Novel contrast medium promises deep insights into cell processes
Imagine tracing the fate of specific cells in deep layers of tissue using minute amounts of an externally triggered contrast medium. The almost unimaginable is within reach today! A new contrast medium in the form of gas vesicles moves this goal closer than we ever dared to dream - until now. Scientists of the Leibniz Institute for Molecular Pharmacology (FMP) in Berlin and the California Institute of Technology in Pasadena designed this contrast medium particularly for use with MRT and ultrasound imaging. Since the cells themselves synthesize the contrast medium, we might soon be able to visualize disease processes never seen before. The work of the scientists promises revolutionary progress for the basic life sciences. The breakthrough was recently published in 'Nature Protocols'.
Optical imaging plays a key role in illuminating biological processes. Using available technologies, we are already able to visualize disease processes on the cellular level. However, there are limits to visualizing techniques. Firstly, cell division naturally dilutes traditional contrast media. By and by, this removes cells from view. Besides, the required light for optical imaging techniques is absent from deep tissue layers.
All these obstacles may soon be problems of the past. Scientists working at the Leibniz Institute for Molecular Pharmacology (FMP) in Berlin jointly with their colleagues from the California Institute of Technology in Pasadena (USA) succeeded in developing an innovative contrast medium for use with magnetic resonance tomography (MRT) and with ultrasonic imaging. Both imaging techniques detect signals from deep tissue layers. As a bonus, the technique does not expose tissue to radiation loads like computed or positron emission tomography (CT or PET).
The target cells themselves produce the contrast medium
The crucial part of the innovation is the ability of cell genes to express the contrast medium. This is reminiscent of the 'green fluorescent protein' (GFP), which revolutionized cell biological studies. Similarly, scientists can trigger target cells to produce their own contrast medium. As the cells divide, the contrast medium will not be diluted but can be traced from the outside.
FMP scientist Dr. Leif Schröder comments on the German-US American collaboration: "The method has crucial advantages for the basic sciences. We now aim to trace the fate of specific cells in organisms, which eluded us until now." The scientific results were published in 'Nature Protocols'.
The new contrast medium consists of so-called gas vesicles. The vesicles are hollow protein structures produced by certain bacteria to adjust their floatation depth in water. The vesicles function like air bladders in fish. Thanks to the work of the US American scientists, it is already possible to trace the gas-filled vesicles with high resolution in mice using ultrasound imaging.
Meanwhile, the FMP scientists prepared MRI protocols for use with the inert gas xenon. This enhanced the signal strength by a factor of about 20,000. Using specific acquisition engineering, the contrast medium may be turned on or off from the outside at never before imagined minute concentrations. Right now, this works only in solution. However, the scientists are in the process of making the unconventional diagnostic procedure available for animal studies. Physicist Leif Schröder estimates that it will take about a year to get the procedure ready for imaging studies in animals using reasonably short test times: "At that time, the procedure will rival the sensitivity of PET scans without the radiation load. So far, this was unimaginable for MRT. If we used conventional MRI methods, the test time would be several hundred thousand years."
The new method is important because it will help scientists to understand disease
So far, there are no plans to use this type of cell-generated contrast medium in patients. Instead, the intended use of such contrast media is restricted to cell biological studies in animal models only. Other scientists should also have the opportunity to use this imaging method.
Dr. Leif Schröder emphasizes: "When things come together in the end, this will be a tremendous breakthrough for diagnostic studies and for the understanding of diseases in animal models." For more than ten years, Dr. Schröder works on applications involving the optimization of MRI studies using hyperpolarized inert gases. Therapy responses could also be visualized using the new contrast medium and imaging procedure and ultimately lead to improved drugs.
The Human Frontiers Science Program (HFSP) also recognized the potential of the approach. For one year now, the innovative research receives HFSP funding as 'High Risk High Gain' project. In additions to all else, the grant rewards the researchers for the interdisciplinary team play between cell biologists, laser physicists and experts in the mathematical modeling of xenon atom magnetization.