Norman Zerbe

André Homeyer, Christian Geißler, Lars Ole Schwen et al.

Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets. However, compiling such datasets is challenging and specific recommendations are missing. A committee of various stakeholders, including commercial AI developers, pathologists, and researchers, discussed key aspects and conducted extensive literature reviews on test datasets in pathology. Here, we summarize the results and derive general recommendations for the collection of test datasets. We address several questions: Which and how many images are needed? How to deal with low-prevalence subsets? How can potential bias be detected? How should datasets be reported? What are the regulatory requirements in different countries? The recommendations are intended to help AI developers demonstrate the utility of their products and to help regulatory agencies and end users verify reported performance measures. Further research is needed to formulate criteria for sufficiently representative test datasets so that AI solutions can operate with less user intervention and better support diagnostic workflows in the future.

Lars Ole Schwen, Tim-Rasmus Kiehl, Rita Carvalho et al.

Pathology laboratories are increasingly using digital workflows. This has the potential of increasing lab efficiency, but the digitization process also involves major challenges. Several reports have been published describing the individual experiences of specific laboratories with the digitization process. However, a comprehensive overview of the lessons learned is still lacking. We provide an overview of the lessons learned for different aspects of the digitization process, including digital case management, digital slide reading, and computer-aided slide reading. We also cover metrics used for monitoring performance and pitfalls and corresponding values observed in practice. The overview is intended to help pathologists, IT decision-makers, and administrators to benefit from the experiences of others and to implement the digitization process in an optimal way to make their own laboratory future-proof.

Norman Zerbe, Lars Ole Schwen, Christian Geißler et al.

Over the past decade, artificial intelligence (AI) methods in pathology have advanced substantially. However, integration into routine clinical practice has been slow due to numerous challenges, including technical and regulatory hurdles in translating research results into clinical diagnostic products and the lack of standardized interfaces. The open and vendor-neutral EMPAIA initiative addresses these challenges. Here, we provide an overview of EMPAIA's achievements and lessons learned. EMPAIA integrates various stakeholders of the pathology AI ecosystem, i.e., pathologists, computer scientists, and industry. In close collaboration, we developed technical interoperability standards, recommendations for AI testing and product development, and explainability methods. We implemented the modular and open-source EMPAIA platform and successfully integrated 14 AI-based image analysis apps from 8 different vendors, demonstrating how different apps can use a single standardized interface. We prioritized requirements and evaluated the use of AI in real clinical settings with 14 different pathology laboratories in Europe and Asia. In addition to technical developments, we created a forum for all stakeholders to share information and experiences on digital pathology and AI. Commercial, clinical, and academic stakeholders can now adopt EMPAIA's common open-source interfaces, providing a unique opportunity for large-scale standardization and streamlining of processes. Further efforts are needed to effectively and broadly establish AI assistance in routine laboratory use. To this end, a sustainable infrastructure, the non-profit association EMPAIA International, has been established to continue standardization and support broad implementation and advocacy for an AI-assisted digital pathology future.

Tom Bisson, Isil Dogan O, Iris Piwonski et al.

Surgical treatment for prostate cancer often involves organ removal, i.e., prostatectomy. Pathology reports on these specimens convey treatment-relevant information. Beyond these reports, the diagnostic process generates extensive and complex information that is difficult to represent in reports, although it is of significant interest to the other medical specialties involved. 3D tissue reconstruction would allow for better spatial visualization, as well as combinations with other imaging modalities. Existing approaches in this area have proven labor-intensive and challenging to integrate into clinical workflows. 3D-SLIVER provides a simplified solution, implemented as an open-source 3DSlicer extension. We outline three specific real-world scenarios to illustrate its potential to improve transparency in diagnostic workflows and contribute to multi-modal research endeavors. Implementing the 3D reconstruction process involved four sub-modules of 3D-SLIVER: digitization of slicing protocol, virtual slicing of arbitrary 3D models based on that protocol, registration of slides with virtual slices using the Coherent Point Drift algorithm, and 3D reconstruction of registered information using convex hulls, Gaussian splatter and linear extrusion. Three use cases to employ 3D-SLIVER are presented: a low-effort approach to pathology workflow integration and two research-related use cases illustrating how to perform retrospective evaluations of PI-RADS predictions and statistically model 3D distributions of morphological patterns. 3D-SLIVER allows for improved interdisciplinary communication among specialties. It is designed for simplicity in application, allowing for flexible integration into various workflows and use cases. Here we focused on the clinical care of prostate cancer patients, but future possibilities are extensive with other neoplasms and in education and research.

Gernot Fiala, Markus Plass, Robert Harb et al.

A Whole Slide Image (WSI) is a high-resolution digital image created by scanning an entire glass slide containing a biological specimen, such as tissue sections or cell samples, at multiple magnifications. These images can be viewed, analyzed, shared digitally, and are used today for Artificial Intelligence (AI) algorithm development. WSIs are used in a variety of fields, including pathology for diagnosing diseases and oncology for cancer research. They are also utilized in neurology, veterinary medicine, hematology, microbiology, dermatology, pharmacology, toxicology, immunology, and forensic science. When assembling cohorts for the training or validation of an AI algorithm, it is essential to know what is present on such a WSI. However, there is currently no standard for this metadata, so such selection has mainly been done through manual inspection, which is not suitable for large collections with several million objects. We propose a general framework to generate a 2D index map for WSI and a profiling mechanism for specific application domains. We demonstrate this approach in the field of clinical pathology, using common syntax and semantics to achieve interoperability between different catalogs. Our approach augments each WSI collection with a detailed tissue map that provides fine-grained information about the WSI content. The tissue map is organized into three layers: source, tissue type, and pathological alterations, with each layer assigning segments of the WSI to specific classes. We illustrate the advantages and applicability of the proposed standard through specific examples in WSI catalogs, Machine Learning (ML), and graph-based WSI representations.