Monitoring left ventricular function in small animals

Small animals such as mice and rats are extensively used to investigate the mechanisms and treatment of human cardiac diseases in vivo. The monitoring of left ventricular function is a key factor in this research. The measurement should be rapid, reproducible, and repeatable and allow the detection of subtle differences in function. Currently, echocardiography is most widely used in cardiac research laboratories for measuring left ventricular dimensions and function in small animals. Although the technique is rapid, the reproducibility of the calculations of left ventricular volumes is limited in some circumstances as a result of assumptions that do not necessarily hold true, such as in the setting of dilated, failing ventricles.

Introduction

Molecular and cellular studies of cardiac disease eventually must test their findings in vivo. Whereas nematodes, Drosophila, and zebra fish can be useful for some experimental studies, mammalian models are preferred for translation to human disease. Here, small animals like mice and rats are favored because they are easy to handle and relatively inexpensive and they have a relatively short reproductive cycle. A large number of cardiac diseases have already been modeled in rodents via microsurgical or pharmacologic interventions. However, with advances in the production of transgenic mice and, more recently, rats, we can expect tremendous growth in the use of these small animals for studying cardiac disease in the future. In many cases the specific biologic question is best answered by use of in vivo cardiovascular molecular imaging techniques (eg, measuring transgene expression or cell tracking). Measurements of cardiac function have historically been made by use of either ex vivo perfused heart preparations or highly invasive in vivo techniques that require euthanizing the animal at the end of the study. However, there is an increasing need for high-throughput noninvasive monitoring of global and regional LV function in small animals. The ability to make these measurements accurately and reproducibly is an important challenge in cardiac imaging research in which nuclear techniques may play a very important role.

In patients LV function can be measured noninvasively via echocardiography, magnetic resonance imaging (MRI), equilibrium radionuclide angiography, myocardial perfusion gated SPECT, or even positron emission tomography (PET). These same imaging techniques can be applied to small animals. Clinical systems have been adapted to accommodate rodents, and dedicated imaging systems are becoming commercially available. This article will review the current status of these various imaging modalities in measuring LV function in small animals, with a more detailed description of the recent developments in nuclear techniques.