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.”
While MRI, PET, and x-ray are well-established types of in vivo imaging that offer the most clinical translational opportunities in preclinical models and patient imaging, optical imaging is gaining in importance. The IVIS platform initially developed by Caliper Life Sciences, which was recently acquired by PerkinElmer, takes advantage of fluorescent and bioluminescent reporters to facilitate noninvasive longitudinal monitoring of a variety of processes in living animals, including cellular trafficking and disease expression.
“Caliper’s platform is applicable to a variety of therapeutic contexts, such as oncology, inflammation and metabolic disease, neuroscience and stem cell biology,” maintained Anna Christensen, product manager, life sciences and technology at PerkinElmer.
The IVIS optical platform has grown to incorporate multispectral fluorescence imaging, 3-D tomography, fast kinetic imaging, integrated x-ray, and microCT.
“Quantum FX microCT is a dedicated high-resolution longitudinal imaging platform for CT-focused applications and offers seamless co-registration with functional optical datasets,” added Christensen.
On the translational side, the IVIS platform has already been leveraged in the progression of over 15 drugs into the clinic with many more in development, continued Christensen.
“Optical imaging is quickly gaining acceptance within the clinic as a diagnostic tool for biopsy profiling and margin identification of resected tumors,” she observed.
“Image-guided optical imaging can help surgeons not only define cleaner tumor margins intra-operatively, but identify metastatic lesions not visible with the naked eye all within the same surgical procedure.”