Nico Karssemeijer

Andreas D. Lauritzen, My Catarina von Euler-Chelpin, Elsebeth Lynge et al.

Purpose: Risk-stratified breast cancer screening might improve early detection and efficiency without comprising quality. However, modern mammography-based risk models do not ensure adaptation across vendor-domains and rely on cancer precursors, associated with short-term risk, which might limit long-term risk assessment. We report a cross-vendor mammographic texture model for long-term risk. Approach: The texture model was robustly trained using two systematically designed case-control datasets. Textural features, indicative of future breast cancer, were learned by excluding samples with diagnosed/potential malignancies from training. An augmentation-based domain adaption technique, based on flavorization of mammographic views, ensured generalization across vendor-domains. The model was validated in 66,607 consecutively screened Danish women with flavorized Siemens views and 25,706 Dutch women with Hologic-processed views. Performances were evaluated for interval cancers (IC) within two years from screening and long-term cancers (LTC) from two years after screening. The texture model was combined with established risk factors to flag 10% of women with the highest risk. Results: In Danish women, the texture model achieved an area under the receiver operating characteristic (AUC) of 0.71 and 0.65 for ICs and LTCs, respectively. In Dutch women with Hologic-processed views, the AUCs were not different from AUCs in Danish women with flavorized views. The AUC for texture combined with established risk factors increased to 0.68 for LTCs. The 10% of women flagged as high-risk accounted for 25.5% of ICs and 24.8% of LTCs. Conclusions: The texture model robustly estimated long-term breast cancer risk while adapting to an unseen processed vendor-domain and identified a clinically relevant high-risk subgroup.

Nikita Moriakov, Jim Peters, Ritse Mann et al.

Lesion volume is an important predictor for prognosis in breast cancer. We make a step towards a more accurate lesion volume measurement on digital mammograms by developing a model that allows to estimate lesion volumes on processed mammograms, which are the images routinely used by radiologists in clinical practice as well as in breast cancer screening and are available in medical centers. Processed mammograms are obtained from raw mammograms, which are the X-ray data coming directly from the scanner, by applying certain vendor-specific non-linear transformations. At the core of our volume estimation method is a physics-based algorithm for measuring lesion volumes on raw mammograms. We subsequently extend this algorithm to processed mammograms via a deep learning image-to-image translation model that produces synthetic raw mammograms from processed mammograms in a multi-vendor setting. We assess the reliability and validity of our method using a dataset of 1778 mammograms with an annotated mass. Firstly, we investigate the correlations between lesion volumes computed from mediolateral oblique and craniocaudal views, with a resulting Pearson correlation of 0.93 [95% confidence interval (CI) 0.92 - 0.93]. Secondly, we compare the resulting lesion volumes from true and synthetic raw data, with a resulting Pearson correlation of 0.998 [95% CI 0.998 - 0.998] . Finally, for a subset of 100 mammograms with a malign mass and concurrent MRI examination available, we analyze the agreement between lesion volume on mammography and MRI, resulting in an intraclass correlation coefficient of 0.81 [95% CI 0.73 - 0.87] for consistency and 0.78 [95% CI 0.66 - 0.86] for absolute agreement. In conclusion, we developed an algorithm to measure mammographic lesion volume that reached excellent reliability and good validity, when using MRI as ground truth.

Babak Ehteshami Bejnordi, Guido Zuidhof, Maschenka Balkenhol et al.

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.

Thijs Kooi, Nico Karssemeijer

We investigate the addition of symmetry and temporal context information to a deep Convolutional Neural Network (CNN) with the purpose of detecting malignant soft tissue lesions in mammography. We employ a simple linear mapping that takes the location of a mass candidate and maps it to either the contra-lateral or prior mammogram and Regions Of Interest (ROI) are extracted around each location. We subsequently explore two different architectures (1) a fusion model employing two datastreams were both ROIs are fed to the network during training and testing and (2) a stage-wise approach where a single ROI CNN is trained on the primary image and subsequently used as feature extractor for both primary and symmetrical or prior ROIs. A 'shallow' Gradient Boosted Tree (GBT) classifier is then trained on the concatenation of these features and used to classify the joint representation. Results shown a significant increase in performance using the first architecture and symmetry information, but only marginal gains in performance using temporal data and the other setting. We feel results are promising and can greatly be improved when more temporal data becomes available.

Babak Ehteshami Bejnordi, Jimmy Linz, Ben Glass et al.

Diagnosis of breast carcinomas has so far been limited to the morphological interpretation of epithelial cells and the assessment of epithelial tissue architecture. Consequently, most of the automated systems have focused on characterizing the epithelial regions of the breast to detect cancer. In this paper, we propose a system for classification of hematoxylin and eosin (H&E) stained breast specimens based on convolutional neural networks that primarily targets the assessment of tumor-associated stroma to diagnose breast cancer patients. We evaluate the performance of our proposed system using a large cohort containing 646 breast tissue biopsies. Our evaluations show that the proposed system achieves an area under ROC of 0.92, demonstrating the discriminative power of previously neglected tumor-associated stroma as a diagnostic biomarker.