Correlation between mammographic density and volumetric fibroglandular tissue estimated on breast MR images

Previous studies have found that mammographic breast density is highly correlated with breast cancer risk. Therefore, mammographic breast density may be considered as an important risk factor in studies of breast cancer treatments. In this paper, we evaluated the accuracy of using mammograms for estimating breast density by analyzing the correlation between the percent mammographic dense area and the percent glandular tissue volume as estimated from MR images. A dataset of 67 cases having MR images (coronal 3-D SPGR T1-weighted pre-contrast) and corresponding 4-view mammograms was used in this study. Mammographic breast density was estimated by an experienced radiologist and an automated image analysis tool, Mammography Density ESTimator (MDEST) developed previously in our laboratory. For the estimation of the percent volume of fibroglandular tissue in breast MR images, a semiautomatic method was developed to segment the fibroglandular tissue from each slice. The tissue volume was calculated by integration over all slices containing the breast. Interobserver variation was measured for 3 different readers. It was found that the correlation between every two of the three readers for segmentation of MR volumetric fibroglandular tissue was 0.99. The correlations between the percent volumetric fibroglandular tissue on MR images and the percent dense area of the CC and MLO views segmented by an experienced radiologist were both 0.91. The correlation between the percent volumetric fibroglandular tissue on MR images and the percent dense area of the CC and MLO views segmented by MDEST was 0.91 and 0.89, respectively. The root-mean-square (rms) residual ranged from 5.4% to 6.3%. The mean bias ranged from 3% to 6%. The high correlation indicates that changes in mammographic density may be a useful indicator of changes in fibroglandular tissue volume in the breast.     

A new method for quantitative analysis of mammographic density

Women with mammographic percent density >50% have a approximately three-fold increased risk of developing breast cancer, potentially making them screening candidates for breast MRI scanning. The purpose of this work is to introduce a new method to quantify mammographic percent density (MPD), and to compare the results with the current standard of care for breast density assessment. Craniocaudal (CC) and mediolateral oblique (MLO) mammograms for 104 patients were digitized and analyzed using an interactive computer-assisted segmentation routine implemented for two purposes: (1) to segment the breast area from background and radiographic markers, and (2) to segment dense from fatty portions of the breast. Our technique was evaluated by comparing the results to qualitative estimates determined by a certified breast radiologist using the BI-RADS Categorical Assessment (1 (fatty) to 4 (dense) scale). Statistically significant correlations (two-tailed, p < 0.01) were observed between calculated MPD and BI-RADS for both CC (Spearman rho = 0.67) and MLO views (Spearman rho = 0.71). For the CC view, statistically significant differences were revealed between the mean MPD for each BI-RADS category except between fatty (BI-RADS 1) and scattered (BI-RADS 2). Finally, for the MLO views, statistically significant differences in the mean MPD between all BI-RADS categories were observed. Comparing the CC and MLO views revealed a strong positive correlation (Pearson r = 0.8) in calculated MPD. In addition, an evaluation of the reproducibility of our segmentation demonstrated the average standard deviation of MPD for a subsample of eight patients, measured five times, was 1.9% (range: 0.03%-9.9%). Eliminating one misassignment reduced the average standard deviation to 0.75% (range: 0.03%-3.16%). Further analysis of approximately 10% of the patient sample revealed strong agreement (ICC = 0.80-0.85) in the reliability of MPD estimates for both mammographic views. Overall, these results demonstrate the feasibility of utilizing our approach for quantitative breast density segmentation, which may be useful for detecting small changes in MPD introduced through chemoprevention, diet, or other interventions.     

A breast density index for digital mammograms based on radiologists’ randing

The purpose of this study was to develop and evaluate a computerized method of calculating a breast density index (BDI) from digitized mammograms that was designed specifically to model radiologists’ perception of breast density. A set of 153 pairs of digitized mammograms (cranio-caudal, CC, and mediolateral oblique, MLO, views) were acquired and preprocessed to reduce detector biases. The sets of mammograms were ordered on an ordinal scale (a scale based only on relative rank-ordering) by two radiologists, and a cardinal (an absolute numerical score) BDI value was calculated from the oridinal ranks. The images were also assigned cardinal BDI values by the radiologists in a subsequent session. Six. mathematical features (including fractal dimension and others) were calculated from the digital mammograms, and were used in conjunction with single value decomposition and multiple linear regression to calculate a computerized BDI. The linear correlation coefficient between different ordinal ranking sessions were as follows: intraradiologist intraprojection (CC/CC):r=0.978; intraradiologist interprojection (CC/MLO):r=0.960; and interradiologist intraprojection (CC/CC):r=0.968. A separate breast density index was derived from three separate ordinal rankings by one radiologist (two with CC views, one with the MLO view). The computer derivedBDI had a correlation coefficient (r) of 0.907 with the radiologists’ ordinalBDI. A comparison between radiologists using a cardinal scoring system (which is closest to how radiologists actually evaluate breast density) showedr=0.914. A breast density index calculated by a computer but modeled after radiologist perception of breast density may be valuable in objectively measuring breast density. Such a metric may prove valuable in numerous areas, including breast cancer risk assessment and in evaluating screening techniques specifically designed to improve imaging of the dense breast.     

Improvement of computerized mass detection on mammograms: fusion of two-view information

Recent clinical studies have proved that computer-aided diagnosis (CAD) systems are helpful for improving lesion detection by radiologists in mammography. However, these systems would be more useful if the false-positive rate is reduced. Current CAD systems generally detect and characterize suspicious abnormal structures in individual mammographic images. Clinical experiences by radiologists indicate that screening with two mammographic views improves the detection accuracy of abnormalities in the breast. It is expected that the fusion of information from different mammographic views will improve the performance of CAD systems. We are developing a two-view matching method that utilizes the geometric locations, and morphological and textural features to correlate objects detected in two different views using a prescreening program. First, a geometrical model is used to predict the search region for an object in a second view from its location in the first view. The distance between the object and the nipple is used to define the search area. After pairing the objects in two views, textural and morphological characteristics of the paired objects are merged and similarity measures are defined. Linear discriminant analysis is then employed to classify each object pair as a true or false mass pair. The resulting object correspondence score is combined with its one-view detection score using a fusion scheme. The fusion information was found to improve the lesion detectability and reduce the number of FPs. In a preliminary study, we used a data set of 169 pairs of cranio-caudal (CC) and mediolateral oblique (MLO) view mammograms. For the detection of malignant masses on current mammograms, the film-based detection sensitivity was found to improve from 62% with a one-view detection scheme to 73% with the new two-view scheme, at a false-positive rate of 1 FP/image. The corresponding cased-based detection sensitivity improved from 77% to 91%.     

Computerized image analysis: estimation of breast density on mammograms

An automated image analysis tool is being developed for the estimation of mammographic breast density. This tool may be useful for risk estimation or for monitoring breast density change in prevention or intervention programs. In this preliminary study, a data set of 4-view mammograms from 65 patients was used to evaluate our approach. Breast density analysis was performed on the digitized mammograms in three stages. First, the breast region was segmented from the surrounding background by an automated breast boundary-tracking algorithm. Second, an adaptive dynamic range compression technique was applied to the breast image to reduce the range of the gray level distribution in the low frequency background and to enhance the differences in the characteristic features of the gray level histogram for breasts of different densities. Third, rule-based classification was used to classify the breast images into four classes according to the characteristic features of their gray level histogram. For each image, a gray level threshold was automatically determined to segment the dense tissue from the breast region. The area of segmented dense tissue as a percentage of the breast area was then estimated. To evaluate the performance of the algorithm, the computer segmentation results were compared to manual segmentation with interactive thresholding by five radiologists. A "true" percent dense area for each mammogram was obtained by averaging the manually segmented areas of the radiologists. We found that the histograms of 6% (8 CC and 8 MLO views) of the breast regions were misclassified by the computer, resulting in poor segmentation of the dense region. For the images with correct classification, the correlation between the computer-estimated percent dense area and the "truth" was 0.94 and 0.91, respectively, for CC and MLO views, with a mean bias of less than 2%. The mean biases of the five radiologists' visual estimates for the same images ranged from 0.1% to 11%. The results demonstrate the feasibility of estimating mammographic breast density using computer vision techniques and its potential to improve the accuracy and reproducibility of breast density estimation in comparison with the subjective visual assessment by radiologists.     

Dosimetric evaluation of the mean glandular dose for mammography in Korean women: a preliminary report

The purpose of this study was to evaluate the thickness of the compressed breast in mediolateral oblique (MLO) and craniocaudal (CC) mammograms, to relate these thickness and breast patterns to mean glandular dose (MGD) in Korean women, and to evaluate the suitability of using the American College of Radiology's Recommendations for Korean women from a quality assurance standpoint. The study population consisted of 92 paired MLO and CC mammograms obtained on one mammographic unit. The digital readouts of compressed breast thickness, applied compression force and tube voltage were recorded. Entrance skin exposure was measured by dosimetry. MGD was calculated by multiplying entrance skin exposure by the exposure-to-absorbed dose conversion factor. The range of breast thickness was 1.3-6.2 cm in CC mammograms with a mean breast thickness of 3.6 cm, and 1.6-6.5 cm in MLO mammograms with a mean breast thickness of 3.9 cm. MGDs in CC and MLO mammograms were 1.77 mSv and 1.88 mSv per view, respectively. Breast composition patterns were divided into 4 groups according to ACR BI-RADS; P1 (n=20), P2 (n=16), P3 (n=48) and P4 (n=8). The MGDs for these groups were: 1.82, 1.84, 1.84, and 1.91 mSv, respectively. When subjects were subdivided by breast thickness into three groups, namely, below 3 cm, 3 cm to 4.2 cm, aaa and above 4.2 cm, the corresponding MGDs were 1.83, 1.86, and 1.91 mSv. According to our initial trial, the mean breast thickness and the MGDs of Korean women are lower than recommended by the American College of Radiology, which are commonly used for quality assurance purposes.     

Improvement of mammographic mass characterization using spiculation meausures and morphological features

We are developing new computer vision techniques for characterization of breast masses on mammograms. We had previously developed a characterization method based on texture features. The goal of the present work was to improve our characterization method by making use of morphological features. Toward this goal, we have developed a fully automated, three-stage segmentation method that includes clustering, active contour, and spiculation detection stages. After segmentation, morphological features describing the shape of the mass were extracted. Texture features were also extracted from a band of pixels surrounding the mass. Stepwise feature selection and linear discriminant analysis were employed in the morphological, texture, and combined feature spaces for classifier design. The classification accuracy was evaluated using the area Az under the receiver operating characteristic curve. A data set containing 249 films from 102 patients was used. When the leave-one-case-out method was applied to partition the data set into trainers and testers, the average test Az for the task of classifying the mass on a single mammographic view was 0.83 +/- 0.02, 0.84 +/- 0.02, and 0.87 +/- 0.02 in the morphological, texture, and combined feature spaces, respectively. The improvement obtained by supplementing texture features with morphological features in classification was statistically significant (p = 0.04). For classifying a mass as malignant or benign, we combined the leave-one-case-out discriminant scores from different views of a mass to obtain a summary score. In this task, the test Az value using the combined feature space was 0.91 +/- 0.02. Our results indicate that combining texture features with morphological features extracted from automatically segmented mass boundaries will be an effective approach for computer-aided characterization of mammographic masses.     

An ellipse-fitting based method for efficient registration of breast masses on two mammographic views

When reading mammograms, radiologists routinely search for and compare suspicious breast lesions identified on two corresponding craniocaudal (CC) and mediolateral oblique (MLO) views. Automatically identifying and matching the same true-positive breast lesions depicted on two views is an important step for developing successful multiview based computer-aided detection (CAD) schemes. The authors developed a method to automatically register breast areas and detect matching strips of interest used to identify the matched mass regions depicted on CC and MLO views. The method uses an ellipse based model to fit the breast boundary contour (skin line) and set a local Cartesian coordinate system for each view. One intersection point between the major/minor axis and the fitted ellipse perimeter passed through breast boundary is selected as the origin and the majoraxis and the minoraxis of the ellipse are used as the two axis of the Cartesian coordinate system. When a mass is identified on one view, the scheme computes its position in the local coordinate system. Then, the distance is mapped onto the local coordinate of the other view. At the end of the mapped distance a registered centerline of the matching strip is created. The authors established an image database that includes 200 test examinations each depicting one verified mass visible on the two views. They tested whether the registered centerline identified on another view can be used to locate the matched mass region. The experiments show that the average distance between the mass region centers and the registered centerlines was +/- 8.3 mm and in 91% of testing cases the registered centerline actually passes through the matched mass regions. A matching strip width of 47 mm was required to achieve 100% sensitivity for the test database. The results demonstrate the feasibility of the proposed method to automatically identify masses depicted on CC and MLO views, which may improve future development of multiview based CAD schemes.     

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.     

Effect of Pixel Resolution on Texture Features of Breast Masses in Mammograms

The effect of pixel resolution on texture features computed using the gray-level co-occurrence matrix (GLCM) was analyzed in the task of discriminating mammographic breast lesions as benign masses or malignant tumors. Regions in mammograms related to 111 breast masses, including 65 benign masses and 46 malignant tumors, were analyzed at pixel sizes of 50, 100, 200, 400, 600, 800, and 1,000 μm. Classification experiments using each texture feature individually provided accuracy, in terms of the area under the receiver operating characteristics curve (AUC), of up to 0.72. Using the Bayesian classifier and the leave-one-out method, the AUC obtained was in the range 0.73 to 0.75 for the pixel resolutions of 200 to 800 μm, with 14 GLCM-based texture features using adaptive ribbons of pixels around the boundaries of the masses. Texture features computed using the ribbons resulted in higher classification accuracy than the same features computed using the corresponding regions within the mass boundaries. The t test was applied to AUC values obtained using 100 repetitions of random splitting of the texture features from the ribbons of masses into the training and testing sets. The texture features computed with the pixel size of 200 μm provided the highest average AUC with statistically highly significant differences as compared to all of the other pixel sizes tested, except 100 μm.     

Usefulness of Texture Analysis for Computerized Classification of Breast Lesions on Mammograms

This work presents the usefulness of texture features in the classification of breast lesions in 5,518 images of regions of interest, which were obtained from the Digital Database for Screening Mammography that included microcalcifications, masses, and normal cases. Sixteen texture features were used, i.e., 13 were based on the spatial gray-level dependence matrix and 3 on the wavelet transform. The nonparametric K-NN classifier was used in the classification stage. The results obtained from receiver operating characteristic analysis indicated that the texture features can be used for separating normal regions and lesions with masses and microcalcifications, yielding the area under the curve (AUC) values of 0.957 and 0.859, respectively. However, the texture features were not very effective for distinguishing between malignant and benign lesions because the AUC was 0.617 for masses and 0.607 for microcalcifications. The study showed that the texture features can be used for the detection of suspicious regions in mammograms.     

Cellular composition of the nipple aspirate specimen of breast fluid. II. Abnormal findings.

Studies of cellular findings in nipple aspirate specimens from 796 women revealed 50 women with abnormal cells and/or microcalcifications. The clinical correlation of these abnormalities with breast cancer appears to be highly significant: abnormal cells were found in 50% of the satisfactory specimens from women who had breast cancer or who had had a previous mastectomy for breast cancer. Continued observation of the women for evidence of regression, persistence, or progression of the cytologic abnormalities is required to determine the significance of the abnormalities. Microcalcifications were present in nipple aspirates from 27% of the women whose mammograms were interpreted as showing calcification. The absence of mammographic confirmation of the cytologic findings of microcalcifications may be an indication for re-evaluation of the existing mammograms and repeat clinical and mammographic examination at more frequent intervals for early localization of small lesions.     

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.     

Breast Density Analysis Using an Automatic Density Segmentation Algorithm

Breast density is a strong risk factor for breast cancer. In this paper, we present an automated approach for breast density segmentation in mammographic images based on a supervised pixel-based classification and using textural and morphological features. The objective of the paper is not only to show the feasibility of an automatic algorithm for breast density segmentation but also to prove its potential application to the study of breast density evolution in longitudinal studies. The database used here contains three complete screening examinations, acquired 2 years apart, of 130 different patients. The approach was validated by comparing manual expert annotations with automatically obtained estimations. Transversal analysis of the breast density analysis of craniocaudal (CC) and mediolateral oblique (MLO) views of both breasts acquired in the same study showed a correlation coefficient of ρ = 0.96 between the mammographic density percentage for left and right breasts, whereas a comparison of both mammographic views showed a correlation of ρ = 0.95. A longitudinal study of breast density confirmed the trend that dense tissue percentage decreases over time, although we noticed that the decrease in the ratio depends on the initial amount of breast density.     

Finding corresponding regions of interest in mediolateral oblique and craniocaudal mammographic views

In this paper we present a method to link potentially suspicious mass regions detected by a Computer-Aided Detection (CAD) scheme in mediolateral oblique (MLO) and craniocaudal (CC) mammographic views of the breast. For all possible combinations of mass candidate regions, a number of features are determined. These features include the difference in the radial distance from the candidate regions to the nipple, the gray scale correlation between both regions, and the mass likelihood of the regions determined by the single view CAD scheme. Linear Discriminant Analysis (LDA) is used to discriminate between correct and incorrect links. The method was tested on a set of 412 cancer cases. In each case a malignant mass, architectural distortion, or asymmetry was annotated. In 92% of these cases the candidate mass detections by CAD included the cancer regions in both views. It was found that in 82% of the cases a correct link between the true positive regions in both views could be established by our method. Possible applications of the method may be found in multiple view analysis to improve CAD results, and for the presentation of CAD results to the radiologist on a mammography workstation.     

Volumetric breast density evaluation from ultrasound tomography images

Previous ultrasound tomography work conducted by our group showed a direct correlation between measured sound speed and physical density in vitro, and increased in vivo sound speed with increasing mammographic density, a known risk factor for breast cancer. Building on these empirical results, the purpose of this work was to explore a metric to quantify breast density using our ultrasound tomography sound speed images in a manner analogous to computer-assisted mammogram segmentation for breast density analysis. Therefore, volumetric ultrasound percent density (USPD) is determined by segmenting high sound speed areas from each tomogram using a k-means clustering routine, integrating these results over the entire volume of the breast, and dividing by whole-breast volume. First, a breast phantom comprised of fat inclusions embedded in fibroglandular tissue was scanned four times with both our ultrasound tomography clinical prototype (with 4 mm spatial resolution) and CT. The coronal transmission tomograms and CT images were analyzed using semiautomatic segmentation routines, and the integrated areas of the phantom's fat inclusions were compared between the four repeated scans. The average variability for inclusion segmentation was approximately 7% and approximately2%, respectively, and a close correlation was observed in the integrated areas between the two modalities. Next, a cohort of 93 patients was imaged, yielding volumetric coverage of the breast (45-75 sound speed tomograms/patient). The association of USPD with mammographic percent density (MPD) was evaluated using two measures: (1) qualitative, as determined by a radiologist's visual assessment using BI-RADS Criteria and (2) quantitative, via digitization and semiautomatic segmentation of craniocaudal and mediolateral oblique mammograms. A strong positive association between BI-RADS category and USPD was demonstrated [Spearman rho = 0.69 (p < 0.001)], with significant differences between all BI-RADS categories as assessed by one-way ANOVA and Scheffé posthoc analysis. Furthermore, comparing USPD to calculated mammographic density yielded moderate to strong positive associations for CC and MLO views (r2 = 0.75 and 0.59, respectively). These results support the hypothesis that utilizing USPD as an analogue to mammographic breast density is feasible, providing a nonionizing, whole-breast analysis.     

乳腺计算机辅助诊断中DCE-MRI图像特征的选择与分析

目的比较动态对比度增强磁共振成像（dynamic contrast—enhanced magnetic resonance imaging,DCE—MRI）图像的形态、纹理和时间强度曲线（time intensity curve,TIC）特征对乳腺病灶良恶性的诊断效果,讨论DCE—MRI图像特征的计算机辅助诊断价值。方法测量224个乳腺病灶样本（良性样本82个,恶性样本142个）的12个形态学特征、56个基于灰度共生矩阵（gray level co—occurrencematrix,GLCM）的纹理特征以及11个TIC特征,采用平均平方距离准则和SVM分类器评估这三类特征的良恶性分辨能力。结果反映病灶血流动力学特性的TIC特征的分类性能最优（SE0．9366,SP0．8293,AUC0．9495）;纹理特征次之（SE0．9225,SP0．7195,AUC0．8835）;形态学特征效果最差（SE0．8451,SP0．6951,AUC0．8079）。研究发现,在上述基础上融合三类特征可优化分类性能。最终结合平滑度、紧致度、熵等9个特征参数进行诊断,对乳腺病灶良恶性的分辨效果最好,AUC达0．9642。结论DCE—MRI的TIC特征对恶性乳腺病灶具有较高的灵敏度,可以提高乳腺计算机辅助诊断的恶性病灶检出率。综合分析形态、纹理和TIC特征可以提高病灶的诊断特异度,降低良性病灶的误诊率。     

A Comprehensive Methodology for Determining the Most Informative Mammographic Features

This study aims to determine the most informative mammographic features for breast cancer diagnosis using mutual information (MI) analysis. Our Health Insurance Portability and Accountability Act-approved database consists of 44,397 consecutive structured mammography reports for 20,375 patients collected from 2005 to 2008. The reports include demographic risk factors (age, family and personal history of breast cancer, and use of hormone therapy) and mammographic features from the Breast Imaging Reporting and Data System lexicon. We calculated MI using Shannon’s entropy measure for each feature with respect to the outcome (benign/malignant using a cancer registry match as reference standard). In order to evaluate the validity of the MI rankings of features, we trained and tested naïve Bayes classifiers on the feature with tenfold cross-validation, and measured the predictive ability using area under the ROC curve (AUC). We used a bootstrapping approach to assess the distributional properties of our estimates, and the DeLong method to compare AUC. Based on MI, we found that mass margins and mass shape were the most informative features for breast cancer diagnosis. Calcification morphology, mass density, and calcification distribution provided predictive information for distinguishing benign and malignant breast findings. Breast composition, associated findings, and special cases provided little information in this task. We also found that the rankings of mammographic features with MI and AUC were generally consistent. MI analysis provides a framework to determine the value of different mammographic features in the pursuit of optimal (i.e., accurate and efficient) breast cancer diagnosis.