Time is money, especially in the race to discover new anti-inflammatory drugs and bring them to market. Pharmaceutical companies typically spend years in the pre-clinical stage of the drug development process, incurring millions of dollars in costs. New medications for diseases such as heart disease, stroke, arthritis and multiple sclerosis could improve treatment for millions of people. Yet a key part of the discovery process — monitoring the movement and speed of white blood cells in living tissue — involves hours of tedious and often inherently flawed handwork.
CellTrek, cell-tracking software developed by a team of U.Va. School of Engineering and Applied Science researchers, jump-starts the current tracking method to provide an automated solution to a fundamental problem: how to track thousands of fast-moving, often obscured, cells in the demanding in vivo, or living, environment. CellTrek essentially cuts through the "noise" surrounding white blood cells, also known as leukocytes, so researchers can collect rapid, accurate data they can use to describe the intensity of the inflammatory process.
"The velocity and the density of these cells are critical indicators of the level of inflammation," explained Scott Acton, one of CellTrek's developers and a professor of electrical and computer engineering. "Nuances in the different distributions of the velocities [can] actually indicate different things to the biologist. One thing might be to evaluate a genetic deficiency, or the presence of some gene, or the presence of a drug that's supposed to be anti-inflammatory or maybe even pro-inflammatory, so in order to investigate all these hypotheses regarding the inflammation process in the microvasculature [small blood vessels], you have to be able to count and track cells, the leucocytes, in vivo."
Acton, whose expertise lies in image analysis techniques such as image segmentation and motion tracking, had specialized in following the movements of military targets — large objects such as vehicles and tanks. In 2000, a chance meeting with Dr. Klaus Ley, a professor of biomedical engineering, led to a new focus on objects at the cellular level. Ley, recently named director of the division of inflammation biology at the La Jolla (Calif.) Institute for Allergy & Immunology, is an expert in the biomechanics of the inflammation process in living tissue.
"When Scott came to U.Va. several years ago as an associate professor, I went to his talk because it was about tracking and I was interested in tracking [leukocytes] and had tried many different algorithms with different engineers," Ley recalled. "He had tracked cyclists at the Tour de France … from a helicopter. The helicopter moved. The cyclists moved and sometimes the cyclists would disappear into a little forest and would come out the other end and he would still be able to track them. I thought, 'Well, if he can track this stuff, he sure can track these cells.'
"He solved the problem of tracking unlabeled leukocytes in living tissue. Nobody had done that before."
Acton, Ley and alumnus Adam Goobic (Engineering '02, '03), developed CellTrek's proprietary software to solve the problems associated with tracking in vivo. Instead of tracking just dozens of leukocytes by hand — a process that can take hours or days — researchers using CellTrek can now track thousands of cells at a time. Automating the collection process also eliminates human error, as researchers are prone to introduce unintended bias (i.e. selecting certain cells over others). An effect known as "jitter," where the image shifts suddenly due to the subject's respiratory and circulatory system, can also introduce error.
CellTrek outperforms hand-tracking in cost, time and accuracy. It's a technology that holds promise in other biomedical research applications, such as tracking microbubbles for ultrasound-guided molecular imaging and drug delivery.
"Because the data collection problem really is the roadblock to discovery in this inflammatory disease process," Acton said, "I think we're at a point in biology where tools for analysis are being developed that should lead to solving many mysteries about morbidity and mortality as far as human disease, but the input side is a major obstacle to getting there."
Looking ahead, Acton believes that engineers, biologists and physicians will find more areas of intersection. "I think there's going to be a great revolution in the next 10 years," he said. "The combination of information that we get from image analysis with information we get from genetics — take that and throw it into what's called a systems biology model … people who do this are like a combination between computer people and biology people. They're using these simulation tools to simulate things that happen in the body, like the inflammatory process. U.Va. is becoming a leader in that area and instead of looking at one [little] piece of the puzzle, it's trying to look at the entire puzzle, to manipulate the whole machine."
Currently, the team hopes to market CellTrek through a start-up, Just Tracking Inc. Acton said that, aside from CellTrek, "Right now, there's no current solution for in vivo.
"We're not established business people,” he said. “But we're a scientist and an engineer who want to get a product to the other scientists so that discovery might be expedited."
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