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Quantification of Breast Tumor Microvascular Permeability with Feruglose-enhanced MR Imaging: Initial Phase II Multicenter Trial¹

¹ From the Dept of Radiology, Univ Hosp, Technical Univ of Munich, Ismaningerstr 22, 81675 Munich, Germany (H.E.D.L., T.M.L., E.J.R.); MR-Ctr and Dept of Anaesthesia and Medical Imaging, Norwegian Univ of Science and Technology, Trondheim, Norway (J.R., K.A.K., O.H.); Dept of Radiology, Univ Hosp of Vienna, Austria (T.H.H., K.T., E.K.); Dept of Radiology, Univ Hosp of Oslo, Norway (A.B.); Div of Statistics, Amersham Health, Oslo, Norway (K.S.); and Ctr of Pharmaceutical and Molecular Imaging, Univ of California, San Francisco (D.S., R.C.B.). Received Aug 24, 2002; revision requested Oct 18; final revision received May 23, 2003; accepted May 27. Supported in part by NIH grant RO1 CA82923. Address correspondence to H.E.D.L. (e-mail: daldrup@roe.med.tum.de).

PURPOSE: To investigate use of the macromolecular contrast agent feruglose for differentiating and grading of human benign and malignant breast tumors on the basis of their microvascular characteristics.

MATERIALS AND METHODS: Sixty-three women with 63 primary breast lesions were examined with dynamic T1-weighted gradient-echo magnetic resonance (MR) imaging after intravenous injection of feruglose. A two-compartment unidirectional kinetic model applied to the dynamic data yielded estimates of the endothelial transfer coefficient, K^PS, and the fractional plasma volume of the tumors. These MR imaging–derived parameters were correlated with the histologic tumor grade and quantified according to the Scarff-Bloom-Richardson (SBR) score by means of Pearson product moment correlation analyses. Differences between malignant and nonmalignant breast lesions with respect to K^PS for feruglose were evaluated by means of the ² test and by calculating the sensitivity, specificity, and positive and negative predictive values.

RESULTS: Histologic analysis revealed 26 benign and 37 malignant tumors. A moderate yet statistically significant correlation between K^PS and SBR score was found (R = 0.496, P < .001). No significant correlation was observed between fractional plasma volume and SBR score (R = 0.085, P = .507). The K^PS values were zero for 19 (73%) of the 26 benign tumors and were greater than zero for 27 (73%) of the 37 carcinomas. This distribution was significantly different (² = 13.035, P = .001). With the criterion K^PS > 0 in carcinomas, sensitivity was 0.73, specificity was 0.73, and the positive predictive value was 0.79.

CONCLUSION: Quantitative measures of tumor microvascular permeability can be used for breast tumor characterization. The probability of breast tumor microvascular hyperpermeability to be associated with malignancy is 79%.

© RSNA, 2003

Index terms: Breast neoplasms, MR, 00.12143 • Iron • Magnetic resonance (MR), contrast media, 00.12143

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