Computer-aided diagnosis of pulmonary nodules on CT scans: segmentation and classification using 3D active contours

We are developing a computer-aided diagnosis (CAD) system to classify malignant and benign lung nodules found on CT scans. A fully automated system was designed to segment the nodule from its surrounding structured background in a local volume of interest (VOI) and to extract image features for classification. Image segmentation was performed with a three-dimensional (3D) active contour (AC) method. A data set of 96 lung nodules (44 malignant, 52 benign) from 58 patients was used in this study. The 3D AC model is based on two-dimensional AC with the addition of three new energy components to take advantage of 3D information: (1) 3D gradient, which guides the active contour to seek the object surface, (2) 3D curvature, which imposes a smoothness constraint in the z direction, and (3) mask energy, which penalizes contours that grow beyond the pleura or thoracic wall. The search for the best energy weights in the 3D AC model was guided by a simplex optimization method. Morphological and gray-level features were extracted from the segmented nodule. The rubber band straightening transform (RBST) was applied to the shell of voxels surrounding the nodule. Texture features based on run-length statistics were extracted from the RBST image. A linear discriminant analysis classifier with stepwise feature selection was designed using a second simplex optimization to select the most effective features. Leave-one-case-out resampling was used to train and test the CAD system. The system achieved a test area under the receiver operating characteristic curve (A(z)) of 0.83 +/- 0.04. Our preliminary results indicate that use of the 3D AC model and the 3D texture features surrounding the nodule is a promising approach to the segmentation and classification of lung nodules with CAD. The segmentation performance of the 3D AC model trained with our data set was evaluated with 23 nodules available in the Lung Image Database Consortium (LIDC). The lung nodule volumes segmented by the 3D AC model for best classification were generally larger than those outlined by the LIDC radiologists using visual judgment of nodule boundaries.     

Computer-aided diagnostic scheme for the detection of lung nodules on chest radiographs: localized search method based on anatomical classification

We developed an advanced computer-aided diagnostic (CAD) scheme for the detection of various types of lung nodules on chest radiographs intended for implementation in clinical situations. We used 924 digitized chest images (992 noncalcified nodules) which had a 500 x 500 matrix size with a 1024 gray scale. The images were divided randomly into two sets which were used for training and testing of the computerized scheme. In this scheme, the lung field was first segmented by use of a ribcage detection technique, and then a large search area (448 x 448 matrix size) within the chest image was automatically determined by taking into account the locations of a midline and a top edge of the segmented ribcage. In order to detect lung nodule candidates based on a localized search method, we divided the entire search area into 7 x 7 regions of interest (ROIs: 64 x 64 matrix size). In the next step, each ROI was classified anatomically into apical, peripheral, hilar, and diaphragm/heart regions by use of its image features. Identification of lung nodule candidates and extraction of image features were applied for each localized region (128 x 128 matrix size), each having its central part (64 x 64 matrix size) located at a position corresponding to a ROI that was classified anatomically in the previous step. Initial candidates were identified by use of the nodule-enhanced image obtained with the average radial-gradient filtering technique, in which the filter size was varied adaptively depending on the location and the anatomical classification of the ROI. We extracted 57 image features from the original and nodule-enhanced images based on geometric, gray-level, background structure, and edge-gradient features. In addition, 14 image features were obtained from the corresponding locations in the contralateral subtraction image. A total of 71 image features were employed for three sequential artificial neural networks (ANNs) in order to reduce the number of false-positive candidates. All parameters for ANNs, i.e., the number of iterations, slope of sigmoid functions, learning rate, and threshold values for removing the false positives, were determined automatically by use of a bootstrap technique with training cases. We employed four different combinations of training and test image data sets which was selected randomly from the 924 cases. By use of our localized search method based on anatomical classification, the average sensitivity was increased to 92.5% with 59.3 false positives per image at the level of initial detection for four different sets of test cases, whereas our previous technique achieved an 82.8% of sensitivity with 56.8 false positives per image. The computer performance in the final step obtained from four different data sets indicated that the average sensitivity in detecting lung nodules was 70.1% with 5.0 false positives per image for testing cases and 70.4% sensitivity with 4.2 false positives per image for training cases. The advanced CAD scheme involving the localized search method with anatomical classification provided improved detection of pulmonary nodules on chest radiographs for 924 lung nodule cases.     

3D shape analysis to reduce false positives for lung nodule detection systems

Using images from the Image Database Consortium and Image Database Resource Initiative (LIDC–IDRI), we developed a methodology for classifying lung nodules. The proposed methodology uses image processing and pattern recognition techniques. To classify volumes of interest into nodules and non-nodules, we used shape measurements only, analyzing their shape using shape diagrams, proportion measurements, and a cylinder-based analysis. In addition, we use the support vector machine classifier. To test the proposed methodology, it was applied to 833 images from the LIDC–IDRI database, and cross-validation with k-fold, where \(k = 5\), was used to validate the results. The proposed methodology for the classification of nodules and non-nodules achieved a mean accuracy of 95.33 %. Lung cancer causes more deaths than any other cancer worldwide. Therefore, precocious detection allows for faster therapeutic intervention and a more favorable prognosis for the patient. Our proposed methodology contributes to the classification of lung nodules and should help in the diagnosis of lung cancer.     

Registration of lung nodules using a semi-rigid model: method and preliminary results

The tracking of lung nodules across computed tomography (CT) scans acquired at different times for the same patient is helpful for the determination of malignancy. We are developing a nodule registration system to facilitate this process. We propose to use a semi-rigid method that considers principal structures surrounding the nodule and allows relative movements among the structures. The proposed similarity metric, which evaluates both the image correlation and the degree of elastic deformation amongst the structures, is maximized by a two-layered optimization method, employing a simulated annealing framework. We tested our method by simulating five cases that represent physiological deformation as well as different nodule shape/size changes with time. Each case is made up of a source and target scan, where the source scan consists of a nodule-free patient CT volume into which we inserted ten simulated lung nodules, and the target scan is the result of applying a known, physiologically based nonrigid transformation to the nodule-free source scan, into which we inserted modified versions of the corresponding nodules at the same, known locations. Five different modification strategies were used, one for each of the five cases: (1) nodules maintain size and shape, (2) nodules disappear, (3) nodules shrink uniformly by a factor of 2, (4) nodules grow uniformly by a factor of 2, and (5) nodules grow nonuniformly. We also matched 97 real nodules in pairs of scans (acquired at different times) from 12 patients and compared our registration to a radiologist's visual determination. In the simulation experiments, the mean absolute registration errors were 1.0+/-0.8 mm (s.d.), 1.1+/-0.7 mm (s.d.), 1.0+/-0.7 mm (s.d.), 1.0+/-0.6 mm (s.d.), and 1.1+/- 0.9 mm (s.d.) for the five cases, respectively. For the 97 nodule pairs in 12 patient scans, the mean absolute registration error was 1.4+/-0.8 mm (s.d.).     

Computer-aided detection of early interstitial lung diseases using low-dose CT images

This study aims to develop a new computer-aided detection (CAD) scheme to detect early interstitial lung disease (ILD) using low-dose computed tomography (CT) examinations. The CAD scheme classifies each pixel depicted on the segmented lung areas into positive or negative groups for ILD using a mesh-grid-based region growth method and a multi-feature-based artificial neural network (ANN). A genetic algorithm was applied to select optimal image features and the ANN structure. In testing each CT examination, only pixels selected by the mesh-grid region growth method were analyzed and classified by the ANN to improve computational efficiency. All unselected pixels were classified as negative for ILD. After classifying all pixels into the positive and negative groups, CAD computed a detection score based on the ratio of the number of positive pixels to all pixels in the segmented lung areas, which indicates the likelihood of the test case being positive for ILD. When applying to an independent testing dataset of 15 positive and 15 negative cases, the CAD scheme yielded the area under receiver operating characteristic curve (AUC = 0.884 ± 0.064) and 80.0% sensitivity at 85.7% specificity. The results demonstrated the feasibility of applying the CAD scheme to automatically detect early ILD using low-dose CT examinations.     

Massive training artificial neural network (MTANN) for reduction of false positives in computerized detection of lung nodules in low-dose computed tomography

In this study, we investigated a pattern-recognition technique based on an artificial neural network (ANN), which is called a massive training artificial neural network (MTANN), for reduction of false positives in computerized detection of lung nodules in low-dose computed tomography (CT) images. The MTANN consists of a modified multilayer ANN, which is capable of operating on image data directly. The MTANN is trained by use of a large number of subregions extracted from input images together with the teacher images containing the distribution for the "likelihood of being a nodule." The output image is obtained by scanning an input image with the MTANN. The distinction between a nodule and a non-nodule is made by use of a score which is defined from the output image of the trained MTANN. In order to eliminate various types of non-nodules, we extended the capability of a single MTANN, and developed a multiple MTANN (Multi-MTANN). The Multi-MTANN consists of plural MTANNs that are arranged in parallel. Each MTANN is trained by using the same nodules, but with a different type of non-nodule. Each MTANN acts as an expert for a specific type of non-nodule, e.g., five different MTANNs were trained to distinguish nodules from various-sized vessels; four other MTANNs were applied to eliminate some other opacities. The outputs of the MTANNs were combined by using the logical AND operation such that each of the trained MTANNs eliminated none of the nodules, but removed the specific type of non-nodule with which the MTANN was trained, and thus removed various types of non-nodules. The Multi-MTANN consisting of nine MTANNs was trained with 10 typical nodules and 10 non-nodules representing each of nine different non-nodule types (90 training non-nodules overall) in a training set. The trained Multi-MTANN was applied to the reduction of false positives reported by our current computerized scheme for lung nodule detection based on a database of 63 low-dose CT scans (1765 sections), which contained 71 confirmed nodules including 66 biopsy-confirmed primary cancers, from a lung cancer screening program. The Multi-MTANN was applied to 58 true positives (nodules from 54 patients) and 1726 false positives (non-nodules) reported by our current scheme in a validation test; these were different from the training set. The results indicated that 83% (1424/1726) of non-nodules were removed with a reduction of one true positive (nodule), i.e., a classification sensitivity of 98.3% (57 of 58 nodules). By using the Multi-MTANN, the false-positive rate of our current scheme was improved from 0.98 to 0.18 false positives per section (from 27.4 to 4.8 per patient) at an overall sensitivity of 80.3% (57/71).     

Reduction of false positives in computerized detection of lung nodules in chest radiographs using artificial neural networks,discriminant analysis,and a rule-based scheme

A computer-aided diagnosis (CAD) scheme is being developed to identify image regions considered suspicious for lung nodules in chest radiographs to assist radiologists in making correct diagnoses. Automated classifiers—an artificial neural network, discriminant analysis, and a rule-based scheme—are used to reduce the number of false-positive detections of the CAD scheme. The CAD scheme first detects nodule candidates from chest radiographs based on a difference image technique. Nine image features characterizing nodules are extracted automatically for each of the nodule candidates. The extracted image features are then used as input data to the classifiers for distinguishing actual nodules from the false-positive detections. The performances of the classifiers are evaluated by receiver-operating characteristic analysis. On the basis of the database of 30 normal and 30 abnormal chest images, the neural network achieves an A_Z value (area under the receiver-operating-characteristic curve) of 0.79 in detecting lung nodules, as tested by the round-robin method. The neural network, after being trained with a training database, is able to eliminate more than 83% of the false-positive detections reported by the CAD scheme. Moreover, the combination of the trained neural network and a rule-based scheme eliminates 96% of the false-positive detections of the CAD scheme.     

Automated detection of lung nodules in CT scans: false-positive reduction with the radial-gradient index

We present a number of approaches based on the radial gradient index (RGI) to achieve false-positive reduction in automated CT lung nodule detection. A database of 38 cases was used that contained a total of 82 lung nodules. For each CT section, a complementary image known as an "RGI map" was constructed to enhance regions of high circularity and thus improve the contrast between nodules and normal anatomy. Thresholds on three RGI parameters were varied to construct RGI filters that sensitively eliminated false-positive structures. In a consistency approach, RGI filtering eliminated 36% of the false-positive structures detected by the automated method without the loss of any true positives. Use of an RGI filter prior to a linear discriminant classifier yielded notable improvements in performance, with the false-positive rate at a sensitivity of 70% being reduced from 0.5 to 0.28 per section. Finally, the performance of the linear discriminant classifier was evaluated with RGI-based features. RGI-based features achieved a substantial improvement in overall performance, with a 94.8% reduction in the false-positive rate at a fixed sensitivity of 70%. These results demonstrate the potential role of RGI analysis in an automated lung nodule detection method.     

Computer-aided diagnosis system for lung nodules based on computed tomography using shape analysis,a genetic algorithm,and SVM

Lung cancer is the major cause of death among patients with cancer worldwide. This work is intended to develop a methodology for the diagnosis of lung nodules using images from the Image Database Consortium and Image Database Resource Initiative (LIDC–IDRI). The proposed methodology uses image processing and pattern recognition techniques. To differentiate the patterns of malignant and benign forms, we used a Minkowski functional, distance measures, representation of the vector of points measures, triangulation measures, and Feret diameters. Finally, we applied a genetic algorithm to select the best model and a support vector machine for classification. In the test stage, we applied the proposed methodology to 1405 (394 malignant and 1011 benign) nodules from the LIDC–IDRI database. The proposed methodology shows promising results for diagnosis of malignant and benign forms, achieving accuracy of 93.19 %, sensitivity of 92.75 %, and specificity of 93.33 %. The results are promising and demonstrate a good rate of correct detections using the shape features. Because early detection allows faster therapeutic intervention, and thus a more favorable prognosis for the patient, herein we propose a methodology that contributes to the area.     

Eigendetection of masses considering false positive reduction and breast density information

The purpose of this article is to present a novel algorithm for the detection of masses in mammographic computer-aided diagnosis systems. Four key points provide the novelty of our approach: (1) the use of eigenanalysis for describing variation in mass shape and size; (2) a Bayesian detection methodology providing a mathematical sound framework, flexible enough to include additional information; (3) the use of a two-dimensional principal components analysis approach to facilitate false positive reduction; and (4) the incorporation of breast density information, a parameter correlated with the performance of most mass detection algorithms and which is not considered in existing approaches. To study the performance of the system two experiments were carried out. The first is related to the ability of the system to detect masses, and thus, free-response receiver operating characteristic analysis was used, showing that the method is able to give high accuracy at a high specificity (80% detection at 1.40 false positives per image). Second, the ability of the system to highlight the pixels belonging to a mass is studied using receiver operating characteristic analysis, resulting in A(z) = 0.89 +/- 0.04. In addition, the robustness of the approach is demonstrated in an experiment where we used the Digital Database for Screening Mammography database for training and the Mammographic Image Analysis Society database for testing the algorithm.     

Optimization of a tomosynthesis system for the detection of lung nodules

Mathematical observers that track human performance can be used to reduce the number of human observer studies needed to optimize imaging systems. The performance of human observers for the detection of a 3.6 mm lung nodule in anatomical backgrounds was measured as a function of varying tomosynthetic angle and compared with mathematical observers. The human observer results showed a dramatic increase in the percent of correct responses, from 80% in the projection images to 96% in the projection images with a tomosynthetic angle of just 3 degrees. This result suggests the potential usefulness of the scanned beam digital x-ray system for this application. Given the small number of images (40) used per tomosynthetic angle and the highly nonstationary statistical nature of the backgrounds, the nonprewhitening eye observer achieved a higher performance than the channelized Hotelling observer using a Laguerre-Gauss basis. The channelized Hotelling observer with internal noise and the eye filter matched to the projection data were shown to track human performance as the tomosynthetic angle changed. The validation of these mathematical observers extends their applicability to the optimization of tomosynthesis systems.     

Rapid 3D radiofrequency field mapping using catalyzed double‐angle method

A new method is presented for rapid and accurate large volumetric radiofrequency (RF) field (B) mapping. This method is a modification of the double‐angle method (DAM), which accelerates imaging speed and applies 3D acquisition to improve B measurement accuracy. It reduces repetition time and scan time by introducing a catalyzation RF pulse chain at the end of each DAM repetition cycle. The catalyzation pulse chain ensures that, after each TR period, the longitudinal magnetizations reach the same state for both measurements at two flip angles for the DAM so that the long TR requirement (TR ≥ 5 T₁) for complete relaxation of longitudinal magnetization of DAM becomes unnecessary. A multi‐echo imaging sequence is additionally incorporated to further improve the efficiency of data acquisition. Simulations demonstrate an excellent flip angle measurement accuracy for catalyzed DAM even with TR << T₁. Phantom and in vivo volunteer studies are presented to demonstrate the catalyzation effect upon B mapping and the application of 3D catalyzed DAM for rapid and accurate large volume RF field mapping. Copyright © 2009 John Wiley & Sons, Ltd.     

Automated detection of lung nodules in CT scans: preliminary results

We have developed a fully automated computerized method for the detection of lung nodules in helical computed tomography (CT) scans of the thorax. This method is based on two-dimensional and three-dimensional analyses of the image data acquired during diagnostic CT scans. Lung segmentation proceeds on a section-by-section basis to construct a segmented lung volume within which further analysis is performed. Multiple gray-level thresholds are applied to the segmented lung volume to create a series of thresholded lung volumes. An 18-point connectivity scheme is used to identify contiguous three-dimensional structures within each thresholded lung volume, and those structures that satisfy a volume criterion are selected as initial lung nodule candidates. Morphological and gray-level features are computed for each nodule candidate. After a rule-based approach is applied to greatly reduce the number of nodule candidates that corresponds to nonnodules, the features of remaining candidates are merged through linear discriminant analysis. The automated method was applied to a database of 43 diagnostic thoracic CT scans. Receiver operating characteristic (ROC) analysis was used to evaluate the ability of the classifier to differentiate nodule candidates that correspond to actual nodules from false-positive candidates. The area under the ROC curve for this categorization task attained a value of 0.90 during leave-one-out-by-case evaluation. The automated method yielded an overall nodule detection sensitivity of 70% with an average of 1.5 false-positive detections per section when applied to the complete 43-case database. A corresponding nodule detection sensitivity of 89% with an average of 1.3 false-positive detections per section was achieved with a subset of 20 cases that contained only one or two nodules per case.     

3D tomographic reconstruction of coronary arteries using a precomputed 4D motion field

In this paper, we present a new method to perform 3D tomographic reconstruction of coronary arteries from cone-beam rotational x-ray angiography acquisitions. We take advantage of the precomputation of the coronary artery motion, modelled as a parametric 4D motion field. Contrary to data gating or data triggering approaches, we homogeneously use all available frames, independently of the cardiac phase. In addition, we artificially subtract angiograms from their background structures. Our method significantly improves the reconstruction, by removing both motion and background artefacts. We have successfully tested it on the datasets from a synthetic phantom and 10 patients.     

Automatic detection of solitary lung nodules using quality threshold clustering,genetic algorithm and diversity index

ObjectiveThe present work has the objective of developing an automatic methodology for the detection of lung nodules.MethodologyThe proposed methodology is based on image processing and pattern recognition techniques and can be summarized in three stages. In the first stage, the extraction and reconstruction of the pulmonary parenchyma is carried out and then enhanced to highlight its structures. In the second stage, nodule candidates are segmented. Finally, in the third stage, shape and texture features are extracted, selected and then classified using a support vector machine.ResultsIn the testing stage, with 140 new exams from the Lung Image Database Consortium image collection, 80% of which are for training and 20% are for testing, good results were achieved, as indicated by a sensitivity of 85.91%, a specificity of 97.70% and an accuracy of 97.55%, with a false positive rate of 1.82 per exam and 0.008 per slice and an area under the free response operating characteristic of 0.8062.ConclusionLung cancer presents the highest mortality rate in addition to one of the smallest survival rates after diagnosis. An early diagnosis considerably increases the survival chance of patients. The methodology proposed herein contributes to this diagnosis by being a useful tool for specialists who are attempting to detect nodules.     

Mixture of expert 3D massive-training ANNs for reduction of multiple types of false positives in CAD for detection of polyps in CT colonography

One of the major challenges in computer-aided detection (CAD) of polyps in CT colonography (CTC) is the reduction of false-positive detections (FPs) without a concomitant reduction in sensitivity. A large number of FPs is likely to confound the radiologist's task of image interpretation, lower the radiologist's efficiency, and cause radiologists to lose their confidence in CAD as a useful tool. Major sources of FPs generated by CAD schemes include haustral folds, residual stool, rectal tubes, the ileocecal valve, and extra-colonic structures such as the small bowel and stomach. Our purpose in this study was to develop a method for the removal of various types of FPs in CAD of polyps while maintaining a high sensitivity. To achieve this, we developed a "mixture of expert" three-dimensional (3D) massive-training artificial neural networks (MTANNs) consisting of four 3D MTANNs that were designed to differentiate between polyps and four categories of FPs: (1) rectal tubes, (2) stool with bubbles, (3) colonic walls with haustral folds, and (4) solid stool. Each expert 3D MTANN was trained with examples from a specific non-polyp category along with typical polyps. The four expert 3D MTANNs were combined with a mixing artificial neural network (ANN) such that different types of FPs could be removed. Our database consisted of 146 CTC datasets obtained from 73 patients whose colons were prepared by standard pre-colonoscopy cleansing. Each patient was scanned in both supine and prone positions. Radiologists established the locations of polyps through the use of optical-colonoscopy reports. Fifteen patients had 28 polyps, 15 of which were 5-9 mm and 13 were 10-25 mm in size. The CTC cases were subjected to our previously reported CAD method consisting of centerline-based extraction of the colon, shape-based detection of polyp candidates, and a Bayesian-ANN-based classification of polyps. The original CAD method yielded 96.4% (27/28) by-polyp sensitivity with an average of 3.1 (224/73) FPs per patient. The mixture of expert 3D MTANNs removed 63% (142/224) of the FPs without the loss of any true positive; thus, the FP rate of our CAD scheme was improved to 1.1 (82/73) FPs per patient while the original sensitivity was maintained. By use of the mixture of expert 3D MTANNs, the specificity of a CAD scheme for detection of polyps in CTC was substantially improved while a high sensitivity was maintained.     

Classification of lung nodules in CT scans using three-dimensional deep convolutional neural networks with a checkpoint ensemble method

Background

Accurately detecting and examining lung nodules early is key in diagnosing lung cancers and thus one of the best ways to prevent lung cancer deaths. Radiologists spend countless hours detecting small spherical-shaped nodules in computed tomography (CT) images. In addition, even after detecting nodule candidates, a considerable amount of effort and time is required for them to determine whether they are real nodules. The aim of this paper is to introduce a high performance nodule classification method that uses three dimensional deep convolutional neural networks (DCNNs) and an ensemble method to distinguish nodules between non-nodules.

Methods

In this paper, we use a three dimensional deep convolutional neural network (3D DCNN) with shortcut connections and a 3D DCNN with dense connections for lung nodule classification. The shortcut connections and dense connections successfully alleviate the gradient vanishing problem by allowing the gradient to pass quickly and directly. Connections help deep structured networks to obtain general as well as distinctive features of lung nodules. Moreover, we increased the dimension of DCNNs from two to three to capture 3D features. Compared with shallow 3D CNNs used in previous studies, deep 3D CNNs more effectively capture the features of spherical-shaped nodules. In addition, we use an alternative ensemble method called the checkpoint ensemble method to boost performance.

Results

The performance of our nodule classification method is compared with that of the state-of-the-art methods which were used in the LUng Nodule Analysis 2016 Challenge. Our method achieves higher competition performance metric (CPM) scores than the state-of-the-art methods using deep learning. In the experimental setup ESB-ALL, the 3D DCNN with shortcut connections and the 3D DCNN with dense connections using the checkpoint ensemble method achieved the highest CPM score of 0.910.

Conclusion

The result demonstrates that our method of using a 3D DCNN with shortcut connections, a 3D DCNN with dense connections, and the checkpoint ensemble method is effective for capturing 3D features of nodules and distinguishing nodules between non-nodules.