More Precise Analysis of Scans for COPD Can Better
Determine Lung Damage, Treatment Results
Parametric response mapping is path to more precise diagnosis, treatment
planning; useful tool for precisely assessing the impact of new
medications and treatments
These PRM images of four different
patients' lungs show how the scan technique can distinguish healthy lung
areas (green) from those with early-stage damage (yellow) and emphysema
(red). University of Michigan Center for Molecular Imaging
Oct. 8, 2012 - A new approach to lung scanning
could improve the diagnosis and treatment of a lung disease that affects
approximately 24 million Americans mostly older people - and is the
country's third-highest cause of death.
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.
The researchers report that the PRM technique for
analyzing CT scans allows them to better distinguish between early-stage
damage to the small airways of the lungs, and more severe damage known
They've also shown 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, Ph.D., the Roger A. Berg Research Professor of radiology,
professor of 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."
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
"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, M.D., M.S., FACS, a radiology professor who leads U-M's
lung imaging program and 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 U-M spinoff company, Imbio, has licensed
U-M'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
Ross and co-author Alnawaz Rehemtulla, Ph.D., the
Ruth Tuttle Freeman Research Professor of Radiation Oncology, co-founded
Imbio and act as scientific advisors to the company. They also co-direct
the U-M Center for Molecular Imaging, which pursues a broad range of
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 3-D 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
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, M.D., M.S., an internal
medicine professor who is also participated in the COPDGene trial.
Most people who
have COPD are at least 40 years old when symptoms begin.
Obstructive Pulmonary Disease (COPD) makes it hard for you to breathe.
Coughing up mucus is often the first sign of COPD. Chronic
emphysema are common COPDs.
airways branch out inside your lungs like an upside-down tree. At the
end of each branch are small, balloon-like air sacs. In healthy people,
both the airways and air sacs are springy and elastic.
When you breathe
in, each air sac fills with air like a small balloon. The balloon
deflates when you exhale. In COPD, your airways and air sacs lose their
shape and become floppy, like a stretched-out rubber band.
smoking is the most common cause of COPD. Breathing in other kinds of
irritants, like pollution, dust or chemicals, may also cause or
contribute to COPD. Quitting smoking
is the best way to avoid developing COPD.
can make you more comfortable, but there is no cure.
"PRM can also help to track COPD progression or
response to treatment over time," says lead author Craig Gabαn,
assistant professor of radiology. Although the current study mostly
looked at a "snapshot" of CT scans taken a one time, it also includes
data on two U-M COPD 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 underway.
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, M.D. M.S., a U-M pulmonologist
and COPDGene investigator. "This is one of many important studies that
is being made possible by the data being collected through NHLBI funded
The research team also included Jennifer Boes,
Komal Chughtai, Charles R. Meyer, and Timothy D. Johnson, and Stefanie
Galbαn. Johnson has a joint appointment in the Department of
Biostatistics in the U-M School of Public Health.
Funding for the study was provided by the National
Institutes of Health, including research grant P50CA93990 from the
National Cancer Institute and COPDGene grants from the National Heart,
Lung and Blood Institute U01HL089897 and U01HL089856 as well as training
grant T32EB005172 from the National Institute of Biomedical Imaging and
Craig Galban, Rehemtulla and Ross have a financial
interest in the underlying technology which has been licensed from the
University of Michigan to Imbio, LLC. Ross and Rehemtulla have a
financial interest in the company itself.