Small Animal in Vivo Imaging System

Small-animal imaging is a valuable tool to investigate new drugs and validate their potential in vivo. CT and MRI are good methods for anatomical and functional imaging, but can not be reliably used for molecular imaging since they require potentially pharmacologically active doses of drugs. Optical methods of imaging can be performed at the tracer level using bioluminescence and fluorescent imaging techniques, but they can only yield planar images which can not give quantitative data. Small-animal imaging with PET and SPECT permits the noninvasive study of novel drugs as well as their effects in animals over substantial periods of time. The methods are directly transferable into the clinic and offer a rapid and cost effective way to develop new therapeutic strategies.

Small animal imaging has many significant advantages: longitudinal studies in the same animal, ability to noninvasively visualize anatomic and physiologic alterations, multiple imaging contrast levels, ability to collect a full three-dimensional data set, and potential for fusing images from multiple imaging modalities.

The special on small animal imaging by high-resolution PET presents the physics of gas chamber detection and the potential reemergence of gas detector systems for small animal studies at 1 mm resolution with appropriate references to other PET animal imaging systems, including PET/CT and PET/MRI. While larger animals have been studied on human imaging systems, dedicated imaging devices with spatial resolutions in the range of millimeters and below are required for small animals such as rats and mice. PET technology of this chapter is based on multiwire proportional chamber (MWPC) detectors. Important aspects of using animal models will be discussed, and specific applications of small animal imaging techniques in the diagnosis of cardiovascular, oncological, and neurological diseases are valuable examples.

The remarkable efforts that are made on molecular imaging technologies demonstrate its potential importance and range of applications. The generation of disease-specific animal models, and the developments of target-specific probes and genetically encoded reporters are another important component. Continued improvements in the instrumentation, the identification of novel targets and genes, and the availability of improved imaging probes should be made. Multimodal imaging probes should provide easier transitions between laboratory studies, including small animal studies and clinical applications. Here, we reviewed basic strategies of noninvasive in vivo imaging methods in small animals to introducing the concept of molecular imaging.

Recent advances in molecular imaging allow us to visualize both cellular and subcellular processes within living subjects at the molecular level as well as at the anatomic level. Molecular imaging is moleculargenetic imaging for visualizing cellular processes by combination of molecular biology and biomedical imaging. This marvelous technique provides research attention not only in molecular cell biology but also in related fields. Remarkable improvement of molecular imaging was achieved in visualization, characterization, and quantification of biologic processes by integration of many different fields such as genetics, pharmacology, chemistry, physics, engineering, and medicine. In particular, the development of controlled gene delivery and gene expression vector systems promotes generation of various types of reporter genes for visualization, for example, chloramphenicol acetyltransferase, b-galactosidase, luciferases, and fluorescent proteins.

Conventionally, a recombinant plasmid, which contains a target gene and a reporter gene, has been used to monitor target gene expression by assaying reporter gene expression. However, this method cannot be used directly in living animals because the invariable light intensity from reporter proteins was not enough to be visualized in animals for non-invasive imaging. Different strategies are required for monitoring gene expression in vivo imaging. Accumulation of specific imaging signal for amplifying its intensity makes it possible to visualize localization, quantification, and repetitive determination of gene expression in vivo noninvasive imaging. More effective strategies have been tried to overcome the obstacles for monitoring gene expression in vivo by recruiting methods from radio-pharmaceutics and physics. Radiolabeled small compounds and paramagnetic probes were developed for imaging specific proteins and magnetic signals, accelerating non-invasive molecular imaging technology.