Andreas Kleppe

Audun L. Henriksen, Ole-Johan Skrede, Lisa van der Schee et al.

Foundation models in histopathology are expected to facilitate the development of high-performing and generalisable deep learning systems. However, current models capture not only biologically relevant features, but also pre-analytic and scanner-specific variation that bias the predictions of task-specific models trained from the foundation model features. Here we show that introducing novel robustness losses during training of downstream task-specific models reduces sensitivity to technical variability. A purpose-designed comprehensive experimentation setup with 27,042 WSIs from 6155 patients is used to train thousands of models from the features of eight popular foundation models for computational pathology. In addition to a substantial improvement in robustness, we observe that prediction accuracy improves by focusing on biologically relevant features. Our approach successfully mitigates robustness issues of foundation models for computational pathology without retraining the foundation models themselves, enabling development of robust computational pathology models applicable to real-world data in routine clinical practice.

Dhananjay Tomar, Alexander Binder, Andreas Kleppe

Domain generalisation in computational histopathology is challenging because the images are substantially affected by differences among hospitals due to factors like fixation and staining of tissue and imaging equipment. We hypothesise that focusing on nuclei can improve the out-of-domain (OOD) generalisation in cancer detection. We propose a simple approach to improve OOD generalisation for cancer detection by focusing on nuclear morphology and organisation, as these are domain-invariant features critical in cancer detection. Our approach integrates original images with nuclear segmentation masks during training, encouraging the model to prioritise nuclei and their spatial arrangement. Going beyond mere data augmentation, we introduce a regularisation technique that aligns the representations of masks and original images. We show, using multiple datasets, that our method improves OOD generalisation and also leads to increased robustness to image corruptions and adversarial attacks. The source code is available at https://github.com/undercutspiky/SFL/

Ole-Johan Skrede, Manohar Pradhan, Maria Xepapadakis Isaksen et al.

Deep learning is expected to aid pathologists by automating tasks such as tumour segmentation. We aimed to develop one universal tumour segmentation model for histopathological images and examine its performance in different cancer types. The model was developed using over 20 000 whole-slide images from over 4 000 patients with colorectal, endometrial, lung, or prostate carcinoma. Performance was validated in pre-planned analyses on external cohorts with over 3 000 patients across six cancer types. Exploratory analyses included over 1 500 additional patients from The Cancer Genome Atlas. Average Dice coefficient was over 80% in all validation cohorts with en bloc resection specimens and in The Cancer Genome Atlas cohorts. No loss of performance was observed when comparing the universal model with models specialised on single cancer types. In conclusion, extensive and rigorous evaluations demonstrate that generic tumour segmentation by a single model is possible across cancer types, patient populations, sample preparations, and slide scanners.

Annika Reinke, Minu D. Tizabi, Carole H. Sudre et al.

While the importance of automatic image analysis is continuously increasing, recent meta-research revealed major flaws with respect to algorithm validation. Performance metrics are particularly key for meaningful, objective, and transparent performance assessment and validation of the used automatic algorithms, but relatively little attention has been given to the practical pitfalls when using specific metrics for a given image analysis task. These are typically related to (1) the disregard of inherent metric properties, such as the behaviour in the presence of class imbalance or small target structures, (2) the disregard of inherent data set properties, such as the non-independence of the test cases, and (3) the disregard of the actual biomedical domain interest that the metrics should reflect. This living dynamically document has the purpose to illustrate important limitations of performance metrics commonly applied in the field of image analysis. In this context, it focuses on biomedical image analysis problems that can be phrased as image-level classification, semantic segmentation, instance segmentation, or object detection task. The current version is based on a Delphi process on metrics conducted by an international consortium of image analysis experts from more than 60 institutions worldwide.