Noninvasive in vivo imaging in animals has two useful utilities, according to University of California at Davis pathologist Alexander Borowsky, M.D., an expert in breast cancer. He makes extensive use of mouse models as a precursor to trials and therapy in humans.
“Firstly, it allows us to use one mouse as its own control, which circumvents any issues in mouse-to-mouse variability,” he explained. “Secondly, compared to other technologies, it is immediately translatable to the clinic.”
Dr. Borowsky highlighted a recent paper in PNAS in which small-animal high-resolution in vivo PET-imaging was demonstrated as a viable surrogate for more invasive standard histological measurements of tumor progression. The latter by their nature, he pointed out, cannot shed light on more subtle indices of tumor growth.
“A great innovation in this study was what we call spatial coregistration,” said Dr. Borowsky. He defined this concept as “using high-resolution histology to achieve careful, anatomically registered validation of the imaging signals.”
The technique has been combined with MRI to achieve more detailed characterization of amyloid plaques in mouse models of Alzheimer disease, which, since they contain iron, can generate confounding data in MRI studies.
Relying on this two-pronged strategy—in vivo data collection and ex vivo validation—Dr. Borowsky’s longer-term goal is to assemble a catalog of associative data that correlates histology and microanatomy with the images collected in the live animal. “This is a problematic task, particularly in cancer,” explained Dr. Borowsky.
Tumors are often a composite of many different cellular densities, angiogenic states, differentiation grades, and other variables. Dr. Borowsky is hopeful for the future, although, “it’s a matter of bringing the bioengineering behind the imaging platforms to a more sophisticated level that can address these subtleties.
“Down the road I think you’re going to see an increasing convergence between the microscope slide and what can be achieved with in vivo imaging. I see plenty of space for more molecular and physiologically-based imaging methods, particularly in the area of optical imaging, that will gradually supplant methodologies with limited resolution, such as PET.”