Purpose: To investigate a fast, objective, and standardized method for analyzing breast dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) applying principal component analysis (PCA) adjusted with a model-based method.Materials and Methods: 3D gradient-echo DCE breast images of 31 malignant and 38 benign lesions, recorded on a 1.5T scanner, were retrospectively analyzed by PCA and by the model-based three-timepoints (3TP) method.Results: Intensity-scaled (IS) and enhancement-scaled (ES) datasets were reduced by PCA yielding a first IS-eigenvector that captured the signal variation between fat and fibroglandular tissue; two IS-eigenvectors and the two first ES-eigenvectors captured contrast-enhanced changes, whereas the remaining eigenvectors captured predominantly noise changes. Rotation of the two contrast-related eigenvectors led to a high congruence between the projection coefficients and the 3TP parameters. The ES-eigenvectors and the rotation angle were highly reproducible across malignant lesions, enabling calculation of a general rotated eigenvector base. Receiver operating characteristic (ROC) curve analysis of the projection coefficients of the two eigenvectors indicated high sensitivity of the first rotated eigenvector to detect lesions (area under the curve [AUC] > 0.97) and of the second rotated eigenvector to differentiate malignancy from benignancy (AUC ¼ 0.87). Conclusion:PCA adjusted with a model-based method provided a fast and objective computer-aided diagnostic tool for breast DCE-MRI.

The role of c-Myc in estrogen regulation of vascular endothelial growth factor (VEGF) and of the vasculature function has been investigated in breast cancer cells and tumors. The studies were performed on MCF7 wild-type cells and MCF7-35im clone, stably transfected with an inducible c-Myc gene. In vitro and ex vivo methods for investigating molecular events were integrated with in vivo magnetic resonance imaging of the vascular function. The results showed that the c-Myc upregulation by estrogen is necessary for the transient induction of VEGF transcription; however, overexpression of c-Myc alone is not sufficient for this induction. Furthermore, both c-Myc and the activated estrogen receptor a (ERa) were shown to co-bind the VEGF promoter in close proximity, indicating a novel mechanism for estrogen regulation of VEGF. Studies of long-term estrogen treatment and overexpression of c-Myc alone demonstrated regulation of stable VEGF expression levels in vitro and in vivo, maintaining steady vascular permeability in tumors. However, withdrawal of estrogen from the tumors resulted in increased VEGF and elevated vascular permeability, presumably due to hypoxic conditions that were found to dominate VEGF overexpression in cultured cells. This work revealed a cooperative role for ERa and c-Myc in estrogen regulation of VEGF and the ability of c-Myc to partially mimic estrogen regulation of angiogenesis. It also illuminated the differences in estrogen regulation of VEGF during transient and long-term sustained treatments and under different microenvironmental conditions, providing a complementary picture of the in vitro and in vivo results.

Dynamic contrast enhanced MRI is applied as an adjuvant tool for breast cancer detection, diagnosis, and follow-up of therapy. Despite improvements through the years in achieving higher spatial and temporal resolution, it still suffers from lack of scanning and processing standardization, and consequently, high variability in the radiological evaluation, particularly differentiating malignant from benign lesions. We describe here a hybrid method for achieving standardization of the radiological evaluation of breast dynamic contrast enhanced (DCE)-magnetic resonance imaging (MRI) protocols, based on integrating the model based three time point (3TP) method with principal component analysis (PCA). The scanning and image processing procedures consisted of three main steps: 1. 3TP standardization of the MRI acquisition parameters according to a kinetic model, 2. Applying PCA to test cases and constructing an eigenvectors' base related to the contrast-enhancement kinetics and 3. Projecting all new cases on the eigenvectors' base and evaluating the clinical outcome. Datasets of overall 96 malignant and 26 benign breast lesions were recorded on 1.5T and 3T scanners, using three different MRI acquisition parameters optimized by the 3TP method. The final radiological evaluation showed similar detection and diagnostic ability for the three different MRI acquisition parameters. The area under the curve of receiver operating characteristic analysis yielded a value of 0.88 ± 0.034 for differentiating malignant from benign lesions. This 3TP + PCA hybrid method is fast and can be readily applied as a computer aided diagnostic tool of breast cancer. The underlying principles of this method can be extended to standardize the evaluation of malignancies in other organs.

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