Three-Time-Point MRI Aids Cancer Diagnosis

REHOVOT, Israel--A new form of high spacial resolution magnetic resonanceimaging (MRI) may improve the diagnosis of breast and other cancers, andmay aid in predicting cancer prognosis and monitoring the effectivenessof therapy, says Hadassa Degani, PhD, of the Weizmann Institute of Science.

"Our approach has the potential to reduce the number of biopsiesperformed to diagnose breast tumors," says Dr. Degani, of the Departmentof Biological Regulation.

The key to the new method is longer MR recordings of water tissue signalsfrom the breast, to allow for high spacial resolution, performed at threespecific time points: once before the injection of contrast medium andtwice afterwards. Thus, the approach is referred to as the three-time-point(3TP) method (see Figure 1 and Figure2).

The contrast-enhanced water tissue signals are recorded three timesover a period of two to four minutes, rather than many times, each forseveral seconds, as in regular MRI.

With the 3TP method, the MR image of the tumor appears on a computerscreen in different colors, which reflect the rate of uptake of the contrastmaterial in the tumor vessels (wash-in); distribution of the contrast materialthroughout 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; moderatewash-out, green; and fast washout, blue.

Color hue and intensity are then correlated to two pathophysiologicalfeatures: microvascular permeability (micro-capillary surface area timespermeability) 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 pathophysiologicalinterpretation of the 3TP images, is obtained from the calibration maps.[The methodology is explained in an article by Dr. Degani and her colleaguesin Nature Medicine (3:780-782, 1997).]

In a retrospective study, the researchers used the 3TP method to successfullyconfirm the diagnosis in 18 cases of breast abnormalities: 10 cases ofbreast cancer and eight of fibroadenoma. In malignant tumors, cells aremore densely packed, and the contrast material tends to move in and outfaster without accumulating. Thus, the colors are distributed chaoticallyin patches, with blue predominating (see Figure2). This pattern indicates high microvascular permeability and lowto medium extracellular fraction.

The spaces between cells are larger in fibroadenoma, and the blood vesselsthat feed these lesions are less leaky and fewer in number. As a result,contrast material tends to accumulate slowly in these benign growths andwashes 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 needsto be tested and evaluated in a large-scale trial before it can be widelyapplied in clinical practice," Dr. Degani says.

High microvascular permeability in cancers is associated with angiogenesisand neovascularization. Intratumoral microvessel density, a marker of angio-genesisgrade, has been shown to be a potent prognostic indicator in a varietyof tumors, including breast. Thus, Dr. Degani says, the 3TP method couldpotentially be used to predict tumor aggressiveness by providing informationabout the microvessels that feed the tumor and enable it to grow and metastasize.

The 3TP method may also prove useful in evaluating the effectivenessof therapy, she says. A reduction in microvessel density and an increasein the space between cells may suggest that therapy is being successful.

Dr. Degani's research team was made up of her doctoral students at theWeizmann Institute as well as radiologists from the Hebrew University-HadassahMedical Center, Jerusalem, and the Kaplan Hospital, Rehovot. Research inDr. Degani's lab has been supported by the National Cancer Institute andNational Institutes of Health, USA; Israel Academy of Sciences; German-IsraeliFoundation for Scientific Research and Development; and the Weizmann Institute'sCanadian Women for Science.