Share thisLaboratory animal researchers increasingly rely on non-invasive in vivo imaging systems to characterize and analyze animal models.
Every major clinical imaging modality now has a laboratory animal specific counterpart, and researchers are beginning to use imaging systems as primary tools for a range of applications including determining pharmaceutical efficacy of new compounds, characterizing disease model pathology, studying gene function, and screening for phenotypes.
An important subset of the available preclinical imaging systems relies on energetic photons (gamma rays or x-rays) to build three dimensional maps of anatomy or radioactive tracer compound distributions. These instruments employ position-sensitive radiation detectors to determine the paths of x-rays or gamma rays emitted by or passing through the animal under test and use computer programs to generate 3D image data. Three of these imaging systems, x-ray computed tomography (CT), single photon computed tomography (SPECT) and positron emission tomography (PET), are reviewed here and representative images are presented.
X-ray Computed Tomography (CT)
Micro x-ray computed tomography (microCT) systems are functionally similar to clinical x-ray computed tomography (CT) systems and are used to generate high resolution images of the laboratory animal anatomy. MicroCT systems generate images of live animals with resolutions ranging from less than 20 microns to 100 microns and scan times ranging from a few minutes to thirty minutes. A commercially available microCT system and a schematic drawing of the key elements are shown in Figure 1, where the key components are an x-ray source, a 2D x-ray detector, and a mechanism to rotate the source and detector around the animal.
During an imaging session, the microCT system acquires a series of 2D x-ray images as the x-ray source and detector rotate 360 degrees around the animal. Each 2D image is called a projection. The projections are then transferred to a high-speed computer which calculates, or reconstructs, a 3D image of the animal. The gray-scale values in the reconstructed image are proportional to the rate of x-ray absorption in the tissue. High density tissue, such as bone, readily absorbs x-rays and appears as bright structure in the image while low density tissue, such as fat, absorbs fewer x-rays and appears as darker structure in the image. The image gray-scale values are typically reported as “Hounsfield Units,” where air has a value of -1000, water has a value of 0 and bone has values of greater than 1000. Figure 2 shows a typical 2D projection acquired during a microCT study of a mouse and a reconstructed 3D microCT image. Most commercially available microCT systems are controlled via graphical user interfaces running on a Microsoft WindowsTM workstation. The systems are easy to use and require relatively little infrastructure aside from a laboratory computer network. They are often an excellent entry point for researchers seeking to add in vivo imaging to their laboratory animal research program.
Animal Preparation
During a scan, animals are typically anesthetized using a vapor such as isoflurane or an injectable compound such as ketamine/xylazine. Animals are typically positioned on the bed using adhesive tape or an elastic gauze, and frequently the animal temperature, respiration, and heart rate are monitored during the scan. In some cases, the image acquisition is synchronized with the respiratory cycle to minimize motion blur. Video cameras are also sometimes included with the scanner to monitor the animal during the study.
Contrast agents are frequently employed to improve the contrast of a specific organ of interest (Figure 3). The most widely used agents are water-soluble iodinated compounds such as those used in clinical studies. These compounds are typically administered via IP injection and are used to help delineate abdominal organs. Barium-based oral contrast agents are also frequently used to improve contrast in the GI tract, and newly available vascular and liver contrast agents designed specifically for laboratory animal research are gaining acceptance.
Representative Studies
Perhaps the two most important areas of research using microCT are oncology and bone research. In oncology studies, microCT is used to identify the presence of solid tumors and to measure the volume of those tumors. Because microCT is non-invasive, tumor development may be monitored at multiple time points over the course of an experimental therapeutic intervention.