Bioimaging of Laboratory Animals: The Visual Translation of Molecular Insights

ADepartment of Energy report released in 1987 stated in a visionary prediction that “Knowledge of the human genome is as necessary to the continuing progress of medicine and other health sciences as knowledge of human anatomy has been for the present state of medicine” (Barnhart 1989). The pursuit of this knowledge has marked an era of rapid genomics-based discovery that continues to yield unique insights into connections between disease and molecular factors. One key method for transforming these initial insights into direct evidence of disease pathogenesis is molecular imaging. Imaging techniques that have been customized for laboratory animals provide scientists with the unprecedented ability to link detailed molecular understanding with the complexity of whole organism physiological responses and anatomical detail. The advancement of knowledge derived from the mammalian genome is likely to depend on the context provided by the unique blending of our knowledge of anatomy with the translational application of imaging technology. The primary objective of this ILAR Journal issue focused on laboratory animal imaging is to provide readers with a compendium of reviews that describe the methods, the limitations, and a few examples of the most common applications of small animal imaging to human disease. Because most disease processes are dynamic, there are inherent limitations to using static tissue-based techniques to study dynamic processes. Among these is that a large number of animals is needed for every experiment to enable the processing of tissue at given time points of interest, and histopathological examination of these tissues using standard microscopy is a daunting task. In addition, there is a degree of variability introduced when the control level of a factor is determined by comparing different animals instead of using each animal as its own control. Experimental designs of longitudinal studies pose particular limitations because a certain degree of understanding about the kinetics of a disease process is critical to the appropriate timing of tissue collections. The imaging modalities available for use with laboratory animals provide a means to explore the molecular mechanism of several diseases, minimize many of the limitations of static tissue-based techniques, and, most importantly, decrease the numbers of animals required. In fact, depending on the application, it is possible to reduce the number of animals required per study by as much as 80% to 90%. This feature is noteworthy because, perhaps unique to the ILAR Journal, there is an intentional effort to publish reviews that include considerations specifically relevant to animal care and use. The first article, by Brenda Klaunberg and Judith Davis, presents an overview of key considerations for laboratory animal imaging center design. This review not only is relevant to readers considering new facility design but also can provide a series of quick checks for existing centers as well as strategies for improvement. Contributing authors Isabel Hildebrandt, Helen Su, and Wolfgang Weber then discuss anesthesia for in vivo imaging of small animals in the context of how animal preparation differs among imaging modalities, and how the imaging procedures themselves can affect animal physiology. A general overview of practical considerations in rodent cardiac imaging is provided by Kennita Johnson as a segue to detailed reviews of specific imaging techniques. This article is a good source of baseline information about the particular challenges of cardiac imaging. The contributions of imaging technology to the biomedical sciences are incontrovertible. In fact, one has only to list the number of Nobel prizes awarded to scientists in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) to appreciate the importance and recognition this field has received. These include the 2003 Nobel Prize for Physiology and Medicine awarded to Paul Lauterbur and Peter Mansfield for the development of MRI. Earlier NMRrelated Nobel Prizes were awarded for Chemistry (Kurt Wuthrich in 2002, Richard R. Ernst in 1991) and Physics (Felix Bloch and Edward M. Purcell in 1952 and Isidor I. Rabi in 1944; http://nobelprize.org). The first manuscript describing the MRI of a rat was published almost 25 years ago, and the technique continues to evolve and expand the scientific advances made possible Myrtle A. Davis, DVM, PhD, is a Research Advisor in Toxicology, Drug Disposition, and Pharmacokinetics at Lilly Research Laboratories in Greenfield, Indiana. Address correspondence and reprint requests to Dr. Myrtle Davis, Toxicology, Drug Disposition, and Pharmacokinetics, Lilly Research Laboratories, 2001 W. Main Street, Greenfield, IN 46140 or email davisma@lilly.com.