REHOVOT, Israel--A new form of high spacial resolution magnetic resonance imaging (MRI) may improve the diagnosis of breast and other cancers, and may aid in predicting cancer prognosis and monitoring the effectiveness of therapy, says Hadassa Degani, PhD, of the Weizmann Institute of Science.
"Our approach has the potential to reduce the number of biopsies performed to diagnose breast tumors," says Dr. Degani, of the Department of Biological Regulation.
The key to the new method is longer MR recordings of water tissue signals from the breast, to allow for high spacial resolution, performed at three specific time points: once before the injection of contrast medium and twice afterwards. Thus, the approach is referred to as the three-time-point (3TP) method (see Figure 1 and Figure 2).
The contrast-enhanced water tissue signals are recorded three times over a period of two to four minutes, rather than many times, each for several seconds, as in regular MRI.
With the 3TP method, the MR image of the tumor appears on a computer screen in different colors, which reflect the rate of uptake of the contrast material in the tumor vessels (wash-in); distribution of the contrast material throughout the intravascular volume of the tumor; and clearance, or wash-out, of the contrast agent. The wash-in rate is represented by color intensity, and the wash-out pattern by color hue. Slow wash-out is coded red; moderate wash-out, green; and fast washout, blue.
Color hue and intensity are then correlated to two pathophysiological features: microvascular permeability (micro-capillary surface area times permeability) and extracellular volume fraction (the space between cells) using a preconstructed calibration map (see Figure1). The color patterns for malignant and benign growths are strikingly different, allowing for a diagnosis.
Optimal selection of the three time points for imaging, as well as pathophysiological interpretation of the 3TP images, is obtained from the calibration maps. [The methodology is explained in an article by Dr. Degani and her colleagues in Nature Medicine (3:780-782, 1997).]
In a retrospective study, the researchers used the 3TP method to successfully confirm the diagnosis in 18 cases of breast abnormalities: 10 cases of breast cancer and eight of fibroadenoma. In malignant tumors, cells are more densely packed, and the contrast material tends to move in and out faster without accumulating. Thus, the colors are distributed chaotically in patches, with blue predominating (see figure 2). This pattern indicates high microvascular permeability and low to medium extracellular fraction.
The spaces between cells are larger in fibroadenoma, and the blood vessels that feed these lesions are less leaky and fewer in number. As a result, contrast material tends to accumulate slowly in these benign growths and washes out slowly. Thus, in fibroadenomas, the color hue is uniformly distributed, with red predominating, indicating low microvascular permeability, and, for the most part, a high fraction of extracellular volume.
"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," Dr. Degani says.
High microvascular permeability in cancers is associated with angiogenesis and neovascularization. Intratumoral microvessel density, a marker of angio-genesis grade, has been shown to be a potent prognostic indicator in a variety of tumors, including breast. Thus, Dr. Degani says, the 3TP method could potentially be used to predict tumor aggressiveness by providing information about the microvessels that feed the tumor and enable it to grow and metastasize.
The 3TP method may also prove useful in evaluating the effectiveness of therapy, she says. A reduction in microvessel density and an increase in the space between cells may suggest that therapy is being successful.
Dr. Degani's research team was made up of her doctoral students at the Weizmann Institute as well as radiologists from the Hebrew University-Hadassah Medical Center, Jerusalem, and the Kaplan Hospital, Rehovot. Research in Dr. Degani's lab has been supported by the National Cancer Institute and National Institutes of Health, USA; Israel Academy of Sciences; German-Israeli Foundation for Scientific Research and Development; and the Weizmann Institute's Canadian Women for Science.