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Norman Zerbe

Publications and source records attributed to Norman Zerbe.

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CoM$^3$eT: A foundation model for medical image analysis through federated, multidimensional context integration

Medical foundation models improve generalization when training AI models with limited labeled data, but remain confined to a single specialty, such as pathology or radiology, and to either sparse or dense outputs, such as classification or segmentation. Here, we present CoM$^3$eT (Co-representation Multidimensional Multitask Medical Transformer), a medical vision foundation model that unifies pathology and radiology, sparse and dense predictions, and two- and higher-dimensional inputs by modeling multidimensional context with attention. CoM$^3$eT outperformed other medical foundation models in an open competition spanning five tomographic, four whole-specimen, and three two-dimensional datasets, covering sparse and dense prediction tasks as well as report generation. When adapted across diverse clinical applications, training fewer than 2.5% of parameters achieved performance comparable to full fine-tuning, enabling research without access to high-performance GPU clusters. Applied to federated learning across hospitals, this approach achieved performance comparable to pooled-data training over internet connections and with consumer-grade hardware.

cs.CV

From slides to AI-ready maps: Standardized multi-layer tissue maps as metadata for artificial intelligence in digital pathology

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 are digitally viewable, analyzable, and shareable, and are widely used for Artificial Intelligence (AI) algorithm development. WSIs play an important role in pathology for disease diagnosis and oncology for cancer research, but are also applied in neurology, veterinary medicine, hematology, microbiology, dermatology, pharmacology, toxicology, immunology, and forensic science. When assembling cohorts for AI training or validation, it is essential to know the content of a WSI. However, no standard currently exists for this metadata, and such a selection has largely relied on manual inspection, which is not suitable for large collections with millions of objects. We propose a general framework to generate 2D index maps (tissue maps) that describe the morphological content of WSIs using common syntax and semantics to achieve interoperability between catalogs. The tissue maps are structured in three layers: source, tissue type, and pathological alterations. Each layer assigns WSI segments to specific classes, providing AI-ready metadata. We demonstrate the advantages of this standard by applying AI-based metadata extraction from WSIs to generate tissue maps and integrating them into a WSI archive. This integration enhances search capabilities within WSI archives, thereby facilitating the accelerated assembly of high-quality, balanced, and more targeted datasets for AI training, validation, and cancer research.

cs.CV

Volumetric Reconstruction of Prostatectomy Specimens from Histology

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.

eess.IV

Joining Forces for Pathology Diagnostics with AI Assistance: The EMPAIA Initiative

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.

cs.CY

Digitization of Pathology Labs: A Review of Lessons Learned

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.

cs.HC

Anonymization of Whole Slide Images in Histopathology for Research and Education

Objective: The exchange of health-related data is subject to regional laws and regulations, such as the General Data Protection Regulation (GDPR) in the EU or the Health Insurance Portability and Accountability Act (HIPAA) in the United States, resulting in non-trivial challenges for researchers and educators when working with these data. In pathology, the digitization of diagnostic tissue samples inevitably generates identifying data that can consist of sensitive but also acquisition-related information stored in vendor-specific file formats. Distribution and off-clinical use of these Whole Slide Images (WSI) is usually done in these formats, as an industry-wide standardization such as DICOM is yet only tentatively adopted and slide scanner vendors currently do not provide anonymization functionality. Methods: We developed a guideline for the proper handling of histopathological image data particularly for research and education with regard to the GDPR. In this context, we evaluated existing anonymization methods and examined proprietary format specifications to identify all sensitive information for the most common WSI formats. This work results in a software library that enables GDPR-compliant anonymization of WSIs while preserving the native formats. Results: Based on the analysis of proprietary formats, all occurrences of sensitive information were identified for file formats frequently used in clinical routine, and finally, an open-source programming library with an executable CLI-tool and wrappers for different programming languages was developed. Conclusions: Our analysis showed that there is no straightforward software solution to anonymize WSIs in a GDPR-compliant way while maintaining the data format. We closed this gap with our extensible open-source library that works instantaneously and offline.

cs.CY

Recommendations on test datasets for evaluating AI solutions in pathology

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.

eess.IV