Improving Suspicious Breast Lesion Characterization Using Lesion Fractional Volume Washout Kinetic Analysis

Introduction: Dynamic contrast-enhanced (DCE) breast MRI has been shown to be very sensitive in cancer detection [1,2]. Most malignant tumors demonstrate an initial enhancement followed by a rapid wash-out (WO) or plateau curve in the post-contrast signal intensity time courses. The WO curve mainly reflects the hypervascularity associated with tumor angiogenesis essential for tumor growth [3-5]. Although most benign lesions exhibit a slower but persistent enhancement without the WO behavior [1], false-positive kinetic curves were frequently observed in many benign lesions including fibroadenomas, proliferative fibrocystic changes, atypical ductal hyperplasia, etc. [6,7]. This results in a low specificity and consequently a smaller positive predictive value (PPV) for biopsies. In a recent study involving a total of 125 suspicious or highly suggestive of malignant lesions (BI-RADS 4 or 5), the biopsies resulted in 42 malignant tumors and 83 benign lesions, showing a 33.6% PPV at the clinic [8]. Our recent preliminary study demonstrates the potential of using WO volume fraction as a new biomarker for differentiating benign from malignant contrast-enhancing breast lesions [9]. The hypothesis is that WO volume fraction, those voxels showing rapid wash-in and wash-out behavior in proportion to total lesion voxels showing rapid wash-in, has the potential to be a biomarker for indicating the degree of hypervascularity associated with tumor angiogenesis. Currently, the usual clinical approach is based on selecting only the most suspicious voxels within a lesion to characterize that lesion and does not incorporate the proportion of the most suspicious wash-out voxels to the total lesion volume. We hypothesized that the WO volume fraction for benign proliferation might be relatively small in comparison to malignant lesions, considering that an aggressive cancer cell growth is most likely accompanied by relatively larger angiogenesis [9]. In this study we investigated using the WO volume fraction as a biomarker for improving the characterization of suspicious contrast-enhancing breast lesions, aiming to improve the PPV of biopsies and consequently to reduce the number of unnecessary biopsies.