Reduction of false positive detection in clustered microcalcifications

In computer-aided detection of microcalcifications (MCs), the detection accuracy is often compromised by frequent occurrence of false positives (FPs), which can be attributed to a number of factors, including imaging noise, inhomogeneity in tissue background, linear structures, and artifacts in mammograms. In this study, the authors investigated a unified classification approach for combating the adverse effects of these heterogeneous factors for accurate MC detection. To accommodate FPs caused by different factors in a mammogram image, the authors developed a classification model to which the input features were adapted according to the image context at a detection location. For this purpose, the input features were defined in two groups, of which one group was derived from the image intensity pattern in a local neighborhood of a detection location, and the other group was used to characterize how a MC is different from its structural background. Owing to the distinctive effect of linear structures in the detector response, the authors introduced a dummy variable into the unified classifier model, which allowed the input features to be adapted according to the image context at a detection location (i.e., presence or absence of linear structures). To suppress the effect of inhomogeneity in tissue background, the input features were extracted from different domains aimed for enhancing MCs in a mammogram image. To demonstrate the flexibility of the proposed approach, the authors implemented the unified classifier model by two widely used machine learning algorithms, namely, a support vector machine (SVM) classifier and an Adaboost classifier. In the experiment, the proposed approach was tested for two representative MC detectors in the literature [difference-of-Gaussians (DoG) detector and SVM detector]. The detection performance was assessed using free-response receiver operating characteristic (FROC) analysis on a set of 141 screen-film mammogram (SFM) images (66 cases) and a set of 188 full-field digital mammogram (FFDM) images (95 cases). The FROC analysis results show that the proposed unified classification approach can significantly improve the detection accuracy of two MC detectors on both SFM and FFDM images. Despite the difference in performance between the two detectors, the unified classifiers can reduce their FP rate to a similar level in the output of the two detectors. In particular, with true-positive rate at 85%, the FP rate on SFM images for the DoG detector was reduced from 1.16 to 0.33 clusters/image (unified SVM) and 0.36 clusters/image (unified Adaboost), respectively; similarly, for the SVM detector, the FP rate was reduced from 0.45 clusters/image to 0.30 clusters/image (unified SVM) and 0.25 clusters/image (unified Adaboost), respectively. Similar FP reduction results were also achieved on FFDM images for the two MC detectors. The proposed unified classification approach can be effective for discriminating MCs from FPs caused by different factors (such as MC-like noise patterns and linear structures) in MC detection. The framework is general and can be applicable for further improving the detection accuracy of existing MC detectors.

Linear structures are a major contributor to false-positives (FPs) in detection of clustered microcalcifications (MCs) in mammograms. We propose a unified classifier approach to incorporate the dichotomous effect of linear structures in MC detection, the purpose being to suppress the FPs associated with linear structures. We introduce a dummy variable in the classifier model as in traditional regression analysis, the role of which is to adapt the input features to the classifier according to the presence of linear structures. In the experiment we demonstrate the proposed approach by using Adaboost decision stumps as the unified classifier. The results on a set of 200 mammogram images (all containing clustered MCs) show that it could reduce the FPs in an existing SVM detector by up to 47.3% with the true-positive rate at 85%.

We propose computer-aided detection (CADe) algorithm for microcalcification (MC) clusters in reconstructed digital breast tomosynthesis (DBT) images. The algorithm consists of prescreening, MC detection, clustering, and false-positive (FP) reduction steps. The DBT images containing the MC-like objects were enhanced by a multiscale Hessian-based three-dimensional (3D) objectness response function and a connected-component segmentation method was applied to extract the cluster seed objects as potential clustering centers of MCs. Secondly, a signal-to-noise ratio (SNR) enhanced image was also generated to detect the individual MC candidates and prescreen the MC-like objects. Each cluster seed candidate was prescreened by counting neighboring individual MC candidates nearby the cluster seed object according to several microcalcification clustering criteria. As a second step, we introduced bounding boxes for the accepted seed candidate, clustered all the overlapping cubes, and examined. After the FP reduction step, the average number of FPs per case was estimated to be 2.47 per DBT volume with a sensitivity of 83.3%.

Mammography is the only technique currently used for detecting microcalcification (MC) clusters, an early indicator of breast cancer. However, mammographic images superimpose a three-dimensional compressed breast image onto two-dimensional projection views, resulting in overlapped anatomical breast structures that may obscure the detection and visualization of MCs. One possible solution to this problem is the use of cone beam computed tomography (CBCT) with a flat-panel (FP) digital detector. Although feasibility studies of CBCT techniques for breast imaging have yielded promising results, they have not shown how radiation dose and x-ray tube voltage affect the accuracy with which MCs are detected by CBCT experimentally. We therefore conducted a phantom study using a FP-based CBCT system with various mean glandular doses and kVp values. An experimental CBCT scanner was constructed with a data acquisition rate of 7.5 frames/s. 10.5 and 14.5 cm diameter breast phantoms made of gelatin were used to simulate uncompressed breasts consisting of 100% glandular tissue. Eight different MC sizes of calcium carbonate grains, ranging from 180-200 microm to 355-425 microm, were used to simulate MCs. MCs of the same size were arranged to form a 5 x 5 MC cluster and embedded in the breast phantoms. These MC clusters were positioned at 2.8 cm away from the center of the breast phantoms. The phantoms were imaged at 60, 80, and 100 kVp. With a single scan (360 degrees), 300 projection images were acquired with 0.5 x, 1x, and 2x mean glandular dose limit for 10.5 cm phantom and with 1x, 2x, and 4x for 14.5 cm phantom. A Feldkamp algorithm with a pure ramp filter was used for image reconstruction. The normalized noise level was calculated for each x-ray tube voltage and dose level. The image quality of the CBCT images was evaluated by counting the number of visible MCs for each MC cluster for various conditions. The average percentage of the visible MCs was computed and plotted as a function of the MGD, the kVp, and the average MC size. The results showed that the MC visibility increased with the MGD significantly but decreased with the breast size. The results also showed that the x-ray tube voltage affects the detection of MCs under different circumstances. With a 50% threshold, the minimum detectable MC sizes for the 10.5 cm phantom were 348(+/-2), 288(+/-7), 257(+/-2) microm at 3, 6, and 12 mGy, respectively. Those for the 14.5 cm phantom were 355 (+/-1), 307 (+/-7), 275 (+/-5) microm at 6, 12, and 24 mGy, respectively. With a 75% threshold, the minimum detectable MC sizes for the 10.5 cm phantom were 367 (+/-1), 316 (+/-7), 265 (+/-3) microm at 3, 6, and 12 mGy, respectively. Those for the 14.5 cm phantom were 377 (+/-3), 334 (+/-5), 300 (+/-2) microm at 6, 12, and 24 mGy, respectively.

Microcalcification (MC) clusters in mammograms can be important early signs of breast cancer in women. Accurate detection of MC clusters is an important but challenging problem. In this paper, we propose the use of a recently developed machine learning technique -- relevance vector machine (RVM) -- for automatic detection of MCs in digitized mammograms. RVM is based on Bayesian estimation theory, and as a feature it can yield a decision function that depends on only a very small number of so-called <i>relevance vectors</i>. We formulate MC detection as a supervised-learning problem, and use RVM to classify if an MC object is present or not at each location in a mammogram image. MC clusters are then identified by grouping the detected MC objects. The proposed method is tested using a database of 141 clinical mammograms, and compared with a support vector machine (SVM) classifier which we developed previously. The detection performance is evaluated using the free-response receiver operating characteristic (FROC) curves. It is demonstrated that the RVM classifier matches closely with the SVM classifier in detection performance, and does so with a much sparser kernel representation than the SVM classifier. Consequently, the RVM classifier greatly reduces the computational complexity, making it more suitable for real-time processing of MC clusters in mammograms.

Microcalcification (MC) clusters in mammograms are one of the primary signs of breast cancer. In the literature, most MC detection methods follow a two-step paradigm: segmenting each MC and analyzing their spatial distributions to form MC clusters. However, segmentation of MCs cannot avoid low sensitivity or high false positive rate due to their variability in size (sometimes <0.1 mm), brightness, and shape (with diverse surroundings). In this paper, we propose a novel self-adversarial learning framework to differentiate and delineate the MC clusters in an end-to-end manner. The class activation mapping (CAM) mechanism is employed to directly generate the contours of MC clusters with the guidance of MC cluster classification and box annotations. We also propose the self-adversarial learning strategy to equip CAM with better detection capability of MC clusters by using the backbone network itself as a discriminator. Experimental results suggest that our method can achieve better performance for MC cluster detection with the contouring of MC clusters and classification of MC types.

Clustered microcalcifications (MCs) in mammograms are an important early sign of breast cancer in women. Their accurate detection is important in computer-aided detection (CADe). In this paper, we integrated the possibilistic fuzzy c-means (PFCM) clustering algorithm and weighted support vector machine (WSVM) for the detection of MC clusters in full-field digital mammograms (FFDM). For each image, suspicious MC regions are extracted with region growing and active contour segmentation. Then geometry and texture features are extracted for each suspicious MC, a mutual information-based supervised criterion is used to select important features, and PFCM is applied to cluster the samples into two clusters. Weights of the samples are calculated based on possibilities and typicality values from the PFCM, and the ground truth labels. A weighted nonlinear SVM is trained. During the test process, when an unknown image is presented, suspicious regions are located with the segmentation step, selected features are extracted, and the suspicious MC regions are classified as containing MC or not by the trained weighted nonlinear SVM. Finally, the MC regions are analyzed with spatial information to locate MC clusters. The proposed method is evaluated using a database of 410 clinical mammograms and compared with a standard unweighted support vector machine (SVM) classifier. The detection performance is evaluated using response receiver operating (ROC) curves and free-response receiver operating characteristic (FROC) curves. The proposed method obtained an area under the ROC curve of 0.8676, while the standard SVM obtained an area of 0.8268 for MC detection. For MC cluster detection, the proposed method obtained a high sensitivity of 92 % with a false-positive rate of 2.3 clusters/image, and it is also better than standard SVM with 4.7 false-positive clusters/image at the same sensitivity.

Background The usefulness of tumor markers in the differential diagnosis of cancer in patients with pleural effusions (PE) remains controversial. Few studies have reported the measurement of human epididymal protein 4 (HE4) in pleural fluid. HE4 is a tumor marker associated with different types of cancer. An elevated serum concentration has been observed in ovarian and lung cancers. Other benign pathologies can increase HE4 levels, which can be detect with different laboratory tests identified with adenosine deaminase (ADA), C-reactive protein (CRP), % polynuclear cell count (%PMN) and glomerular filtration rate (GFR) can be used in order to detect possible false positives. The objective of this study was to assess the diagnostic usefulness of HE4 in malignant pleural effusions by comparing HE4 concentrations between benign and malignant samples, while considering the causes of HE4 false positives. Methods HE4, ADA, differential leukocyte count, CRP and GFR concentrations were determined in 238 pleural effusion samples. Diagnostic efficacy analysis using receiver operating curves (ROC) identified the ability of HE4 to detect malignancy, searching for cut-off points with 100% specificity. Results HE4 concentrations showed significant differences (P&amp;lt;0.01) between malignant (median 1065pmol/L) and benign (median 699pmol/L) pleural effusions. Significant differences (P&amp;lt;0.01) were found in HE4 concentrations for gynecological and lung cancer origin (median 7397 pmol/L and 5150 pmol/L respectively) and other malignant pleural effusions (median 1065 pmol/L). Patients with benign diseases with renal failure showed a higher HE4 concentration (median 964pmol/L) than in patients without these pathologies (median 696pmol/L) identified with GFR&amp;lt;30 mL/min. No differences were demonstrated in HE4 concentration levels using ADA, differential leukocyte count or CRP, so only glomerular filtration rate was considered cause of false positives. A sensitivity of 23% was obtained for HE4, with a cut-off point of 3050pmol/L and a specificity of 100% for the whole group. In the potential false positive group, the sensitivity of HE4 was 28% with a cutoff point of 3050 pmol/L with a specificity of 100%. In the group without potential false positives, we obtained a sensitivity of 30% with a specificity of 100% for a cutoff point of 1992pmol/L. When we used a specific cut-off point for each group, we obtained a sensitivity of 38% with a specificity of 100%. Conclusions HE4 levels are higher in malignant pleural effusions compared to other pathologies. HE4 levels allow the identification of malignant pleural effusions with moderate sensitivity and maximum specificity. HE4 levels can differentiate between tumors of gynecological or lung origin and others. Glomerular filtration rate (GFR&amp;lt;30 mL/min) was considered the main cause of false positives. If we identify possible false positives, we can use specific cut-offs and improve sensitivity up to 38% with maximum specificity compared to using a single cut-off for all effusions.

This paper attempts to pinpoint different techniques for Pectoral Muscle (PM) segmentation, Microcalcification (MC) detection and classification in digital mammograms. The segmentation of PM and detection of MC and its classification are mostly based on image processing and data mining techniques. The review centered on major techniques in image processing and data mining that is employed for PM segmentation, MC detection and classification in digital mammograms. Breast cancer is one of the significant causes of death among women aged above 40. Mammography is considered the most successful means for prompt and timely detection of breast cancers. One notable visual indication of the malignant growth is the appearance of Masses, Architectural Distortions, and Microcalcification Clusters (MCCs). There are some disadvantages and hurdles for mankind viewers, and it is hard for radiologists to supply both precise and steady assessment for a large number of mammograms created in extensive screening. Computer Aided Detection has been employed to help radiologists in detecting MC and MCCs. The automatic recognition of malignant MCCs could be very helpful for diagnostic purpose. In this paper, we summarize the methods of automatic detection and classification of MCs in digitized mammograms. Pectoral muscle segmentation techniques are also summarized. The techniques used for segmentation of PM, MC detection and classification in a digitized mammogram are reviewed.

In this paper, we propose a novel combinational SVM algorithm via a set of decision rules to achieve better performances in microcalcification detection inside digital mammograms towards computer aided breast cancer diagnosis. Based on the discovery that the polynomial SVM is sensitive to MC (microcalcification) pixels and the linear SVM is sensitive to non-MC pixels, we designed an adaptive threshold mechanism via establishment of their correspondences to exploit the complementary nature between the polynomial SVM and the linear SVM. Experiments show that the proposed algorithm successfully reduced false positive detection rate while keeping the true positive detection rate competitive.

In digital breast tomosynthesis (DBT) imaging, a microcalcification (MC) cluster may span across different slices and blurring exists in the out-of-focus slices. We developed a radiomics approach to extract features from focus slice and combine multiple spatial domains to reduce false positives (FPs) in an automated pipeline of detecting MC clusters. We performed a retrospective study on a cohort of 290 Chinese women patients with a total of 580 DBT volumes. We developed an automated MC detection pipeline that consists of two stages: an initial detection to identify a set of MC candidates that may include many FPs, followed by a radiomics-based classification model to identify and reduce the FPs. We extract both two-dimensional (2D) and three-dimensional (3D) radiomics features from multiple spatial domains, including a focus slice, projection image, and tomographic volume. A linear discriminant classifier was used coupled with a sequential forward feature selection procedure. The free-response operating characteristics (FROC) curve and partial area under the FROC curve (pAUC) in the FP rate range of 0 to 2 per DBT volume were used to evaluate the model's performance. At a sensitivity of 90%, the FP rate was reduced from 1.3 to 0.2 per DBT volume after applying the multi-domain-based classification on the initial detections. The multi-domain yielded a significantly higher pAUC compared to the initial detection (increase of pAUC=0.2278, P<0.0001), focus slice (increase of pAUC=0.0345, P=0.0152), project image (increase of pAUC=0.1043, P<0.0001), and tomographic volume (increase of pAUC=0.0791, P=0.0032). The radiomic features extracted from the three domains may provide complementary information and their integration can significantly reduce FPs in automated detection of MCs in DBT volumes on a large Chinese women population.

Computerized detection of clustered microcalcifications (MCs) in mammograms often suffers from the occurrence of false positives (FPs), which can vary greatly from case to case. We investigate how to apply statistical estimation to determine the number of FPs that are present in a detected MC lesion. First, we describe the number of true positives (TPs) by a Poisson-binomial probability distribution, wherein a logistic regression model is trained to determine the probability for an individual detected MC to be a TP based on its detector output. Afterward, we model the spatial occurrence of FPs in a lesion area by a spatial point process (SPP), of which the distribution parameters are estimated from the detections in the lesion and its surrounding region. Furthermore, to improve the estimation accuracy, we incorporate the Poisson-binomial distribution of the number of TPs into the SPP model using maximum a posteriori estimation. In the experiments, we demonstrated the proposed approach on the detection results from a set of 188 full-field digital mammography (FFDM) images (95 cases) by three existing MC detectors. The results showed that there was a strong consistency between the estimated and the actual number of TPs (or FPs) for these detectors. When the fraction of FPs in detection was varied from 20% to 50%, both the mean and median values of the estimation error were within 11% of the total number of detected MCs in a lesion. In particular, when the number of FPs increased to as high as 11.38 in a cluster on average, the error was 2.51 in the estimated number of FPs. In addition, lesions estimated to be more accurate in detection were shown to have better classification accuracy (for being malignant or benign) than those estimated to be less accurate.

In this article the authors evaluate a recently proposed variable dose (VD)-digital breast tomosynthesis (DBT) acquisition technique in terms of the detection accuracy for breast masses and microcalcification (MC) clusters. With this technique, approximately half of the total dose is used for one center projection and the remaining dose is split among the other tomosynthesis projection views. This acquisition method would yield both a projection view and a reconstruction view. One of the aims of this study was to evaluate whether the center projection alone of the VD acquisition can provide equal or superior MC detection in comparison to the 3D images from uniform dose (UD)-DBT. Another aim was to compare the mass-detection capabilities of 3D reconstructions from VD-DBT and UD-DBT. In a localization receiver operating characteristic (LROC) observer study of MC detection, the authors compared the center projection of a VD acquisitioh scheme (at 2 mGy dose) with detector pixel size of 100 microm with the UD-DBT reconstruction (at 4 mGy dose) obtained with a voxel size of 100 microm. MCs with sizes of 150 and 180 microm were used in the study, with each cluster consisting of seven MCs distributed randomly within a small volume. Reconstructed images in UD-DBT were obtained from a projection set that had a total of 4 mGy dose. The current study shows that for MC detection, using the center projection alone of VD acquisition scheme performs worse with area under the LROC curve (AL) of 0.76 than when using the 3D reconstructed image using the UD acquisition scheme (AL=0.84). A 2D ANOVA found a statistically significant difference (p=0.038) at a significance level of 0.05. In the current study, although a reconstructed image was also available using the VD acquisition scheme, it was not used to assist the MC detection task which was done using the center projection alone. In the case of evaluation of detection accuracy of masses, the reconstruction with VD-DBT (AL=0.71) was compared to that obtained from the UD-DBT (AL=0.78). The authors found no statistically significant difference between the two (p-value=0.22), although all the observers performed better for UD-DBT.

This paper presents a computer-aided diagnosis (CAD) system for automatic detection of clustered microcalcifications (MCs) in digitized mammograms. The proposed system consists of two main steps. First, potential MC pixels in the mammograms are segmented out by using four mixed features consisting of two wavelet features and two gray level statistical features and then the potential MC pixels are labeled into potential individual MC objects by their spatial connectivity. Second, MCs are detected by extracting a set of 17 features from the potential individual MC objects. The classifier which is used in the first step is a multilayer feedforward neural network classifier but for the second step we have used Adaboost with SVM-based component classifier. Component classifiers which we used in our combining method are SVM classifiers with RBF kernel. The method was applied to a database of 40 mammograms (Nijmegen database) containing 105 clusters of MCs. A free-response operating characteristics (FROC) curve is used to evaluate the performance of CAD system. Results show that the proposed system gives quite satisfactory performance. In particular, 89.55% mean true positive detection rate is achieved at the cost of 0.921 false positive per image.

Detection of microcalcifications in digital mammograms using combined model-based and statistical textural features