Molecular imaging in small animals - Roles for micro-CT

X-ray micro-CT is currently used primarily to generate 3D images of micro-architecture (and the function that can be deduced from it) and the regional distribution of administered radiopaque indicators, within intact rodent organs or biopsies from large animals and humans. Current use of X-ray micro-CT can be extended in three ways to increase the quantitative imaging of molecular transport and accumulation within such specimens. (1) By use of heavy elements, other than the usual iodine, attached to molecules of interest or to surrogates for those molecules. The accumulation of the indicator in the physiological compartments, and the transport to and from such compartments, can be quantitated from the imaged spatial distribution of these contrast agents. (2) The high spatial resolution of conventional X-ray attenuation-based CT images can be used to improve the quantitative nature of radionuclide-based tomographic images (SPECT & PET) by providing correction for attenuation of the emitted gamma rays and the accurate delineation of physiological spaces known to selectively accumulate those indicators. Similarly, other imaging modalities which also localize functions in 2D images (such as histological sections subsequently obtained from the same specimen), can provide a synergistic combination with CT-based 3D microstructure. (3) By increasing the sensitivity and specificity of X-ray CT image contrast by use of methods such as: K-edge subtraction imaging, X-ray fluorescence imaging, imaging of the various types of scattered X-ray and the consequences of the change in the speed of X-rays through different tissues, such as refraction and phase shift. These other methods of X-ray imaging can increase contrast by more than an order of magnitude over that due to conventionally-used attenuation of X-ray. To fully exploit their potentials, much development of radiopaque indicators, scanner hardware and image reconstruction and analysis software will be needed.