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Methods for out-of-distribution (OOD) detection that scale to 3D data are crucial components of any real-world clinical deep learning system. Classic denoising diffusion probabilistic models (DDPMs) have been recently proposed as a robust way to perform reconstruction-based OOD detection on 2D datasets, but do not trivially scale to 3D data. In this work, we propose to use Latent Diffusion Models (LDMs), which enable the scaling of DDPMs to high-resolution 3D medical data. We validate the proposed approach on near- and far-OOD datasets and compare it to a recently proposed, 3D-enabled approach using Latent Transformer Models (LTMs). Not only does the proposed LDM-based approach achieve statistically significant better performance, it also shows less sensitivity to the underlying latent representation, more favourable memory scaling, and produces better spatial anomaly maps. Code is available at https://github.com/marksgraham/ddpm-ood, Comment: Accepted at MICCAI 2023

Background: Electronic Health Records hold detailed longitudinal information about each patient's health status and general clinical history, a large portion of which is stored within the unstructured text. Existing approaches focus mostly on structured data and a subset of single-domain outcomes. We explore how temporal modelling of patients from free text and structured data, using deep generative transformers can be used to forecast a wide range of future disorders, substances, procedures or findings. Methods: We present Foresight, a novel transformer-based pipeline that uses named entity recognition and linking tools to convert document text into structured, coded concepts, followed by providing probabilistic forecasts for future medical events such as disorders, substances, procedures and findings. We processed the entire free-text portion from three different hospital datasets totalling 811336 patients covering both physical and mental health. Findings: On tests in two UK hospitals (King's College Hospital, South London and Maudsley) and the US MIMIC-III dataset precision@10 0.68, 0.76 and 0.88 was achieved for forecasting the next disorder in a patient timeline, while precision@10 of 0.80, 0.81 and 0.91 was achieved for forecasting the next biomedical concept. Foresight was also validated on 34 synthetic patient timelines by five clinicians and achieved relevancy of 97% for the top forecasted candidate disorder. As a generative model, it can forecast follow-on biomedical concepts for as many steps as required. Interpretation: Foresight is a general-purpose model for biomedical concept modelling that can be used for real-world risk forecasting, virtual trials and clinical research to study the progression of disorders, simulate interventions and counterfactuals, and educational purposes.

Deep generative models have emerged as promising tools for detecting arbitrary anomalies in data, dispensing with the necessity for manual labelling. Recently, autoregressive transformers have achieved state-of-the-art performance for anomaly detection in medical imaging. Nonetheless, these models still have some intrinsic weaknesses, such as requiring images to be modelled as 1D sequences, the accumulation of errors during the sampling process, and the significant inference times associated with transformers. Denoising diffusion probabilistic models are a class of non-autoregressive generative models recently shown to produce excellent samples in computer vision (surpassing Generative Adversarial Networks), and to achieve log-likelihoods that are competitive with transformers while having fast inference times. Diffusion models can be applied to the latent representations learnt by autoencoders, making them easily scalable and great candidates for application to high dimensional data, such as medical images. Here, we propose a method based on diffusion models to detect and segment anomalies in brain imaging. By training the models on healthy data and then exploring its diffusion and reverse steps across its Markov chain, we can identify anomalous areas in the latent space and hence identify anomalies in the pixel space. Our diffusion models achieve competitive performance compared with autoregressive approaches across a series of experiments with 2D CT and MRI data involving synthetic and real pathological lesions with much reduced inference times, making their usage clinically viable.

The ability to perform accurate prognosis of patients is crucial for proactive clinical decision making, informed resource management and personalised care. Existing outcome prediction models suffer from a low recall of infrequent positive outcomes. We present a highly-scalable and robust machine learning framework to automatically predict adversity represented by mortality and ICU admission from time-series vital signs and laboratory results obtained within the first 24 hours of hospital admission. The stacked platform comprises two components: a) an unsupervised LSTM Autoencoder that learns an optimal representation of the time-series, using it to differentiate the less frequent patterns which conclude with an adverse event from the majority patterns that do not, and b) a gradient boosting model, which relies on the constructed representation to refine prediction, incorporating static features of demographics, admission details and clinical summaries. The model is used to assess a patient's risk of adversity over time and provides visual justifications of its prediction based on the patient's static features and dynamic signals. Results of three case studies for predicting mortality and ICU admission show that the model outperforms all existing outcome prediction models, achieving PR-AUC of 0.891 (95$%$ CI: 0.878 - 0.969) in predicting mortality in ICU and general ward settings and 0.908 (95$%$ CI: 0.870-0.935) in predicting ICU admission., Comment: 14 pages

Electronic health records (EHR) contain large volumes of unstructured text, requiring the application of Information Extraction (IE) technologies to enable clinical analysis. We present the open-source Medical Concept Annotation Toolkit (MedCAT) that provides: a) a novel self-supervised machine learning algorithm for extracting concepts using any concept vocabulary including UMLS/SNOMED-CT; b) a feature-rich annotation interface for customising and training IE models; and c) integrations to the broader CogStack ecosystem for vendor-agnostic health system deployment. We show improved performance in extracting UMLS concepts from open datasets (F1:0.448-0.738 vs 0.429-0.650). Further real-world validation demonstrates SNOMED-CT extraction at 3 large London hospitals with self-supervised training over ~8.8B words from ~17M clinical records and further fine-tuning with ~6K clinician annotated examples. We show strong transferability (F1 > 0.94) between hospitals, datasets, and concept types indicating cross-domain EHR-agnostic utility for accelerated clinical and research use cases., Comment: Preprint: 27 Pages, 3 Figures