About 250,000 Americans a year die of coronary heart disease without being hospitalized, and most of these are sudden deaths caused by cardiac arrest. Due to similarities of cardiovascular physiology and genetic structure to humans, biomedical research has increasingly employed the mouse in models of human disease, which has provided powerful tools for investigating the effects of genes and their mutations on cardiovascular disease and for developing interventions to manage the disease. The electrocardiogram (ECG) has been used in the mouse as a noninvasive imaging tool for monitoring the function of the heart and screening for abnormal heartbeats. However, presently it is difficult to noninvasively screen the ECG of various mouse models in ways that are safe, repeatable, practical, or cost effective. Therefore, progress is needed to improve the throughput of cardiac electrical imaging and to improve handling of small animals during imaging. Similar to the ECG, magnetocardiography (MCG) is a noninvasive imaging technique that allows recording of cardiac electrical activity, but by noncontact sensing of very weak magnetic fields emitted by the heart from small currents produced by the heart cells. Therefore, the overall goal of our research is to build an MCG system that allows noninvasive, safe, and rapid screening of the electrical activity of the heart in conscious small animals such as mice. This Phase I STTR application will establish the scientific/technical merits through the following specific aims: (1) build a prototype MCG system to determine the feasibility of noninvasive, noncontact, real-time monitoring of cardiac electrical activity in mice; (2) test the MCG system on mice under various physical and physiological conditions and validate the electrical activity recorded by MCG with simultaneously recorded ECG; and (3) apply offline numeric methods to the mouse MCG to determine the frequency content of recorded signals, examine filters that improve the signal-to-noise relationship, and ascertain components of cardiac electrical activity. Advantages of the proposed MCG technique include: (1) noninvasive, as nothing touches the mouse and no surgical techniques are required; (2) noncontact, since skin preparation and body surface electrodes are not needed; (3) low risk, for improving animal handling and maintenance during imaging; (4) safe, where no objects or radiation enter the body; (5) fast, as mass recording can be performed on conscious mice and no sedation is required; and (6) practical, where repeat serial imaging can be conducted in longitudinal studies from birth to adulthood. In line with the program announcement, the proposed approach can make small animal imaging technology more accessible to molecular biologists and pharmaceutical scientists desiring to use animal models as tools for biomedical research and drug discovery, which in turn will improve the benefit-risk and benefit-cost relationships of patient care.
