Characterization of mammographic masses based on level set segmentation with new image features and patient information

Computer-aided diagnosis (CAD) for characterization of mammographic masses as malignant or benign has the potential to assist radiologists in reducing the biopsy rate without increasing false negatives. The purpose of this study was to develop an automated method for mammographic mass segmentation and explore new image based features in combination with patient information in order to improve the performance of mass characterization. The authors' previous CAD system, which used the active contour segmentation, and morphological, textural, and spiculation features, has achieved promising results in mass characterization. The new CAD system is based on the level set method and includes two new types of image features related to the presence of microcalcifications with the mass and abruptness of the mass margin, and patient age. A linear discriminant analysis (LDA) classifier with stepwise feature selection was used to merge the extracted features into a classification score. The classification accuracy was evaluated using the area under the receiver operating characteristic curve. The authors' primary data set consisted of 427 biopsy-proven masses (200 malignant and 227 benign) in 909 regions of interest (ROIs) (451 malignant and 458 benign) from multiple mammographic views. Leave-one-case-out resampling was used for training and testing. The new CAD system based on the level set segmentation and the new mammographic feature space achieved a view-based Az value of 0.83 +/- 0.01. The improvement compared to the previous CAD system was statistically significant (p = 0.02). When patient age was included in the new CAD system, view-based and case-based Az values were 0.85 +/- 0.01 and 0.87 +/- 0.02, respectively. The study also demonstrated the consistency of the newly developed CAD system by evaluating the statistics of the weights of the LDA classifiers in leave-one-case-out classification. Finally, an independent test on the publicly available digital database for screening mammography with 132 benign and 197 malignant ROIs containing masses achieved a view-based Az value of 0.84 +/- 0.02.     

Analysis of temporal changes of mammographic features: computer-aided classification of malignant and benign breast masses

A new classification scheme was developed to classify mammographic masses as malignant and benign by using interval change information. The masses on both the current and the prior mammograms were automatically segmented using an active contour method. From each mass, 20 run length statistics (RLS) texture features, 3 speculation features, and 12 morphological features were extracted. Additionally, 20 difference RLS features were obtained by subtracting the prior RLS features from the corresponding current RLS features. The feature space consisted of the current RLS features, the difference RLS features, the current and prior speculation features, and the current and prior mass sizes. Stepwise feature selection and linear discriminant analysis classification were used to select and merge the most useful features. A leave-one-case-out resampling scheme was used to train and test the classifier using 140 temporal image pairs (85 malignant, 55 benign) obtained from 57 biopsy-proven masses (33 malignant, 24 benign) in 56 patients. An average of 10 features were selected from the 56 training subsets: 4 difference RLS features, 4 RLS features, and 1 speculation feature from the current image, and 1 speculation feature from the prior, were most often chosen. The classifier achieved an average training Az of 0.92 and a test Az of 0.88. For comparison, a classifier was trained and tested using features extracted from the 120 current single images. This classifier achieved an average training Az of 0.90 and a test Az of 0.82. The information on the prior image significantly (p = 0.015) improved the accuracy for classification of the masses.     

Computerized characterization of breast masses on three-dimensional ultrasound volumes

We are developing computer vision techniques for the characterization of breast masses as malignant or benign on radiologic examinations. In this study, we investigated the computerized characterization of breast masses on three-dimensional (3-D) ultrasound (US) volumetric images. We developed 2-D and 3-D active contour models for automated segmentation of the mass volumes. The effect of the initialization method of the active contour on the robustness of the iterative segmentation method was studied by varying the contour used for its initialization. For a given segmentation, texture and morphological features were automatically extracted from the segmented masses and their margins. Stepwise discriminant analysis with the leave-one-out method was used to select effective features for the classification task and to combine these features into a malignancy score. The classification accuracy was evaluated using the area Az under the receiver operating characteristic (ROC) curve, as well as the partial area index Az(0.9), defined as the relative area under the ROC curve above a sensitivity threshold of 0.9. For the purpose of comparison with the computer classifier, four experienced breast radiologists provided malignancy ratings for the 3-D US masses. Our dataset consisted of 3-D US volumes of 102 biopsied masses (46 benign, 56 malignant). The classifiers based on 2-D and 3-D segmentation methods achieved test Az values of 0.87+/-0.03 and 0.92+/-0.03, respectively. The difference in the Az values of the two computer classifiers did not achieve statistical significance. The Az values of the four radiologists ranged between 0.84 and 0.92. The difference between the computer's Az value and that of any of the four radiologists did not achieve statistical significance either. However, the computer's Az(0.9) value was significantly higher than that of three of the four radiologists. Our results indicate that an automated and effective computer classifier can be designed for differentiating malignant and benign breast masses on 3-D US volumes. The accuracy of the classifier designed in this study was similar to that of experienced breast radiologists.     

Classification of breast masses in ultrasonic B scans using Nakagami and K distributions

Classification of breast masses in greyscale ultrasound images is undertaken using a multiparameter approach. Five parameters reflecting the non-Rayleigh nature of the backscattered echo were used. These parameters, based mostly on the Nakagami and K distributions, were extracted from the envelope of the echoes at the site, boundary, spiculated region and shadow of the mass. They were combined to create a linear discriminant. The performance of this discriminant for the classification of breast masses was studied using a data set consisting of 70 benign and 29 malignant cases. The Az value for the discriminant was 0.96 +/- 0.02, showing great promise in the classification of masses into benign and malignant ones. The discriminant was combined with the level of suspicion values of the radiologist leading to an Az value of 0.97 +/- 0.014. The parameters used here can be calculated with minimal clinical intervention, so the method proposed here may therefore be easily implemented in an automated fashion. These results also support the recent reports suggesting that ultrasound may help as an adjunct to mammography in breast cancer diagnostics to enhance the classification of breast masses.     

Computer-aided diagnosis in mammography: classification of mass and normal tissue by texture analysis

Computer-aided diagnosis schemes are being developed to assist radiologists in mammographic interpretation. In this study, we investigated whether texture features could be used to distinguish between mass and non-mass regions in clinical mammograms. Forty-five regions of interest (ROIs) containing true masses with various degrees of visibility and 135 ROIs containing normal breast parenchyma were extracted manually from digitized mammograms as case samples. Spatial-grey-level-dependence (SGLD) matrices of each ROI were calculated and eight texture features were calculated from the SGLD matrices. The correlation and class-distance properties of extracted texture features were analysed. Selected texture features were input into a modified decision-tree classification scheme. The performance of the classifier was evaluated for different feature combinations and orders of features on the tree. A classification accuracy of about 89% sensitivity and 76% specificity was obtained for ordered features, sum average, correlation, and energy, during the training procedure. With a leave-one-out method, the test result was about 76% sensitivity and 64% specificity. The results of this preliminary study demonstrate the feasibility of using texture information for classification of mass and normal breast tissue, which will be likely to be useful for classifying true and false detections in computer-aided diagnosis programmes.     

Characterization of mammographic masses using a gradient-based segmentation algorithm and a neural classifier

Computerized methods have recently shown a great potential in providing radiologists with a second opinion about the visual diagnosis of the malignancy of mammographic masses. The computer-aided diagnosis (CAD) system we developed for the mass characterization is mainly based on a segmentation algorithm and on the neural classification of several features computed on the segmented mass. Mass-segmentation plays a key role in most computerized systems. Our technique is a gradient-based one, showing the main characteristic that no free parameters have been evaluated on the data set used in this analysis, thus it can directly be applied to data sets acquired in different conditions without any ad hoc modification. A data set of 226 masses (109 malignant and 117 benign) has been used in this study. The segmentation algorithm works with a comparable efficiency both on malignant and benign masses. Sixteen features based on shape, size and intensity of the segmented masses are extracted and analyzed by a multi-layered perceptron neural network trained with the error back-propagation algorithm. The capability of the system in discriminating malignant from benign masses has been evaluated in terms of the receiver-operating characteristic (ROC) analysis. A feature selection procedure has been carried out on the basis of the feature discriminating power and of the linear correlations interplaying among them. The comparison of the areas under the ROC curves obtained by varying the number of features to be classified has shown that 12 selected features out of the 16 computed ones are powerful enough to achieve the best classifier performances. The radiologist assigned the segmented masses to three different categories: correctly-, acceptably- and non-acceptably-segmented masses. We initially estimated the area under ROC curve only on the first category of segmented masses (the 88.5% of the data set), then extending the classification to the second subclass (reaching the 97.8% of the data set) and finally to the whole data set, obtaining A(z)=0.805+/-0.030, 0.787+/-0.024 and 0.780+/-0.023, respectively.     

Classification of breast masses via nonlinear transformation of features based on a kernel matrix

We propose methods to perform a certain nonlinear transformation of features based on a kernel matrix, before the classification step, aiming to improve the discriminating power of the comparatively weak edge-sharpness and texture features of breast masses in mammograms, and seek better incorporation of features representing different radiological characteristics than shape features only. Kernel principal component analysis (KPCA) is applied to improve the discriminating power of each single feature in an expanded feature space and the discriminating capability of different feature combinations in other transformed, more informative, lower-dimensional feature spaces. A kernel partial least squares (KPLS) method is developed to derive score vectors for a shape feature set, and an edge-sharpness and texture feature set, respectively, with minimal covariance between each other, to help in achieving improved diagnosis using multiple radiological characteristics of breast masses. Fisher's linear discriminant analysis (FLDA) is employed to evaluate the classification capability of the transformed features. The methods were tested with a set of 57 regions in mammograms, of which 20 are related to malignant tumors and 37 to benign masses, represented using five shape features, three edge-sharpness features, and 14 texture features. The classification performance of the edge-sharpness and texture features, via KPCA transformation, was significantly improved from 0.75 to 0.85 in terms of the area under the receiver operating characteristics curve (Az). The classification performance of all of the shape, edge-sharpness, and texture features, via KPLS transformation, was improved from 0.95 to 1.0 in Az value.     

A completely automated CAD system for mass detection in a large mammographic database

Mass localization plays a crucial role in computer-aided detection (CAD) systems for the classification of suspicious regions in mammograms. In this article we present a completely automated classification system for the detection of masses in digitized mammographic images. The tool system we discuss consists in three processing levels: (a) Image segmentation for the localization of regions of interest (ROIs). This step relies on an iterative dynamical threshold algorithm able to select iso-intensity closed contours around gray level maxima of the mammogram. (b) ROI characterization by means of textural features computed from the gray tone spatial dependence matrix (GTSDM), containing second-order spatial statistics information on the pixel gray level intensity. As the images under study were recorded in different centers and with different machine settings, eight GTSDM features were selected so as to be invariant under monotonic transformation. In this way, the images do not need to be normalized, as the adopted features depend on the texture only, rather than on the gray tone levels, too. (c) ROI classification by means of a neural network, with supervision provided by the radiologist's diagnosis. The CAD system was evaluated on a large database of 3369 mammographic images [2307 negative, 1062 pathological (or positive), containing at least one confirmed mass, as diagnosed by an expert radiologist]. To assess the performance of the system, receiver operating characteristic (ROC) and free-response ROC analysis were employed. The area under the ROC curve was found to be Az = 0.783 +/- 0.008 for the ROI-based classification. When evaluating the accuracy of the CAD against the radiologist-drawn boundaries, 4.23 false positives per image are found at 80% of mass sensitivity.     

Incorporation of an iterative, linear segmentation routine into a mammographic mass CAD system

In previous research, we have developed a computer-aided detection (CAD) system designed to detect masses in mammograms. The previous version of our system employed a simple but imprecise method to localize the masses. In this research, we present a more robust segmentation routine for use with mammographic masses. Our hypothesis is that by more accurately describing the morphology of the masses, we can improve the CAD system's ability to distinguish masses from other mammographic structures. To test this hypothesis, we incorporated the new segmentation routine into our CAD system and examined the change in performance. The developed iterative, linear segmentation routine is a gray level-based procedure. Using the identified regions from the previous CAD system as the initial seeds, the new segmentation algorithm refines the suspicious mass borders by making estimates of the interior and exterior pixels. These estimates are then passed to a linear discriminant, which determines the optimal threshold between the interior and exterior pixels. After applying the threshold and identifying the object's outline, two constraints on the border are applied to reduce the influence of background noise. After the border is constrained, the process repeats until a stopping criterion is reached. The segmentation routine was tested on a study database of 183 mammographic images extracted from the Digital Database for Screening Mammography. Eighty-three of the images contained 50 malignant and 50 benign masses; 100 images contained no masses. The previously developed CAD system was used to locate a set of suspicious regions of interest (ROIs) within the images. To assess the performance of the segmentation algorithm, a set of 20 features was measured from the suspicious regions before and after the application of the developed segmentation routine. Receiver operating characteristic (ROC) analysis was employed on the ROIs to examine the discriminatory capabilities of each individual feature before and after the segmentation routine. A statistically significant performance increase was found in many of the individual features, particularly those describing the mass borders. To examine how the incorporation of the segmentation routine affected the performance of the overall CAD system, free-response ROC (FROC) analysis was employed. When considering only malignant masses, the FROC performance of the system with the segmentation routine appeared better than the previous system. When detecting 90% of the malignant masses, the previous system achieved 4.9 false positives per image (FPpI) compared to the post-segmentation system's 4.2 FPpI. At 80% sensitivity, the respective FPpI were 3.5 and 1.6.     

Combined adaptive enhancement and region-growing segmentation of breast masses on digitized mammograms.

As an ongoing effort to develop a computer aid for detection of masses on mammograms, we recently designed an object-based region-growing technique to improve mass segmentation. This segmentation method utilizes the density-weighted contrast enhancement (DWCE) filter as a pre-processing step. The DWCE filter adaptively enhances the contrast between the breast structures and the background. Object-based region growing was then applied to each of the identified structures. The region-growing technique uses gray-scale and gradient information to adjust the initial object borders and to reduce merging between adjacent or overlapping structures. Each object is then classified as a breast mass or normal tissue based on extracted morphological and texture features. In this study we evaluated the sensitivity of this combined segmentation scheme and its ability to reduce false positive (FP) detections on a data set of 253 digitized mammograms, each of which contained a biopsy-proven breast mass. It was found that the segmentation scheme detected 98% of the 253 biopsy-proven breast masses in our data set. After final FP reduction, the detection resulted in 4.2 FP per image at a 90% true positive (TP) fraction and 2.0 FPs per image at an 80% TP fraction. The combined DWCE and object-based region growing technique increased the initial detection sensitivity, reduced merging between neighboring structures, and reduced the number of FP detections in our automated breast mass detection scheme.     

Identification of masses in digital mammogram using gray level co-occurrence matrices

Digital mammogram has become the most effective technique for early breast cancer detection modality. Digital mammogram takes an electronic image of the breast and stores it directly in a computer. The aim of this study is to develop an automated system for assisting the analysis of digital mammograms. Computer image processing techniques will be applied to enhance images and this is followed by segmentation of the region of interest (ROI). Subsequently, the textural features will be extracted from the ROI. The texture features will be used to classify the ROIs as either masses or non-masses. In this study normal breast images and breast image with masses used as the standard input to the proposed system are taken from Mammographic Image Analysis Society (MIAS) digital mammogram database. In MIAS database, masses are grouped into either spiculated, circumscribed or ill-defined. Additional information includes location of masses centres and radius of masses. The extraction of the textural features of ROIs is done by using gray level co-occurrence matrices (GLCM) which is constructed at four different directions for each ROI. The results show that the GLCM at 0o, 45o, 90o and 135o with a block size of 8X8 give significant texture information to identify between masses and non-masses tissues. Analysis of GLCM properties i.e. contrast, energy and homogeneity resulted in receiver operating characteristics (ROC) curve area of Az = 0.84 for Otsu's method, 0.82 for thresholding method and Az = 0.7 for K-mean clustering. ROC curve area of 0.8-0.9 is rated as good results. The authors' proposed method contains no complicated algorithm. The detection is based on a decision tree with five criterions to be analysed. This simplicity leads to less computational time. Thus, this approach is suitable for automated real-time breast cancer diagnosis system.     

Characterization of clustered microcalcifications in digitized mammograms using neural networks and support vector machines

OBJECTIVE: Detection and characterization of microcalcification clusters in mammograms is vital in daily clinical practice. The scope of this work is to present a novel computer-based automated method for the characterization of microcalcification clusters in digitized mammograms. METHODS AND MATERIAL: The proposed method has been implemented in three stages: (a) the cluster detection stage to identify clusters of microcalcifications, (b) the feature extraction stage to compute the important features of each cluster and (c) the classification stage, which provides with the final characterization. In the classification stage, a rule-based system, an artificial neural network (ANN) and a support vector machine (SVM) have been implemented and evaluated using receiver operating characteristic (ROC) analysis. The proposed method was evaluated using the Nijmegen and Mammographic Image Analysis Society (MIAS) mammographic databases. The original feature set was enhanced by the addition of four rule-based features. RESULTS AND CONCLUSIONS: In the case of Nijmegen dataset, the performance of the SVM was Az=0.79 and 0.77 for the original and enhanced feature set, respectively, while for the MIAS dataset the corresponding characterization scores were Az=0.81 and 0.80. Utilizing neural network classification methodology, the corresponding performance for the Nijmegen dataset was Az=0.70 and 0.76 while for the MIAS dataset it was Az=0.73 and 0.78. Although the obtained high classification performance can be successfully applied to microcalcification clusters characterization, further studies must be carried out for the clinical evaluation of the system using larger datasets. The use of additional features originating either from the image itself (such as cluster location and orientation) or from the patient data may further improve the diagnostic value of the system.     

Development of tolerant features for characterization of masses in mammograms

In this paper, four new features for the analysis of breast masses are presented. These features were designed to be insensitive to the exact shape of the contour of the masses, so that an approximate contour, such as the one extracted via an automated segmentation algorithm, can be employed in their computation. Two of the features, Sp_SI and Sp_GO, measure the degree of spiculation of a mass and its likelihood of being spiculated. One of these features, Sp_GO, is a measure of the relative gradient orientation of pixels that correspond to possible spicules. The other feature, Sp_SI, is based on a comparison of mutual information measures between selected components of the mammographic images. The last two features, Fz₁ and Fz₂, measure the local fuzziness of the mass margins based on points defined automatically. The features were tested for characterization (i.e. discrimination between circumscribed and spiculated masses) and diagnosis (i.e. discrimination between benign and malignant masses) of breast masses using a set of 319 masses and three different classifiers. In the characterization experiments the features produced a result of approximately 89% correct classification. In the diagnosis experiments, the performance achieved was approximately 81% of correct classification.     

Computerized analysis of mammographic parenchymal patterns for assessing breast cancer risk: effect of ROI size and location

The long-term goal of our research is to develop computerized radiographic markers for assessing breast density and parenchymal patterns that may be used together with clinical measures for determining the risk of breast cancer and assessing the response to preventive treatment. In our earlier studies, we found that women at high risk tended to have dense breasts with mammographic patterns that were coarse and low in contrast. With our method, computerized texture analysis is performed on a region of interest (ROI) within the mammographic image. In our current study, we investigate the effect of ROI size and ROI location on the computerized texture features obtained from 90 subjects (30 BRCA1/BRCA2 gene-mutation carriers and 60 age-matched women deemed to be at low risk for breast cancer). Mammograms were digitized at 0.1 mm pixel size and various ROI sizes were extracted from different breast regions in the craniocaudal (CC) view. Seventeen features, which characterize the density and texture of the parenchymal patterns, were extracted from the ROIs on these digitized mammograms. Stepwise feature selection and linear discriminant analysis were applied to identify features that differentiate between the low-risk women and the BRCA1/BRCA2 gene-mutation carriers. ROC analysis was used to assess the performance of the features in the task of distinguishing between these two groups. Our results show that there was a statistically significant decrease in the performance of the computerized texture features, as the ROI location was varied from the central region behind the nipple. However, we failed to show a statistically significant decrease in the performance of the computerized texture features with decreasing ROI size for the range studied.     

Computerized interpretation of breast MRI: investigation of enhancement-variance dynamics

The advantages of breast MRI using contrast agent Gd-DTPA in the diagnosis of breast cancer have been well established. The variation of interpretation criteria and absence of interpretation guidelines, however, is a major obstacle for applications of MRI in the routine clinical practice of breast imaging. Our study aims to increase the objectivity and reproducibility of breast MRI interpretation by developing an automated interpretation approach for ultimate use in computer-aided diagnosis. The database in this study contains 121 cases: 77 malignant and 44 benign masses as revealed by biopsy. Images were obtained using a T1-weighted 3D spoiled gradient echo sequence. After the acquisition of the precontrast series, Gd-DTPA contrast agent was injected intravenously by power injection with a dose of 0.2 mmol/kg. Five postcontrast series were then taken with a time interval of 60 s. Each series contained 64 coronal slices with a matrix of 128 x 256 pixels and an in-plane resolution of 1.25 x 1.25 mm2. Slice thickness ranged from 2 to 3 mm depending on breast size. The lesions were delineated by an experienced radiologist as well as independently by computer using an automatic volume-growing algorithm. Fourteen features that were extracted automatically from the lesions could be grouped into three categories based on (I) morphology, (II) enhancement kinetics, and (III) time course of enhancement-variation over the lesion. A stepwise feature selection procedure was employed to select an effective subset of features, which were then combined by linear discriminant analysis (LDA) into a discriminant score, related to the likelihood of malignancy. The classification performances of individual features and the combined discriminant score were evaluated with receiver operating characteristic (ROC) analysis. With the radiologist-delineated lesion contours, stepwise feature selection yielded four features and an Az value of 0.80 for the LDA in leave-one-out cross-validation testing. With the computer-segmented lesion volumes, it yielded six features and an Az value of 0.86 for the LDA in the leave-one-out testing.     

Computer-aided detection of breast masses on full field digital mammograms

We are developing a computer-aided detection (CAD) system for breast masses on full field digital mammographic (FFDM) images. To develop a CAD system that is independent of the FFDM manufacturer's proprietary preprocessing methods, we used the raw FFDM image as input and developed a multiresolution preprocessing scheme for image enhancement. A two-stage prescreening method that combines gradient field analysis with gray level information was developed to identify mass candidates on the processed images. The suspicious structure in each identified region was extracted by clustering-based region growing. Morphological and spatial gray-level dependence texture features were extracted for each suspicious object. Stepwise linear discriminant analysis (LDA) with simplex optimization was used to select the most useful features. Finally, rule-based and LDA classifiers were designed to differentiate masses from normal tissues. Two data sets were collected: a mass data set containing 110 cases of two-view mammograms with a total of 220 images, and a no-mass data set containing 90 cases of two-view mammograms with a total of 180 images. All cases were acquired with a GE Senographe 2000D FFDM system. The true locations of the masses were identified by an experienced radiologist. Free-response receiver operating characteristic analysis was used to evaluate the performance of the CAD system. It was found that our CAD system achieved a case-based sensitivity of 70%, 80%, and 90% at 0.72, 1.08, and 1.82 false positive (FP) marks/image on the mass data set. The FP rates on the no-mass data set were 0.85, 1.31, and 2.14 FP marks/image, respectively, at the corresponding sensitivities. This study demonstrated the usefulness of our CAD techniques for automated detection of masses on FFDM images.