When the call went out last year for seed proposals aimed at developing a possible new research initiative at the Beckman Institute, three of the 11 proposals selected for funding involved biological imaging.
A long list of Beckman faculty members and colleagues from outside the Institute proposed projects that involve using bioimaging for advancing medical research in the areas of breast cancer, speech birth defects, and targeted delivery of drugs and other agents at the molecular level.
The growing interest in bioimaging and biological engineering for medical and other scientific uses can be measured by the goals of funding agencies and through the use of various imaging modalities, including magnetic resonance imaging, optical imaging, and ultrasound imaging by researchers from an increasing number of disciplines. The magnets at Beckman’s own Biomedical Imaging Center, for example, have been used in expected ways such as neuroscientists imaging the brain, and in surprising fashion, like engineers imaging microfluidic flow. Bioimaging is one of four cornerstone research lines at the recently created Department of Bioengineering at the University of Illinois at Urbana-Champaign.
If a new Beckman Institute research initiative were added within the near future, bioimaging would seem to be a likely candidate. Beckman Director Pierre Wiltzius said discussion of a new research initiative is still a few months off, but added that bioimaging would be a natural fit.
“For the Beckman Institute this is a very natural area for us to be in because that is the interface where we want to be at, between the physical sciences and the life sciences, biological sciences, and social sciences,” Wiltzius said. “Where it gets interesting in the context of the Beckman Institute being driven by interdisciplinary research is that bioimaging in itself can also be interdisciplinary, or multimodal, with many different techniques applied at the same time. That is something that is very much by nature a Beckman-like topic.”
Wiltzius said there are a couple of reasons for the emergence of bioimaging as a field of study.
“I think generally there is a lot of emphasis on bioimaging. In optical imaging this is indeed driven by technological advances that come all the way from new infrared light sources invented in the telecommunications industry and new detectors, signal processing and so on,” he said. “The other reason is that as a lot of these tools have been developed in the physical sciences and engineering, they do find new applications in the life sciences and biological sciences.”
Beckman faculty member Michael Insana is playing a leading role in bioimaging developments at the University of Illinois and at the Institute. Insana, who was chosen to head the new Bioimaging Science and Technology group at Beckman, is co-author of one of the seed proposals and is a faculty member in the Department of Bioengineering.
Insana said a possible research initiative centered on bioimaging would complement a broader push to integrate bioimaging theory and research with real-world applications.
“From my point of view in bioengineering we’re trying to put together a new department,” Insana said. “How are we going to be able to compete with people like Duke and Johns Hopkins, and other places with strong medical schools? The things we thought about focusing on were really important and interesting problems in the biological sciences for which new technologies can be applied. The area that I, and many of us in this group, have been funded to work on is cancer.”
The seed proposal from Insana and four other Beckman collaborators – Thomas Huang, Zhi-Pei Liang, Stephen Boppart, and Rohit Bhargava – is for developing molecular imaging technologies for imaging breast cancer.
Carle Hospital in Urbana is dedicating an entire floor of its new Mills Breast Cancer Institute, set to open in 2008, to research by scientists associated with the University of Illinois. Insana said his group hopes to be a part of this new facility for fighting cancer.
“We’re thinking how is it we can develop our science and technology with the eventual goal of perhaps interfacing with them,” Insana said. “That’s the context in which we’re building.”
Boppart, who has been working on using optical coherence tomography as a non-invasive or minimally invasive method for detecting breast cancer, has already located his new imaging equipment at Carle and conducted trials there. A current focus of Insana’s Ultrasonic Imaging Laboratory is on the elasticity of cancer tissue. Liang has worked on improving MRI techniques for better detection of cancer. Along with Huang’s expertise in image analysis and Bhargava’s knowledge of imaging tools and cancer pathology, the group looks to have all the components to succeed in its goal of developing new and comprehensive methods to fight breast cancer.
“What we’re hoping to do is to study certain aspects of the problem from the tiniest scale all the way up to the very largest scale,” Insana said. “So each of our technologies in this group looks at a different aspect of breast cancer. There really isn’t someone who has put all this together to come up with a fairly comprehensive view of what’s going on in the progression of cancer as it transforms into a metastatic process. What we’re trying to do with that particular process is eventually feed it into a model of how cancer is formed and progresses.”
Wiltzius said the collaboration with Carle is exciting, but this research line will go beyond any one project.
“We will be collaborating in strategic areas with Carle and the new breast cancer institute,” Wiltzius said. “But it will be well beyond that. We’ll collaborate where it makes sense but we will certainly be broader in terms of our imaging activities, particularly when it comes to neuroimaging.”
Imaging of the brain has been a key component for Beckman psychology researchers for many years, but improving techniques and developing new imaging modalities is a goal for both neuroscientists and engineers. Brad Sutton, a member of the BST group and an assistant professor in the Bioengineering Department, was the chief engineer for BIC’s 3Tesla headscanning magnet used for neuroimaging. Part of Sutton’s research is geared toward improving MRI signal processing for brain scans.
In addition, neuroscientists at Beckman are developing their own imaging techniques. Kara Federmeier uses an electrophysiological cap developed at her laboratory to measure event-related brain potentials (ERPs) that are used to gauge how the brain reacts to certain stimuli. Gabriele Gratton and Monica Fabiani, directors of the Cognitive Neuroimaging Laboratory, have developed a system called EROS (Event-Related Optical Signal) that uses light and optic fiber bundle detectors for dynamic imaging of brain activity. Fellow Cognitive Neuroscience group member Denise Park and BIC director Art Kramer use the 3T magnet for both MRI and functional MRI studies of the brain.
The Environmental Scanning Electron Microscope of Beckman’s Imaging Technology Group (ITG) is used by both researchers in the life sciences and students involved in ITG’s Bugscope program to view cells without completely dehydrating them. ITG also features a micro-CT scanner useful for bioengineers interested in imaging bone structure.
The funding is following the bioimaging trend. In August, the National Institutes of Health’s National Center for Research Resources announced High-End Instrumentation (HEI) grants totaling $21.5 million so research facilities could acquire cutting-edge imaging equipment such as MRI and computed tomography technology for “advancing biomedical research and increasing knowledge of the underlying causes of human disease.” Industry is joining the governmental and academic push to take advantage of emerging bioimaging and bioengineering breakthroughs.
Insana said that researchers from large pharmaceutical companies to universities are incorporating bioimaging and bioengineering into their thinking when it comes to drug discovery and delivery and the development of cutting edge biological treatments to develop and test new methods and treatments. He said researchers envision using imaging to custom design for a particular disease process, for example, and then test for reactions to a targeted drug delivery method for treating that disease.
“Imaging is a way to do this without the expensive, time-consuming (methods of the past),” Insana said. “Imaging can look at a smaller group of animals and watch them progress over time.”
Insana added that most imaging techniques are non-invasive and non-destructive, so studies can be done with living organisms without perturbing the system. Researchers are also developing ways to deliver drugs at the same time they are imaging a system. Imaging is also playing a role in functional genomics. Insana said researchers in the Bioengineering Department using computational methods employ imaging data to model a phenotype or a cell that expresses diseases such as cancer.
“So a big view of what we’re working on is, can we take all of this imaging information and all of these different scales and feed that back into this functional genomic model so we can study not only the DNA component but how the environmental factors, things like hormones, other metabolic factors, feed back and maybe influence the way the genome influences the disease and progresses,” Insana said. “Then maybe we can get a pretty good idea about why cancer is so different in so many different patients.”
The Bioengineering Department is so new that it only began accepting graduate students in 2004. Beckman faculty members make up most of the department’s faculty. Bruce Wheeler, leader of Beckman’s NeuroTech group, is interim head of the department, while Beckman researchers Yingxiao Wang, Sutton, Bhargava, and Insana are professors in Bioengineering.
“We sort of revamped the entire process with a couple of principles in mind, which I found quite exciting,” Insana said of the department. “If you’re in, say electrical engineering, you know exactly what your undergrads coming in have in terms of their core courses. In bioengineering we take people from biology, chemistry, all kinds of places. So our challenge is to try to get them up to speed very quickly so they can become productive, and yet still maintain some sort of a base knowledge. That’s essentially what a discipline is. We had to generate a discipline.”
At Beckman, the Bioimaging Science and Technology group Insana heads includes Sutton, Bhargava, and Wang, but also has researchers like Boppart, whose focus is on biophotonics, and Kenneth Suslick from the Chemistry Department. This interdisciplinary approach and improvements in imaging technology offer a powerful combination for advancing medical research.
“In each of these imaging modalities the sensors are getting much more sensitive, broader band, so we’re delivering much higher quality images,” Insana said. “But at the same time we’re starting to understand how these radiation systems are interacting with the body.
“We’re bringing chemists into the imaging realm and these chemists are developing probes – meaning little tiny molecules – that are very novel and able to deliver a contrast media to various areas. So this is bringing together people from chemical engineering who are doing drug delivery that are interested in bringing drugs into these probes, chemists who are interested in how to attach a sensitive molecule to a vehicle, and imaging people who are really interested in how to tune their systems to be very, very sensitive to these probes without disturbing them.”
Insana came here in 2005 after serving as head of the graduate program in the Bioengineering Department at California- Davis. He was drawn by the reputation of the U of I’s College of Engineering, the chance to help build a new department at Illinois, and by the opportunities offered for collaborations and new research at Beckman.
“It’s the No. 4-ranked engineering college and the kinds of things that I do are really related to electrical engineering for imaging and biology,” Insana said. “More recently I’m moving into materials science and mechanical engineering, so it’s very, very interdisciplinary. When I saw what Beckman does, the fact they can take people from all these different disciplines and put them together, it was just a wonderful place and it’s been that way for me.”