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
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.