Using a new highly sensitive imaging process, researchers have identified two adrenaline tumors in a live mouse. The process, called bioluminescence tomography (BLT), was invented by Virginia Tech professor Ge Wang and his colleagues. “Adrenaline tumors are just one example of a tumor and our non-invasive technology can be used to study all types of tumors,” Wang said.

Wang, the Samuel Reynolds Pritchard Professor of Engineering, is a member of Virginia Tech’s School of Biomedical Engineering and Science (SBES), part of the Virginia Tech Institute for Critical Technology and Applied Science (ICTAS).

BLT imaging uses luciferase enzymes for the in vivo mapping of specifically tagged cells in living, small animals, especially mice. After the substance luciferin is injected into an animal, the tagged cells emit photons in a spectral range around the infrared region, “quite like fireflies we see in the summer,” Wang explained.

These types of photons can penetrate biological tissues by a few centimeters and be detected by a cooled charge-coupled device (CCD) based camera. BLT imaging represents an emerging concept for molecular imaging, and it has several unique advantages. For example, it produces much more sensitive, specific images of gene expressions than conventional methods do, which include x-ray computed tomography and magnetic resonance imaging.

Wang and his research group invented BLT in 2002. In 2004, he and his collaborators wrote the first paper on BLT, and today more than 10 groups worldwide are actively working in this new area. Wang relocated last year from the University of Iowa to Virginia Tech to lead the university’s biomedical imaging division.

“The introduction of BLT relative to planar bioluminescent imaging can be compared to the development of x-ray computed tomography (CT) based on radiography," Wang said. "Without BLT, bioluminescent imaging is basically qualitative. With BLT, quantitative and three-dimensional analyses on bioluminescent molecular probes become feasible inside a living mouse.”

BLT is a high-tech procedure. In contrast to the straight-ray imaging modalities like x-ray computed tomography, bioluminescence imaging is typically diffusion dominated. The system involves complex hardware design, in vivo mouse modeling, and sophisticated reconstruction methodology.

Wang’s group is currently developing a second-generation BLT system that can simultaneously collect diffused photons of different colors on the body surface of a mouse through customized optical paths. Also, the system may use the mechanism of temperature modulation to improve the BLT reconstruction.

According to the National Institutes of Health (NIH) Roadmap, optical molecular imaging plays an instrumental role in the development of medicine. Great efforts, including those with bioluminescence imaging techniques, are being made to understand the link between genes and phenotypic expressions under normal and disease conditions. Bioluminescence imaging of genetic signatures, specific proteins, and biological pathways may contribute to the development of predictive, preventive, and personalized medicine by facilitating disease diagnosis, therapy monitoring, and drug development in small animal models of human diseases.

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