What is the Pulse Physiology Engine?

The Pulse Physiology Engine is a C++ based, open source, multi-platform (Windows, Mac, and Linux), comprehensive human physiology simulator that will drive medical education, research, and training technologies. The engine enables accurate and consistent physiology simulation across the medical community. The engine can be used as a standalone application or integrated with simulators, sensor interfaces, and models of all fidelities. We plan to further advance the engine and explore new avenues of research, such as pediatrics, patient-specific modeling and virtual surgery planning/rehearsal.

The Pulse Physiology Engine is a fork of the BioGears Physiology Engine. This fork was driven by several community needs, including:

1. Active, Publicly Available Repository

The Pulse git repository was created with the BioGears 6.1.1 code archive. The Pulse team actively develops on this repository with contributions from other community members. The public repository provides a central location for the community to view and test active development, report issues and contribute to the Pulse Physiology Engine. This is a truly open and community-driven project.

2. Cross-Platform Build Process Improvements

Pulse has refactored the build process to require only CMake, a cross-platform family of tools designed to build, test and package software. This removes the need for any platform and compiler customized build scripts, which has greatly simplified the process for 3rd party users to build and integrate Pulse into their applications. With this change, Pulse can easily be built with the GCC, Clang, MSVC, and Ninja compilers on any of our supported platforms (Windows, Mac, Linux, and AArch64).

3. License Updates

The licensing goal of the engine is to maintain a permissive Apache 2.0 license (free to use with no restrictions) to encourage use of the open-source software in academic, government and commercial products. Several open-source libraries are used by the engine and have permissive licenses that do not affect the use of the engine in future products and applications. However, the Code Synthesis XSD GNU General Public License with FLOSS exception created a significant open-source licensing limitation, which restricts any proprietary extensions of the physiology engine.

Any use of the engine, without modification, is exempt from the GPL license and does not need to be made public (open-source). Any extensions to the engine must be made publicly available without cost, or a Proprietary License for Code Synthesis must be purchased for the product/application using the modified engine to comply with the license terms for Code Synthesis.

To resolve this license issue, Pulse has replaced the Xerces and Code Synthesis libraries with the Google Protocol Buffer library. This library is licensed under BSD 3-clause and allows anyone to modify the Pulse Physiology Engine in anyway without any requirement to make their project code base publicly available.

4. Improved Data Management and Test Suite Reporting

The provided test suite executes scenarios and compares the generated results file to the "gold standard" data file for the same scenario. Pulse removed the SMTP requirement for viewing the test report, and instead generates a summary on disk that can be viewed by a user. This change reduces the required infrastructure needed to perform unit, verification and validation testing. The set of "gold standard" data files for the physiology engine is very large (~500MB). Keeping these files in the git repository can easily bloat the repository. Pulse has addressed this issue by hosting all verification sets in a publicly available data server, associating different versions to the git repository history though a collection of hash files in the git repository. CMake is then used to provide management between the data server and the specific code version from the git repository. This separation provides a repository with a small footprint to allow for quick pulling and branching, while maintaining a historical associations with the large data set needed for testing.

What are some possible physiology engine applications?

Virtual Environments
Manikin-Based Simulations
Clinical Explorations

There is a wide range of potential applications, a few include:

  • Powering serious games for medical education and training
  • Producing responsive physiology in real time for manikin training
  • Integrating a single-system model into the engine to understand full-body physiologic response
  • Providing inputs and outputs for sensor systems
  • Teaching and education
  • Pairing with virtual surgery planning/rehearsal

What can the physiology engine do?

An instance of an engine models a single patient's physiology.

  • The patient is defined by parameters, such as height, weight, systolic and diastolic pressure.
  • You can initialize the patient with specific chronic and/or disease states via conditions.
  • You can modify the patients external environmental conditions (weather, submerge in water, etc.)
  • You can apply various actions (acute insults/injuries, interventions, conscious breathing, exercise, etc.) to be applied to the patient.
  • The patient can also interact with equipment models, such as an Anesthesia and/or an ECG Machine as well as an Inhaler via actions.
  • You can integrate the engine into your applications.

Pulse Physiology Explorer

The Pulse Physiology Engine is a powerful tool in computing the physiological responses to acute injury and treatment. However, without a visualization tool the information is difficult to understand. As part of the Kitware physiology repository, we have developed a new visualization tool built on Qt and ParaView to provide a visualization tool to use and display the data generated by the physiology engine.

For more information on getting and using this tool, visit the Explorer Wiki

What kind of data can I get from the physiology engine?

Available data is defined within the engine in three major ways:

  • System data, such as Cardiovascular, Respiratory, etc.
    • Analogous to system vitals
      • Examples: heart rate, oxygen consumption, mean arterial pressure, etc.
  • Compartment data
    • Flow, pressure, and volume related to specific region of the body or component of equipment
      • Examples: Cerebral Blood Flow, Right Lung Volume, Right Heart Pressure
    • Substance specific data related to a specific part of the body or component of equipment
      • Examples: The Extracellular concentration of succinylcholine in the brain tissue, anesthesia machine gas inlet oxygen volume fraction
  • Assessments
    • Formed at the level of a clinician's report, Intended to mimic test results
      • Example: Pulmonary Function Test

What are your models and how did you validate them?

The engine is a closed-loop whole body physiology model that combines physics-based lumped-parameter models and control system feedback mechanisms to model real-time system level physiologic behaviors. Lumped-parameter models use electrical circuit analogs to represent the major physiologic systems.

Models/results are validated using a combination of peer-reviewed publications and subject matter expertise. The validation process includes:

  • Defining key parameters for system validation
  • Performing literature reviews to gather published data in the form of waveforms, and max, min, and mean values
  • Using custom developed tools to compare data, perform analysis, and generate plots and tables of results

The primary purpose of model validation is to ensure that the model has an appropriate domain of validity given the goals of the modeling process. In the future, we plan to investigate sensitivity and uncertainty analyses to further quantify the validity of our models. We would welcome and support, in as much as we are able, any validation or uncertainty quantification effort by the community.

We provide reports for each System Methodology included in the physiology engine.
These documents cover the design, implementation, assumptions, limitations, and validation of each model.

Physiology Systems


Modeling Support

How do I integrate the physiology engine into my application?

The engine has a modular architecture to reduce costs for applications that need a physiology engine and want to develop or extend a physiology model.

This architecture contains :

We created a Software Development Kit (SDK) to help developers integrate the engine into software applications. This SDK provides pre-built libraries and headers, as well as examples of how to programmatically using the provided interfaces. The provided application programming interfaces (APIs) provide full control over the engine to execute various actions and retrieve a range of calculated physiological outputs.

How can I modify or extend the models in the physiology engine?

The engine uses an extensible architecture to promote integration with external models with varying levels of fidelity. System-level model fidelity can be increased or decreased by adding or removing nodes and sub-circuits.

All integration/extension will require a custom build of our Source Code. The Common Data Model and Software Framework provides a standard for data interchange between models. The deliberate identification of data requirements must precede any model modification or addition to determine if an extension of the Common Data Model is required. If the existing data model is sufficient to meet your modeling needs, you may be able to implement changes satisfactorily just by modifying the source code for the physiologic system of interest. If a Common Data Model extension is necessary, modification of the source code becomes more complicated. The quickest and easiest way to modify the engine to meet your needs is to work with Kitware - email: kitwa.nosp@m.re@k.nosp@m.itwar.nosp@m.e.co.nosp@m.m.

We can help with requirements definition, provide development support, and/or make modifications for you.

How do I ensure my changes/model are good?

We include scenarios and their results for verification and validation. These results provide a baseline we can use to measure deviations to results when the code is modified. As changes are implemented in the code base, we rerun all scenarios and compare the new results with baseline results to see how the implemented changes manifest in system data. Any new result that is over 2% error is marked as a failure. This data is used extensively to validate each system individually, as well as the combined effects of insults and interventions. See the Methodology Reports for more details. The scenarios output requests match the columns in the results file; we recommend that these scenarios remain unmodified.

How can I contribute to the physiology engine?

Take a look at our Contribution Guide.


Why does it take so long to initialize the physiology engine?

The engine represents a single, variable patient. Patient variability requires that the engine analyze the provided patient baseline values and stabilize the physiology to those values. This initialization can take several minutes, but once complete, the engine state can be saved to a file as protobuf binary or json. You can then load this state and instantaneously start execution of the simulation without any initialization time. Please consult the example in the SDK for how to take advantage of this feature and eliminate any initialization time in your application.

What is the fidelity of the physiology engine?

One definition of fidelity is "The degree to which a model or simulation represents the state and behavior of a real world object or the perception of a real world object, feature, condition, or chosen standard in a measurable or perceivable manner; a measure of the realism of a model or simulation [180] . " The validation documentation (in the System Methodology reports) describes how well the engine reproduces physiology at the system level. Like the human body, the engine is a self-compensating system of physiological systems with outcomes based on interventions [204] , and therefore can be considered high-fidelity.

Sometimes the word fidelity is used to refer to the spatial (anatomical) level of resolution of a model. The engine is a closed loop total body physiology model that combines physics-based lumped-parameter models and control system feedback mechanisms to model real-time system-level physiologic behaviors. Spatial resolution is limited by the lumped-parameter approach to sections of organs (what may arguably be referred to as the tissue level). However, the engine uses an extensible architecture to promote integration with external models with varying levels of fidelity (resolution or granularity). For more details, please see the recorded Committee on Credible Practice of Modeling & Simulation in Healthcare webinar.

Are there any publications related to the models that you have developed and choose to implement in the engine?

A list of publications and presentations about the engine can be found on the Publications page. Many of the physiology models in the engine are adapted or implemented directly from models described in literature. The implementation methodology is described in detail in the System Methodology and sub-system documentation, and all of the source publications are cited in the methodology reports and listed in the Bibliography. You can also find blog posts about work related to the physiology engine at https://blog.kitware.com.

What kind of uncertainty quantification do you do perform in your physiology model?

We have not performed a systematic forward propagation or inverse quantification of model uncertainty, nor have we conducted a formal sensitivity analysis. We plan to begin this type of analysis in the near future. However, we can quantify the numerical uncertainty introduced in solving the lumped-parameter fluid dynamics of the two foundation sub-models (Cardiovascular and Respiratory). The engine currently uses a bi-conjugate gradient method specific for sparse square systems (using the Eigen third party packages). This is an iterative method and we use the default tolerance for their solver, which is as close to zero as reasonable (around 1e-16).

Who is developing the physiology engine?

The community at large is contributing to the advancement of the Pulse Physiology Engine with oversight provided by Kitware, Inc..

Can I contact the physiology team to work on my current or upcoming project?

Absolutely. We always welcome new and challenging opportunities to work with research partners and sponsors. Please email us at kitwa.nosp@m.re@k.nosp@m.itwar.nosp@m.e.co.nosp@m.m.

What is the long-term plan for the physiology engine?

Our team's goal is to first and foremost develop the most advanced, open source, whole-body engine created to date. We plan to continue advancing physiologic models and incorporating state of the art models into the physiology engine to ensure we remain at the forefront of physiologic modeling research. We also plan to continue working with the user community to ensure the engine becomes the standard in physiology modeling by integrating it into a variety of applications.

Our system architecture was developed in a way that will make the system easy to extend for new models and external interfaces. The Apache 2.0 license allows for both open-source and proprietary applications to promote widespread use across government, military, academic, and commercial markets.

Is the physiology engine a game?

No, it is an series of mathematical models (engine) that can power immersive learning and serious games for medical training. The engine can provide a realistic training experience by producing real-time results to trauma and treatment. A physiology engine can enhance the user experience of applications by providing a comprehensive physiological response to insults and interventions.

Where do I log a bug for the physiology engine?

Logging bugs helps us improve the engine and we appreciate your feedback. You can report issues in gitlab.

What is your relationship with the Virtual Physiological Human (VPH) project.

The Virtual Physiological Human is a European initiative with the eventual goal of producing a complete mechanistic model of the entire human body. With the engine, we have simulated whole-body physiology with reasonable accuracy for a target population. The goal of the VPH project is individualized medical simulation. We are currently exploring expanding the physiology engine into patient-specific modeling. The engine results have been presented to the VPH community during the 2016 conference [174].

What is the advantage of the Common Data Model (CDM)?

For details about the Common Data Model, please see our Common Data Model and Software Framework documentation.

How fast does the physiology engine run? How can I make it faster?

The engine currently runs at about 5 to 10 times real time, depending on your machine's specifications. The included models and systems are included with the goal of creating the most complete engine possible. If your application does not require all of the existing models/systems, then you can strip features by modifying the source code in the same way that you would integrate a new model. Reducing the scope of the models will increase the speed of calculation.

Do you plan to provide support for interpreter-level model input, for example with the Python language?

We do not have any immediate plans to provide support for those languages. We do have support for Java. We are working towards creating a C# interface on top of our C++ interface. But feel free to report this and other feature requests as issues at gitlab.