CLUE: A Clinical Language Understanding Evaluation for LLMs

Large Language Models (LLMs) have shown the potential to significantly contribute to patient care, diagnostics, and administrative processes. Emerging biomedical LLMs address healthcare-specific challenges, including privacy demands and computational constraints. However, evaluation of these models has primarily been limited to non-clinical tasks, which do not reflect the complexity of practical clinical applications. Additionally, there has been no thorough comparison between biomedical and general-domain LLMs for clinical tasks. To fill this gap, we present the Clinical Language Understanding Evaluation (CLUE), a benchmark tailored to evaluate LLMs on real-world clinical tasks. CLUE includes two novel datasets derived from MIMIC IV discharge letters and four existing tasks designed to test the practical applicability of LLMs in healthcare settings. Our evaluation covers several biomedical and general domain LLMs, providing insights into their clinical performance and applicability. CLUE represents a step towards a standardized approach to evaluating and developing LLMs in healthcare to align future model development with the real-world needs of clinical application. We publish our evaluation and data generation scripts: https://github.com/TIO-IKIM/CLUE.

Comprehensive Study on German Language Models for Clinical and Biomedical Text Understanding

Recent advances in natural language processing (NLP) can be largely attributed to the advent of pre-trained language models such as BERT and RoBERTa. While these models demonstrate remarkable performance on general datasets, they can struggle in specialized domains such as medicine, where unique domain-specific terminologies, domain-specific abbreviations, and varying document structures are common. This paper explores strategies for adapting these models to domain-specific requirements, primarily through continuous pre-training on domain-specific data. We pre-trained several German medical language models on 2.4B tokens derived from translated public English medical data and 3B tokens of German clinical data. The resulting models were evaluated on various German downstream tasks, including named entity recognition (NER), multi-label classification, and extractive question answering. Our results suggest that models augmented by clinical and translation-based pre-training typically outperform general domain models in medical contexts. We conclude that continuous pre-training has demonstrated the ability to match or even exceed the performance of clinical models trained from scratch. Furthermore, pre-training on clinical data or leveraging translated texts have proven to be reliable methods for domain adaptation in medical NLP tasks.

Skeleton Recall Loss for Connectivity Conserving and Resource Efficient Segmentation of Thin Tubular Structures

Accurately segmenting thin tubular structures, such as vessels, nerves, roads or concrete cracks, is a crucial task in computer vision. Standard deep learning-based segmentation loss functions, such as Dice or Cross-Entropy, focus on volumetric overlap, often at the expense of preserving structural connectivity or topology. This can lead to segmentation errors that adversely affect downstream tasks, including flow calculation, navigation, and structural inspection. Although current topology-focused losses mark an improvement, they introduce significant computational and memory overheads. This is particularly relevant for 3D data, rendering these losses infeasible for larger volumes as well as increasingly important multi-class segmentation problems. To mitigate this, we propose a novel Skeleton Recall Loss, which effectively addresses these challenges by circumventing intensive GPU-based calculations with inexpensive CPU operations. It demonstrates overall superior performance to current state-of-the-art approaches on five public datasets for topology-preserving segmentation, while substantially reducing computational overheads by more than 90%. In doing so, we introduce the first multi-class capable loss function for thin structure segmentation, excelling in both efficiency and efficacy for topology-preservation.

Rethinking Annotator Simulation: Realistic Evaluation of Whole-Body PET Lesion Interactive Segmentation Methods

Interactive segmentation plays a crucial role in accelerating the annotation, particularly in domains requiring specialized expertise such as nuclear medicine. For example, annotating lesions in whole-body Positron Emission Tomography (PET) images can require over an hour per volume. While previous works evaluate interactive segmentation models through either real user studies or simulated annotators, both approaches present challenges. Real user studies are expensive and often limited in scale, while simulated annotators, also known as robot users, tend to overestimate model performance due to their idealized nature. To address these limitations, we introduce four evaluation metrics that quantify the user shift between real and simulated annotators. In an initial user study involving four annotators, we assess existing robot users using our proposed metrics and find that robot users significantly deviate in performance and annotation behavior compared to real annotators. Based on these findings, we propose a more realistic robot user that reduces the user shift by incorporating human factors such as click variation and inter-annotator disagreement. We validate our robot user in a second user study, involving four other annotators, and show it consistently reduces the simulated-to-real user shift compared to traditional robot users. By employing our robot user, we can conduct more large-scale and cost-efficient evaluations of interactive segmentation models, while preserving the fidelity of real user studies. Our implementation is based on MONAI Label and will be made publicly available.

DALSA: Domain Adaptation for Supervised Learning From Sparsely Annotated MR Images

We propose a new method that employs transfer learning techniques to effectively correct sampling selection errors introduced by sparse annotations during supervised learning for automated tumor segmentation. The practicality of current learning-based automated tissue classification approaches is severely impeded by their dependency on manually segmented training databases that need to be recreated for each scenario of application, site, or acquisition setup. The comprehensive annotation of reference datasets can be highly labor-intensive, complex, and error-prone. The proposed method derives high-quality classifiers for the different tissue classes from sparse and unambiguous annotations and employs domain adaptation techniques for effectively correcting sampling selection errors introduced by the sparse sampling. The new approach is validated on labeled, multi-modal MR images of 19 patients with malignant gliomas and by comparative analysis on the BraTS 2013 challenge data sets. Compared to training on fully labeled data, we reduced the time for labeling and training by a factor greater than 70 and 180 respectively without sacrificing accuracy. This dramatically eases the establishment and constant extension of large annotated databases in various scenarios and imaging setups and thus represents an important step towards practical applicability of learning-based approaches in tissue classification.

How we won BraTS 2023 Adult Glioma challenge? Just faking it! Enhanced Synthetic Data Augmentation and Model Ensemble for brain tumour segmentation

Deep Learning is the state-of-the-art technology for segmenting brain tumours. However, this requires a lot of high-quality data, which is difficult to obtain, especially in the medical field. Therefore, our solutions address this problem by using unconventional mechanisms for data augmentation. Generative adversarial networks and registration are used to massively increase the amount of available samples for training three different deep learning models for brain tumour segmentation, the first task of the BraTS2023 challenge. The first model is the standard nnU-Net, the second is the Swin UNETR and the third is the winning solution of the BraTS 2021 Challenge. The entire pipeline is built on the nnU-Net implementation, except for the generation of the synthetic data. The use of convolutional algorithms and transformers is able to fill each other's knowledge gaps. Using the new metric, our best solution achieves the dice results 0.9005, 0.8673, 0.8509 and HD95 14.940, 14.467, 17.699 (whole tumour, tumour core and enhancing tumour) in the validation set.

Deep PCCT: Photon Counting Computed Tomography Deep Learning Applications Review

Medical imaging faces challenges such as limited spatial resolution, interference from electronic noise and poor contrast-to-noise ratios. Photon Counting Computed Tomography (PCCT) has emerged as a solution, addressing these issues with its innovative technology. This review delves into the recent developments and applications of PCCT in pre-clinical research, emphasizing its potential to overcome traditional imaging limitations. For example PCCT has demonstrated remarkable efficacy in improving the detection of subtle abnormalities in breast, providing a level of detail previously unattainable. Examining the current literature on PCCT, it presents a comprehensive analysis of the technology, highlighting the main features of scanners and their varied applications. In addition, it explores the integration of deep learning into PCCT, along with the study of radiomic features, presenting successful applications in data processing. While acknowledging these advances, it also discusses the existing challenges in this field, paving the way for future research and improvements in medical imaging technologies. Despite the limited number of articles on this subject, due to the recent integration of PCCT at a clinical level, its potential benefits extend to various diagnostic applications.

Cyto R-CNN and CytoNuke Dataset: Towards reliable whole-cell segmentation in bright-field histological images

Background: Cell segmentation in bright-field histological slides is a crucial topic in medical image analysis. Having access to accurate segmentation allows researchers to examine the relationship between cellular morphology and clinical observations. Unfortunately, most segmentation methods known today are limited to nuclei and cannot segmentate the cytoplasm. Material & Methods: We present a new network architecture Cyto R-CNN that is able to accurately segment whole cells (with both the nucleus and the cytoplasm) in bright-field images. We also present a new dataset CytoNuke, consisting of multiple thousand manual annotations of head and neck squamous cell carcinoma cells. Utilizing this dataset, we compared the performance of Cyto R-CNN to other popular cell segmentation algorithms, including QuPath's built-in algorithm, StarDist and Cellpose. To evaluate segmentation performance, we calculated AP50, AP75 and measured 17 morphological and staining-related features for all detected cells. We compared these measurements to the gold standard of manual segmentation using the Kolmogorov-Smirnov test. Results: Cyto R-CNN achieved an AP50 of 58.65% and an AP75 of 11.56% in whole-cell segmentation, outperforming all other methods (QuPath $19.46/0.91\%$; StarDist $45.33/2.32\%$; Cellpose $31.85/5.61\%$). Cell features derived from Cyto R-CNN showed the best agreement to the gold standard ($\bar{D} = 0.15$) outperforming QuPath ($\bar{D} = 0.22$), StarDist ($\bar{D} = 0.25$) and Cellpose ($\bar{D} = 0.23$). Conclusion: Our newly proposed Cyto R-CNN architecture outperforms current algorithms in whole-cell segmentation while providing more reliable cell measurements than any other model. This could improve digital pathology workflows, potentially leading to improved diagnosis. Moreover, our published dataset can be used to develop further models in the future.

Sliding Window FastEdit: A Framework for Lesion Annotation in Whole-body PET Images

Deep learning has revolutionized the accurate segmentation of diseases in medical imaging. However, achieving such results requires training with numerous manual voxel annotations. This requirement presents a challenge for whole-body Positron Emission Tomography (PET) imaging, where lesions are scattered throughout the body. To tackle this problem, we introduce SW-FastEdit - an interactive segmentation framework that accelerates the labeling by utilizing only a few user clicks instead of voxelwise annotations. While prior interactive models crop or resize PET volumes due to memory constraints, we use the complete volume with our sliding window-based interactive scheme. Our model outperforms existing non-sliding window interactive models on the AutoPET dataset and generalizes to the previously unseen HECKTOR dataset. A user study revealed that annotators achieve high-quality predictions with only 10 click iterations and a low perceived NASA-TLX workload. Our framework is implemented using MONAI Label and is available: https://github.com/matt3o/AutoPET2-Submission/