The researchers also demonstrated that the parameters can be used to accurately diagnose and assess the severity of lung diseases in an animal model. The research is detailed in Scientific Reports.
In a statement, Marie Muller, co-senior author and an associate professor of mechanical and aerospace engineering at North Carolina State University, said: “Diseases can affect lungs in many different ways. They can change the microstructure of the lung, the elasticity of the lung tissue, the type and amount of fluid in the lungs, and so on. Each of these changes can be measured using ultrasound. Our goal with this work was to establish clear parameters for these lung characteristics and determine which combination of parameters is associated with different lung diseases.”
Muller continued: “To be clear, we’re talking about numeric measurements for each parameter. So, if there are three parameters associated with a disease, we’d have three numbers – one for each parameter. We can then use a mathematical formula that combines those three numbers to create a biomarker score. That score not only tells us whether a specific health problem is present, but how severe the problem is.”
The researchers began by generating parameters for measuring a variety of lung characteristics, such as the density of alveoli or the amount of fluid in the lungs. The researchers also adapted existing ultrasound parameters used in other organs for use on lung tissue. Altogether, this resulted in a total of 60 parameters.
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The researchers then measured all 60 parameters in the lungs of rats that were healthy or had various stages of fibrosis or edema.
“We then used statistical methods to identify which combinations of parameters were both associated with a given health condition and sensitive enough to measure the severity of a health problem,” said Muller.
Through this process, the researchers found that five of the parameters were necessary for assessing fibrosis and edema, namely three for fibrosis and two for edema.
“One of the challenges with many diagnostic tools is that there is often a trade-off between sensitivity and specificity,” said Muller. “A highly sensitive test may virtually guarantee that you detect a problem, but it also usually means that there can be a lot of false positives. On the other hand, a highly specific test will almost never give you a false positive, but it may also miss quite a few health problems it is supposed to detect, or not be able to assess the severity of a specific disease. We’re excited about this new diagnostic tool because it is both highly sensitive and highly specific.”
According to NC State, one way they were able to assess the sensitivity of the new tool is by making use of fibrosis treatments. As rats who had fibrosis received treatment, the new diagnostic tool was able to measure improvements in the rats’ lung tissue.
The researchers have developed data processing software that can be used in conjunction with existing ultrasound hardware to determine the numbers for each parameter measurement, as well as establishing the biomarker scores for edema and fibrosis.
“Next steps involve computational simulations, in vitro testing, and animal model testing to establish that this technique can work in cases where the ultrasound has to penetrate a much thicker chest wall. If that goes well, we’ll pursue clinical trials,” said Muller.
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