Context.-Nodal metastasis of a primary tumor influences therapy decisions for a variety of cancers. Histologic identification of tumor cells in lymph nodes can be laborious and error-prone, especially for small tumor foci.Objective.-To evaluate the application and clinical implementation of a state-of-the-art deep learning-based artificial intelligence algorithm (LYmph Node Assistant or LYNA) for detection of metastatic breast cancer in sentinel lymph node biopsies.Design.-Whole slide images were obtained from hematoxylin-eosin-stained lymph nodes from 399 patients (publicly available Camelyon16 challenge dataset). LYNA was developed by using 270 slides and evaluated on the remaining 129 slides. We compared the findings to those obtained from an independent laboratory (108 slides from 20 patients/86 blocks) using a different scanner to measure reproducibility.Results.-LYNA achieved a slide-level area under the receiver operating characteristic (AUC) of 99% and a tumor-level sensitivity of 91% at 1 false positive per patient on the Camelyon16 evaluation dataset. We also identified 2 ''normal'' slides that contained micrometastases. When applied to our second dataset, LYNA achieved an AUC of 99.6%. LYNA was not affected by common histology artifacts such as overfixation, poor staining, and air bubbles.Conclusions.-Artificial intelligence algorithms can exhaustively evaluate every tissue patch on a slide, achieving higher tumor-level sensitivity than, and comparable slidelevel performance to, pathologists. These techniques may improve the pathologist's productivity and reduce the number of false negatives associated with morphologic detection of tumor cells. We provide a framework to aid practicing pathologists in assessing such algorithms for adoption into their workflow (akin to how a pathologist assesses immunohistochemistry results).

We present a variational integration of nonlinear shape statistics into a Mumford-Shah based segmentation process. The nonlinear statistics are derived from a set of training silhouettes by a novel method of density estimation which can be considered as an extension of kernel PCA to a probabilistic framework.We assume that the training data forms a Gaussian distribution after a nonlinear mapping to a higher-dimensional feature space. Due to the strong nonlinearity, the corresponding density estimate in the original space is highly non-Gaussian.Applications of the nonlinear shape statistics in segmentation and tracking of 2D and 3D objects demonstrate that the segmentation process can incorporate knowledge on a large variety of complex real-world shapes. It makes the segmentation process robust against misleading information due to noise, clutter and occlusion.

Each year, the treatment decisions for more than 230, 000 breast cancer patients in the U.S. hinge on whether the cancer has metastasized away from the breast. Metastasis detection is currently performed by pathologists reviewing large expanses of biological tissues. This process is labor intensive and error-prone. We present a framework to automatically detect and localize tumors as small as 100 × 100 pixels in gigapixel microscopy images sized 100, 000×100, 000 pixels. Our method leverages a convolutional neural network (CNN) architecture and obtains state-of-the-art results on the Camelyon16 dataset in the challenging lesion-level tumor detection task. At 8 false positives per image, we detect 92.4% of the tumors, relative to 82.7% by the previous best automated approach. For comparison, a human pathologist attempting exhaustive search achieved 73.2% sensitivity. We achieve image-level AUC scores above 97% on both the Camelyon16 test set and an independent set of 110 slides. In addition, we discover that two slides in the Came-lyon16 training set were erroneously labeled normal. Our approach could considerably reduce false negative rates in metastasis detection.

These authors contributed equally to this work.The brightfield microscope is instrumental in the visual examination of both biological and physical samples at sub-millimeter scales. One key clinical application has been in cancer histopathology, where the microscopic assessment of the tissue samples is used for the diagnosis and staging of cancer and thus guides clinical therapy 1 . However, the interpretation of these samples is inherently subjective, resulting in significant diagnostic variability 2,3 . Moreover, in many regions of the world, access to pathologists is severely limited due to lack of trained personnel 4 . In this regard, Artificial Intelligence (AI) based tools promise to improve the access and quality of healthcare 5-7 . However, despite significant advances in AI research, integration of these tools into real-world cancer diagnosis workflows remains challenging because of the costs of image digitization and difficulties in deploying AI solutions 8 , 9 . Here we propose a cost-effective solution to the integration of AI: the Augmented Reality Microscope (ARM). The ARM overlays AI-based information onto the current view of the sample through the optical pathway in real-time, enabling seamless integration of AI into the regular microscopy workflow. We demonstrate the utility of ARM in the detection of lymph node metastases in breast cancer and the identification of prostate cancer with a latency that supports real-time workflows. We anticipate that ARM will remove barriers towards the use of AI in microscopic analysis and thus improve the accuracy and efficiency of cancer diagnosis. This approach is applicable to other microscopy tasks and AI algorithms in the life sciences 10 and beyond 11,12 .Microscopic examination of samples is the gold standard for the diagnosis of cancer, autoimmune diseases, infectious diseases, and more. In cancer, the microscopic examination of stained tissue sections is critical for diagnosing and staging the patient's tumor, which informs treatment decisions and prognosis. In cancer, microscopy analysis faces three major challenges. As a form of image interpretation, these examinations are inherently subjective, exhibiting considerable inter-observer and intra-observer variability 2,3 . Moreover, clinical guidelines 1 and studies 13 have begun to require quantitative assessments as part of the effort towards better patient risk stratification 1 . For example, breast cancer staging requires counting mitotic cells and quantification of the tumor burden in lymph nodes by measuring the largest tumor focus. However, despite being helpful in treatment planning, quantification is laborious and error-prone. Lastly, access to disease experts can be limited in both developed and developing countries 4 , exacerbating the problem.