2016 01 18_imsh_do_d_specialsession_biogears

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18 January 2016

Jeff Webb

BioGears:Designing and Building an Extensible, Modular, Open

Source Human Physiology Engine

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1. Background and Scope

2. Software Architecture and Implementation

3. Physiology Modeling Approach

4. Remaining Work

Agenda

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• Organization: Applied Research Associates, Inc. (ARA)

• Telemedicine & Advanced Technology Research Center

(TATRC) Award #: W81XWH-13-2-0068

• Principal Investigator: Mr. Jeff Webb

• Amount: $6,959,593

• Period of Performance: Sept 2013 – Sept 2018

• Disclaimer: This work is supported by the US Army Medical

Research and Materiel Command. The views, opinions and/or findings

contained in this report are those of the author(s) and should not be

construed as an official Department of the Army position, policy, or

decision unless so designated by other documentation.

Project Information

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High Level Objectives

• Create a publicly available physiology research platform that enables accurate and consistent simulated physiology across training applications

• Lower the barrier to create medical training content

• Engage the community to develop and extend physiology models

• Meet the training needs of the military

• Expand the body of knowledge regarding the use of simulated physiology for medical education

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Physiology Engine Overview

•Chronic Conditions

• Insults & Interventions

Cardiovascular system

computes hemodynamics

Respiratory system computes

pulmonary functions

Renal and Gastrointestinal

systems compute nutrient

consumption and clearance

Substances system computes

diffusion, gas exchange, and

drug effects

Energy balance system

computes temperature, exercise

readiness, and nutrient usage

Endocrine and Nervous systems

maintain homeostasis through

feedback mechanisms

Drugs

Hormones

Nutrients

Blood

•PK Model

•PD Model

•Hemoglobin

•Gases

• Ions

•Epinephrine•Norepinephrine

• Insulin

•Fat

•Sugars

•Proteins

•Library of Drugs

•Drug administration

through multiple routes

•Electrocardiogram

•Anesthesia Machine

• Inhaler

•CPR

•Pulmonary Function Test

•Complete Blood Count

•Urine Panel

FeaturesSystems Substances

Environment modifies ambient

values and thermal properties

Patients

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Tasks & Milestone

2013

2014

2016

2017

Milestone: Project Kick Off (Sept 15, 2013)

Creation of Common Data Model

Re-architecture of Physiology Engine

Base System Development

Base System Validation

Milestone: Mini Build Release and Website Launch (Oct 2014)

Base System Additions & Improvements

Secondary System Development & Validation

Feature Development & Validation

Community Outreach & Conference PlanningMilestone: Beta Build Release and Users’ Group Conference

(Fall 2015)

System Development and Engine Maintenance

User Community Support

Continued Community Outreach

Publications & Conference Presentations

(9/2017 – 9/2018) Website Maintenance Only

Current

2018

2015

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24Months after contract ARA released the Beta

Build under an Apache 2.0 permissive open

source license (October 2015).

Downloads of the engine and related files since

the Mini Build Release (October 2014)!2,000+

Teams we are actively interacting with to

integrate BioGears into their projects and

products.12+

Where We Are

Pages of physiology modeling methodology and

software documentation, and validation data

available to our user community.1,400+

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Feedback mechanisms to modify elements for next

time-step

Preprocess

Calculates entire engine state for the next time-step

Process

Advances time by moving next time-step to current

Postprocess

Engine Overview

Computation Approach:• Time-stepping transient analysis for linearization of differential equations

• Currently 90Hz for 2x real-time simulation

• Dynamically change/add/remove elements to represent physiological mechanisms

• Stabilization analysis for initialization and implementation of conditions

• Designed with low computational overhead

• Faster than real-time on typical PC, multiple instances on single or multicore processors

• Build Targets include Windows, Mac, Linux, and Raspberry Pi

Modeling Approach:

• Top-down approach to model development with bottom-up hooks for engine expansion

• Multi-scale for varying fidelity, allowing integration of models from any level

Body Systems Organs Tissues Cells Proteins Genes

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• Common Data Model (CDM): Well-defined, intuitive, interchangeable format to standardize interfaces• Standardized inputs, outputs,

units, and naming conventions to aid model additions and external model integrators

• Application Programming Interface (API): Easy integration and interaction in any programming language• Data organized logically by

Anatomy so that users are able to easily find and pull relevant data

• Software Development Kit (SDK): Application examples and stand-alone execution• Tutorials, How-to’s, scenario

examples

Software Architecture

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Physiology Modeling Approach

Brain

Heart

Arms

Legs

Core

Lumped Parameter Modeling:

• Discrete entities that approximate the behavior of a distributed system

• Electronic-Hydraulic/Thermal Analogy: body system fluid dynamics and thermodynamics modeled using electrical circuit math

• Generalized definitions of Nodes, Paths, and Elements for simple understanding, implementation, and modification

• Calculate entire state of the body every time-step

• Dynamic time-step capable

Advantages:

• Modular and extensible

• Model fidelity easily modified by adding/removing nodes and elements to circuit

• Fully dynamic physics based mechanistic models (rather than state based) – cascading effects

• Unlimited stacking/combining of conditions, insults, interventions, interfaces, etc.

• Homeostasis based modeling with pathophysiology actions

• Able to integrate existing/new models

• Not necessarily lumped parameter

• Mixed fidelity

• Able to simultaneously run any number of instances/patients

LiverGut

Kidneys

Core

Lungs

Cardiovascular System Example

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Included BioGears ToolsCircuit Solver

• Fully dynamic Modified Nodal Analysis solver for any valid closed-loop circuit

• Solves circuit types with any units: Electrical, Fluid, Thermal

Circuit Transporter

• Substances move with the fluid to each node in the circuit

• Gas exchange occurs between the pulmonary vasculature and the alveoli

• Diffusion occurs between the blood and tissue based on concentration, flow, and substance properties

Unit Converter

Unit/Feature Testing

• Validate individual tools

• Verify individual feedback

• Alerts user to introduced bugs

Verification Testing

• Full scenario suite to test all patient files, patient actions, substance effects, and equipment performance

• Each scenario indicates the physiologic outputs for comparison and generates error plots

Validation Testing

• Spreadsheet with referenced baselines

• Color coded error tables automatically generated for all System and relevant compartment data

Developer GUI

VentilatorPressureLossScenarioResultsReport 1 1 21.258999824523926

YpieceDisconnectScenarioResultsReport 1 1 23.98900008201599

AirwayInsultObstructionResultsReport 0 1 14.930999994277954

AtropineScenarioResultsReport 0 1 13.121000051498413

BasicScenario1ResultsReport 0 1 18.195000171661377

Verification Results Example

Developer GUI

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Connection types:

• Direct circuit connection – e.g. Anesthesia Machine and Respiratory

• Feedback – e.g. Nervous and Endocrine

• Substance exchange – e.g. Respiratory and Cardiovascular gas exchange

Patient Parameters:

• Properties defined that modify system setup, circuit values, and feedback parameters

• Examples: gender, weight, heart rate baseline, etc.

Physiology System Interaction

EnvironmentPK/PD

Cardiovascular

Blood

Tissue

Extravascular

Respiratory

Anesthesia Machine

Renal

Gastrointestinal

Energy

Nervous

Endocrine

Inhaler

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• Anatomical Compartments defined by sub-circuits and allow access via an anatomy tree

• Compartment fluid propertiesare combined from children• Volume is a sum

• InFlow is a sum

• OutFlow is a sum

• Pressure comes from an assigned child node (sum does not make sense)

• Substance quantities (mass, concentration, etc.) are calculated on demand

Left Kidney

Left Renal Artery

Left Renal Vein

Left Nephron

Left Afferent Arteriole

Left Glomerular Capillaries

Left Efferent Arteriole

Left Peritubular Capillaries

Left Bowmans Capsules

Left Tubules

Left Ureter

Compartment Example: Kidney Definition

Key:

Vascular

Urine

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Current System Capabilities

Systems Acute Insults & Interventions Chronic Conditions Events

Cardiovascular& Blood Chemistry

Cardiac ArrestCPRHemorrhagePericardial Effusion

AnemiaArrhythmiaBradycardiaTachycardiaHeart FailurePericardial EffusionPulmonary Shunt

AsystoleBradycardia & TachycardiaBradypnea & TachypneaBrain & Myocardium Oxygen DeficitCardiac ArrestHypercapnia & HypoxiaHyperglycemia & HypoglycemiaHypovolemic ShockPulseless Rhythm

Respiratory Airway ObstructionBronchoconstrictionAsthma AttackCOPD BronchitisIntubation

PneumothoraxConscious RespirationOcclusive DressingNeedle Decompression

COPDLobar Pneumonia

Energy & Environment

ExerciseEnvironment ChangesThermal Application

DehydrationStarvationEnvironment Changes

FasciculationFatigueHyperthermiaHeat StrokeMetabolic/Respiratory Acidosis & Alkalosis

Renal & GI

UrinateConsume Meal

Renal Stenosis Diuresis & AntidiuresisNatriuresisDehydrationFunctional Incontinence

Drugs& Substances& Inhaler

IV Fluid AdministrationIV Drug Administration

IM Drug AdministrationInhaler Drug Administration

Anesthesia Machine ConfigurationExpiratory/Inspiratory Valve Leaks/ObstructionsSoda Lime FailureMask/Tube LeakVaporizer Failure

Ventilator Pressure LossOxygen Port/Tank Pressure LossEndotracheal IntubationEsophageal Intubation

Oxygen Bottle ExhaustedRelief Valve Active

Note: More to come

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Provided Data Examples

Systems System Vital Examples(Hundreds Total)

Compartment Examples(Thousands Total)

Assessments(Exhaustive)

Cardiovascular Heart RateCardiac OutputMean Arterial PressureBlood Volume

Pulmonary FlowBrain PressureHeart VolumesSubstance Concentrations

Complete Blood CountComprehensive Metabolic Panel

Blood Chemistry Blood pHOxygen SaturationShunt FractionHemoglobin Content

Respiratory Respiration RateTidal VolumeTotal Lung VolumePulmonary Resistance

Lung VolumesLung PressuresAir FlowSubstance Volume Fractions

Pulmonary Function Test

Energy Respiratory QuotientTotal Metabolic Rate

Skin TempHeat Transfer Rate

Environment Ambient TemperatureClothing Resistance

Renal Glomerular Filtration RateUrine Specific Gravity

Renal Blood FlowBladder Substance Concentrations

Urinalysis

GI Digestion Rate Stomach Contents

Drugs & Substances Partition CoefficientsAnesthesia Level

Plasma ConcentrationTissue Concentration

Anesthesia Machine Oxygen Bottle VolumeVentilator Pressure

Vaporizer substance fractionsTube flows

Note: These are only example outputs – there are many, many more

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• Multi-Trauma, 22 y/o Male• Body Condition: Soldier• Insults: Trauma leading to massive hemorrhage, tension pneumothorax• Assessments: Bleeding rate, heart rate, blood pressure, respiration rate, O2 saturation• Interventions: Tourniquet, Needle Decompression, narcotics, fluid resuscitation

• Heat Stroke, 25 y/o Male• Body Condition: Physically fit• Insults: Strenuous work at high altitude resulting in heat stroke• Assessments: Core temperature, sweat rate, heart rate, CBC• Interventions: Active cooling, I.V. fluids

• Asthma Attack, 40 y/o Female• Body Condition: Suffers from asthma, no other known issues• Insults: Asthma attack• Assessments: Respiration rate, EtCO2, Heart rate, BP, SPO2, PFT• Interventions: Administer beta agonist

• Environment Exposure, 17 y/o Female• Body Condition: Hypothermia, variable insulation of clothing• Insults: Cold air or water exposure• Assessments: Core and peripheral temperature, Heart Rate, Respiration Rate• Interventions: Removal from environment, active heating, increase clothing

Showcase Scenarios for Combined Effects

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1. Verification: Unit tests ensure correct implementation and sound physics principles for all tools

2. System Level Validation: All major systems (cardiovascular, respiratory, blood chemistry, etc.) are validated for clinical output level data

3. Compartment Level Calibration: Individual organs (kidney, liver, etc.) or functional units (trachea, alveoli, etc.) are validated wherever possible

4. Scenario Calibration & Validation: Every insult, intervention, and assessment includes a matrix with validation data for whole body combined effects from multiple systems

5. Combined Scenario Validation: All four showcases and several other scenarios validated for combined effects – heavily leveraged SME consultants Bryan Bergeron MD and Nicholas Moss PhD

System System Parameters Compartment Parameters

Patient 17 0

Blood Chemistry 30 27

Cardiovascular 18 63

Respiratory 12 35

Energy 9 0

Renal 45 78

Major System Validation Parameter Count

Calibration and Validation

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Worked with subcontractor UNC Eshelman School of PharmacyPharmacodynamics also validated through scenario validationAll drugs validated in this manor

PK/Clearance Validation Examples

Bolus

InfusionBolus

Bolus

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Using BioGears

• Canned or Dynamic Scenarios• Training and Simulation Scenarios• Physiology and Modeling Classroom

Education• Data Analysis• Physiologic Response Scenarios

Use-Case Options

• Simulations and serious games• Manikins and task trainers• Classroom curriculum • Research• Clinical testing• Device development• Other extensions

User Types

1. Needs and Requirements Assessment2. Validation and Calibration Data Determination3. Model Design and Implementation4. Model Verification – Unit Tests to Verify Functionality5. Model Calibration – Tuning Parameters to Meet Initial Data6. Model Validation – Use of Model/Feature in Combination To Validate

Functionality

Model/Feature Development Steps

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Current:

• Bug fixing and system refinement

• Optimization and increased simulation speed

• State serialization

• Modularity (“Hack-able”)

• Fatigue

• Renal Feedback

• Calibrate cardiovascular pulmonary pressures

Near-Term:

• Acid-base balance – O2 & CO2 saturation modifications

• Total body substance balance and new substances

• Nervous system additions

• Exocrine additions

• Endocrine additions

• Vascular fluid exchange

• Pneumothorax updates

• Gastrointestinal updates

Long-Term:

• Patient modifications (age, gender, body mass, etc)

• Intoxications

• Lactic acidosis

• Airborne agents (Nerve/Pulmonary/Smoke/CO) and vaporization

• Diuretics

• More blood assessments and pulmonary function test improvment

High Level Remaining Tasks

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Questions?Contact:

Jeff Webb

[email protected]

919-582-3435

Website:

www.BioGearsEngine.com