Compared to conventional x-ray tomography, early photon tomography (EPT) is not only a sensitive technique for imaging of lung tumors in living organisms, but also has the potential to reveal biochemical changes that reflect disease progression undetected by conventional x-ray imaging, according to research published online before print Nov. 17 in the Proceedings of the National Academy of Sciences.
Fluorescence can be used to analyze the regulation and expression of genes, to locate proteins in cells and tissues, to follow metabolic pathways and to study the location and migration of cells. Of particular importance is the combination of fluorescence imaging with novel techniques that allow tomographic 3D visualization of objects in living organisms.
At the Helmholtz Zentrum München – German Research Center for Environmental Health in Neuherberg, Germany, together with the Technische Universität München in München, Germany, Vasilis Ntziachristos, MD, of the Institute for Biological and Medical Imaging, said he is concerned with the development and refinement of such new technologies.
According to the authors, the quality of optical imaging in tissues is naturally limited, since beyond a penetration depth of a few hundred micrometers the photons are massively scattered due to interactions with cell membranes and organelles which results in blurred images.
Ntziachristos, together with colleagues from the Harvard Medical School and the Massachusetts General Hospital in Boston, imaged lung tumors in living mice. They injected a substance into the animals that normally does not fluoresce, but becomes fluorescent after contact with certain cysteine proteases such as cathepsins. The amount of these proteases is enriched in lung tumors, which allow fluorescence imaging of the tumor tissue, according to the authors.
They found that, compared to continuous illumination measurements a combination of the less scattered photons with 360-degree illumination-detection resulted in sharper and more accurate images of mice under investigation.
While early-photons are typically associated with reduced signal available for image formation, the authors said that due to the wide-field implementation, EPT operates with very small reduction in average signal strength as in conventional tomographic methods operating using continuous light illumination. In this respect EPT is a practical method for significantly improving the performance of fluorescence tomography in animals over existing implementations, the researchers concluded.
“At present EPT is practicable only with small animals, but further development of the equipment can allow niche applications of the technique also with larger organisms including humans,” Ntziachristos and colleagues noted.