Medical Device Daily National Editor

Of all the diagnostic assessments that remain vague offering a large variety of grey areas of interpretation (read, guesses), and frequently being flat-out wrong the precise understanding of breathing problems is among the most difficult.

Using a decision "tree," clinicians confronted with shortness of breath may first attempt to determine if this is primarily lung function difficulty or a cardiovascular problem if, of course, the need for that determination is ever first realized; breathing problems in young people are usually assumed to be asthma, since youthfulness automatically tends to rule out heart disease.

If the diagnostic points to pulmonary ills, the clinician asks the usual questions about allergies, smoking and family history of lung cancer.

But what then?

Spirometry tests though serving to verify a lung function problem may reflect weakened musculature around the lungs but not much about what's specifically going on at the cellular level. Non-smokers can develop emphysema. Severe asthma may be the result of unidentifiable allergens, and the most severe of all may be classified as chronic obstructive pulmonary disease (COPD) a term that can be as casually catch-all as "the flu."

And so while the clinician is likely to provide a fairly precise definition of the trouble (rather than a more accurate "not sure" acknowledgment), therapies chosen are often one-size-fits-all inhalers.

Focused on solving the multiple conundrums provided by asthma and related breathing problems is a research team at the University of Virginia Health System (Charlottesville), led by Chengbo Wang, PhD, assistant professor of radiology.

Using a specialized modified MRI technique, the researchers found that asthma is associated with remodeling of microstructural lung tissues at the alveolar level, rather than simply the result of airway restriction, the main cause usually cited for the wheezing and gasping for air that marks asthma.

Appropriate to the complexity of the disease, Wang acknowledged that the exact nature of this remodeling still must be discovered and more research done, especially as it relates to the specifics concerning the "trapping" of air in the smaller lung airways.

"Airway restriction is believed to the main path-physiology change [in asthma]," Wang told Medical Device Daily, and, "traditionally, the terminal airspaces and local microstructures in the acinar or alveolar level are hypothesized to be untouched."

Thus, Wang's team expected to find little or no changes in microstructures in the study's 14 asthma subjects, compared to a 14-person health group, but the technique that was used showed that such changes do occur.

In order to develop what is called apparent diffusion coefficient (ADC) data, the researchers created a hybrid MRI diffusion pulse sequence to measure the diffusion of hyperpolarized helium-3 inhaled by the subjects. Using what Wang termed a "stimulated-echo-based, long-time-scale diffusion measurement technique," the imaging was done via breathhold measurements of subjects, the sensitivity of diffusion time extended "from several milliseconds to several seconds."

"I combined these two sequences together," he told MDD, "to create a hybrid MR diffusion pulse sequence, which can measure both short- and long-time-scale hyperpolarized helium-3 diffusion during a single breathhold. It saves gas, minimizes measurement errors and allows doing a pixel-by-pixel comparison. This opens a new way to investigate the small airspace diseases."

Based on previous work and assumptions concerning asthma, Wang said that its expectations were that ADC measurements would find no change, or small decrease, in the ADC measurements. However, the helium-3 atoms moved a greater distance in the lungs of patients with asthma than in healthy subjects, and Wang said that the study now "suggests remodeling of lung tissue but that does not mean this remodeling will necessarily enlarge the alveolar, it is still a mystery."

He said, "We found structural alterations in asthmatics, which were not expected. These findings contribute to a new understanding of the patho-physiology of asthma."

For the study, the team used a 1.5 Tesla Magnetom Sonata MRI scanner from Siemens Medical Solutions (Malvern, Pennsylvania), modified with and a vest-shaped chest coil from Clinical MR Solutions (Brookfield, Wisconsin). In a less-than-15 second breathhold, the subjects inhaled the helium gas, the gas polarized by a prototype Helium Polarizer from Magnetic Imaging Technologies (Durham, North Carolina). And Wang acknowledged that the work raises still more questions concerning the cellular changes found, hopefully to be answered with additional research.

"From my MRI technique, we can say that there are some microstructural changes deep in the lung of those asthmatics," he said. "However, we really have no idea what kind of specific 'remodeling' it is, or what structures we are detecting, although we believe these changes are in the acinar or alveolar level.

For this research, Wang recently received the W.S. Moore Young Investigator Award for Clinical Science from the International Society for Magnetic Resonance in Medicine (Berkeley, California), the organization specifically crediting Wang's "innovative approach and excellent presentation."

Wang noted that his work is only one step in an ongoing investigation that could lead to the development of new therapies for asthma and more careful selection and targeting of therapies for breathing problems.

"My new technique can easily distinguish COPD from asthma, and I think it may have some clinical usage if we can develop some specific medicines for each disease in future.

"This is a big project," he added. "We currently are using multi-modalities to compare the results. We have collected CT, PET, hyperpolarized helium-3 and spirometry data for all subjects, and now we are analyzing the data. The results will come out soon."

The immediate diagnostic usefulness of Wang's research method is not clear, since it is difficult to see how MRI would be used for an office-based diagnosis of breathing problems, given its expense and necessary infrastructure.

But Wang told MDD he would not rule this out for the future.

"This is a good question," he said. "The polarization procedure [we used] is done outside the scanner so that it does not need a high field. Some groups have already published some interesting results using low-field scanner, such as 0.1, 0.2 Tesla [machines]. And researchers are trying to build low-cost MRI scanners, which may greatly lower the cost. Combined with strong polarization of hyperpolarized gas and low-field MRI scanners, the equipment won't be too expensive. So I believe this technique will have a good future."

Wang's study has been published in the July issue of Journal of Magnetic Resonance Imaging.

He used similar MRI techniques last year to show the first evidence of structural lung damage from secondhand cigarette smoke.