Embracing the Dark Side
By Keith Loria
Radiology Today
Vol. 23 No. 3 P. 14

A new imaging technique may help change the future of radiology.

More than four million people die of serious respiratory ailments each year, but a new imaging technique known as dark-field imaging may help decrease that number substantially.

Partially destroyed alveoli and an overinflation of the lungs are typical examples of the life-threatening ailment COPD. A team led by Franz Pfeiffer, PhD, chair of biomedical physics and director of the Munich Institute of Biomedical Engineering at Technical University of Munich, developed the dark-field X-ray technique, which better diagnoses COPD. Pfeiffer explains that, currently, detailed diagnostic information is only available using three-dimensional CT approaches, in which a computer assembles many individual images.

“Conventional X-ray imaging is based on the attenuation of X-rays on their way through the tissue,” he says. “Dark-field technology, on the other hand, uses the wave nature of X-ray light, which is discarded in conventional X-ray imaging. This allows us to visualize the structure of objects that are, for the most part, transparent.”

The structures appear as bright images on a dark background; thus, the name dark-field imaging was born.

“Dark-field imaging exploits the wave properties of light,” says Theresa Urban, MSc, chair of biomedical physics at Technical University of Munich, who served as a researcher on the project. “The related effects, like refraction and small-angle scattering, happen always and, for visible light, this is used routinely in microscopy.”

With typical X-ray imaging, which features extremely high-energy requirements on the X-ray source, it is often difficult to measure these effects. For this reason, high-energy X-ray imaging has been limited to large synchrotron facilities, such as those using an interferometer with two gratings.

“At that time, only attenuation and refraction were used as contrast mechanisms,” Urban says.

But in 2006, Pfeiffer found a way to use the technique with smaller, conventional X-ray sources, such as the ones used in clinics, by introducing a third grating into the interferometer. Because it is much easier to operate a conventional X-ray source in a normal laboratory rather than in a synchrotron, this transition sparked a great deal of research activity. By 2008, Pfeiffer and colleagues found that, in addition to attenuation and refraction, the small-angle scattering of the X-rays at material interfaces could also be used to generate a contrast modality, known as the dark-field signal.

“The potential for radiologic applications revealed itself quickly, when they imaged in-vivo mice and found that the lung, with its many interfaces between air and tissue, causes a strong dark-field signal,” Urban says. “Ever since, research groups have worked hard on bringing this technique to the clinics, at first by continuing the effort of performing studies in small animal disease models and next by evaluating the technique in larger animals and deceased human bodies.”

Finally, in 2018, the team was able to begin with the first clinical study on dark-field chest radiography at the University Hospital of the Technical University of Munich.

“Essentially, it’s translating concepts that have been around a couple of decades now to X-ray,” Pfeiffer says. “It’s not that easy because X-rays have wavelengths that are 10,000 times smaller than visible light and, therefore, it gets harder to pick up these tiny infraction angles.”

How It Works
Conventional radiography uses the attenuation of X-rays when they pass through material, but dark-field radiography uses small-angle scattering, which happens whenever X-rays pass the interface between two different materials, causing them to change their direction a bit, Pfeiffer says.

“We can measure both the attenuation and the change in direction of the X-rays by extending a conventional radiography device with an interferometer,” he says. “The interferometer imprints a pattern of many small, periodically repeating areas of high and low intensity into the beam, which we use as a reference. When a sample is inserted in the beam, different things happen to this pattern. If the X-rays are attenuated, the mean intensity of the pattern is reduced. If they experience small-angle scattering, the contrast of the pattern is reduced. This reduction of contrast of the reference pattern constitutes the dark-field signal.”

By analyzing the reference intensity pattern without and with a sample, radiologists can obtain both the conventional attenuation and the new dark-field signal from a single measurement. The low effective dose of 35 μSv for an average-sized person is in the same range as conventional chest radiography.

“Instead of just looking at the attenuation in the tissue, you look at the change of what happens when it continues as a wave,” Pfeiffer says. “For X-rays, it hasn’t been possible for a long time. This method uses optical grading—filters you can add to an X-ray setup so you can detect these wave interactions.”

That comes in handy, he notes, when looking at lung structure.

Potential Uses
For medical applications, dark-field imaging is most promising whenever the microstructural properties of tissue or an organ change due to a pathology, Urban explains. This is often the case for pulmonary conditions.

“In a healthy lung, there are lots of interfaces and, consequently, a strong dark-field signal,” she says. “Many lung diseases affect the integrity of the alveolar structure. Pulmonary emphysema, for example, destroys the alveoli and leaves larger air spaces. In pneumonia, they are filled with liquid. Lung tumors replace them with tumor tissue.”

These diseases all reduce the overall volume of air-tissue interfaces and, therefore, lead to a distinct reduction of the dark-field signal. This also works if the attenuating properties of the tissue have not yet changed.

“Conventional chest radiography also suffers from the lung being overlaid by other attenuating tissue, such as muscles, the ribs, and the heart,” Urban says. “Since these tissues do not generate any dark-field signal, this is not an issue in dark-field radiography, and the lung can be assessed without impeding overlaying structures.”

Pfeiffer notes dark-field imaging, because it can pick up the microstructure of the investigated sample, allows a clinician to look at the microstructure of the tissue without having to resolve it directly.

“In the medical context, that means we suddenly get access to tissue microstructure,” he says. “One example is the lung, because it basically contains only microstructure and is made by nature to contain a large gas exchange. Whenever you have a disease that begins in the lungs, you can start seeing this with dark-field imaging long before it would be picked up by regular X-rays.”

The research team has shown the resulting diagnostic benefit of dark-field radiography for various lung diseases in extensive studies on small animals and are working on emphysema and COVID-19 pneumonia in two currently running clinical studies.

“Apart from pulmonary imaging, dark-field radiography has also shown promising results for mammography, where the microcalcifications lead to a dark-field signal, and for musculoskeletal applications, where, for example, osteoporosis changes the microstructure of the bones,” Urban says.

An examination utilizing dark-field chest X-ray technology involves a significantly lower radiation dose than CT due to dark-field chest X-rays requiring only one exposure per patient, compared with the large number of individual images taken from different directions that are necessary with CT.

“We expect the radiation exposure to be reduced by a factor of 50,” Pfeiffer says, adding that his initial clinical results have confirmed that dark-field X-rays provide additional image information on the underlying microstructure of the lung.

The Wave of the Future?
While this may seem like a game changer in the industry, there is currently no commercial clinical dark-field system available, so it’s not something that will be heavily utilized anytime soon.

“The clinical operation of our prototype system is very similar to conventional radiography systems and can be easily done by medical staff,” Urban says. “We believe that dark-field radiography at this point in time is scalable to a broad application because the technique requires standard X-ray imaging components, which are already broadly available, and the components of the interferometer, which have been optimized in the past five years, allowing for a reproducible production and high quality.”

Still, a significant challenge will lie in advancing the prototype to a commercially available product. Pfeiffer, who notes that there is a great deal of interest in the radiology community, expects it to happen within a few years.

Another challenge will be convincing the radiology community that this technique is worth investigating further.

“These [investigations] are necessary to confirm our initial results in larger cohorts and by other users, as well as to see what further applications are possible,” Pfeiffer says. “We hope that we can do so by publishing our results and communicating them at conferences and every other opportunity.”

Pfeiffer says dark-field imaging’s ability to get information about the structural properties of a specimen under investigation results in a high sensitivity for lung diseases at a low effective patient dose. This is important because three of the six leading causes of death worldwide are lung diseases.

“For a successful treatment, it is crucial to diagnose them at an early stage,” he says. “We could, for example, show that dark-field radiography allows an early diagnosis of pulmonary emphysema, something that is not possible with conventional radiography but only with CT, which comes with a high patient dose and is therefore not usually used for screening.”

Because the radiation dose associated with dark-field radiography is approximately 50 times lower than for a low-dose thorax CT, Urban believes it could be used for screening programs such as to identify COPD in smokers. The high sensitivity at a low dose could also be beneficial for regular follow-up scans for treatment monitoring.

“It is an inherent property of dark-field chest radiography that we always obtain both conventional attenuation and dark-field radiographs from a single measurement,” Urban says. “So, the conventional image is not lost, but dark-field chest radiography, rather, offers the radiologist both contrast modalities to base their diagnosis on.”

— Keith Loria is a freelance writer based in Oakton, Virginia. He is a regular contributor to Radiology Today.