Imaging the body's activities
Using powerful microscopes, scientists can view the molecules of matter right in their own labs. But several UW-Madison biomedical engineering researchers are working on ways to improve both the biological understanding and imaging techniques that could enable doctors to view cellular activities deep within the human body in real time.
Biomedical Engineering Assistant Professor Nimmi Ramanujam and Pharmacology Assistant Professor Patricia Keely are studying how mammary tumor cells interact with collagen, a protein across which they migrate when cancer cells metastasize. Using an argon laser and charge-coupled device, or CCD-based detection system, the two are simultaneously imaging mammary tumor cells and collagen in mouse and rat models, and tracking the cells' interaction with collagen. "We hope this leads to a better understanding of how collagen affects mammary-cell migration and behavior, which could ultimately be important to understanding tumor progression or metastasis," says Keely.
The project is just one of several under a $1.2 million National Cancer Institute grant that's funding collaborations between biologists and imagers here on campus. Thomas Grist, professor of biomedical engineering and radiology, is the project's principal investigator. "Our goal is to set up a framework and the infrastructure so that these collaborations start happening on a routine basis and we can provide imaging capabilities to biologists who have specific questions that might be answered by imaging," he says. At the same time, he hopes the interactions will yield advancements in technologies such as magnetic resonance imaging (MRI) or positron emission tomography.
An imager himself, Grist is working with Marek Malecki, a visiting professor of animal science, to develop a contrast agent that will work with MRI. Malecki is bioengineering antibodies or parts of antibodies that can target certain molecules or cells in the body. "And it's a combination of understanding the imaging, but also understanding how to clone these small antibody fragments," says Grist. "They're basically bioengineered — they're not made in a chemistry lab."
Biomedical Engineering Assistant Professor Walter Block (also medical physics) is part of a team hoping to develop MRI strategies with the speed and coverage of computed tomography. Because of the time it takes to acquire a magnetic resonance image, he says, MRI traditionally has imaged static structures such as the brain, knee or spine. As faster, more powerful methods are developed, MRI can image moving structures, such as the heart and abdomen, with thin slices prescribed at the regions of interest.
Block's group, which includes Biomedical Engineering Professor Charles Mistretta (also medical physics and radiology) and Radiology and Neurological Surgery Professor Howard Rowley, is focusing on imaging large, three-dimensional volumes, or stacks of two-dimensional cross-sections, that cover broad regions of the body, similar to a CT scan. "Improving on CT, however," he says, "the MR data can be processed to show several time-resolved imaging volumes due to a different acquisition paradigm."
The result is simpler, enhanced capabilities for showing both blood-flow patterns and blood-vessel pathology with contrast-enhanced magnetic resonance angiography. Block's group also is working on non-contrast-enhanced angiography.
While the grant's main purpose is to increase understanding biology and imaging as they relate to cancer, Grist says findings could apply to other areas, including cardiovascular diseases. The key is that both analysis and imaging will be conducted in vivo, or within the body in real time. "In terms of medical imaging, this is going to be the frontier," he says. "I'd say this century will be the century of developing tools to understand what's happening on a molecular basis."