Detecting Diseases by Combining Images and Lab Results

Interview with Detlev Ganten

Prof. Detlev Ganten, 65, is Chairman of the Board of Charité—Universitätsmedizin Berlin, one of the largest university medical centers in Europe. The center has 15,000 employees, 3,200 beds and an annual budget of 1 bill. €. From 1991 until 2004 Ganten was founding director of the Max Delbrück Center for Molecular Medicine (MDC) in Berlin. As a research scientist, he has elucidated fundamental mechanisms in the development of high blood pressure. He has received many honors for his work, including the Max Planck Research Prize, the Okamoto Prize, Japan, and the CIBA Prize of the Council for High Blood Pressure Research, American Heart Association. Ganten is also Editor of the Journal of Molecular Medicine.

Molecular medicine, particularly the combined application of in vitro and in vivo knowledge, is on the horizon. In what ways will we benefit from the advent of this new, hybrid science?

Ganten: In the near future, diagnostics will see the first real benefits. One important principle in medicine is "diagnosis comes before therapy." That explains why the major research institutes all over the world are currently focusing on the development and establishment of new diagnostic methods. Despite all the enthusiasm about new types of therapy, physicians must begin by making a clear diagnosis; and that is possible only if they understand the pathophysiology of disease—in other words, how pathological changes alter the body’s normal functions, and what causes these changes. Only then can they provide their patients with optimal therapy. Because of their sense of responsibility for patients, good physicians tend to be conservative with regard to therapy options and don’t automatically choose the latest innovations. The preferred methods are those with a proven track record.

Nevertheless, there are physicians who question established medical traditions and try out new methods.

Ganten: That’s primarily the realm of university hospitals and their doctors, who ideally approach a topic with the commitment and enthusiasm—and in some cases the obsessiveness—of medical researchers. Of course, they too focus primarily on the patient’s well-being. They don’t regard patients as research objects; instead, they implement procedures that only they can take responsibility for as physicians, human beings, and physical and emotional caregivers. This is the kind of outstanding physician we need at the university.

The Imaging Science Institute (ISI) opened by the Charité and Siemens in 2004 is the second center for radiological research in Germany that is jointly operated by an instrument supplier and a university hospital in a public-private partnership. Has this business model proved to be successful?

Ganten: Definitely. I’ve heard only positive reports from Siemens and colleagues at ISI. The ISI is a good, future-oriented project that the Charité would like to continue to work with for a long time to come. In general, I believe public-private partnerships are a matter of course. After all, any separation of public and private funding is an artificial one—all of this money is earned by members of society and it’s merely channeled in different directions. What’s crucial is that the interfaces be clearly defined, because there are always problems in the start-up phase of a new cooperative project. And of course the interests of both sides have to be taken into account.

What are ISI researchers focusing on?

Ganten: They’re focusing primarily on three areas: the cardiovascular system, oncology and neurology. The aim is to develop innovative future technologies on the basis of molecular imaging, optimize existing imaging processes, and investigate the efficacy of medications. ISI researchers are also conducting investigations to determine which kinds of radiological check-ups are useful and are formulating recommendations for physicians accordingly. One research focus is the development of customized molecular contrast agents complete with MR technology for the field of cardiology.

What kind of progress do you expect to see in this area?

Ganten: In the future, molecular imaging will provide information about the level of risk diseases pose to a patient’s health. For example, in patients with cardiovascular disease it could show the level of inflammation around plaques, and thus help us to distinguish so-called vulnerable plaques from the more stable ones. Innovative contrast agents will dock directly on individual cells and show the metabolic activities that are taking place at the molecular level. That way it will be possible to see, for example, whether plaques are shedding particles that could cause lethal blockage of blood vessels. Our contrast agents are not yet targeted with sufficient precision to do this, but that could change in a few years. At that point, catheter-based examinations of the heart for diagnostic purposes may become a thing of the past. They would then be used only in connection with an intervention, such as the dilatation of a blood vessel. In addition, physicians will be able to use molecular imaging to observe the development of tumors, their growth and the effects of therapy. And this will be far more precise than the conventional imaging processes in use today.

In your opinion, how specific will molecular markers be?

Ganten:Basically, just as specific as medications. Only in very rare cases will we have a marker that specifically responds to a certain type of tumor or a pathophysiological process. Assuming we succeed, it will take a long time before we can use a single method to make a diagnosis that is so clear that further examination becomes unnecessary. That’s why molecular imaging must always be accompanied by a thorough traditional anamnesis and a careful clinical examination of the patient. Relying on one method as a medical cure-all isn’t realistic.

Will molecular imaging open the door to earlier detection of metastases than is possible today?

Ganten: That’s what we’re hoping, of course. But even when the tiniest metastases are visible in an image as minuscule dots, that doesn’t provide us with any absolutely reliable information about the severity or the cause of the disease. Initially, a physician simply doesn’t know if a tumor or an alteration in a blood vessel is clinically significant, or if the patient’s symptoms are caused by what can be seen in the image. To know that, he or she must know the clinical course of disease. A snapshot of this sort is important, and in certain cases it can be a lifesaver, but in the field of medicine we assign particularly high priority to observing the course of disease and knowing the dynamics of a process. And it’s here that the advantages of molecular imaging processes once again play a key role, because they allow us to look into the interior of cells at regular intervals. They are also non-invasive, cause minimal discomfort and are relatively fast, which enables us to serve many patients in a short period of time. They will also become less and less expensive in the future.

In vitro diagnostics (IVD) is moving in the direction of identifying diseases at the cellular level. Could this ever evolve to the point that it would become more important than in vivo diagnostics? Would we then need imaging processes only for examining accident victims, for example to identify complicated bone fractures?

Ganten: No, I don’t think that will ever happen. In vitro diagnostics will continue to develop rapidly, and it will increasingly make a valuable contribution to specific sensitive types of diagnostics. It will also be very helpful when it comes to monitoring the course of disease. But it’s not enough simply to know the patient has had a heart attack, a cerebral hemorrhage, a tumor, or breast cancer. It’s inconceivable that a physician would decide on a specific therapy—whether it’s a coronary bypass operation, neurosurgery, a mastectomy or radiation therapy—without knowing the precise location and extent of the problem. That’s why it’s the combination of molecular imaging and IVD that will produce clear progress. The relative prominence of the two will be determined by the special indications of each case and their respective costs and cost-efficiency.

Could IVD serve as an early warning system for cardiovascular diseases—perhaps in the form of blood tests to identify risk factors for vulnerable plaques? The patient would then be able to take medications before plaques form or even before arteriosclerosis develops ...

Ganten: I don’t think that kind of an early warning system would work, because an abstract lab report with various parameters doesn’t convince the patient. For example, a man who has high cholesterol levels and knows it doesn’t necessarily feel it’s urgent to change his lifestyle. But an image of the interior of his body, which might for example show his damaged blood vessels, is far more convincing than any presentation of the lab parameters can be. Of course, we can’t call this an early warning system, because visible changes are, by definition, signs of massive damage. But physicians can often use images to encourage patients to care for their health.

                                                                  Interview conducted by Ulrike Zechbauer