Deep learning for dual detection of microsatellite instability and POLE mutations in colorectal cancer histopathology.

In the spectrum of colorectal tumors, microsatellite-stable (MSS) tumors with DNA polymerase ε (POLE) mutations exhibit a hypermutated profile, holding the potential to respond to immunotherapy similarly to their microsatellite-instable (MSI) counterparts. Yet, due to their rarity and the associated testing costs, systematic screening for these mutations is not commonly pursued. Notably, the histopathological phenotype resulting from POLE mutations is theorized to resemble that of MSI. This resemblance not only could facilitate their detection by a transformer-based Deep Learning (DL) system trained on MSI pathology slides, but also indicates the possibility for MSS patients with POLE mutations to access enhanced treatment options, which might otherwise be overlooked. To harness this potential, we trained a Deep Learning classifier on a large dataset with the ground truth for microsatellite status and subsequently validated its capabilities for MSI and POLE detection across three external cohorts. Our model accurately identified MSI status in both the internal and external resection cohorts using pathology images alone. Notably, with a classification threshold of 0.5, over 75% of POLE driver mutant patients in the external resection cohorts were flagged as "positive" by a DL system trained on MSI status. In a clinical setting, deploying this DL model as a preliminary screening tool could facilitate the efficient identification of clinically relevant MSI and POLE mutations in colorectal tumors, in one go.

A guide to artificial intelligence for cancer researchers.

Artificial intelligence (AI) has been commoditized. It has evolved from a specialty resource to a readily accessible tool for cancer researchers. AI-based tools can boost research productivity in daily workflows, but can also extract hidden information from existing data, thereby enabling new scientific discoveries. Building a basic literacy in these tools is useful for every cancer researcher. Researchers with a traditional biological science focus can use AI-based tools through off-the-shelf software, whereas those who are more computationally inclined can develop their own AI-based software pipelines. In this article, we provide a practical guide for non-computational cancer researchers to understand how AI-based tools can benefit them. We convey general principles of AI for applications in image analysis, natural language processing and drug discovery. In addition, we give examples of how non-computational researchers can get started on the journey to productively use AI in their own work.

Histopathological evaluation of abdominal aortic aneurysms with deep learning.

Computational analysis of histopathological specimens holds promise in identifying biomarkers, elucidating disease mechanisms, and streamlining clinical diagnosis. However, the application of deep learning techniques in vascular pathology remains underexplored. Here, we present a comprehensive evaluation of deep learning-based approaches to analyze digital whole-slide images of abdominal aortic aneurysm samples from 369 patients from three European centers. Deep learning demonstrated robust performance in predicting inflammatory characteristics, particularly in the adventitia, as well as fibrosis grade and remaining elastic fibers in the tunica media. Overall, this study represents the first comprehensive evaluation of computational pathology in vascular disease and has the potential to contribute to improved understanding of abdominal aortic aneurysm pathophysiology and personalization of treatment strategies, particularly when integrated with radiological phenotypes and clinical outcomes.

A simple clinical score to reduce unnecessary testing for Puumala hantavirus.

BACKGROUND: Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), an endemic form of transient acute renal injury (AKI). Serological testing is the mainstay of diagnosis. It was the aim of the present study to assist decision-making for serological testing by constructing a simple tool that predicts the likelihood of PUUV positivity. METHODS: We conducted a comparative cohort study of all PUUV-tested cases at Aachen University tertiary care center in Germany between mid-2013 and mid-2021. N = 293 qualified for inclusion; N = 30 had a positive test result and clinical NE; N = 263 were negative. Two predictive point scores, the Aachen PUUV Score (APS) 1 and 2, respectively, were derived with the aid of logistic regression and receiver operating characteristic (ROC) analysis by determining the presence of four admission parameters. For internal validation, the internal Monte Carlo method was applied. In addition, partial external validation was performed using an independent historic cohort of N = 41 positive cases of NE. RESULTS: APS1 is recommended for clinical use as it estimated the probability of PUUV positivity in the entire medical population tested. With a range from 0 to 6 points, it yielded an area under the curve of 0.94 by allotting 2 points each for fever or headache and 1 point each for AKI or LDH>300 U/L. A point sum of 0-2 safely predicted negativity for PUUV, as was confirmed in the NE validation cohort. CONCLUSION: Here, we present a novel, easy-to-use tool to guide the diagnostic management of suspected PUUV infection/NE and to safely avoid unnecessary serological testing, as indicated by point sum class 0-2. Since 67% of the cohort fell into this stratum, half of the testing should be avoidable in the future.

Reporting guidelines in medical artificial intelligence: a systematic review and meta-analysis.

BACKGROUND: The field of Artificial Intelligence (AI) holds transformative potential in medicine. However, the lack of universal reporting guidelines poses challenges in ensuring the validity and reproducibility of published research studies in this field. METHODS: Based on a systematic review of academic publications and reporting standards demanded by both international consortia and regulatory stakeholders as well as leading journals in the fields of medicine and medical informatics, 26 reporting guidelines published between 2009 and 2023 were included in this analysis. Guidelines were stratified by breadth (general or specific to medical fields), underlying consensus quality, and target research phase (preclinical, translational, clinical) and subsequently analyzed regarding the overlap and variations in guideline items. RESULTS: AI reporting guidelines for medical research vary with respect to the quality of the underlying consensus process, breadth, and target research phase. Some guideline items such as reporting of study design and model performance recur across guidelines, whereas other items are specific to particular fields and research stages. CONCLUSIONS: Our analysis highlights the importance of reporting guidelines in clinical AI research and underscores the need for common standards that address the identified variations and gaps in current guidelines. Overall, this comprehensive overview could help researchers and public stakeholders reinforce quality standards for increased reliability, reproducibility, clinical validity, and public trust in AI research in healthcare. This could facilitate the safe, effective, and ethical translation of AI methods into clinical applications that will ultimately improve patient outcomes.

Artificial Intelligence (AI) refers to computer systems that can perform tasks that normally require human intelligence, like recognizing patterns or making decisions. AI has the potential to transform healthcare, but research on AI in medicine needs clear rules so caregivers and patients can trust it. This study reviews and compares 26 existing guidelines for reporting on AI in medicine. The key differences between these guidelines are their target areas (medicine in general or specific medical fields), the ways they were created, and the research stages they address. While some key items like describing the AI model recurred across guidelines, others were specific to the research area. The analysis shows gaps and variations in current guidelines. Overall, transparent reporting is important, so AI research is reliable, reproducible, trustworthy, and safe for patients. This systematic review of guidelines aims to increase the transparency of AI research, supporting an ethical and safe progression of AI from research into clinical practice.

Data Extraction from Free-Text Reports on Mechanical Thrombectomy in Acute Ischemic Stroke Using ChatGPT: A Retrospective Analysis.

Background Procedural details of mechanical thrombectomy in patients with ischemic stroke are important predictors of clinical outcome and are collected for prospective studies or national stroke registries. To date, these data are collected manually by human readers, a labor-intensive task that is prone to errors. Purpose To evaluate the use of the large language models (LLMs) GPT-4 and GPT-3.5 to extract data from neuroradiology reports on mechanical thrombectomy in patients with ischemic stroke. Materials and Methods This retrospective study included consecutive reports from patients with ischemic stroke who underwent mechanical thrombectomy between November 2022 and September 2023 at institution 1 and between September 2016 and December 2019 at institution 2. A set of 20 reports was used to optimize the prompt, and the ability of the LLMs to extract procedural data from the reports was compared using the McNemar test. Data manually extracted by an interventional neuroradiologist served as the reference standard. Results A total of 100 internal reports from 100 patients (mean age, 74.7 years ± 13.2 [SD]; 53 female) and 30 external reports from 30 patients (mean age, 72.7 years ± 13.5; 18 male) were included. All reports were successfully processed by GPT-4 and GPT-3.5. Of 2800 data entries, 2631 (94.0% [95% CI: 93.0, 94.8]; range per category, 61%-100%) data points were correctly extracted by GPT-4 without the need for further postprocessing. With 1788 of 2800 correct data entries, GPT-3.5 produced fewer correct data entries than did GPT-4 (63.9% [95% CI: 62.0, 65.6]; range per category, 14%-99%; P < .001). For the external reports, GPT-4 extracted 760 of 840 (90.5% [95% CI: 88.3, 92.4]) correct data entries, while GPT-3.5 extracted 539 of 840 (64.2% [95% CI: 60.8, 67.4]; P < .001). Conclusion Compared with GPT-3.5, GPT-4 more frequently extracted correct procedural data from free-text reports on mechanical thrombectomy performed in patients with ischemic stroke. © RSNA, 2024 Supplemental material is available for this article.

Artificial intelligence in liver cancer - new tools for research and patient management.

Liver cancer has high incidence and mortality globally. Artificial intelligence (AI) has advanced rapidly, influencing cancer care. AI systems are already approved for clinical use in some tumour types (for example, colorectal cancer screening). Crucially, research demonstrates that AI can analyse histopathology, radiology and natural language in liver cancer, and can replace manual tasks and access hidden information in routinely available clinical data. However, for liver cancer, few of these applications have translated into large-scale clinical trials or clinically approved products. Here, we advocate for the incorporation of AI in all stages of liver cancer management. We present a taxonomy of AI approaches in liver cancer, highlighting areas with academic and commercial potential, and outline a policy for AI-based liver cancer management, including interdisciplinary training of researchers, clinicians and patients. The potential of AI in liver cancer is immense, but effort is required to ensure that AI can fulfil expectations.

Using histopathology latent diffusion models as privacy-preserving dataset augmenters improves downstream classification performance.

Latent diffusion models (LDMs) have emerged as a state-of-the-art image generation method, outperforming previous Generative Adversarial Networks (GANs) in terms of training stability and image quality. In computational pathology, generative models are valuable for data sharing and data augmentation. However, the impact of LDM-generated images on histopathology tasks compared to traditional GANs has not been systematically studied. We trained three LDMs and a styleGAN2 model on histology tiles from nine colorectal cancer (CRC) tissue classes. The LDMs include 1) a fine-tuned version of stable diffusion v1.4, 2) a Kullback-Leibler (KL)-autoencoder (KLF8-DM), and 3) a vector quantized (VQ)-autoencoder deploying LDM (VQF8-DM). We assessed image quality through expert ratings, dimensional reduction methods, distribution similarity measures, and their impact on training a multiclass tissue classifier. Additionally, we investigated image memorization in the KLF8-DM and styleGAN2 models. All models provided a high image quality, with the KLF8-DM achieving the best Frechet Inception Distance (FID) and expert rating scores for complex tissue classes. For simpler classes, the VQF8-DM and styleGAN2 models performed better. Image memorization was negligible for both styleGAN2 and KLF8-DM models. Classifiers trained on a mix of KLF8-DM generated and real images achieved a 4% improvement in overall classification accuracy, highlighting the usefulness of these images for dataset augmentation. Our systematic study of generative methods showed that KLF8-DM produces the highest quality images with negligible image memorization. The higher classifier performance in the generatively augmented dataset suggests that this augmentation technique can be employed to enhance histopathology classifiers for various tasks.

The digital revolution in pathology: Towards a smarter approach to research and treatment.

Artificial intelligence (AI) applications in oncology are at the forefront of transforming healthcare during the Fourth Industrial Revolution, driven by the digital data explosion. This review provides an accessible introduction to the field of AI, presenting a concise yet structured overview of the foundations of AI, including expert systems, classical machine learning, and deep learning, along with their contextual application in clinical research and healthcare. We delve into the current applications of AI in oncology, with a particular focus on diagnostic imaging and pathology. Numerous AI tools have already received regulatory approval, and more are under active development, bringing clear benefits but not without challenges. We discuss the importance of data security, the need for transparent and interpretable models, and the ethical considerations that must guide AI development in healthcare. By providing a perspective on the opportunities and challenges, this review aims to inform and guide researchers, clinicians, and policymakers in the adoption of AI in oncology.

A systematic pan-cancer study on deep learning-based prediction of multi-omic biomarkers from routine pathology images.

BACKGROUND: The objective of this comprehensive pan-cancer study is to evaluate the potential of deep learning (DL) for molecular profiling of multi-omic biomarkers directly from hematoxylin and eosin (H&E)-stained whole slide images. METHODS: A total of 12,093 DL models predicting 4031 multi-omic biomarkers across 32 cancer types were trained and validated. The study included a broad range of genetic, transcriptomic, and proteomic biomarkers, as well as established prognostic markers, molecular subtypes, and clinical outcomes. RESULTS: Here we show that 50% of the models achieve an area under the curve (AUC) of 0.644 or higher. The observed AUC for 25% of the models is at least 0.719 and exceeds 0.834 for the top 5%. Molecular profiling with image-based histomorphological features is generally considered feasible for most of the investigated biomarkers and across different cancer types. The performance appears to be independent of tumor purity, sample size, and class ratio (prevalence), suggesting a degree of inherent predictability in histomorphology. CONCLUSIONS: The results demonstrate that DL holds promise to predict a wide range of biomarkers across the omics spectrum using only H&E-stained histological slides of solid tumors. This paves the way for accelerating diagnosis and developing more precise treatments for cancer patients.

Molecular profiling tests are used to check cancers for changes in certain genes, proteins, or other molecules. Results of such tests can be used to identify the most effective treatment for cancer patients. Faster and more accessible alternatives to standard tests are needed to improve cancer care. This study investigates whether deep learning (DL), a series of advanced computer techniques, can perform molecular profiling directly from routinely-collected images of tumor specimens used for diagnostic purposes. Over 12,000 DL models were utilized to evaluate thousands of biomarkers using statistical approaches. The results indicate that DL can effectively detect molecular changes in a tumor from these images, for many biomarkers and tumor types. The study shows that DL-based molecular profiling from images is possible. Introducing this type of approach into routine clinical workflows could potentially accelerate treatment decisions and improve outcomes.

Deep learning in cancer genomics and histopathology.

Histopathology and genomic profiling are cornerstones of precision oncology and are routinely obtained for patients with cancer. Traditionally, histopathology slides are manually reviewed by highly trained pathologists. Genomic data, on the other hand, is evaluated by engineered computational pipelines. In both applications, the advent of modern artificial intelligence methods, specifically machine learning (ML) and deep learning (DL), have opened up a fundamentally new way of extracting actionable insights from raw data, which could augment and potentially replace some aspects of traditional evaluation workflows. In this review, we summarize current and emerging applications of DL in histopathology and genomics, including basic diagnostic as well as advanced prognostic tasks. Based on a growing body of evidence, we suggest that DL could be the groundwork for a new kind of workflow in oncology and cancer research. However, we also point out that DL models can have biases and other flaws that users in healthcare and research need to know about, and we propose ways to address them.

Large language models and multimodal foundation models for precision oncology.

The technological progress in artificial intelligence (AI) has massively accelerated since 2022, with far-reaching implications for oncology and cancer research. Large language models (LLMs) now perform at human-level competency in text processing. Notably, both text and image processing networks are increasingly based on transformer neural networks. This convergence enables the development of multimodal AI models that take diverse types of data as an input simultaneously, marking a qualitative shift from specialized niche models which were prevalent in the 2010s. This editorial summarizes these developments, which are expected to impact precision oncology in the coming years.

3-Dimensional Reconstruction From Histopathological Sections: A Systematic Review.

Although pathological tissue analysis is typically performed on single 2-dimensional (2D) histologic reference slides, 3-dimensional (3D) reconstruction from a sequence of histologic sections could provide novel opportunities for spatial analysis of the extracted tissue. In this review, we analyze recent works published after 2018 and report information on the extracted tissue types, the section thickness, and the number of sections used for reconstruction. By analyzing the technological requirements for 3D reconstruction, we observe that software tools exist, both free and commercial, which include the functionality to perform 3D reconstruction from a sequence of histologic images. Through the analysis of the most recent works, we provide an overview of the workflows and tools that are currently used for 3D reconstruction from histologic sections and address points for future work, such as a missing common file format or computer-aided analysis of the reconstructed model.

Regression-based Deep-Learning predicts molecular biomarkers from pathology slides.

Deep Learning (DL) can predict biomarkers from cancer histopathology. Several clinically approved applications use this technology. Most approaches, however, predict categorical labels, whereas biomarkers are often continuous measurements. We hypothesize that regression-based DL outperforms classification-based DL. Therefore, we develop and evaluate a self-supervised attention-based weakly supervised regression method that predicts continuous biomarkers directly from 11,671 images of patients across nine cancer types. We test our method for multiple clinically and biologically relevant biomarkers: homologous recombination deficiency score, a clinically used pan-cancer biomarker, as well as markers of key biological processes in the tumor microenvironment. Using regression significantly enhances the accuracy of biomarker prediction, while also improving the predictions' correspondence to regions of known clinical relevance over classification. In a large cohort of colorectal cancer patients, regression-based prediction scores provide a higher prognostic value than classification-based scores. Our open-source regression approach offers a promising alternative for continuous biomarker analysis in computational pathology.

Large language models streamline automated machine learning for clinical studies.

A knowledge gap persists between machine learning (ML) developers (e.g., data scientists) and practitioners (e.g., clinicians), hampering the full utilization of ML for clinical data analysis. We investigated the potential of the ChatGPT Advanced Data Analysis (ADA), an extension of GPT-4, to bridge this gap and perform ML analyses efficiently. Real-world clinical datasets and study details from large trials across various medical specialties were presented to ChatGPT ADA without specific guidance. ChatGPT ADA autonomously developed state-of-the-art ML models based on the original study's training data to predict clinical outcomes such as cancer development, cancer progression, disease complications, or biomarkers such as pathogenic gene sequences. Following the re-implementation and optimization of the published models, the head-to-head comparison of the ChatGPT ADA-crafted ML models and their respective manually crafted counterparts revealed no significant differences in traditional performance metrics (p ≥ 0.072). Strikingly, the ChatGPT ADA-crafted ML models often outperformed their counterparts. In conclusion, ChatGPT ADA offers a promising avenue to democratize ML in medicine by simplifying complex data analyses, yet should enhance, not replace, specialized training and resources, to promote broader applications in medical research and practice.