New Perspective On Asthma

Vol. 14 •Issue 3 • Page 46
New Perspective On Asthma

Researchers Use Magnetic Resonance Imaging to Study Airways

How do you feel?” the researcher asked a healthy volunteer participating in an experiment at Boston’s Brigham & Women’s Hospital, Harvard Medical School. The volunteer had just inhaled the maximum allowable dose of methacholine. “Like Bob is sitting on my chest,” came the reply, obviously with some effort.

Light chuckles came from most of the study staff present. You don’t have to know Bob to guess his physical build.

It’s believed that airway constriction caused by methacholine in healthy subjects is similar to airway constriction naturally occurring in people with asthma. To better understand the pathophysiology of asthma, researchers are acquiring images of the lungs from both healthy and asthmatic subjects, using an experimental magnetic resonance imaging (MRI) technology that could make its way into clinical applications within several years.

Traditional MRI relies on the hydrogen atoms in water molecules lining up with the powerful magnetic field of the MRI magnet, similar to small magnets lining up with the field of a big magnet. Specific radio frequency pulses perturb these aligned hydrogen atoms and induce a signal, which can then be detected and processed to form MR images.

Traditional MRI can’t be used to look at the lungs and its diseases. Why? Unless a person is drowning, there’s too little water in the lungs to produce enough signal for creating pictures.

Enter the technique of MRI with hyperpolarized noble gases.

Contained in a glass cell with nothing else but rubidium, heated to 170 C, placed in a weak magnetic field, and illuminated with a 100-watt laser, helium (3He) gas atoms also line up with the magnetic field. When inhaled by an animal or a human, pictures of where the gas goes can be taken with the same MRI hardware and techniques as used in conventional MRI.

Mitchell Albert, PhD, in the radiology department at the Brigham & Women’s Hospital was one of the co-inventors of hyperpolarized noble gas MRI in the mid-1990s, publishing the first lung MR images using this technology in the journal Nature in 1994. Since then, MRI researchers have been pushing to improve 3He gas polarization and coming up with ways of performing 3He MRI of the lungs to obtain different information.

The 3He polarizer looks like something a mad scientist would build. In addition to the laser and glass cell, a vacuum pump, an air pump, and a maze of glass and metal tubes, among other parts, all sit on a utility cart.


The simplest form of MRI that can be performed with hyperpolarized 3He is called static ventilation imaging. MR images are acquired as the subject holds his/her breath after inhaling the 3He gas. The resulting pictures show where the 3He has traveled to after inhalation. MR images from a healthy person’s lungs should look almost uniform in brightness. Dark patches on the pictures indicate which part of the lung is getting less or no air, possibly due to disease.

What sets Dr. Albert’s group apart from most other 3He MRI researchers is its focus on acquiring images and information about the airways. After all, asthma is a disease involving the closure of airways, and the heterogeneous ventilation patterns observed are but a result of the airway constriction.

For doctors or drug researchers trying to treat the deprivation of air for parts of the lung, it would be helpful to know which airways to open. So, instead of acquiring MR images after the 3He gas has been inhaled, the lung pictures are taken while the 3He is being inhaled. This shows the airways or the paths through which the 3He passes, rather than showing where the gas stays during breathhold. Because the imaging methods involve taking pictures of the lung as the subject is inhaling the gas, they’re called dynamic imaging procedures.

Focusing on the airways during 3He MRI of the lung isn’t anything new. 3He MRI researchers at Duke University, the University of Virginia, and the University of Sheffield have succeeded in obtaining airway images as well, whether it’s with humans or lab rats. But all these groups have achieved airway imaging using “exotic” MRI pulse sequences as in scanning routines not conventionally available on all MRI machines.

3He MRI of the airways at the Brigham & Women’s Hospital uses the most basic gradient echo pulse sequence, a scanning routine you can find in any introductory MRI textbook. This widespread availability could translate to lower costs for the average hospital when 3He MRI becomes a regular imaging procedure.

The International Society of Magnetic Resonance in Medicine recently accepted a paper from Dr. Albert’s group describing its work measuring airway diameters from the dynamic MR images, and comparing the measured values to those from a widely accepted anatomical model.

Measuring airway diameters from acquired images is nothing new either — computed tomography (CT) has been used to accomplish this task previously, but the same achievement with 3He MRI is significant. CT basically takes X-ray pictures of a person’s body from different angles to construct a three-dimensional view of the imaged portion. The problem is X-rays involve ionizing radiation, whose risks are well-known. An alternative imaging method that doesn’t use ionizing radiation would be much more preferable.


The obvious next step in the gradual maturation of hyperpolarized 3He MRI is developing clinical applications for it. Already, either using 3He MRI alone, or in conjunction with conventional MRI, researchers have been looking at lung diseases such as bronchitis, cystic fibrosis, chronic obstructive pulmonary disease, emphysema, bronchiolitis obliterans and pulmonary embolism.

Asthma, with its widespread prevalence and serious effect on the quality of life, is a prime candidate. When a person is suspected of having asthma, spirometry can help confirm or deny those suspicions, and even provide an approximate score for the asthma’s degree of severity. Sounds great, until the asthmatic or the doctor asks, “Which of the airways are causing this problem?”

At the Boston University Department of Biomedical Engineering, the Respiratory and Physiological Systems Identification Laboratory, headed by the Department Chair Kenneth Lutchen, PhD, is one of the many research groups developing more sophisticated pulmonary function tests that would yield more information than spirometry. Already, their specially programmed ventilators, together with mathematical lung models, have enabled them to narrow their guesses for which airways are constricted for asthmatics.

Now, with a new concept they’ve named “image-functional modeling,” they’re taking their analytical tools to the next level, seeking to combine information from lung images with the mathematical models. Before long, from the ventilator measurements of asthmatic subjects, the models might even predict exactly which airways are constricting and by how much.


As projects on refining 3He MRI techniques and extracting information from the captured images are going full-steam ahead, a handful of researchers are looking to push the envelope by exploiting another surprising characteristic of hyperpolarized 3He MRI: The strong magnetic fields typically needed by conventional MRI aren’t necessary to perform 3He MRI. In fact, Dr. Albert’s lab is on the path to finding out what kind of images can be delivered by an MRI system with a magnetic field 100 times smaller than the clinical machines.

This area of study is still in its infancy, but it’s hard not to be excited by its promises: lesser space needed by the smaller machines that are sufficient for creating the weaker magnetic fields, and cheaper costs associated with the easier maintenance of such units. Perhaps one day, mini-3He MRI systems will be common equipment at family clinics, enabling physicians to look inside the lungs during diagnosis. Perhaps one day, an army field surgeon could use this to assess the degree of lung damage from a soldier’s chest gunshot wound before prioritizing whom to treat first.

Just don’t be surprised if one day you find yourself operating an MRI console, and the patient in the MRI scanner speaks to you in this funny, squeaky voice — no, he didn’t just inhale from a birthday balloon. Well, he basically did.

Tzeng is a PhD candidate in Boston University’s department of biomedical engineering. His PhD research is in the Hyperpolarized Noble Gas MRI Laboratory at the Brigham & Women’s Hospital, Harvard Medical School, Boston.