Every breath you take

PNNL scientists have designed a virtual computer model of the nose, larynx and lungs of a rat in hopes of better understanding how pollutants affect those systems.

A virtual lung model developed at the US Department of Energy’s Pacific Northwest National Laboratory may help predict the impact of pollutants on respiratory systems and provide new insights into asthma, a condition afflicting 15 million American adults.

The computer model, called the virtual respiratory tract, provides an unprecedented, three-dimensional view of how pollutants enter, travel through and collect in the entire respiratory system.

PNNL’s prototype system models the nose, larynx and lungs of a rat. Efforts are underway to similarly model the respiratory systems of monkeys and humans.

Understanding biological impacts from pollution has become more important as respiratory ailments have increased, as evidenced by the nearly doubling of asthma sufferers since 1980. By learning how particulates travel through the lungs, scientists can design treatments that more precisely target drug delivery for pulmonary diseases. And, they can study how pollutants impact lungs of healthy people compared with those who suffer from respiratory ailments.

‘We designed a tool that will open up new possibilities for understanding how our environment affects our bodies,’ said Rick Corley, principal investigator and a PNNL environmental toxicologist. ‘The virtual respiratory tract is a major accomplishment in modelling biological systems. It will be the springboard for detailed modelling of the body’s organs as a complete system.’

Using the virtual respiratory tract, PNNL scientists can analyse the influence of various factors, such as the amount of pollutants or length of exposure, on healthy versus diseased lungs by manipulating the computer model. For example, they can begin to simulate how gases, vapours and particulates may act differently within lungs of people suffering from cystic fibrosis, emphysema and asthma.

The model is sufficiently detailed to track individual particles as they move within the rat’s respiratory system. In fact, Corley says, the model’s exceptional resolution could drive development or use of new technologies to measure pollutants and their potential impact in the respiratory tract at much greater precision than is currently feasible.

PNNL scientists designed the highly detailed virtual respiratory tract by combining the capabilities of supercomputers, rapid semi-automated computer modelling and nuclear magnetic resonance imaging systems. The equipment is located in the William R. Wiley Environmental Molecular Sciences Laboratory, a DOE user facility located at PNNL.

Creation of PNNL’s virtual respiratory tract began in the nuclear magnetic resonance spectrometer facility, which contains instruments capable of producing magnetic resonance images similar to those used in diagnostic medicine – but characterised by much higher spatial resolution.

With the NMR technology, laboratory scientists captured images of a rat’s upper respiratory tract and lungs in unprecedented detail. Then, a semi-automated software package called NWGrid analysed the data, reconstructed it into a computer model and integrated information to show how airflows carrying particles might move inside the imaged respiratory tract during breathing.

‘The grid program allows us to translate raw NMR data into a computer image very quickly,’ said Harold Trease, PNNL computational physicist. ‘We can go from data sets to a working model in hours compared with weeks or months required by other approaches.

‘This increased speed will allow us to replicate the studies many times over, which will give us greater precision, or to broaden our studies and create a database of information on healthy and diseased lungs.’

The laboratory’s Biomolecular Networks Initiative has supported development of the virtual respiratory tract with about $400,000 over two years. In the upcoming third year of research, scientists will refine the model using data obtained with newly developed NMR imaging techniques.

They also will continue to collaborate with other institutions nationwide, including the University of California, Davis, which has conducted extensive research into asthma using animal models, and the University of Washington’s pulmonary biology and bioengineering programs.