Randall Britten

The Cardiac Atlas Project—an imaging database for computational modeling and statistical atlases of the heart

Motivation: Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape and wall motion and characterize cardiac function among and within population groups. Results: Three main open-source software components were developed: (i) a database with web-interface; (ii) a modeling client for 3D + time visualization and parametric description of shape and motion; and (iii) open data formats for semantic characterization of models and annotations. The database was implemented using a three-tier architecture utilizing MySQL, JBoss and Dcm4chee, in compliance with the DICOM standard to provide compatibility with existing clinical networks and devices. Parts of Dcm4chee were extended to access image specific attributes as search parameters. To date, approximately 3000 de-identified cardiac imaging examinations are available in the database. All software components developed by the CAP are open source and are freely available under the Mozilla Public License Version 1.1 (http://www.mozilla.org/MPL/MPL-1.1.txt). Availability: http://www.cardiacatlas.org Contact: a.young@auckland.ac.nz Supplementary information: Supplementary data are available at Bioinformatics online.

Minimum Information About a Simulation Experiment (MIASE).

Reproducibility of experiments is a basic requirement for science. Minimum Information (MI) guidelines have proved a helpful means of enabling reuse of existing work in modern biology. The Minimum Information Required in the Annotation of Models (MIRIAM) guidelines promote the exchange and reuse of biochemical computational models. However, information about a model alone is not sufficient to enable its efficient reuse in a computational setting. Advanced numerical algorithms and complex modeling workflows used in modern computational biology make reproduction of simulations difficult. It is therefore essential to define the core information necessary to perform simulations of those models. The Minimum Information About a Simulation Experiment (MIASE, Glossary in Box 1) describes the minimal set of information that must be provided to make the description of a simulation experiment available to others. It includes the list of models to use and their modifications, all the simulation procedures to apply and in which order, the processing of the raw numerical results, and the description of the final output. MIASE allows for the reproduction of any simulation experiment. The provision of this information, along with a set of required models, guarantees that the simulation experiment represents the intention of the original authors. Following MIASE guidelines will thus improve the quality of scientific reporting, and will also allow collaborative, more distributed efforts in computational modeling and simulation of biological processes.

The Physiome Model Repository 2

MOTIVATION The Physiome Model Repository 2 (PMR2) software was created as part of the IUPS Physiome Project (Hunter and Borg, 2003), and today it serves as the foundation for the CellML model repository. Key advantages brought to the end user by PMR2 include: facilities for model exchange, enhanced collaboration and a detailed change history for each model. AVAILABILITY PMR2 is available under an open source license at http://www.cellml.org/tools/pmr/; a fully functional instance of this software can be accessed at http://models.physiomeproject.org/.

OpenCMISS: A multi-physics & multi-scale computational infrastructure for the VPH/Physiome project

The VPH/Physiome Project is developing the model encoding standards CellML (cellml.org) and FieldML (fieldml.org) as well as web-accessible model repositories based on these standards (models.physiome.org). Freely available open source computational modelling software is also being developed to solve the partial differential equations described by the models and to visualise results. The OpenCMISS code (opencmiss.org), described here, has been developed by the authors over the last six years to replace the CMISS code that has supported a number of organ system Physiome projects. OpenCMISS is designed to encompass multiple sets of physical equations and to link subcellular and tissue-level biophysical processes into organ-level processes. In the Heart Physiome project, for example, the large deformation mechanics of the myocardial wall need to be coupled to both ventricular flow and embedded coronary flow, and the reaction-diffusion equations that govern the propagation of electrical waves through myocardial tissue need to be coupled with equations that describe the ion channel currents that flow through the cardiac cell membranes. In this paper we discuss the design principles and distributed memory architecture behind the OpenCMISS code. We also discuss the design of the interfaces that link the sets of physical equations across common boundaries (such as fluid-structure coupling), or between spatial fields over the same domain (such as coupled electromechanics), and the concepts behind CellML and FieldML that are embodied in the OpenCMISS data structures. We show how all of these provide a flexible infrastructure for combining models developed across the VPH/Physiome community.

An overview of the CellML API and its implementation

BackgroundCellML is an XML based language for representing mathematical models, in a machine-independent form which is suitable for their exchange between different authors, and for archival in a model repository. Allowing for the exchange and archival of models in a computer readable form is a key strategic goal in bioinformatics, because of the associated improvements in scientific record accuracy, the faster iterative process of scientific development, and the ability to combine models into large integrative models.However, for CellML models to be useful, tools which can process them correctly are needed. Due to some of the more complex features present in CellML models, such as imports, developing code ab initio to correctly process models can be an onerous task. For this reason, there is a clear and pressing need for an application programming interface (API), and a good implementation of that API, upon which tools can base their support for CellML.ResultsWe developed an API which allows the information in CellML models to be retrieved and/or modified. We also developed a series of optional extension APIs, for tasks such as simplifying the handling of connections between variables, dealing with physical units, validating models, and translating models into different procedural languages.We have also provided a Free/Open Source implementation of this application programming interface, optimised to achieve good performance.ConclusionsTools have been developed using the API which are mature enough for widespread use. The API has the potential to accelerate the development of additional tools capable of processing CellML, and ultimately lead to an increased level of sharing of mathematical model descriptions.

CellML metadata standards, associated tools and repositories

The development of standards for encoding mathematical models is an important component of model building and model sharing among scientists interested in understanding multi-scale physiological processes. CellML provides such a standard, particularly for models based on biophysical mechanisms, and a substantial number of models are now available in the CellML Model Repository. However, there is an urgent need to extend the current CellML metadata standard to provide biological and biophysical annotation of the models in order to facilitate model sharing, automated model reduction and connection to biological databases. This paper gives a broad overview of a number of new developments on CellML metadata and provides links to further methodological details available from the CellML website.

Sharing and reusing cardiovascular anatomical models over the Web: a step towards the implementation of the virtual physiological human project.

Sharing and reusing anatomical models over the Web offers a significant opportunity to progress the investigation of cardiovascular diseases. However, the current sharing methodology suffers from the limitations of static model delivery (i.e. embedding static links to the models within Web pages) and of a disaggregated view of the model metadata produced by publications and cardiac simulations in isolation. In the context of euHeart—a research project targeting the description and representation of cardiovascular models for disease diagnosis and treatment purposes—we aim to overcome the above limitations with the introduction of euHeartDB, a Web-enabled database for anatomical models of the heart. The database implements a dynamic sharing methodology by managing data access and by tracing all applications. In addition to this, euHeartDB establishes a knowledge link with the physiome model repository by linking geometries to CellML models embedded in the simulation of cardiac behaviour. Furthermore, euHeartDB uses the exFormat—a preliminary version of the interoperable FieldML data format—to effectively promote reuse of anatomical models, and currently incorporates Continuum Mechanics, Image Analysis, Signal Processing and System Identification Graphical User Interface (CMGUI), a rendering engine, to provide three-dimensional graphical views of the models populating the database. Currently, euHeartDB stores 11 cardiac geometries developed within the euHeart project consortium.

FieldML, a proposed open standard for the Physiome project for mathematical model representation

The FieldML project has made significant progress towards the goal of addressing the need to have open standards and open source software for representing finite element method (FEM) models and, more generally, multivariate field models, such as many of the models that are core to the euHeart project and the Physiome project. FieldML version 0.5 is the most recently released format from the FieldML project. It is an XML format that already has sufficient capability to represent the majority of euHeart’s explicit models such as the anatomical FEM models and simulation solution fields. The details of FieldML version 0.5 are presented, as well as its limitations and some discussion of the progress being made to address these limitations.

The VPH-Physiome Project: Standards, tools and databases for multi-scale physiological modelling

The VPH/Physiome project is developing tools and model databases for computational physiology based on three primary model encoding standards: CellML, SBML and FieldML. For the modelling community these standards are the equivalent of the DICOM standard for the clinical imaging community and it is important that the tools adhere to these standards to ensure that models from different groups can be curated, annotated, reused and combined. This chapter discusses the development and use of the VPH/Physiome standards, tools and databases, and also discusses the minimum information standards and ontology-based metadata standards that are complementary to the markup language standards. Data standards are not as well developed as the model encoding standards (with the DICOM standard for medical image encoding being the outstanding exception) but one new data standard being developed as part of the VPH/Physiome suite is BioSignalML and this is described here also. The PMR2 (Physiome Model Repository 2) database for CellML and FieldML files is also described, together with the Application Programming Interfaces (APIs) that facilitate access to the models from the visualization (cmgui and GIMIAS) or computational (OpenCMISS, OpenCell/OpenCOR and other) software.

The cardiac atlas project: development of a framework integrating cardiac images and models

We describe the software design, architecture and infrastructure employed in the Cardiac Atlas Project (CAP), an international collaboration to establish a web-accessible structural and functional atlas of the normal and pathological heart. Cardiac imaging data is de-identified in a HIPAA compliant manner using the LONI Debabeler with customized DICOM mappings. A production database and web-interface were employed based on existing tools developed by LONI. A new open-source database and web interface have been developed for research purposes. After consideration and evaluation of several software frameworks, the research database has been implemented based on a 3-tier architecture utilizing MySQL, JBoss and Dcm4chee. Parts of Dcm4chee have been extended to enable access to MRI specific attributes and arbitrary search parameters. An XML schema has been designed representing the elements associated with the creation and curation of volumetric shape models. The research database is implemented compliant to the DICOM standard, thus providing compatibility with existing clinical networks and devices. A modeling tool, the CAP client, has been developed to enable browsing of 3D image data and creation and modification of volumetric shape models. All software components developed by the CAP are open source and are freely available under the Mozilla license.