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Large language models (LLMs) have shown potential in biomedical applications, leading to efforts to fine-tune them on domain-specific data. However, the effectiveness of this approach remains unclear. This study evaluates the performance of biomedically fine-tuned LLMs against their general-purpose counterparts on a variety of clinical tasks. We evaluated their performance on clinical case challenges from the New England Journal of Medicine (NEJM) and the Journal of the American Medical Association (JAMA) and on several clinical tasks (e.g., information extraction, document summarization, and clinical coding). Using benchmarks specifically chosen to be likely outside the fine-tuning datasets of biomedical models, we found that biomedical LLMs mostly perform inferior to their general-purpose counterparts, especially on tasks not focused on medical knowledge. While larger models showed similar performance on case tasks (e.g., OpenBioLLM-70B: 66.4% vs. Llama-3-70B-Instruct: 65% on JAMA cases), smaller biomedical models showed more pronounced underperformance (e.g., OpenBioLLM-8B: 30% vs. Llama-3-8B-Instruct: 64.3% on NEJM cases). Similar trends were observed across the CLUE (Clinical Language Understanding Evaluation) benchmark tasks, with general-purpose models often performing better on text generation, question answering, and coding tasks. Our results suggest that fine-tuning LLMs to biomedical data may not provide the expected benefits and may potentially lead to reduced performance, challenging prevailing assumptions about domain-specific adaptation of LLMs and highlighting the need for more rigorous evaluation frameworks in healthcare AI. Alternative approaches, such as retrieval-augmented generation, may be more effective in enhancing the biomedical capabilities of LLMs without compromising their general knowledge., Comment: 10 pages, 3 tables, 1 figure

Pathological structures in medical images are typically deviations from the expected anatomy of a patient. While clinicians consider this interplay between anatomy and pathology, recent deep learning algorithms specialize in recognizing either one of the two, rarely considering the patient's body from such a joint perspective. In this paper, we develop a generalist segmentation model that combines anatomical and pathological information, aiming to enhance the segmentation accuracy of pathological features. Our Anatomy-Pathology Exchange (APEx) training utilizes a query-based segmentation transformer which decodes a joint feature space into query-representations for human anatomy and interleaves them via a mixing strategy into the pathology-decoder for anatomy-informed pathology predictions. In doing so, we are able to report the best results across the board on FDG-PET-CT and Chest X-Ray pathology segmentation tasks with a margin of up to 3.3% as compared to strong baseline methods. Code and models will be publicly available at github.com/alexanderjaus/APEx.

Processing histopathological Whole Slide Images (WSI) leads to massive storage requirements for clinics worldwide. Even after lossy image compression during image acquisition, additional lossy compression is frequently possible without substantially affecting the performance of deep learning-based (DL) downstream tasks. In this paper, we show that the commonly used JPEG algorithm is not best suited for further compression and we propose Stain Quantized Latent Compression (SQLC ), a novel DL based histopathology data compression approach. SQLC compresses staining and RGB channels before passing it through a compression autoencoder (CAE ) in order to obtain quantized latent representations for maximizing the compression. We show that our approach yields superior performance in a classification downstream task, compared to traditional approaches like JPEG, while image quality metrics like the Multi-Scale Structural Similarity Index (MS-SSIM) is largely preserved. Our method is online available.

Objective: Federated Learning (FL) enables collaborative model training while keeping data locally. Currently, most FL studies in radiology are conducted in simulated environments due to numerous hurdles impeding its translation into practice. The few existing real-world FL initiatives rarely communicate specific measures taken to overcome these hurdles, leaving behind a significant knowledge gap. Minding efforts to implement real-world FL, there is a notable lack of comprehensive assessment comparing FL to less complex alternatives. Materials & Methods: We extensively reviewed FL literature, categorizing insights along with our findings according to their nature and phase while establishing a FL initiative, summarized to a comprehensive guide. We developed our own FL infrastructure within the German Radiological Cooperative Network (RACOON) and demonstrated its functionality by training FL models on lung pathology segmentation tasks across six university hospitals. We extensively evaluated FL against less complex alternatives in three distinct evaluation scenarios. Results: The proposed guide outlines essential steps, identified hurdles, and proposed solutions for establishing successful FL initiatives conducting real-world experiments. Our experimental results show that FL outperforms less complex alternatives in all evaluation scenarios, justifying the effort required to translate FL into real-world applications. Discussion & Conclusion: Our proposed guide aims to aid future FL researchers in circumventing pitfalls and accelerating translation of FL into radiological applications. Our results underscore the value of efforts needed to translate FL into real-world applications by demonstrating advantageous performance over alternatives, and emphasize the importance of strategic organization, robust management of distributed data and infrastructure in real-world settings.

Point cloud registration aligns 3D point clouds using spatial transformations. It is an important task in computer vision, with applications in areas such as augmented reality (AR) and medical imaging. This work explores the intersection of two research trends: the integration of AR into image-guided surgery and the use of deep learning for point cloud registration. The main objective is to evaluate the feasibility of applying deep learning-based point cloud registration methods for image-to-patient registration in augmented reality-guided surgery. We created a dataset of point clouds from medical imaging and corresponding point clouds captured with a popular AR device, the HoloLens 2. We evaluate three well-established deep learning models in registering these data pairs. While we find that some deep learning methods show promise, we show that a conventional registration pipeline still outperforms them on our challenging dataset., Comment: 5 pages, 4 figures; accepted at IEEE ISBI 2024

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., Comment: Accepted at LREC-COLING 2024

Large Language Models (LLMs) are expected to significantly contribute to patient care, diagnostics, and administrative processes. Emerging biomedical LLMs aim to address healthcare-specific challenges, including privacy demands and computational constraints. Assessing the models' suitability for this sensitive application area is of the utmost importance. However, evaluation has primarily been limited to non-clinical tasks, which do not reflect the complexity of practical clinical applications. To fill this gap, we present the Clinical Language Understanding Evaluation (CLUE), a benchmark tailored to evaluate LLMs on clinical tasks. CLUE includes six tasks to test the practical applicability of LLMs in complex healthcare settings. Our evaluation includes a total of $25$ LLMs. In contrast to previous evaluations, CLUE shows a decrease in performance for nine out of twelve biomedical models. Our benchmark 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 open-source all evaluation scripts and datasets for future research at https://github.com/TIO-IKIM/CLUE.

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., Comment: Accepted at ECCV 2024

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., Comment: 10 pages, 5 figures, 1 table

In traumatic medical emergencies, the patients heavily depend on cranioplasty - the craft of neurocranial repair using cranial implants. Despite the improvements made in recent years, the design of a patient-specific implant (PSI) is among the most complex, expensive, and least automated tasks in cranioplasty. Further research in this area is needed. Therefore, we created a prototype application with a graphical user interface (UI) specifically tailored for semi-automatic implant generation, where the users only need to perform high-level actions. A general outline of the proposed implant generation process involves setting an area of interest, aligning the templates, and then creating the implant in voxel space. Furthermore, we show that the alignment can be improved significantly, by only considering clipped geometry in the vicinity of the defect border. The software prototype will be open-sourced at https://github.com/3Descape/Cranial_Implant_Design, Comment: 6 pages

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.

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.

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.

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.