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CT ‘maps’ show lung damage by type

U. MICHIGAN (US) — A new way to analyze CT scans can distinguish between early-stage damage to the small airways of the lungs and more severe damage known as emphysema.

The approach could improve the diagnosis and treatment of a lung disease that affects approximately 24 million Americans and is the third-highest cause of death in the US.

In a new paper published online in Nature Medicine, a team from the University of Michigan Medical School reports on a technique called parametric response mapping, or PRM. They used PRM to analyze computed tomography, or CT, scans of the lungs of patients with chronic obstructive pulmonary disease, known as COPD, who took part in the national COPDGene study funded by the National Heart, Lung and Blood Institute.

From left to right and top to bottom, PRM images of the lungs of a healthy person, two people with mild to moderate COPD, and a person with severe emphysema. Green is healthy tissue, yellow is small airway damage, and red is more severe damage. (Credit: University of Michigan)


The researchers showed that the overall severity of a patient’s disease, as measured with PRM, matches closely with the patient’s performance on standard lung tests based on breathing ability.

“Essentially, with the PRM technique, we’ve been able to tell sub-types of COPD apart, distinguishing functional small airway disease or fSAD from emphysema and normal lung function,” says Brian Ross, a professor of radiology and biological chemistry and senior author of the new paper.

“We believe this offers a new path to more precise diagnosis and treatment planning, and a useful tool for precisely assessing the impact of new medications and other treatments.”

‘The missing link’

COPD limits a patient’s breathing ability, causing shortness of breath, coughing, wheezing, and reduced ability to exercise, walk, and do other things. Over time, many COPD patients become disabled as their disease worsens.

Most often associated with smoking, COPD can also result from long-term exposure to dust, and certain gases and chemicals.

“In the last decade, CT scan techniques for imaging COPD have improved steadily, but PRM is the missing link—giving us a robust way to see small airway disease and personalize treatment,” says Ella Kazerooni, a radiology professor who is a member of the COPDGene trial.

Originally developed to show the response of brain tumors to treatment, the PRM technique allows researchers to identify COPD specific changes in three-dimensional lung regions over time.

Already, a spinoff company, Imbio, has licensed the University of Michigan’s patents on the PRM technique, and is developing the technology for use in early prediction of treatment response of brain tumors and other cancers. Now Imbio has begun developing PRM for COPD subtype diagnosis and tracking.

3D lung map

With the PRM technique, the researchers use powerful computer techniques to overlay the CT scan taken during a full inhalation with an image taken during a full exhalation. The overlaid, or registered, CT images share the same geometric space, so that the lung tissue in the inflated and deflated lungs aligns.

The density of healthy lung tissue will change more between the two images than the density of diseased lung, allowing researchers to create a three-dimensional “map” of the patient’s lungs.

PRM assign colors to each small 3D area, called a voxel, according to the difference in signal changes within each of the areas between the two scans. Green means healthy, yellow means a reduced ability to push air out of the small sacs, and red means severely reduced ability.

PRM could take COPD sub-typing to the next level, say the authors of the new paper. “By distinguishing small airway abnormality from that involving the lung parenchyma, such as emphysema, PRM could help physicians personalize therapy for individual COPD patients—and select patients for clinical trials of new treatment options more precisely”, says Fernando Martinez, an internal medicine professor who also participated in the COPDGene trial.

“PRM can also help to track COPD progression or response to treatment over time,” says lead author Craig Gabán, assistant professor of radiology.

Although the current study mostly looked at a “snapshot” of CT scans taken at one time, it also includes data on two patients who were imaged over more than two years. More longitudinal data is needed to make sure that PRM works well for long-term tracking and studies are already under way.

While a simple breathing test called spirometry is still considered the best way to diagnose the disease, spirometry has limitations in its ability to distinguish between different types of lung damage that COPD patients experience.

“The PRM technique is a step forward in being able to better sub-classify patients with COPD so that targeted therapies can be developed,” says co-author MeiLan Han, pulmonologist and COPDGene investigator.

The National Institutes of Health supported the work.

Source: University of Michigan

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