German Researchers Use EnSight to Unlock Mysteries of the Circulatory System A young woman checked into University Hospital Freiburg in southwestern Germany, complaining of numbness in her arms and signs of a mild stroke. Relying on conventional diagnostic techniques, local physicians soon found that the young woman was suffering from a fairly uncommon condition consisting of a blood clot in the aortic arch, a part of the body’s main artery, the aorta. by Douglas Clark The condition was effectively treated with a standard treatment: a simple prescription of a blood-thinning agent, such as aspirin or warfarin. But with the stroke reversed and other symptoms relieved, the young woman no doubt still had questions and concerns about her health. Was this a one-time occurrence, and would there be any further medical consequences? And what had caused this to happen in the first place?

These were just some of the questions that 30-year-old physician and training radiologist Dr. Alex Frydrychowicz also asked himself about the woman’s case. Unfortunately, standard diagnostic techniques currently provide no satisfying explanations for these questions. That’s why this young doctor has taken it upon himself to find his own answers that may one day help patients exactly like this young woman.

Hopes of redefining standard diagnostics Today, circulatory conditions like the one this young woman suffered from are diagnosed using three-dimensional contrast-enhanced magnetic resonance (MR) angiography, a process by which dye is added to the bloodstream to provide contrast between blood and internal structures of the body. Images are then recorded using magnetic resonance imaging equipment. This technique very effectively reveals any arterial blockage, such as the clot in the young woman’s case. Unfortunately, it doesn’t allow doctors to fully understand the blood-flow conditions that may have contributed to the blockage, or to look for resulting flow disturbances that could potentially cause subsequent health problems.

Dr. Frydrychowicz’s current research is aimed at redefining these diagnostic standards and, eventually, widening the range of treatment options. His inspiration to do so, however, didn’t strike him at the bedside of this female patient; rather, it came to him in a lecture hall many months earlier.

A year and a half ago, Frydrychowicz attended a talk given by his now-collaborator, physicist Michael Markl, PhD, who was discussing his work in cardiac-wall imaging. During his doctoral work at Freiburg University and post-doctoral work at Stanford University, Markl had developed cardiac and blood-flow imaging techniques that relied on MR scans and EnSight visualizations. Frydrychowicz was immediately struck by the diagnostic potential of Markl’s work.

“I was just sitting there listening to him and had four or five ideas about what to do with this technique—and at that time he had no clinical collaborator,” recalls Frydrychowicz.

The two were a perfect match and soon paired up to begin applying the technique to various arteries. Their work together began with imaging of the aortic, iliac, and femoral arteries. Their team now boasts 12 members in Freiburg, and they’ve since been joined by two groups of research partners in Switzerland. The Swiss partners are currently studying blood-flow in the cerebral arteries, as well as designing replicas of arteries to simulate blood-flow in the lab.

Of the growing collaboration, Frydrychowicz says, “It’s rather fascinating to meet people who have different ideas for this technique and to be able to work with them—there are a million and a half vessels to look at.”

Flow visualizations tell a more complete story Markl’s technique differs from conventional diagnostics methods because it relies on three-dimensional time-resolved MR scans that integrate three-directional flow information. This allows the team to study the size and shape of internal structures, as well as record more-complex information about blood-flow throughout the artery. The flow data are then fed into a software program called EnSight, from Computational Engineering International (CEI), where blood-flow can be visualized and analyzed in detail.

EnSight has been critical to the team’s work, because without it, the same level of flow analysis would be impossible. Commenting on EnSight’s usefulness in his work, Frydrychowicz explains that “Michael started using EnSight in his work at Stanford, and we continued using it here, because there is no other program that is comparable.”

The team has also developed its own software to study findings and to better understand flow conditions’ effects on specific arterial wall parameters.

“By combining the visualization with our [in-house] software tool and the ability to extract certain flow features, we can really say that pressure is changing on the [arterial] walls. And if we can really understand what is going on in, say, aneurysms, then we can use that for medical purposes,” says Frydrychowicz.

Getting to the heart of the matter By linking specific flow conditions with specific medical conditions, the team is headed towards its goal—and aneurysms are one important area of focus in their work. Aneurysms form when a weak spot in the wall of the artery begins to stretch under the pressure of blood flowing through the artery. As the blood pressure stretches the weak spot in the artery, the area essentially begins to blow up like a balloon, forming an aneurysm. The condition is potentially fatal, because the arterial wall can eventually stretch to the point of rupturing.

Aneurysms are a specific target for the team because current diagnosis and care don’t take into consideration the effects of blood-flow characteristics. Today, for example, specific flow conditions are not considered when deciding whether surgery is needed to treat the ailment. Rather, the decision to operate is mainly based on the size of the aneurysm, and on how quickly it grows. Not all cases, however, fit neatly into these two parameters. Some patients who are at risk according to size and growth-rate assessments may not necessarily benefit from surgery, for example. And avoiding unneeded surgery would be a lifesaving measure in itself, since the procedures has a risky 5% mortality rate.

Frydrychowicz is quick to point out specific instances he has seen in his own research. “I just had a patient who was doing underwater rugby—a very stressful activity—and he had a 7 to 8cm aneurysm, but nothing happened. So why is his aneurysm not rupturing or growing, while others are? In the end, it may have nothing to do with size,” Frydrychowicz points out. “I think if we follow up on 100 patients [with aneurysms] we can really say something about it, and that’s where we’re headed.”

While Dr. Frydrychowicz’s work is still in the research phase, with approximately 60 adult patients studied so far, he estimates that in two to three years, the team will have collected and analyzed the data they need. If successful, the benefits to patients are clear: more specific diagnoses, and for some patients, the avoidance of not only costly but very risky surgery.

So, while the young woman mentioned earlier may not be able to benefit from Dr. Frydrychowicz’s research today, she and other patients may soon. Until then, she can rest assured that by taking part in the research study herself, she may well have contributed to the advancement of medical care, as well as to her own future well-being.

More information The magic of magnets As the name implies, radiology once focused on X-rays, but today magnetic resonance imaging (MRI) is also a diagnostic mainstay. Unlike X-rays, MRI relies on radiofrequency waves and a powerful magnetic field to produce images of tissue and internal organs. Learn more about MRI basics, and read about MRI's development and the technology behind it.

Understanding aneurysms Aneurysms most often occur in the arteries, but they can actually occur in any blood vessel. Read more about aneurysms and the various forms they take.

Blocking the way Clotting is critical to health, but the formation of a clot, also known as a thrombus, in the bloodstream can lead to serious medical conditions, and even death, because it can block the proper flow of blood throughout the body. Understand more about how clots form and the conditions they can lead to.

EnSight and medical research Read more about how other medical researchers are using EnSight to better understand the body and develop more-effective medical treatments.

3D Visualization Used in Engineering Finds a Home in Human Heart Research, linkoping.pdf

N.C. State Researchers Recreate Aerosol Inhalation in Virtual Reality, ncsu-particles.pdf

Research at the University Hospital Freiburg To read more about the work being done in Dr. Frydrychowicz’s and Dr. Markl’s department at the University Hospital Freiburg, click here.

For further reading about the medical case of the young woman discussed in this article, see the article Dr. Frydrychowicz and his colleagues published in the American Heart Association’s Circulation magazine: Alex Frydrychowicz, Ernst Weigang, Andreas Harloff, Friedhelm Beyersdorf, Jürgen Hennig, Mathias Langer, and Michael Markl. “Time-Resolved 3-Dimensional Magnetic Resonance Velocity Mapping at 3 T Reveals Drastic Changes in Flow Patterns in a Partially Thrombosed Aortic Arch.” Circulation 2006 113: e460 - e461.