Pictures of the Future    Fall 2006

Transforming Treatment

Using interventional magnetic resonance imaging, Johns Hopkins Medical Institutions in Baltimore, Siemens Corporate Research, and Siemens Medical are developing strategies for curing arrhythmias and regenerating infarcted hearts. Behind it all is the development of a groundbreaking new interface for all MR treatments.

^{Above: By making it possible to rapidly combine 2D images, Siemens’ new IFE software interface can generate 3D images of selected areas (thoracic aorta / red), thus opening the door to real time treatment of medical conditions using magnetic resonance (MR) imaging. Left: In combination with a catheter that provides its own MR signal (green), the new interface makes it possible to visualize delivery of potentially regenerative stem cells to the site of an infarction}

Millions of people suffer from arrhythmias—irregularities in the heart’s natural rhythm that can range from minor fluctuations to life-threatening spasms. One of the most serious forms of arrhythmia is ventricular tachycardia, a condition in which heart rate increases to such an extent that cardiac arrest can result. The condition is triggered by nests of living cells that form electrical circuits in the scar tissue that takes the place of muscle after a heart attack. Two to three million people suffer from this condition in the U.S. alone, and approximately 300,000 of them die each year.

Although ventricular tachycardia can be managed with medications, it can, in some cases, be cured. The key, however, is a tricky procedure that involves the introduction of a catheter into the heart that is capable of ablating (burning) the living cells in the scar tissue, and thus eliminating arrhythmia-causing currents. In addition, the tissue around the infarct is ablated to create a barrier against electrical currents that could arise from living cells in the infarct that may have been missed.

But using conventional X-ray-based technology to visualize the perimeter of an infarction while ablating a thin layer of cells around it is so complex and risky that few cardiologists are willing and able to perform the procedure on those patients who need it most.

Blocking a River. Magnetic resonance imaging offers hope for a much quicker, less expensive, and, above all, much safer procedure. "The problem with current, X-ray-based, technology is that you can’t see what you’ve ablated," says Dr. Henry Halperin, a professor of medicine and biomedical engineering at The Johns Hopkins Hospital. "It’s like trying to build a dam without being able to check for leaks. That’s important because an arrhythmia is like a river. To stop it, you have to block it." Adds Christine Lorenz, PhD, from Siemens Corporate Research and Siemens Medical Solutions in Baltimore, Maryland, who coordinates the Johns Hopkins-Siemens partnership in interventional MR development, "We expect that under MR guidance it will be possible to cut the time it takes to safely perform this procedure from the current six to eight hours to between one and two hours, while seeing a huge improvement in outcome."

In principle, MR offers the ideal environment for visualizing and blocking arrhythmias. It can provide high resolution, real time images on a continuous basis without exposing the patient to radiation. But the technology still has a major drawback: the lack of an intuitive user interface for the new world of 3D interventional work. Such an interface demands a far more dynamic, interactive environment than is available today. Furthermore, reflecting MR’s growing attractiveness, the interface must be simple enough for non-radiologists to operate without specialized training. "The user interface is the single most important enabling technology that will allow interventional MR to take off," says Albert C. Lardo, PhD, director of Hopkins’ Image Guided Cardiotherapy Laboratory. "Without it, no interventional cardiologist will feel comfortable conducting procedures. They want the interface to fit their training and experience."

Sound reasonable? Of course, but consider this: MR allows users to see much more than any X-ray fluoroscopy system can. While the later typically displays 2D static or short cine sequences after each X-ray exposure, MR offers 3D imaging with a full range of digital visualization opportunities. "We want to see the heart in three dimensions from any angle. We want to be able to open the heart virtually and remove parts of it to get a better view; and we want all of this with full anatomical and electrophysiological information, so that we can see where the catheter is and be able to guide it in real time," say Halperin.

That adds up to a tall order for any interface. Nevertheless, remarkable progress has already been achieved. Says Dara L. Kraitchman, VMD, PhD, an associate professor of radiology at Johns Hopkins University, and a specialist in cardiac function, "Following six months of testing, the interface is already far better than anything else around. In fact, there really is nothing else from any other vendor that begins to compare with what we now have with Siemens." Such an interface is important for researchers like Kraitchman because it allows them to track cells using MR. A pioneer in cardiac stem cell tracking, Kraitchman explains that in order to prepare stem cells for injection, a tiny payload of paramagnetic iron oxide can be made to enter each cell’s cytoplasm by exposing the cells to an agent that coats the iron oxide and causes the cell membrane to be "tickled" just enough to accept it.

Known as IFE (Interactive Front End), the new interface "talks" to syngo, Siemens’ highly successful, multi-modality (it works with ultrasound, MR, CT, PET and nuclear medicine) image acquisition and processing software platform, which thousands of physicians are already familiar with. "In spite of MR’s enormous complexity, IFE has a very simple goal," explains Siemens’ Lorenz. "Users should not have to stop and rethink anything." Adds Jeffrey Bundy, PhD, senior director, MR R&D, USA, "IFE is one part of the larger MR picture. A current trend is to use MR not only to diagnose problems, but to solve them. One of the significant goals of working with top centers such as Johns Hopkins is to define new and more efficacious applications for our many products and solutions."

Life-Saving Cells. Siemens’ new interface could be the key that opens the vast capabilities of magnetic resonance imaging not only to broader applications in diagnostic medicine, but to a wide range of new treatments and avenues of research. Already, for the first time anywhere, it has made it possible to watch real time 3D images generated from the tip of a specially-designed catheter made of non-magnetic metals, while guiding the catheter into a patient’s heart. Once in the heart, the catheter’s built-in MR coils were able to map the locations of arrhythmias by distinguishing pockets of live cells (which consume iron-carrying hemoglobin and therefore appear bright in MR), from dead cells in an infarcted area. "The next step will be to use the interface in conjunction with ablation," says Halperin, who performed the procedure.

Even more ambitious plans are on tap. "We have perhaps the world’s most advanced program in stem cell imaging and tracking," says Dr. Jonathan S. Lewin, chairman of the Johns Hopkins Department of Radiology. What Lewin foresees—and what is being meticulously researched and tested at Hopkins—is the use of stem cells to regenerate cardiac tissue following a heart attack. "What we have done is to tag the walls of stem cells with iron particles and use MR to watch the cells over weeks as they migrate into target tissues and set up shop to begin a therapeutic process. The ability to guide injection and observe the migration is something that has never been done before with any other imaging modality," says Lewin. The results have been encouraging. "Our animal studies have shown very clearly that cardiac function strengthens following stem cell injections," says Lardo. Adds Halperin, "In five to ten years it may be possible to offer stem cell therapy to treat people who have had heart attacks."

Insulin Factories. Opportunities for expanding the Johns Hopkins-Siemens partnership abound. With one Siemens MR scanner delivered and four more on the way—two of which will be used exclusively for research—the pace of development is set to accelerate. On the agenda is an expanded research program to investigate MR-guided injections of pancreatic islet cells—the body’s microscopic insulin factories. Tagged with iron oxide and encapsulated in a unique, porous coating that shields the cells from antibodies while allowing insulin out and nutrients in, such cells have already been shown to produce insulin when removed from the pancreas of a human being and injected under MR guidance into the liver of a test animal. "We are on the cusp of an interventional cure for type 1 diabetes," says Lewin. "Working with Siemens in this and other areas, we are finding that the entire development process is much more rapid than it ever was before."
                                                                                                            Arthur F. Pease