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Objective: The early detection of breast cancer is one of the most important predictors in determining the prognosis for women with malignant tumours. Dynamic contrast-enhanced magnetic-resonance imaging (DCE-MRI) is an important imaging modality for detecting and interpreting the different breast lesions from a time sequence of images and has proved to be a very sensitive modality for breast-cancer diagnosis. However, DCE-MRI exhibits only a moderate specificity, thus leading to a high rate of false positives, resulting in unnecessary biopsies that are stressful and physically painful for the patient and lead to an increase in the cost of treatment. There is a strong medical need for a DCE-MRI computer-aided diagnosis tool that would offer a reliable support to the physician's decision providing a high level of sensitivity and specificity., Methods: In our study we investigated the possibility of increasing differentiation between the malignant and the benign lesions with respect to the spatial variation of the temporal enhancements of three parametric maps, i.e., the initial enhancement (IE) map, the post-initial enhancement (PIE) map and the signal enhancement ratio (SER) map, by introducing additional methods along with the grey-level co-occurrence matrix, i.e., a second-order statistical method already applied for quantifying the spatiotemporal variations. We introduced the grey-level run-length matrix and the grey-level difference matrix, representing two additional, second-order statistical methods, and the circular Gabor as a frequency-domain-based method. Each of the additional methods is for the first time applied to the DCE-MRI data to differentiate between the malignant and the benign breast lesions. We applied the least-square minimum-distance classifier (LSMD), logistic regression and least-squares support vector machine (LS-SVM) classifiers on a total of 115 (78 malignant and 37 benign) breast DCE-MRI cases. The performances were evaluated using ten experiments of a ten-fold cross-validation., Results: Our experimental analysis revealed the PIE map, together with the feature subset in which the discriminating ability of the co-occurrence features was increased by adding the newly introduced features, to be the most significant for differentiation between the malignant and the benign lesions. That diagnostic test - the aforementioned combination of parametric map and the feature subset achieved the sensitivity of 0.9193 which is statistically significantly higher compared to other diagnostic tests after ten-experiments of a ten-fold cross-validation and gave a statistically significantly higher specificity of 0.7819 for the fixed 95% sensitivity after the receiver operating characteristic (ROC) curve analysis. Combining the information from all the three parametric maps significantly increased the area under the ROC curve (AUC) of the aforementioned diagnostic test for the LSMD and logistic regression; however, not for the LS-SVM. The LSMD classifier yielded the highest area under the ROC curve when using the combined information, increasing the AUC from 0.9651 to 0.9755., Conclusion: Introducing new features to those of the grey-level co-occurrence matrix significantly increased the differentiation between the malignant and the benign breast lesions, thus resulting in a high sensitivity and improved specificity., (Copyright © 2013 Elsevier B.V. All rights reserved.)