Structural and Functional Biological Mapping Projects
The determination of the human genome sequence represents a major achievement of collaborative science, involving expertise from molecular biology, biotechnology, computer science and mathematics. All of these disciplines have benefited from the Human Genome Project, even though it was essentially a data collection exercise without an overarching driving hypothesis. In order to fully exploit this information, and extend these collaborations to the logical next step, many groups have begun to construct physiological databases, linked with anatomical, functional and clinical data gleaned from a variety of sources. This information must be integrated across many scales, from molecular interactions to organ system function. There have been several initiatives begun in this endeavor, centered on different organ systems and pathology targets. Projects pertinent to this application include the Integrative Biology Project, the ECG signal database, the Cardiac Gene Expression database, the Medical Image File Archive Project, anatomical ontology databases, the Foundational Model of Anatomy, Informatics for Integrating Biology and the Bedside, and the Physiome Project.
The current CAP proposal will facilitate collaboration between the ABI Physiome Project and the CCB Computational Brain Atlas research programs (cardiac modeling and brain mapping), will further combine common objectives and strategies, and will develop common infrastructural tools for the construction and exploitation of physiological and pathological databases of structure and function. The CAP database will be initially populated from clinical cardiac MRI, derived functional analyses and associated clinical data.
Cardiac MRI
CMR imaging provides an abundant source of detailed, quantitative data on heart structure and function. Advantages of CMR include its non-invasive nature, well tolerated and safe (non-ionising) procedures, ability to modulate contrast in response to several mechanisms, and ability to provide high quality functional information in any plane and any direction. Its three-dimensional (3D) tomographic nature allows excellent views of the entire heart, irrespective of cardiac orientation and cardiac chamber shape. CMR imaging has provided detailed information on 3D ventricular shape and geometry, regional systolic and diastolic strain, material microstructure, blood flow, perfusion and viability. It is considered the most accurate method to measure ventricular volumes and systolic function. The high precision and accuracy of CMR has led to its increasing application worldwide in cardiac research trials and clinical practice.
More and more observational studies and clinical trials are now utilizing CMR. Unfortunately, the information obtained in these studies (at considerable expense and effort) is typically applied only to local study endpoints and no systematic attempt has been made to make these data available for wider research purposes. The CAP will establish a global database of CMR examinations, derived from public good funded studies, clinical trials and contributing centers around the world. This will establish standardized ranges of cardiac structure and function on a regional basis, and provide a valuable resource for the evaluation of morphological and functional variation in patient subgroups.
Mathematical Characterization of Cardiac Structure and Function
Model-based image analysis procedures provide a powerful mechanism for the fast, accurate assessment of CMR data, and facilitate biophysical analyses and standardized functional mapping procedures. Since the mathematical models employed for motion analysis are registered to the anatomy of the heart, they can be used to derive statistical descriptions of characteristic patterns of regional wall motion in health and disease. This leads to the identification of differences in the characteristic pattern of regional heart wall motion between disease or treatment groups.
