
• Thomas Heldt, Ph.D. candidate, Massachusetts
  Institute of Technology