Small-animal molecular imaging methods.

Abstract

The ability to trace or identify specific molecules within a specific anatomic location provides insight into metabolic pathways, tissue components, and tracing of solute transport mechanisms. With the increasing use of small animals for research, such imaging must have sufficiently high spatial resolution to allow anatomic localization as well as sufficient specificity and sensitivity to provide an accurate description of the molecular distribution and concentration. Imaging methods based on electromagnetic radiation, such as PET, SPECT, MRI, and CT, are increasingly applicable because of recent advances in novel scanner hardware and image reconstruction software and the availability of novel molecules that have enhanced sensitivity in these methodologies. Small-animal PET has been advanced by the development of detector arrays that provide higher resolution and positron-emitting elements that allow new molecular tracers to be labeled. Micro-MRI has been improved in terms of spatial resolution and sensitivity through increased magnet field strength and the development of special-purpose coils and associated scan protocols. Of particular interest is the associated ability to image local mechanical function and solute transport processes, which can be directly related to the molecular information. This ability is further strengthened by the synergistic integration of PET with MRI. Micro-SPECT has been improved through the use of coded aperture imaging approaches as well as image reconstruction algorithms that can better deal with the photon-limited scan data. The limited spatial resolution can be partially overcome by integrating SPECT with CT. Micro-CT by itself provides exquisite spatial resolution of anatomy, but recent developments in high-spatial-resolution photon counting and spectrally sensitive imaging arrays, combined with x-ray optical devices, hold promise for actual molecular identification by virtue of the chemical bond lengths of molecules, especially biopolymers. Given the increasing use of small animals for evaluating new clinical imaging techniques and providing more insight into pathophysiologic phenomena as well as the availability of improved detection systems, scanning protocols, and associated software, the sensitivity and specificity of molecular imaging are increasing.