SIEMENS

Munich’s “Klinikum rechts der Isar” university hospital has an outstanding international reputation for scientific advances. In 2008 the successful transplantation at the hospital of two complete arms caused a sensation around the world. In November 2010 the hospital was in the spotlight again with another first when Siemens Healthcare installed the world’s first fully integrated whole-body MRPET system in the hospital’s Nuclear Medicine Clinic. The system has been undergoing clinical use testing since then.

The special feature of the 3-tesla hybrid system named Biograph mMR — the “m” stands for molecular — is that it combines two important imaging techniques in one system: positron emission tomography (PET) and magnetic resonance imaging (MRI). There are a number of significant differences between the ways in which these two techniques function (see box, following page), but they both supply mutually complementary information about diseases. Whereas an MR system can generate images of the human anatomy at millimeter-scale resolution, a PET scanner is especially useful for studying the metabolism of cells.

“The Biograph mMR now makes it possible for us to create whole-body images with MR and PET at the same time and to superimpose them,” says Professor Markus Schwaiger, the director of Klinikum rechts der Isar’s Nuclear Medicine Clinic. Schwaiger has high hopes for the clinical trials. “We’re concentrating on applications in the field of oncology — on patients suffering from cancer, in other words. What interests us is the extra value the system offers compared with current examination methods. We hope it will help us make better and more precise diagnoses,” he says.

Schwaiger’s hopes should be justified, because doctors using the Biograph mMR during an examination can see not only whether the size of a tumor has decreased but also, for example, whether its energy consumption and thus its metabolism has slowed down. From this information they can infer that the tumor is responding to medication and that the therapy (such as a chemotherapy) should be continued.

Biograph mMR could also support the diagnosis of neurodegenerative diseases. This might be accomplished, for example, by identifying certain areas of the brain that show decreasing metabolic activity, which is an indicator of dementia, among other illnesses. Professor Hermann Requardt, CEO of the Siemens Healthcare Sector, expects the combination of PET and MR in a single system to generate major benefits. “We can overcome the challenges to our health care systems only if we identify diseases as early and as precisely as possible, treat them appropriately, and keep an eye on costs,” he says. “After all, nothing is more expensive than therapy that doesn’t work, or a therapy to treat an illness that the patient doesn’t even have.”

“Clinical use testing will help us to monitor the progress of diseases. We will use the resulting information to develop a dedicated plan of treatment for each individual patient,” explains Schwaiger. “Furthermore, we expect that the new combined technology will help us to identify tumors and perform biopsies with far greater precision than would otherwise be the case, while offering a significant improvement in patient comfort.” At the same time, the new machine is expected to facilitate progress in the development of new biomarkers and to deliver insights that will help to develop new types of treatment for cancer, heart disease, and neurological disorders. Since MRs do not use ionizing radiation to visualize the body — they work with magnetic fields — this technique is especially suitable for examinations of children and for follow-up examinations.

In addition to its spatial and temporal precision, Biograph mMR offers the unique advantage of being able to simultaneously acquire MR and PET images of the whole body in about 30 minutes. Previously, two separate examinations were required, after which the two images would be combined — a time-consuming process with reduced precision, as patients and their organs always move, however slightly, between examinations. Simultaneous imaging by the Biograph mMR therefore enables a more precise diagnosis and is also more comfortable for patients, since they only have to be examined once.

Combining Forces. What did it take to combine MR and PET into a single system? “For one thing, there were all kinds of technical problems in terms of combining two very large machines. But above all, we had to overcome technological limits,” says Walter Märzendorfer, head of Siemens Healthcare’s Magnetic Resonance Business Unit. To do so, Siemens’ Molecular Imaging (MI) Business Unit in Hoffman Estates, Illinois and Märzendorfer’s Business Unit in Erlangen, Germany, pooled their expertise and included a huge global network of development partners in the effort — among them researchers from the University Hospital in Tübingen, Germany’s Jülich research center, the Athinoula A. Martinos Center in Boston, and Emory University in Atlanta, Georgia. “It was exemplary teamwork,” says Märzendorfer.

One important approach pursued by developers was to make crucial changes to the existing PET detector. PET scans create gamma quanta in a patient’s body. These quanta lead to the emission of photons in the scintillation crystals located at the front of the detector. In the past, these photons were electronically amplified by photomultipliers (electron tubes several centimeters long) before they were measured. But an MR system’s magnetic field would so strongly deflect the cascade of electrons generated by photomultipliers that it would be impossible to measure any clear signal — a seemingly insurmountable obstacle to the integration of the two technologies.

The solution? “In the Biograph mMR we replaced the photomultipliers with avalanche photodiodes (APD), which are only a fraction of the size of electron tubes,” says Dr. Matthias Schmand, head of Siemens Healthcare’s PET Detector Research and Development program. Although the APDs likewise measure an electron flow that is caused by photons, this takes place within a semiconductor layer system that does not react sensitively to external magnetic fields. “At the same time, the APDs made it possible to overcome a second hurdle: They’re small enough to be integrated into the housing of an MR,” explains Schmand.

Heading for Personalized Medicine. Before the Biograph mMR goes to serial production — which is initially scheduled for the European market in the second half of 2011 — Siemens and the Nuclear Medicine Clinic at Klinikum rechts der Isar will review how the system fits into daily hospital routines, including training of personnel and patient examination scheduling. The German Research Foundation (DFG) is also playing a major role in this respect by providing broad financial support for research in the area of MR-PET imaging in Germany.

In addition to the Biograph mMR in Munich, several more units will be installed during 2011, with devices planned for Tübingen, Essen, and Leipzig. “The Biograph mMR will be an important tool for driving personalized medicine forward and better understanding diseases such as Alzheimer’s,” says Märzendorfer. A technological revolution is thus under way at the Klinikum rechts der Isar. Nevertheless, it will not be the first time in its 177 year history that this hospital sets new standards in the medical world.