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

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 χ² 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 (χ² = 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%.