REHOVOT, Israel, July 3, 1997...A non-invasive method for distinguishing between different types of tumors, such as malignant and benign, has been developed by Prof. Hadassa Degani of the Weizmann Institute of Science. The approach may also help predict the prognosis of cancer and monitor the effectiveness of therapy.
In a study reported in the July issue of Nature Medicine, Prof. Degani and colleagues showed how the method can be successfully employed to diagnose tumors of the breast.
The method consists of injecting a contrast-enhancing dye-like material into the patient's bloodstream and using magnetic resonance imaging (MRI) to monitor the way in which this material is taken up and cleared out by the tumor tissue. Because the uptake and clearance differ for malignant and benign tumors, such monitoring makes it possible to make a diagnosis: an image of the tumor shows up on a computer screen in different colors that reflect the distribution of the contrast material, and the color patterns for malignant and benign growths are strikingly different.
"Our approach has the potential to reduce the number of biopsies performed to diagnose tumors," says Prof. Degani, a member of the Weizmann Institute's Biological Regulation Department. "Most breast tumors detected by mammography are revealed to be benign on biopsy, so that a noninvasive approach like MRI could help reduce the rate of unnecessary procedures."
"We have demonstrated that our approach works, but it now needs to be tested and evaluated in a large-scale trial before it can be widely applied in clinical practice," Prof. Degani says.
Apart from diagnosis, Degani's new method of contrast-enhanced MRI could also give a cancer prognosis because it provides information about the tiny blood vessels that feed the tumor. These vessels enable the cancer to grow and spread, and their density and ability to deliver materials to the tumor may make it possible to determine the tumor's potential aggressiveness.
Monitoring the blood vessels and the spaces between cells may also help evaluate the effectiveness of therapy: a reduction in the density of the vessels and an increase in the inter-cellular spaces may suggest that therapy is being successful.
In addition, if the cost of MRI continues to decline, in the future the new approach may be considered for mass screening as well.
Prof. Degani's team was made up of her doctoral students at the Weizmann Institute as well as radiologists from the Hebrew University-Hadassa Medical Center in Jerusalem and the Kaplan Hospital in Rehovot.
High resolution reveals tumor properties
In magnetic resonance imaging, an image of an organ is obtained by recording signals emanating from the nuclei of atoms, such as hydrogen atoms, that make up the water in the tissues. Adding a contrast material enhances the signals somewhat, but in general the signals are too weak to produce a resolution comparable to that obtained under a microscope.
In Degani's method, however, the resolution is very high because the water tissue signals, enhanced by the contrast material, are recorded over an extended period; about 2 to 4 minutes instead of the usual several seconds.
The approach is referred to as the Three Time Point method, or 3TP, because imaging of the breast is performed three times: before the contrast material is injected and twice afterwards, at intervals of several minutes.
The images reveal how the contrast material enters the tumor, moves inside it and clears out, as well as the pattern in which it is distributed throughout the tumor tissue. These processes are dependent on spaces between cells, on the presence of blood vessels and the extent to which these vessels leak out substances.
Benign and cancerous tumors may differ markedly in these properties. Inter-cellular spaces are larger in fibroadenoma, the most common type of benign breast tumor, and the blood vessels that feed these tumors are less leaky and fewer in number. As a result, contrast material tends to accumulate slowly in these benign growths, and washes out slowly. In contrast, in malignant tumors, this material tends to get in and out faster without accumulating.
In the 3TP method, these differences show up in color: red for areas of slow wash-out, green for steady levels and blue for fast wash-out.
In the study reported in the July Nature Medicine, Prof. Degani's team successfully showed the method's ability to obtain diagnosis of breast tumors in 18 women, eight of whom had fibroadenomas and 10 had cancer. Fibroadenomas looked predominantly red, with patches of green, while cancerous tumors had a great deal of blue. In addition, the colors in benign tumors were uniform and well-defined, while in the cancerous growths the colors were distributed in chaotic, uneven patches.
The 3TP method is based on detailed studies of tissue physiology and disease processes, and its effectiveness was previously demonstrated in extensive laboratory and animal studies. Although it has so far been primarily tested in breast tumors, it is applicable to diagnosis of tumors in other parts of the body.
Prof. Degani's research on breast cancer using magnetic resonance imaging and spectroscopy has been supported by the National Cancer Institute, the National Institutes of Health, the Israel Academy of Sciences, the German-Israeli Foundation for Scientific Research and Development and the Weizmann Institute's Canadian Women for Science.
The Weizmann Institute of Science, in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. Its 2,400 scientists, students, technicians, and engineers pursue basic research in the quest for knowledge and the enhancement of the human condition. New ways of fighting disease and hunger, protecting the environment, and harnessing alternative sources of energy are high priorities.
*Photos and graphics of Prof. Degani's research are available.