Principal component analysis of breast DCE-MRI adjusted with a model-based method.

PURPOSE: To investigate a fast, objective, and standardized method for analyzing breast dynamic contrast-enhanced 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 = 0.87). CONCLUSION: PCA adjusted with a model-based method provided a fast and objective computer-aided diagnostic tool for breast DCE-MRI.

Estrogen regulation of vascular endothelial growth factor in breast cancer in vitro and in vivo: the role of estrogen receptor alpha and c-Myc.

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 alpha (ERalpha) 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 ERalpha 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.