Computer aided detection of clusters of microcalcifications on full field digital mammograms

We are developing a computer-aided detection (CAD) system to identify microcalcification clusters (MCCs) automatically on full field digital mammograms (FFDMs). The CAD system includes six stages: preprocessing; image enhancement; segmentation of microcalcification candidates; false positive (FP) reduction for individual microcalcifications; regional clustering; and FP reduction for clustered microcalcifications. At the stage of FP reduction for individual microcalcifications, a truncated sum-of-squares error function was used to improve the efficiency and robustness of the training of an artificial neural network in our CAD system for FFDMs. At the stage of FP reduction for clustered microcalcifications, morphological features and features derived from the artificial neural network outputs were extracted from each cluster. Stepwise linear discriminant analysis (LDA) was used to select the features. An LDA classifier was then used to differentiate clustered microcalcifications from FPs. A data set of 96 cases with 192 images was collected at the University of Michigan. This data set contained 96 MCCs, of which 28 clusters were proven by biopsy to be malignant and 68 were proven to be benign. The data set was separated into two independent data sets for training and testing of the CAD system in a cross-validation scheme. When one data set was used to train and validate the convolution neural network (CNN) in our CAD system, the other data set was used to evaluate the detection performance. With the use of a truncated error metric, the training of CNN could be accelerated and the classification performance was improved. The CNN in combination with an LDA classifier could substantially reduce FPs with a small tradeoff in sensitivity. By using the free-response receiver operating characteristic methodology, it was found that our CAD system can achieve a cluster-based sensitivity of 70, 80, and 90 % at 0.21, 0.61, and 1.49 FPs/image, respectively. For case-based performance evaluation, a sensitivity of 70, 80, and 90 % can be achieved at 0.07, 0.17, and 0.65 FPs/image, respectively. We also used a data set of 216 mammograms negative for clustered microcalcifications to further estimate the FP rate of our CAD system. The corresponding FP rates were 0.15, 0.31, and 0.86 FPs/image for cluster-based detection when negative mammograms were used for estimation of FP rates.     

Computer aided detection of microcalcifications in digital mammograms

Microcalcification detection is widely used for early diagnosis of breast cancer. Nevertheless, mammogram visual analysis is a complex task for expert radiologists. In this paper, we present a new method for computer aided detection of microcalcifications in digital mammograms. The detection is performed on the wavelet transformed image. The calcifications are separated from the background by exploiting the evaluation of Renyi's information at the different decomposition levels of the wavelet transform. Experiments are performed on a standard and publicly available dataset and the results are evaluated with respect to recent achievements reported in the literature.     

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.     

Computer-aided detection of clustered microcalcifications on digital mammograms

A computer-aided diagnosis scheme to assist radiologists in detecting clustered microcalcifications from mammograms is being developed. Starting with a digital mammogram, the scheme consists of three steps. First, the image is filtered so that the signal-to-noise ratio of microcalcifications is increased by suppression of the normal background structure of the breast. Secondly, potential microcalcifications are extracted from the filtered image with a series of three different techniques: a global thresholding based on the grey-level histogram of the full filtered image, an erosion operator for eliminating very small signals, and a local adaptive grey-level thresholding. Thirdly, some false-positive signals are eliminated by means of a texture analysis technique, and a non-linear clustering algorithm is then used for grouping the remaining signals. With this method, the scheme can detect approximately 85% of true clusters, with an average of two false clusters detected per image.     

An improved method for simulating microcalcifications in digital mammograms

The assessment of the performance of a digital mammography system requires an observer study with a relatively large number of cases with known truth which is often difficult to assemble. Several investigators have developed methods for generating hybrid abnormal images containing simulated microcalcifications. This article addresses some of the limitations of earlier methods. The new method is based on digital images of needle biopsy specimens. Since the specimens are imaged separately from the breast, the microcalcification attenuation profile scan is deduced without the effects of over and underlying tissues. The resulting templates are normalized for image acquisition specific parameters and reprocessed to simulate microcalcifications appropriate to other imaging systems, with different x-ray, detector and image processing parameters than the original acquisition system. This capability is not shared by previous simulation methods that have relied on extracting microcalcifications from breast images. The method was validated by five experienced mammographers who compared 59 pairs of simulated and real microcalcifications in a two-alternative forced choice task designed to test if they could distinguish the real from the simulated lesions. They also classified the shapes of the microcalcifications according to a standardized clinical lexicon. The observed probability of correct choice was 0.415, 95% confidence interval (0.284, 0.546), showing that the radiologists were unable to distinguish the lesions. The shape classification revealed substantial agreement with the truth (mean kappa = 0.70), showing that we were able to accurately simulate the lesion morphology. While currently limited to single microcalcifications, the method is extensible to more complex clusters of microcalcifications and to three-dimensional images. It can be used to objectively assess an imaging technology, especially with respect to its ability to adequately visualize the morphology of the lesions, which is a critical factor in the benign versus malignant classification of a lesion detected in screening mammography.     

A wavelet-based algorithm for detecting clustered microcalcifications in digital mammograms.

A computerized scheme to detect clustered microcalcifications in digital mammograms has been developed. Detection of individual microcalcifications in regions of interest (ROIs) was also performed. The mammograms were previously classified into fatty and dense, according to their breast tissue. The most appropriate wavelet basis and reconstruction levels were selected. To select the wavelet basis, 40 profiles of microcalcifications were decomposed and reconstructed using different types of wavelet functions and different combinations of wavelet coefficients. The symlets with a basis of length 8 were chosen for fatty tissue. For dense tissue, the Daubechies' wavelets with a four-element basis were employed. Two methods to detect individual microcalcifications were evaluated: (a) two-dimensional wavelet transform, and (b) one-dimensional wavelet transform. The second technique yielded the best results, and was used to detect clustered microcalcifications in the complete mammogram. When detecting individual microcalcifications by using two-dimensional wavelet transform we have obtained, for fatty ROIs, a sensitivity of 71.11% at a false positive rate of 7.13 per image. For dense ROIs the sensitivity was 60.76% and the false positive rate, 7.33. The areas (A1) under the AFROC curves were 0.33+/-0.04 and 0.28+/-0.02, respectively. The one-dimensional wavelet transform method yielded 80.44% of sensitivity and 6.43 false positives per image (A1=0.39+/-0.03) for fatty ROIs, and 62.17% and 5.82 false positives per image (A1=0.37+/-0.02) for dense ROIs. For the detection of clusters of microcalcifications in the entire mammogram, the sensitivity was 80.00% with 0.94 false positives per image (A1=0.77+/-0.09) for fatty mammograms, and 72.85% of sensitivity at a false positive detection rate of 2.21 per image (A1=0.64+/-0.07) for dense mammograms. Globally, a sensitivity of 76.43% at a false positive detection rate of 1.57 per image was obtained.     

Quantification of breast arterial calcification using full field digital mammography

Breast arterial calcification is commonly detected on some mammograms. Previous studies indicate that breast arterial calcification is evidence of general atherosclerotic vascular disease and it may be a useful marker of coronary artery disease. It can potentially be a useful tool for assessment of coronary artery disease in women since mammography is widely used as a screening tool for early detection of breast cancer. However, there are currently no available techniques for quantification of calcium mass using mammography. The purpose of this study was to determine whether it is possible to quantify breast arterial calcium mass using standard digital mammography. An anthropomorphic breast phantom along with a vessel calcification phantom was imaged using a full field digital mammography system. Densitometry was used to quantify calcium mass. A calcium calibration measurement was performed at each phantom thickness and beam energy. The known (K) and measured (M) calcium mass on 5 and 9 cm thickness phantoms were related by M=0.964K -0.288 mg (r=0.997 and SEE=0.878 mg) and M=1.004K+0.324 mg (r=0.994 and SEE = 1.32 mg), respectively. The results indicate that accurate calcium mass measurements can be made without correction for scatter glare as long as careful calcium calibration is made for each breast thickness. The results also indicate that composition variations and differences of approximately 1 cm between calibration phantom and breast thickness introduce only minimal error in calcium measurement. The uncertainty in magnification is expected to cause up to 5% and 15% error in calcium mass for 5 and 9 cm breast thicknesses, respectively. In conclusion, a densitometry technique for quantification of breast arterial calcium mass was validated using standard full field digital mammography. The results demonstrated the feasibility and potential utility of the densitometry technique for accurate quantification of breast arterial calcium mass using standard digital mammography.     

An SVM classifier to separate false signals from microcalcifications in digital mammograms.

In this paper we investigate the feasibility of using an SVM (support vector machine) classifier in our automatic system for the detection of clustered microcalcifications in digital mammograms. SVM is a technique for pattern recognition which relies on the statistical learning theory. It minimizes a function of two terms: the number of misclassified vectors of the training set and a term regarding the generalization classifier capability. We compare the SVM classifier with an MLP (multi-layer perceptron) in the false-positive reduction phase of our detection scheme: a detected signal is considered either microcalcification or false signal, according to the value of a set of its features. The SVM classifier gets slightly better results than the MLP one (Az value of 0.963 against 0.958) in the presence of a high number of training data; the improvement becomes much more evident (Az value of 0.952 against 0.918) in training sets of reduced size. Finally, the setting of the SVM classifier is much easier than the MLP one.     

Segmentation of suspicious clustered microcalcifications in mammograms

We have developed a multistage computer-aided diagnosis (CAD) scheme for the automated segmentation of suspicious microcalcification clusters in digital mammograms. The scheme consisted of three main processing steps. First, the breast region was segmented and its high-frequency content was enhanced using unsharp masking. In the second step, individual microcalcifications were segmented using local histogram analysis on overlapping subimages. For this step, eight histogram features were extracted for each subimage and were used as input to a fuzzy rule-based classifier that identified subimages containing microcalcifications and assigned the appropriate thresholds to segment any microcalcifications within them. The final step clustered the segmented microcalcifications and extracted the following features for each cluster: the number of microcalcifications, the average distance between microcalcifications, and the average number of times pixels in the cluster were segmented in the second step. Fuzzy logic rules incorporating the cluster features were designed to remove nonsuspicious clusters, defined as those with typically benign characteristics. A database of 98 images, with 48 images containing one or more microcalcification clusters, provided training and testing sets to optimize the parameters and evaluate the CAD scheme, respectively. The results showed a true positive rate of 93.2% and an average of 0.73 false positive clusters per image. A comparison of our results with other reported segmentation results on the same database showed comparable sensitivity and at the same time an improved false positive rate. The performance of the CAD scheme is encouraging for its use as an automatic tool for efficient and accurate diagnosis of breast cancer.     

Computer-aided detection system for clustered microcalcifications: comparison of performance on full-field digital mammograms and digitized screen-film mammograms

We have developed a computer-aided detection (CAD) system to detect clustered microcalcifications automatically on full-field digital mammograms (FFDMs) and a CAD system for screen-film mammograms (SFMs). The two systems used the same computer vision algorithms but their false positive (FP) classifiers were trained separately with sample images of each modality. In this study, we compared the performance of the CAD systems for detection of clustered microcalcifications on pairs of FFDM and SFM obtained from the same patient. For case-based performance evaluation, the FFDM CAD system achieved detection sensitivities of 70%, 80% and 90% at an average FP cluster rate of 0.07, 0.16 and 0.63 per image, compared with an average FP cluster rate of 0.15, 0.38 and 2.02 per image for the SFM CAD system. The difference was statistically significant with the alternative free-response receiver operating characteristic (AFROC) analysis. When evaluated on data sets negative for microcalcification clusters, the average FP cluster rates of the FFDM CAD system were 0.04, 0.11 and 0.33 per image at detection sensitivity level of 70%, 80% and 90% compared with an average FP cluster rate of 0.08, 0.14 and 0.50 per image for the SFM CAD system. When evaluated for malignant cases only, the difference of the performance of the two CAD systems was not statistically significant with AFROC analysis.     

Computerized detection of clustered microcalcifications in digital mammograms: applications of artificial neural networks.

Artificial neural networks have been applied to the differentiation of actual "true" clusters from normal parenchymal patterns and also to the differentiation of actual clusters from false-positive clusters as reported by a computerized scheme for the detection of microcalcifications in digital mammograms. The differentiation was carried out in both the spatial and frequency domains. The performance of the neural networks was evaluated quantitatively by means of receiver operating characteristic (ROC) analysis. It was found that the networks could distinguish clustered microcalcifications from normal nonclustered areas in the frequency domain, and that they could eliminate approximately 50% of false-positive clusters of microcalcifications while preserving 95% of the positive clusters, when applied to the results of the automated detection scheme. A large, comprehensive training database is needed for neural networks to perform reliably in clinical situations.     

A controlled phantom study of a noise equalization algorithm for detecting microcalcifications in digital mammograms

We report on some extensions and further developments of a well-known microcalcification detection algorithm based on adaptive noise equalization. Tissue equivalent phantom images with and without labeled microcalcifications were subjected to this algorithm, and analyses of results revealed some shortcomings in the approach. Particularly, it was observed that the method of estimating the width of distributions in the feature space was based on assumptions which resulted in the loss of similarity preservation characteristics. A modification involving a change of estimator statistic was made, and the modified approach was tested on the same phantom images. Other modifications for improving detectability such as downsampling and use of alternate local contrast filters were also tested. The results indicate that these modifications yield improvements in detectability, while extending the generality of the approach. Extensions to real mammograms and further directions of research are discussed.     

Joint two-view information for computerized detection of microcalcifications on mammograms

We are developing new techniques to improve the accuracy of computerized microcalcification detection by using the joint two-view information on craniocaudal (CC) and mediolateral-oblique (MLO) views. After cluster candidates were detected using a single-view detection technique, candidates on CC and MLO views were paired using their radial distances from the nipple. Candidate pairs were classified with a similarity classifier that used the joint information from both views. Each cluster candidate was also characterized by its single-view features. The outputs of the similarity classifier and the single-view classifier were fused and the cluster candidate was classified as a true microcalcification cluster or a false-positive (FP) using the fused two-view information. A data set of 116 pairs of mammograms containing microcalcification clusters and 203 pairs of normal images from the University of South Florida (USF) public database was used for training the two-view detection algorithm. The trained method was tested on an independent test set of 167 pairs of mammograms, which contained 71 normal pairs and 96 pairs with microcalcification clusters collected at the University of Michigan (UM). The similarity classifier had a very low FP rate for the test set at low and medium levels of sensitivity. However, the highest mammogram-based sensitivity that could be reached by the similarity classifier was 69%. The single-view classifier had a higher FP rate compared to the similarity classifier, but it could reach a maximum mammogram-based sensitivity of 93%. The fusion method combined the scores of these two classifiers so that the number of FPs was substantially reduced at relatively low and medium sensitivities, and a relatively high maximum sensitivity was maintained. For the malignant microcalcification clusters, at a mammogram-based sensitivity of 80%, the FP rates were 0.18 and 0.35 with the two-view fusion and single-view detection methods, respectively. When the training and test sets were switched, a similar improvement was obtained, except that both the fusion and single-view detection methods had superior test performances on the USF data set than those on the UM data set. Our results indicate that correspondence of cluster candidates on two different views provides valuable additional information for distinguishing FPs from true microcalcification clusters.     

Optimization of exposure parameters in full field digital mammography

Optimization of exposure parameters (target, filter, and kVp) in digital mammography necessitates maximization of the image signal-to-noise ratio (SNR), while simultaneously minimizing patient dose. The goal of this study is to compare, for each of the major commercially available full field digital mammography (FFDM) systems, the impact of the selection of technique factors on image SNR and radiation dose for a range of breast thickness and tissue types. This phantom study is an update of a previous investigation and includes measurements on recent versions of two of the FFDM systems discussed in that article, as well as on three FFDM systems not available at that time. The five commercial FFDM systems tested, the Senographe 2000D from GE Healthcare, the Mammomat Novation DR from Siemens, the Selenia from Hologic, the Fischer Senoscan, and Fuji's 5000MA used with a Lorad M-IV mammography unit, are located at five different university test sites. Performance was assessed using all available x-ray target and filter combinations and nine different phantom types (three compressed thicknesses and three tissue composition types). Each phantom type was also imaged using the automatic exposure control (AEC) of each system to identify the exposure parameters used under automated image acquisition. The figure of merit (FOM) used to compare technique factors is the ratio of the square of the image SNR to the mean glandular dose. The results show that, for a given target/filter combination, in general FOM is a slowly changing function of kVp, with stronger dependence on the choice of target/filter combination. In all cases the FOM was a decreasing function of kVp at the top of the available range of kVp settings, indicating that higher tube voltages would produce no further performance improvement. For a given phantom type, the exposure parameter set resulting in the highest FOM value was system specific, depending on both the set of available target/filter combinations, and on the receptor type. In most cases, the AECs of the FFDM systems successfully identified exposure parameters resulting in FOM values near the maximum ones, however, there were several examples where AEC performance could be improved.     

Spectral analysis of full field digital mammography data

The spectral content of mammograms acquired from using a full field digital mammography (FFDM) system are analyzed. Fourier methods are used to show that the FFDM image power spectra obey an inverse power law; in an average sense, the images may be considered as 1/f fields. Two data representations are analyzed and compared (1) the raw data, and (2) the logarithm of the raw data. Two methods are employed to analyze the power spectra (1) a technique based on integrating the Fourier plane with octave ring sectioning developed previously, and (2) an approach based on integrating the Fourier plane using rings of constant width developed for this work. Both methods allow theoretical modeling. Numerical analysis indicates that the effects due to the transformation influence the power spectra measurements in a statistically significant manner in the high frequency range. However, this effect has little influence on the inverse power law estimation for a given image regardless of the data representation or the theoretical analysis approach. The analysis is presented from two points of view (1) each image is treated independently with the results presented as distributions, and (2) for a given representation, the entire image collection is treated as an ensemble with the results presented as expected values. In general, the constant ring width analysis forms the foundation for a spectral comparison method for finding spectral differences, from an image distribution sense, after applying a nonlinear transformation to the data. The work also shows that power law estimation may be influenced due to the presence of noise in the higher frequency range, which is consistent with the known attributes of the detector efficiency. The spectral modeling and inverse power law determinations obtained here are in agreement with that obtained from the analysis of digitized film-screen images presented previously. The form of the power spectrum for a given image is approximately l/f2beta with beta approximately 1.4-1.5.     

Incomplete skin representation in digital mammograms

Flat-panel digital detector systems have limited dynamic range and saturate at a particular x-ray exposure. Hence some of the breast edge may not be represented in the displayed image. We developed a model to estimate the amount of skin loss. Model predictions agreed well with phantom measurements. In our database of 884 clinical digital mammograms, 98% had saturated backgrounds. The estimated skin loss exceeded 0.5 mm in 5% of images and 1.0 mm in 0.7% of images. Any skin thickening that is present should still be visualized, so we conclude that any skin-line loss may not be of clinical significance.     

Segmentation of suspicious densities in digital mammograms

State-of-the-art algorithms for detection of masses in mammograms are very sensitive but they also detect many normal regions with slightly suspicious features. Based on segmentations of detected regions, shape and intensity features can be computed that discriminate between normal and abnormal regions. These features can be used to discard false positive detections and hence improve the specificity of the detection method. In this work two different methods to segment suspect regions were examined. A number of different implementations of a region growing method were compared to a discrete dynamic contour method. Both methods were applied to a consecutive data set of 132 mammograms containing masses and architectural distortions, taken from the Dutch screening program. Evaluation of the performance of the methods was done in two different ways. In the first experiment, the segmentations of masses were compared to annotations made by the radiologist. In the second experiment, a number of features were computed for all segmented areas, normal and abnormal, based on which regions were classified with a neural network. The most sophisticated region growing method and the method using the dynamic contour model had a similar performance when evaluation was based on the overlap of the annotations. The second experiment showed that the contours generated by the discrete dynamic contour model were more suited for computation of discriminating features. Contrast features were especially useful to improve the performance of the detection method.     

Computer-aided diagnosis scheme for histological classification of clustered microcalcifications on magnification mammograms

The histological classification of clustered microcalcifications on mammograms can be difficult, and thus often require biopsy or follow-up. Our purpose in this study was to develop a computer-aided diagnosis scheme for identifying the histological classification of clustered microcalcifications on magnification mammograms in order to assist the radiologists' interpretation as a "second opinion." Our database consisted of 58 magnification mammograms, which included 35 malignant clustered microcalcifications (9 invasive carcinomas, 12 noninvasive carcinomas of the comedo type, and 14 noninvasive carcinomas of the noncomedo type) and 23 benign clustered microcalcifications (17 mastopathies and 6 fibroadenomas). The histological classifications of all clustered microcalcifications were proved by pathologic diagnosis. The clustered microcalcifications were first segmented by use of a novel filter bank and a thresholding technique. Five objective features on clustered microcalcifications were determined by taking into account subjective features that experienced the radiologists commonly use to identify possible histological classifications. The Bayes decision rule with five objective features was employed for distinguishing between five histological classifications. The classification accuracies for distinguishing between three malignant histological classifications were 77.8% (7/9) for invasive carcinoma, 75.0% (9/12) for noninvasive carcinoma of the comedo type, and 92.9% (13/14) for noninvasive carcinoma of the noncomedo type. The classification accuracies for distinguishing between two benign histological classifications were 94.1% (16/17) for mastopathy, and 100.0% (6/6) for fibroadenoma. This computerized method would be useful in assisting radiologists in their assessments of clustered microcalcifications.     

Effective x-ray attenuation measurements with full field digital mammography

This work shows that effective x-ray attenuation coefficients may be estimated by applying Beer's Law to phantom image data acquired with the General Electric Senographe 2000D full field digital mammography system. Theoretical developments are provided indicating that an approximate form of the Beer's relation holds for polychromatic x-ray beams. The theoretical values were compared with experimentally determined measured values, which were estimated at various detector locations. The measured effective attenuation coefficients are in agreement with those estimated with theoretical developments and numerical integration. The work shows that the measured quantities show little spatial variation. The main ideas are demonstrated with polymethylmethacrylate and breast tissue equivalent phantom imaging experiments. The work suggests that the effective attenuation coefficients may be used as known values for radiometric standardization applications that compensate for the image acquisition influences. The work indicates that it is possible to make quantitative attenuation coefficient measurements from a system designed for clinical purposes.     

Detection of single and clustered microcalcifications in mammograms using fractals models and neural networks

Microcalcifications (microCas) are often early signs of breast cancer. However, detecting them is a difficult visual task and recognizing malignant lesions is a complex diagnostic problem. In recent years, several research groups have been working to develop computer-aided diagnosis (CAD) systems for X-ray mammography. In this paper, we propose a method to detect and classify microcalcifications. In order to discover the presence of microCas clusters, particular attention is paid to the analysis of the spatial arrangement of detected lesions. A fractal model has been used to describe the mammographic image, thus, allowing the use of a matched filtering stage to enhance microcalcifications against the background. A region growing algorithm, coupled with a neural classifier, detects existing lesions. Subsequently, a second fractal model is used to analyze their spatial arrangement so that the presence of microcalcification clusters can be detected and classified. Reported results indicate that fractal models provide an adequate framework for medical image processing; consequently high correct classification rates are achieved.