Reduction of false positives in lung nodule detection using a two-level neural classification

The authors have developed a neural-digital computer-aided diagnosis system, based on a parameterized two-level convolution neural network (CNN) architecture and on a special multilabel output encoding procedure. The developed architecture was trained, tested, and evaluated specifically on the problem of diagnosis of lung cancer nodules found on digitized chest radiographs. The system performs automatic "suspect" localization, feature extraction, and diagnosis of a particular pattern-class aimed at a high degree of "true-positive fraction" detection and low "false-positive fraction" detection. In this paper, the authors aim at the presentation of the two-level neural classification method in reducing false-positives in their system. They employed receiver operating characteristics (ROC) method with the area under the ROC curve (A(z)) as the performance index to evaluate all the simulation results. The two-level CNN showed superior performance (A(z)=0.93) to the single-level CNN (A(z)=0.85). The proposed two-level CNN architecture is proven to be promising and to be extensible, problem-independent, and therefore, applicable to other medical or difficult diagnostic tasks in two-dimensional (2-D) image environments.     

Computer-aided characterization of mammographic masses: accuracy of mass segmentation and its effects on characterization.

Mass segmentation is used as the first step in many computer-aided diagnosis (CAD) systems for classification of breast masses as malignant or benign. The goal of this paper was to study the accuracy of an automated mass segmentation method developed in our laboratory, and to investigate the effect of the segmentation stage on the overall classification accuracy. The automated segmentation method was quantitatively compared with manual segmentation by two expert radiologists (R1 and R2) using three similarity or distance measures on a data set of 100 masses. The area overlap measures between R1 and R2, the computer and R1, and the computer and R2 were 0.76 +/- 0.13, 0.74 +/- 0.11, and 0.74 +/- 0.13, respectively. The interobserver difference in these measures between the two radiologists was compared with the corresponding differences between the computer and the radiologists. Using three similarity measures and data from two radiologists, a total of six statistical tests were performed. The difference between the computer and the radiologist segmentation was significantly larger than the interobserver variability in only one test. Two sets of texture, morphological, and spiculation features, one based on the computer segmentation, and the other based on radiologist segmentation, were extracted from a data set of 249 films from 102 patients. A classifier based on stepwise feature selection and linear discriminant analysis was trained and tested using the two feature sets. The leave-one-case-out method was used for data sampling. For case-based classification, the area Az under the receiver operating characteristic (ROC) curve was 0.89 and 0.88 for the feature sets based on the radiologist segmentation and computer segmentation, respectively. The difference between the two ROC curves was not statistically significant.     

Classification of malignant and benign masses based on hybrid ART2LDA approach

A new type of classifier combining an unsupervised and a supervised model was designed and applied to classification of malignant and benign masses on mammograms. The unsupervised model was based on an adaptive resonance theory (ART2) network which clustered the masses into a number of separate classes. The classes were divided into two types: one containing only malignant masses and the other containing a mix of malignant and benign masses. The masses from the malignant classes were classified by ART2. The masses from the mixed classes were input to a supervised linear discriminant classifier (LDA). In this way, some malignant masses were separated and classified by ART2 and the less distinguishable benign and malignant masses were classified by LDA. For the evaluation of classifier performance, 348 regions of interest (ROI's) containing biopsy proven masses (169 benign and 179 malignant) were used. Ten different partitions of training and test groups were randomly generated using an average of 73% of ROI's for training and 27% for testing. Classifier design, including feature selection and weight optimization, was performed with the training group. The test group was kept independent of the training group. The performance of the hybrid classifier was compared to that of an LDA classifier alone and a backpropagation neural network (BPN). Receiver operating characteristics (ROC) analysis was used to evaluate the accuracy of the classifiers. The average area under the ROC curve (A(z)) for the hybrid classifier was 0.81 as compared to 0.78 for the LDA and 0.80 for the BPN. The partial areas above a true positive fraction of 0.9 were 0.34, 0.27 and 0.31 for the hybrid, the LDA and the BPN classifier, respectively. These results indicate that the hybrid classifier is a promising approach for improving the accuracy of classification in CAD applications.     

ROC analysis of ultrasound tissue characterization classifiers for breast cancer diagnosis

Breast cancer diagnosis through ultrasound tissue characterization was studied using receiver operating characteristic (ROC) analysis of combinations of acoustic features, patient age, and radiological findings. A feature fusion method was devised that operates even if only partial diagnostic data are available. The ROC methodology uses ordinal dominance theory and bootstrap resampling to evaluate A(z) and confidence intervals in simple as well as paired data analyses. The combined diagnostic feature had an A(z) of 0.96 with a confidence interval of at a significance level of 0.05. The combined features show statistically significant improvement over prebiopsy radiological findings. These results indicate that ultrasound tissue characterization, in combination with patient record and clinical findings, may greatly reduce the need to perform biopsies of benign breast lesions.     

Temporal change analysis for characterization of mass lesions in mammography

In this paper, we present a fully automated computer-aided diagnosis (CAD) program to detect temporal changes in mammographic masses between two consecutive screening rounds. The goal of this work was to improve the characterization of mass lesions by adding information about the tumor behavior over time. Towards this goal we previously developed a regional registration technique that finds for each mass lesion on the current view a location on the prior view where the mass was most likely to develop. For the task of interval change analysis, we designed two kinds of temporal features: difference features and similarity features. Difference features indicate the (relative) change in feature values determined on prior and current views. These features may be especially useful for lesions that are visible on both views. Similarity features measure whether two regions are comparable in appearance and may be useful for lesions that are visible on the prior view as well as for newly developing lesions. We evaluated the classification performance with and without the use of temporal features on a dataset consisting of 465 temporal mammogram pairs, 238 benign, and 227 malignant. We used cross validation to partition the dataset into a training set and a test set. The training set was used to train a support vector machine classifier and the test set to evaluate the classifier. The average A(z) value (area under the receiver operating characteristic curve) for classifying each lesion was 0.74 without temporal features and 0.77 with the use of temporal features. The improvement obtained by adding temporal features was statistically significant (P = 0.005). In particular, similarity features contributed to this improvement. Furthermore, we found that the improvement was comparable for masses that were visible and for masses that were not visible on the prior view. These results show that the use of temporal features is an effective approach to improve the characterization of masses.     

面向肺结节多语义特征分类的不确定性多任务损失方法

肺结节的早期诊断对后续的治疗非常重要.尽管深度学习方法在肺结节良恶性分类等任务中取得了良好的结果,但是这些方法没有提供有意义的诊断功能,导致获得的结果缺乏客观性.越来越多的研究者引入了肺结节的其他语义特征来解决这个问题,但是多个语义特征的引入会造成模型的负迁移.为了解决肺结节多个语义特征之间同步共享知识的程度不同造成的...     

Classification of dynamic contrast-enhanced magnetic resonance breast lesions by support vector machines

Early detection of breast cancer is one of the most important factors in determining prognosis for women with malignant tumors. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been shown to be the most sensitive modality for screening high-risk women. Computer-aided diagnosis (CAD) systems have the potential to assist radiologists in the early detection of cancer. A key component of the development of such a CAD system will be the selection of an appropriate classification function responsible for separating malignant and benign lesions. The purpose of this study is to evaluate the effects of variations in temporal feature vectors and kernel functions on the separation of malignant and benign DCE-MRI breast lesions by support vector machines (SVMs). We also propose and demonstrate a classifier visualization and evaluation technique. We show that SVMs provide an effective and flexible framework from which to base CAD techniques for breast MRI, and that the proposed classifier visualization technique has potential as a mechanism for the evaluation of classification solutions.     

Optimizing Case-based detection performance in a multiview CAD system for mammography

When reading mammograms, radiologists combine information from multiple views to detect abnormalities. Most computer-aided detection (CAD) systems, however, use primitive methods for inclusion of multiview context or analyze each view independently. In previous research it was found that in mammography lesion-based detection performance of CAD systems can be improved when correspondences between MLO and CC views are taken into account. However, detection at case level detection did not improve. In this paper, we propose a new learning method for multiview CAD systems, which is aimed at optimizing case-based detection performance. The method builds on a single-view lesion detection system and a correspondence classifier. The latter provides class probabilities for the various types of region pairs and correspondence features. The correspondence classifier output is used to bias the selection of training patterns for a multiview CAD system. In this way training can be forced to focus on optimization of case-based detection performance. The method is applied to the problem of detecting malignant masses and architectural distortions. Experiments involve 454 mammograms consisting of four views with a malignant region visible in at least one of the views. To evaluate performance, five-fold cross validation and FROC analysis was performed. Bootstrapping was used for statistical analysis. A significant increase of case-based detection performance was found when the proposed method was used. Mean sensitivity increased by 4.7% in the range of 0.01-0.5 false positives per image.     

Computer-aided diagnosis of solid breast nodules: use of an artificial neural network based on multiple sonographic features

A computer-aided diagnosis (CAD) algorithm identifying breast nodule malignancy using multiple ultrasonography (US) features and artificial neural network (ANN) classifier was developed from a database of 584 histologically confirmed cases containing 300 benign and 284 malignant breast nodules. The features determining whether a breast nodule is benign or malignant were extracted from US images through digital image processing with a relatively simple segmentation algorithm applied to the manually preselected region of interest. An ANN then distinguished malignant nodules in US images based on five morphological features representing the shape, edge characteristics, and darkness of a nodule. The structure of ANN was selected using k-fold cross-validation method with k = 10. The ANN trained with randomly selected half of breast nodule images showed the normalized area under the receiver operating characteristic curve of 0.95. With the trained ANN, 53.3% of biopsies on benign nodules can be avoided with 99.3% sensitivity. Performance of the developed classifier was reexamined with new US mass images in the generalized patient population of total 266 (167 benign and 99 malignant) cases. The developed CAD algorithm has the potential to increase the specificity of US for characterization of breast lesions.     

Automatic detection and quantification of tree-in-bud (TIB) opacities from CT scans

This study presents a novel computer-assisted detection (CAD) system for automatically detecting and precisely quantifying abnormal nodular branching opacities in chest computed tomography (CT), termed tree-in-bud (TIB) opacities by radiology literature. The developed CAD system in this study is based on 1) fast localization of candidate imaging patterns using local scale information of the images, and 2) M?bius invariant feature extraction method based on learned local shape and texture properties of TIB patterns. For fast localization of candidate imaging patterns, we use ball-scale filtering and, based on the observation of the pattern of interest, a suitable scale selection is used to retain only small size patterns. Once candidate abnormality patterns are identified, we extract proposed shape features from regions where at least one candidate pattern occupies. The comparative evaluation of the proposed method with commonly used CAD methods is presented with a dataset of 60 chest CTs (laboratory confirmed 39 viral bronchiolitis human parainfluenza CTs and 21 normal chest CTs). The quantitative results are presented as the area under the receiver operator characteristics curves and a computer score (volume affected by TIB) provided as an output of the CAD system. In addition, a visual grading scheme is applied to the patient data by three well-trained radiologists. Interobserver and observer-computer agreements are obtained by the relevant statistical methods over different lung zones. Experimental results demonstrate that the proposed CAD system can achieve high detection rates with an overall accuracy of 90.96%. Moreover, correlations of observer-observer (R(2)=0.8848, and observer-CAD agreements (R(2)=0.824, validate the feasibility of the use of the proposed CAD system in detecting and quantifying TIB patterns.     

Computerized analysis of multiple-mammographic views: potentialusefulness of special view mammograms in computer-aided diagnosis

PURPOSE: To investigate the potential usefulness of special view mammograms in the computer-aided diagnosis of mammographic breast lesions. MATERIALS AND METHODS: Previously, we developed a computerized method for the classification of mammographic mass lesions on standard-view mammograms, i.e., mediolateral oblique (MLO) view and/or cranial caudal (CC) views. In this study, we evaluate the performance of our computerized classification method on an independent database consisting of 70 cases (33 malignant and 37 benign cases), each having CC, MLO, and special view mammograms (spot compression or spot compression magnification views). The mass lesion identified in each of the three mammographic views was analyzed using our previously developed and trained computerized classification method. Performance in the task of distinguishing between malignant and benign lesions was evaluated using receiver operating characteristic analysis. On this independent database, we compared the performance of individual computer-extracted mammographic features, as well as the computer-estimated likelihood of malignancy, for the standard and special views. RESULTS: Computerized analysis of special view mammograms alone in the task of distinguishing between malignant and benign lesions yielded an Az of 0.95, which is significantly higher (p < 0.005) than that obtained from the MLO and CC views (Az values of 0.78 and 0.75, respectively). Use of only the special views correctly classified 19 of 33 benign cases (a specificity of 58%) at 100% sensitivity, whereas use of the CC and MLO views alone correctly classified 4 and 8 of 33 benign cases (specificities of 12% and 24%, respectively). In addition, we found that the average computer output of the three views (Az of 0.95) yielded a significantly better performance than did the maximum computer output from the mammographic views. CONCLUSIONS: Computerized analysis of special view mammograms provides an improved prediction of the benign versus malignant status of mammographic mass lesions.     

Automatic detection of abnormalities in chest radiographs using local texture analysis

A fully automatic method is presented to detect abnormalities in frontal chest radiographs which are aggregated into an overall abnormality score. The method is aimed at finding abnormal signs of a diffuse textural nature, such as they are encountered in mass chest screening against tuberculosis (TB). The scheme starts with automatic segmentation of the lung fields, using active shape models. The segmentation is used to subdivide the lung fields into overlapping regions of various sizes. Texture features are extracted from each region, using the moments of responses to a multiscale filter bank. Additional "difference features" are obtained by subtracting feature vectors from corresponding regions in the left and right lung fields. A separate training set is constructed for each region. All regions are classified by voting among the k nearest neighbors, with leave-one-out. Next, the classification results of each region are combined, using a weighted multiplier in which regions with higher classification reliability weigh more heavily. This produces an abnormality score for each image. The method is evaluated on two databases. The first database was collected from a TB mass chest screening program, from which 147 images with textural abnormalities and 241 normal images were selected. Although this database contains many subtle abnormalities, the classification has a sensitivity of 0.86 at a specificity of 0.50 and an area under the receiver operating characteristic (ROC) curve of 0.820. The second database consist of 100 normal images and 100 abnormal images with interstitial disease. For this database, the results were a sensitivity of 0.97 at a specificity of 0.90 and an area under the ROC curve of 0.986.     

Analysis of tumor vascularity using three-dimensional power Doppler ultrasound images

Tumor vascularity is an important factor that has been shown to correlate with tumor malignancy and was demonstrated as a prognostic indicator for a wide range of cancers. Three-dimensional (3-D) power Doppler ultrasound (PDUS) offers a convenient tool for investigators to inspect the signals of blood flow and vascular structures in breast cancer. In this paper, a new computer-aided diagnosis (CAD) system for quantifying Doppler ultrasound images based on 3-D thinning algorithm and neural network is proposed. We extracted the skeleton of blood vessels from 3-D PDUS data to facilitate the capturing of morphological changes. Nine features including vessel-to-volume ratio, number of vascular trees, length of vessels, number of branching, mean of radius, number of cycles, and three tortuosity measures, were extracted from the thinning result. Benign and malignant tumors can therefore be differentiated by a score computed by a multilayered perceptron (MLP) neural network using these features as parameters. The proposed system was tested on 221 breast tumors, including 110 benign and 111 malignant lesions. The accuracy, sensitivity, specificity, and positive and negative predictive values were 88.69% (196/221), 91.89% (102/111), 85.45% (94/110), 86.44% (102/118), and 91.26% (94/103), respectively. The Az value of the ROC curve was 0.94. The results demonstrate a correlation between the morphology of blood vessels and tumor malignancy, indicating that the newly proposed method can retrieves a high accuracy in the classification of benign and malignant breast tumors.     

Gradient and texture analysis for the classification of mammographic masses

Computer-aided classification of benign and malignant masses on mammograms is attempted in this study by computing gradient-based and texture-based features. Features computed based on gray-level co-occurrence matrices (GCMs) are used to evaluate the effectiveness of textural information possessed by mass regions in comparison with the textural information present in mass margins. A method involving polygonal modeling of boundaries is proposed for the extraction of a ribbon of pixels across mass margins. Two gradient-based features are developed to estimate the sharpness of mass boundaries in the ribbons of pixels extracted from their margins. A total of 54 images (28 benign and 26 malignant) containing 39 images from the Mammographic Image Analysis Society (MIAS) database and 15 images from a local database are analyzed. The best benign versus malignant classification of 82.1%, with an area (Az) of 0.85 under the receiver operating characteristics (ROC) curve, was obtained with the images from the MIAS database by using GCM-based texture features computed from mass margins. The classification method used is based on posterior probabilities computed from Mahalanobis distances. The corresponding accuracy using jack-knife classification was observed to be 74.4%, with Az = 0.67. Gradient-based features achieved Az = 0.6 on the MIAS database and Az = 0.76 on the combined database. The corresponding values obtained using jack-knife classification were observed to be 0.52 and 0.73 for the MIAS and combined databases, respectively.     

Polygonal modeling of contours of breast tumors with the preservation of spicules

Malignant breast tumors typically appear in mammograms with rough, spiculated, or microlobulated contours, whereas most benign masses have smooth, round, oval, or macrolobulated contours. Several studies have shown that shape factors that incorporate differences as above can provide high accuracies in distinguishing between malignant tumors and benign masses based upon their contours only. However, global measures of roughness, such as compactness, are less effective than specially designed features based upon spicularity and concavity. We propose a method to derive polygonal models of contours that preserve spicules and details of diagnostic importance. We show that an index of spiculation derived from the turning functions of the polygonal models obtained by the proposed method yields better classification accuracy than a similar measure derived using a previously published method. The methods were tested with a set of 111 contours of 65 benign masses and 46 malignant tumors. A high classification accuracy of 0.94 in terms of the area under the receiver operating characteristics curve was obtained.     

Characterization of spiculation on ultrasound lesions

Spiculation is a stellate distortion caused by the intrusion of breast cancer into surrounding tissue. Its existence is an important clue to characterizing malignant tumors. Many successful mammographic methods have been proposed to detect tumors with spiculation. Traditional two-dimensional (2-D) ultrasound cannot easily find spiculations because spiculations normally appear parallel to the surface of the skin. Recently, three-dimensional (3-D) ultrasound has been gradually used in clinical applications and it has been proven to be useful in determining the architectural distortion or spiculation that surrounds a breast tumor. This paper aims to identify spiculation from 3-D ultrasonic volume data of a tumor found by a physician. In the proposed method, each coronal slice of volume data is successively extracted and then analyzed as a 2-D ultrasound image by the proposed spiculation detection method. First, in each horizontal slice, the modified rotating structuring element (ROSE) operation is used to find the central region in which spiculation lines converge. Second, the stick algorithm is used to estimate the direction of the edge of each pixel around the central region. A pixel whose edge points toward the central region is marked as a potential spiculation. Finally, the marked pixels are collected around the central region and their distribution is analyzed to determine whether spiculation is present. The 3-D test datasets were obtained using the Voluson 530 or 730, Kretztechnik, Austria. First, the proposed method was tested on 104 2-D typical coronal images (selected by an experienced physician) extracted from 52 3-D ultrasonic datasets. Finally, 225 3-D pathologically proven datasets were tested to evaluate the performance. Spiculations are more easily observed in the coronal view than in the other two views. That is, the 3-D ultrasound is a powerful tool for identifying spiculations. Furthermore, 16% (19/120) of benign cases and 90% (94/105) of malignant cases are detected as spiculations.     

Random field models in the textural analysis of ultrasonic images of the liver

Conventional two-dimensional (2-D) texture parameters serve as the "gold standard" of texture analysis. The authors compared a new stochastic model, based on autoregressive periodic random field models (APRFM) with conventional texture analysts (CTA) parameter, which were defined as measures of the co-occurrence matrix, i.e., entropy, contrast, correlation, uniformity, and maximum frequency. By fitting the model to a given texture pattern, the estimated model parameters are suitable texture features. In 81 patients, divided into patients without (N=19) and with (N=62) microfocal lesions of the liver, a set of 24 CTA and 16 APRFM parameters were calculated from ultrasonic liver images. To ensure simple computation the APRFM parameters were based on the unilateral type of pixel neighborhood. Regenerated texture by APRFM was visually comparable with the original texture. Reclassification analysis using the classification and regression tree (CART) discriminant analysis system and the area under the receiver operating characteristic (ROC) curve was used to assess the texture classification potency of APRFM- and CTA-parameters. Discriminating between liver with and without microfocal lesions, the best results were seen for the APRFM parameter.     

A study on several machine-learning methods for classification of malignant and benign clustered microcalcifications

In this paper, we investigate several state-of-the-art machine-learning methods for automated classification of clustered microcalcifications (MCs). The classifier is part of a computer-aided diagnosis (CADx) scheme that is aimed to assisting radiologists in making more accurate diagnoses of breast cancer on mammograms. The methods we considered were: support vector machine (SVM), kernel Fisher discriminant (KFD), relevance vector machine (RVM), and committee machines (ensemble averaging and AdaBoost), of which most have been developed recently in statistical learning theory. We formulated differentiation of malignant from benign MCs as a supervised learning problem, and applied these learning methods to develop the classification algorithm. As input, these methods used image features automatically extracted from clustered MCs. We tested these methods using a database of 697 clinical mammograms from 386 cases, which included a wide spectrum of difficult-to-classify cases. We analyzed the distribution of the cases in this database using the multidimensional scaling technique, which reveals that in the feature space the malignant cases are not trivially separable from the benign ones. We used receiver operating characteristic (ROC) analysis to evaluate and to compare classification performance by the different methods. In addition, we also investigated how to combine information from multiple-view mammograms of the same case so that the best decision can be made by a classifier. In our experiments, the kernel-based methods (i.e., SVM, KFD, and RVM) yielded the best performance (Az = 0.85, SVM), significantly outperforming a well-established, clinically-proven CADx approach that is based on neural network (Az = 0.80).     

Use of Normal Tissue Context in Computer-Aided Detection of Masses in Mammograms

When reading mammograms, radiologists do not only look at local properties of suspicious regions but also take into account more general contextual information. This suggests that context may be used to improve the performance of computer-aided detection (CAD) of malignant masses in mammograms. In this study, we developed a set of context features that represent suspiciousness of normal tissue in the same case. For each candidate mass region, three normal reference areas were defined in the image at hand. Corresponding areas were also defined in the contralateral image and in different projections. Evaluation of the context features was done using 10-fold cross validation and case based bootstrapping. Free response receiver operating characteristic (FROC) curves were computed for feature sets including context features and a feature set without context. Results show that the mean sensitivity in the interval of 0.05–0.5 false positives/image increased more than 6% when context features were added. This increase was significant $({ p}≪0.0001)$. Context computed using multiple views yielded a better performance than using a single view (mean sensitivity increase of 2.9%, ${ p}≪0.0001$). Besides the importance of using multiple views, results show that best CAD performance was obtained when multiple context features were combined that are based on different reference areas in the mammogram.      

Detection of breast masses in mammograms by density slicing and texture flow-field analysis.

We propose a method for the detection of masses in mammographic images that employs Gaussian smoothing and sub-sampling operations as preprocessing steps. The mass portions are segmented by establishing intensity links from the central portions of masses into the surrounding areas. We introduce methods for analyzing oriented flow-like textural information in mammograms. Features based on flow orientation in adaptive ribbons of pixels across the margins of masses are proposed to classify the regions detected as true mass regions or false-positives (FPs). The methods yielded a mass versus normal tissue classification accuracy represented as an area (Az) of 0.87 under the receiver operating characteristics (ROCs) curve with a dataset of 56 images including 30 benign disease, 13 malignant disease, and 13 normal cases selected from the mini Mammographic Image Analysis Society database. A sensitivity of 81% was achieved at 2.2 FPs/image. Malignant tumor versus normal tissue classification resulted in a higher Az value of 0.9 under the ROC curve using only the 13 malignant and 13 normal cases with a sensitivity of 85% at 2.45 FPs/image. The mass detection algorithm could detect all the 13 malignant tumors successfully, but achieved a success rate of only 63% (19/30) in detecting the benign masses. The mass regions that were successfully segmented were further classified as benign or malignant disease by computing five texture features based on gray-level co-occurrence matrices (GCMs) and using the features in a logistic regression method. The features were computed using adaptive ribbons of pixels across the boundaries of the masses. Benign versus malignant classification using the GCM-based texture features resulted in Az = 0.79 with 19 benign and 13 malignant cases.