Context-aware stacked convolutional neural networks for classification of breast carcinomas in whole-slide histopathology images

Automated classification of histopathological whole-slide images (WSI) of breast tissue requires analysis at very high resolutions with a large contextual area. In this paper, we present context-aware stacked convolutional neural networks (CNN) for classification of breast WSIs into normal/benign, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). We first train a CNN using high pixel resolution patches to capture cellular level information. The feature responses generated by this model are then fed as input to a second CNN, stacked on top of the first. Training of this stacked architecture with large input patches enables learning of fine-grained (cellular) details and global interdependence of tissue structures. Our system is trained and evaluated on a dataset containing 221 WSIs of H&E stained breast tissue specimens. The system achieves an AUC of 0.962 for the binary classification of non-malignant and malignant slides and obtains a three class accuracy of 81.3% for classification of WSIs into normal/benign, DCIS, and IDC, demonstrating its potentials for routine diagnostics

Automatic Diagnosis for Prostate Cancer Using Run-Length Matrix Method

Prostate cancer is the most common type of cancer and the second leading cause of cancer death among men in US1. Quantitative assessment of prostate histology provides potential automatic classification of prostate lesions and prediction of response to therapy. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. In this application, we utilize a texture analysis method based on the run-length matrix for identifying tissue abnormalities in prostate histology. A tissue sample was collected from a radical prostatectomy, H&E fixed, and assessed by a pathologist as normal tissue or prostatic carcinoma (PCa). The sample was then subsequently digitized at 50X magnification. We divided the digitized image into sub-regions of 20 X 20 pixels and classified each sub-region as normal or PCa by a texture analysis method. In the texture analysis, we computed texture features for each of the sub-regions based on the Gray-level Run-length Matrix(GL-RLM). Those features include LGRE, HGRE and RPC from the run-length matrix, mean and standard deviation of the pixel intensity. We utilized a feature selection algorithm to select a set of effective features and used a multi-layer perceptron (MLP) classifier to distinguish normal from PCa. In total, the whole histological image was divided into 42 PCa and 6280 normal regions. Three-fold cross validation results show that the proposed method achieves an average classification accuracy of 89.5% with a sensitivity and specificity of 90.48% and 89.49%, respectively

Validating Pareto Optimal Operation Parameters of Polyp Detection Algorithms for CT Colonography

We evaluated a Pareto front-based multi-objective evolutionary algorithm for optimizing our CT colonography (CTC) computer-aided detection (CAD) system. The system identifies colonic polyps based on curvature and volumetric based features, where a set of thresholds for these features was optimized by the evolutionary algorithm. We utilized a two-fold cross-validation (CV) method to test if the optimized thresholds can be generalized to new data sets. We performed the CV method on 133 patients; each patient had a prone and a supine scan. There were 103 colonoscopically confirmed polyps resulting in 188 positive detections in CTC reading from either the prone or the supine scan or both. In the two-fold CV, we randomly divided the 133 patients into two cohorts. Each cohort was used to obtain the Pareto front by a multi-objective genetic algorithm, where a set of optimized thresholds was applied on the test cohort to get test results. This process was repeated twice so that each cohort was used in the training and testing process once. We averaged the two training Pareto fronts as our final training Pareto front and averaged the test results from the two runs in the CV as our final test results. Our experiments demonstrated that the averaged testing results were close to the mean Pareto front determined from the training process. We conclude that the Pareto front-based algorithm appears to be generalizable to new test data

Mammographic texture resemblance generalizes as an independent risk factor for breast cancer

INTRODUCTION: Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast density. We examine if these findings generalize to another population. METHODS: Texture patterns were recorded in digitalized pre-diagnosis (3.7 years) film mammograms of a nested case–control study within the Dutch screening program (S1) comprising of 245 breast cancers and 250 matched controls. The patterns were recognized in the same study using cross-validation to form resemblance scores associated with breast cancer. Texture patterns from S1 were examined in an independent nested case–control study within the Mayo Mammography Health Study cohort (S2) of 226 cases and 442 matched controls: mammograms on average 8.5 years prior to diagnosis, risk factor information and percent mammographic density (PD) estimated using Cumulus were available. MTR scores estimated from S1, S2 and S1 + S2 (the latter two as cross-validations) were evaluated in S2. MTR scores were analyzed as both quartiles and continuously for association with breast cancer using odds ratios (OR) and adjusting for known risk factors including age, body mass index (BMI), and hormone usage. RESULTS: The mean ages of S1 and S2 were 58.0 ± 5.7 years and 55.2 ± 10.5 years, respectively. The MTR scores on S1 showed significant capability to discriminate cancers from controls (area under the operator characteristics curve (AUC) = 0.63 ± 0.02, P <0.001), which persisted after adjustment for PD. S2 showed an AUC of 0.63, 0.61, and 0.60 based on PD, MTR scores trained on S2, and MTR scores trained on S1, respectively. When adjusted for PD, MTR scores of S2 trained on S1 showed an association with breast cancer for the highest quartile alone: OR in quartiles of controls as reference; 1.04 (0.59 to 1.81); 0.95 (0.52 to 1.74); 1.84 (1.10 to 3.07) respectively. The combined continuous model with both PD and MTR scores based on S1 had an AUC of 0.66 ± 0.03. CONCLUSIONS: The local texture patterns associated with breast cancer risk in S1 were also an independent risk factor in S2. Additional textures identified in S2 did not significantly improve risk segregation. Hence, the textural patterns that indicated elevated risk persisted under differences in X-ray technology, population demographics, follow-up time and geography

Quantitative analysis of airway abnormalities in CT

A coupled surface graph cut algorithm for airway wall segmentation from Computed Tomography (CT) images is presented. Using cost functions that highlight both inner and outer wall borders, the method combines the search for both borders into one graph cut. The proposed method is evaluated on 173 manually segmented images extracted from 15 different subjects and shown to give accurate results, with 37% less errors than the Full Width at Half Maximum (FWHM) algorithm and 62% less than a similar graph cut method without coupled surfaces. Common measures of airway wall thickness such as the Interior Area (IA) and Wall Area percentage (WA%) was measured by the proposed method on a total of 723 CT scans from a lung cancer screening study. These measures were significantly different for participants with Chronic Obstructive Pulmonary Disease (COPD) compared to asymptomatic participants. Furthermore, reproducibility was good as confirmed by repeat scans and the measures correlated well with the outcomes of pulmonary function tests, demonstrating the use of the algorithm as a COPD diagnostic tool. Additionally, a new measure of airway wall thickness is proposed, Normalized Wall Intensity Sum (NWIS). NWIS is shown to correlate better with lung function test values and to be more reproducible than previous measures IA, WA% and airway wall thickness at a lumen perimeter of 10 mm (PI10)

Using computer-aided detection in mammography as a decision support

Contains fulltext : 87548.pdf (publisher's version ) (Closed access)OBJECTIVE: To evaluate an interactive computer-aided detection (CAD) system for reading mammograms to improve decision making. METHODS: A dedicated mammographic workstation has been developed in which readers can probe image locations for the presence of CAD information. If present, CAD findings are displayed with the computed malignancy rating. A reader study was conducted in which four screening radiologists and five non-radiologists participated to study the effect of this system on detection performance. The participants read 120 cases of which 40 cases had a malignant mass that was missed at the original screening. The readers read each mammogram both with and without CAD in separate sessions. Each reader reported localized findings and assigned a malignancy score per finding. Mean sensitivity was computed in an interval of false-positive fractions less than 10%. RESULTS: Mean sensitivity was 25.1% in the sessions without CAD and 34.8% in the CAD-assisted sessions. The increase in detection performance was significant (p = 0.012). Average reading time was 84.7 +/- 61.5 s/case in the unaided sessions and was not significantly higher when interactive CAD was used (85.9 +/- 57.8 s/case). CONCLUSION: Interactive use of CAD in mammography may be more effective than traditional CAD for improving mass detection without affecting reading time.1 oktober 201

Consequences of digital mammography in population-based breast cancer screening: initial changes and long-term impact on referral rates

Contains fulltext : 89208.pdf (publisher's version ) (Closed access)OBJECTIVES: To investigate the referral pattern after the transition to full-field digital mammography (FFDM) in a population-based breast cancer screening programme. METHODS: Preceding the nationwide digitalisation of the Dutch screening programme, an FFDM feasibility study was conducted. Detection and referral rates for FFDM and screen-film mammography (SFM) were compared for first and subsequent screens. Furthermore, radiological characteristics of referrals in digital screening were assessed. RESULTS: A total of 312,414 screening mammograms were performed (43,913 digital and 268,501 conventional), with 4,473 consecutive referrals (966 following FFDM). Initially the FFDM referral rate peaked, and many false-positive results were noted as a consequence of pseudolesions and increased detection of (benign) microcalcifications. A higher overall referral rate was observed in FFDM screening in both first and subsequent examinations (p < .001), with a significant increase in cancer detection (p = .010). CONCLUSION: As a result of initial inexperience with digital screening images implementing FFDM in a population-based breast cancer screening programme may lead to a strong, but temporary increase in referral. Dedicated training in digital screening for radiographers and screening radiologists is therefore recommended. Referral rates decrease and stabilise (learning curve effect) at a higher level than in conventional screening, yet with significantly enhanced cancer detection.1 september 201

Volumetric breast density affects performance of digital screening mammography

PURPOSE: To determine to what extent automatically measured volumetric mammographic density influences screening performance when using digital mammography (DM). METHODS: We collected a consecutive series of 111,898 DM examinations (2003-2011) from one screening unit of the Dutch biennial screening program (age 50-75 years). Volumetric mammographic density was automatically assessed using Volpara. We determined screening performance measures for four density categories comparable to the American College of Radiology (ACR) breast density categories. RESULTS: Of all the examinations, 21.6% were categorized as density category 1 ('almost entirely fatty') and 41.5, 28.9, and 8.0% as category 2-4 ('extremely dense'), respectively. We identified 667 screen-detected and 234 interval cancers. Interval cancer rates were 0.7, 1.9, 2.9, and 4.4‰ and false positive rates were 11.2, 15.1, 18.2, and 23.8‰ for categories 1-4, respectively (both p-trend < 0.001). The screening sensitivity, calculated as the proportion of screen-detected among the total of screen-detected and interval tumors, was lower in higher density categories: 85.7, 77.6, 69.5, and 61.0% for categories 1-4, respectively (p-trend < 0.001). CONCLUSIONS: Volumetric mammographic density, automatically measured on digital mammograms, impacts screening performance measures along the same patterns as established with ACR breast density categories. Since measuring breast density fully automatically has much higher reproducibility than visual assessment, this automatic method could help with implementing density-based supplemental screening