New Constellations 2019 | Page 56

PULMONOLOGY • CONTINUED FROM PREVIOUS PAGE You solve for the unknowns using equations derived from Maxwell’s laws, a set of mathematical models that describe electrical fields — the same ones that power technologies like generators, radar, electric motors and wireless communications. Iterative algorithms then solve the governing equations to produce what’s called a candidate distribution, essentially a guess at how conductivity is distributed within the field, with the goal of matching the inputs to the outputs. The algorithm will then adjust the variables and run the equations again and again until it gets within a margin of error. The system plots the conductivity distribution as pixels, and those pixels form an image. Areas of high conductivity — like the heart — are rendered in red. Low conductivity — like the lungs — in blue. Run continuously, the image becomes an animation. “You can see where air and blood are going,” says Dr. DeBoer. “Breath to breath, beat to beat.” “You’re going from hundreds of measurements on the outside to thousands of pixels inside,” says Michelle Mellenthin, PhD, a post-doctoral fellow in biomedical engineering at the University of Colorado School of Medicine who, as a graduate student of Dr. Mueller’s, built a prototype EIT device. “The math is incredibly complex.” Dr. Mueller has been working on the math, specifically inverse problems for medical imaging, for 20 years. Until recently, that work was confined to the lab. She was giving a talk on EIT’s potential in cardiac imaging when she met Robin Deterding, MD, Chief of Pediatric Pulmonology at Children’s Colorado. “I immediately thought of air trapping in cystic fibrosis,” says Dr. Deterding. “That was my first clinical project,” says Dr. Mueller. “Before that I was only looking at healthy subjects, looking at ventilation and perfusion and refining the algorithms. I wasn’t satisfied doing 54 that. I wanted to make a clinical difference. I was looking for a partner.” Validating a new view Dr. Mueller found that partner in Dr. DeBoer, who had a research interest in pulmonary imaging. When she saw Dr. Mueller’s animations — the lungs in cross section, filling and emptying of blue, the heart pulsing red — she knew she was looking at potential. “It’s very exciting,” Dr. DeBoer says. “There’s no radiation, no sedation. It’s very safe. You can put it on a baby, you can put it on an adult. We’re doing studies in the ICU and the OR. You could even do studies at home.” Indeed, Children’s Colorado is already testing the device with several patient populations. It could help treat regional pneumonia, a common comorbidity of neuromuscular disease. In the NICU, it could help manage bronchopulmonary dysplasia. It could help treat patients on mechanical ventilation and young children with asthma. It can reveal aspects of heart function, blood flow, fluid accumulation in the lungs. It can show the boundary between living and dead tissue. It can show regions of lung collapse and of hyperinflation. Compared to CT, it reliably reproduces anatomy and abnormality. Compared to spirometry, it measures very accurate lung volumes. Dr. DeBoer’s team published those results in Physiologic Measurement last year. “Our goal is to use it all the time, routinely, over a period of three years,” says Dr. DeBoer. “If it works, it can go everywhere.” But there will be challenges. For one thing, EIT in its current iteration is not particularly user-friendly. Dr. Mueller travels with the device and helps set it up and gather the data. She processes it afterward, in her lab. Then she sends the images to Dr. DeBoer for analysis. That’s not ideal. Direct algorithms, first used clinically by Dr. Mueller’s team, solve several complicated equations in one step to produce an image in real time. In a new collaboration with GE Global Research, Dr. Mueller is developing that group’s prototype into a highly-portable, hospital-friendly system that can do just that, in a configuration easy enough for a nurse to set up. Then there are the inherent challenges of testing a novel medical device. “It’s definitely learning on both sides,” says Dr. DeBoer. “Dr. Mueller could say, ‘This signal is abnormal, what do you think it means?’ And then we have to go back and try to figure that out. There aren’t many studies — maybe any studies. We’re certainly the biggest group in cystic fibrosis.” And in some ways, it’s the sheer number of people involved — and their expertise — that makes the difference. It’s engineers and pulmonologists, cooperation between institutions, partnerships with industry. That’s what it takes. “It’s difficult to validate,” says Dr. Mueller, “when you’re seeing things that haven’t been seen before.” ● Biomedical engineer Michelle Mellenthin, PhD, solders a circuit-board, part of the continual process of refining a new technology for the clinic (top). EIT is so safe its test subjects have been entirely human, but Dr. Mellenthin hopes a mouse model can help her develop the technology from a mechanical engineering angle. She’s still working out the kinks of miniaturization (bottom). To see more on EIT for cystic fibrosis, visit childrenscolorado.org/EIT. NEW CONSTELLATIONS 55