Association Rule Mining (ARM) aims to discover patterns between features in datasets in the form of propositional rules, supporting both knowledge discovery and interpretable machine learning in high-stakes decision-making. However, in high-dimensional settings, rule explosion and computational overhead render popular algorithmic approaches impractical without effective search space reduction, challenges that propagate to downstream tasks. Neurosymbolic methods, such as Aerial+, have recently been proposed to address the rule explosion in ARM. While they tackle the high dimensionality of the data, they also inherit limitations of neural networks, particularly reduced performance in low-data regimes. This paper makes three key contributions to association rule discovery in high-dimensional tabular data. First, we empirically show that Aerial+ scales one to two orders of magnitude better than state-of-the-art algorithmic and neurosymbolic baselines across five real-world datasets. Second, we introduce the novel problem of ARM in high-dimensional, low-data settings, such as gene expression data from the biomedicine domain with around 18k features and 50 samples. Third, we propose two fine-tuning approaches to Aerial+ using tabular foundation models. Our proposed approaches are shown to significantly improve rule quality on five real-world datasets, demonstrating their effectiveness in low-data, high-dimensional scenarios.

The field of computer vision applied to videos of minimally invasive surgery is ever-growing. Workflow recognition pertains to the automated recognition of various aspects of a surgery: including which surgical steps are performed; and which surgical instruments are used. This information can later be used to assist clinicians when learning the surgery; during live surgery; and when writing operation notes. The Pituitary Vision (PitVis) 2023 Challenge tasks the community to step and instrument recognition in videos of endoscopic pituitary surgery. This is a unique task when compared to other minimally invasive surgeries due to the smaller working space, which limits and distorts vision; and higher frequency of instrument and step switching, which requires more precise model predictions. Participants were provided with 25-videos, with results presented at the MICCAI-2023 conference as part of the Endoscopic Vision 2023 Challenge in Vancouver, Canada, on 08-Oct-2023. There were 18-submissions from 9-teams across 6-countries, using a variety of deep learning models. A commonality between the top performing models was incorporating spatio-temporal and multi-task methods, with greater than 50% and 10% macro-F1-score improvement over purely spacial single-task models in step and instrument recognition respectively. The PitVis-2023 Challenge therefore demonstrates state-of-the-art computer vision models in minimally invasive surgery are transferable to a new dataset, with surgery specific techniques used to enhance performance, progressing the field further. Benchmark results are provided in the paper, and the dataset is publicly available at: this https URL.

Histopathological analysis of Whole Slide Images (WSIs) has seen a surge in the utilization of deep learning methods, particularly Convolutional Neural Networks (CNNs). However, CNNs often fall short in capturing the intricate spatial dependencies inherent in WSIs. Graph Neural Networks (GNNs) present a promising alternative, adept at directly modeling pairwise interactions and effectively discerning the topological tissue and cellular structures within WSIs. Recognizing the pressing need for deep learning techniques that harness the topological structure of WSIs, the application of GNNs in histopathology has experienced rapid growth. In this comprehensive review, we survey GNNs in histopathology, discuss their applications, and explore emerging trends that pave the way for future advancements in the field. We begin by elucidating the fundamentals of GNNs and their potential applications in histopathology. Leveraging quantitative literature analysis, we identify four emerging trends: Hierarchical GNNs, Adaptive Graph Structure Learning, Multimodal GNNs, and Higher-order GNNs. Through an in-depth exploration of these trends, we offer insights into the evolving landscape of GNNs in histopathological analysis. Based on our findings, we propose future directions to propel the field forward. Our analysis serves to guide researchers and practitioners towards innovative approaches and methodologies, fostering advancements in histopathological analysis through the lens of graph neural networks.

Causal abstraction techniques such as Interchange Intervention Training (IIT) have been proposed to infuse neural network with expert knowledge encoded in causal models, but their application to real-world problems remains limited. This article explores the application of IIT in predicting blood glucose levels in Type 1 Diabetes Mellitus (T1DM) patients. The study utilizes an acyclic version of the simglucose simulator approved by the FDA to train a Multi-Layer Perceptron (MLP) model, employing IIT to impose causal relationships. Results show that the model trained with IIT effectively abstracted the causal structure and outperformed the standard one in terms of predictive performance across different prediction horizons (PHs) post-meal. Furthermore, the breakdown of the counterfactual loss can be leveraged to explain which part of the causal mechanism are more or less effectively captured by the model. These preliminary results suggest the potential of IIT in enhancing predictive models in healthcare by effectively complying with expert knowledge.

Methods for query answering over incomplete knowledge graphs retrieve entities that are \emph{likely} to be answers, which is particularly useful when such answers cannot be reached by direct graph traversal due to missing edges. However, existing approaches have focused on queries formalized using first-order-logic. In practice, many real-world queries involve constraints that are inherently vague or context-dependent, such as preferences for attributes or related categories. Addressing this gap, we introduce the problem of query answering with soft constraints. We formalize the problem and introduce two efficient methods designed to adjust query answer scores by incorporating soft constraints without disrupting the original answers to a query. These methods are lightweight, requiring tuning only two parameters or a small neural network trained to capture soft constraints while maintaining the original ranking structure. To evaluate the task, we extend existing QA benchmarks by generating datasets with soft constraints. Our experiments demonstrate that our methods can capture soft constraints while maintaining robust query answering performance and adding very little overhead. With our work, we explore a new and flexible way to interact with graph databases that allows users to specify their preferences by providing examples interactively.

Deep learning has proven to be a suitable alternative to least-squares (LSQ) fitting for parameter estimation in various quantitative MRI (QMRI) models. However, current deep learning implementations are not robust to changes in MR acquisition protocols. In practice, QMRI acquisition protocols differ substantially between different studies and clinical settings. The lack of generalizability and adoptability of current deep learning approaches for QMRI parameter estimation impedes the implementation of these algorithms in clinical trials and clinical practice. Neural Controlled Differential Equations (NCDEs) allow for the sampling of incomplete and irregularly sampled data with variable length, making them ideal for use in QMRI parameter estimation. In this study, we show that NCDEs can function as a generic tool for the accurate prediction of QMRI parameters, regardless of QMRI sequence length, configuration of independent variables and QMRI forward model (variable flip angle T1-mapping, intravoxel incoherent motion MRI, dynamic contrast-enhanced MRI). NCDEs achieved lower mean squared error than LSQ fitting in low-SNR simulations and in vivo in challenging anatomical regions like the abdomen and leg, but this improvement was no longer evident at high SNR. NCDEs reduce estimation error interquartile range without increasing bias, particularly under conditions of high uncertainty. These findings suggest that NCDEs offer a robust approach for reliable QMRI parameter estimation, especially in scenarios with high uncertainty or low image quality. We believe that with NCDEs, we have solved one of the main challenges for using deep learning for QMRI parameter estimation in a broader clinical and research setting.

Three-dimensional facial stereophotogrammetry provides a detailed representation of craniofacial soft tissue without the use of ionizing radiation. While manual annotation of landmarks serves as the current gold standard for cephalometric analysis, it is a time-consuming process and is prone to human error. The aim in this study was to develop and evaluate an automated cephalometric annotation method using a deep learning-based approach. Ten landmarks were manually annotated on 2897 3D facial photographs by a single observer. The automated landmarking workflow involved two successive DiffusionNet models and additional algorithms for facial segmentation. The dataset was randomly divided into a training and test dataset. The training dataset was used to train the deep learning networks, whereas the test dataset was used to evaluate the performance of the automated workflow. The precision of the workflow was evaluated by calculating the Euclidean distances between the automated and manual landmarks and compared to the intra-observer and inter-observer variability of manual annotation and the semi-automated landmarking method. The workflow was successful in 98.6% of all test cases. The deep learning-based landmarking method achieved precise and consistent landmark annotation. The mean precision of 1.69 (+/-1.15) mm was comparable to the inter-observer variability (1.31 +/-0.91 mm) of manual annotation. The Euclidean distance between the automated and manual landmarks was within 2 mm in 69%. Automated landmark annotation on 3D photographs was achieved with the DiffusionNet-based approach. The proposed method allows quantitative analysis of large datasets and may be used in diagnosis, follow-up, and virtual surgical planning.

Prediction models are increasingly proposed for guiding treatment decisions, but most fail to address the special role of treatments, leading to inappropriate use. This paper highlights the limitations of using standard prediction models for treatment decision support. We identify `causal blind spots' in three common approaches to handling treatments in prediction modelling: including treatment as a predictor, restricting data based on treatment status and ignoring treatments. When predictions are used to inform treatment decisions, confounders, colliders and mediators, as well as changes in treatment protocols over time may lead to misinformed decision-making. We illustrate potential harmful consequences in several medical applications. We advocate for an extension of guidelines for development, reporting and evaluation of prediction models to ensure that the intended use of the model is matched to an appropriate risk estimand. When prediction models are intended to inform treatment decisions, prediction models should specify upfront the treatment decisions they aim to support and target a prediction estimand in line with that goal. This requires a shift towards developing predictions under the specific treatment options under consideration (`predictions under interventions'). Predictions under interventions need causal reasoning and inference techniques during development and validation. We argue that this will improve the efficacy of prediction models in guiding treatment decisions and prevent potential negative effects on patient outcomes.

Feature attribution methods have become a staple method to disentangle the complex behavior of black box models. Despite their success, some scholars have argued that such methods suffer from a serious flaw: they do not allow a reliable interpretation in terms of human concepts. Simply put, visualizing an array of feature contributions is not enough for humans to conclude something about a model's internal representations, and confirmation bias can trick users into false beliefs about model behavior. We argue that a structured approach is required to test whether our hypotheses on the model are confirmed by the feature attributions. This is what we call the "semantic match" between human concepts and (sub-symbolic) explanations. Building on the conceptual framework put forward in Cin\`a et al. [2023], we propose a structured approach to evaluate semantic match in practice. We showcase the procedure in a suite of experiments spanning tabular and image data, and show how the assessment of semantic match can give insight into both desirable (e.g., focusing on an object relevant for prediction) and undesirable model behaviors (e.g., focusing on a spurious correlation). We couple our experimental results with an analysis on the metrics to measure semantic match, and argue that this approach constitutes the first step towards resolving the issue of confirmation bias in XAI.

In recent years, theoretical results and simulation evidence have shown Bayesian additive regression trees to be a highly-effective method for nonparametric regression. Motivated by cost-effectiveness analyses in health economics, where interest lies in jointly modelling the costs of healthcare treatments and the associated health-related quality of life experienced by a patient, we propose a multivariate extension of BART which is applicable in regression analyses with several dependent outcome variables. Our framework allows for continuous or binary outcomes and overcomes some key limitations of existing multivariate BART models by allowing each individual response to be associated with different ensembles of trees, while still handling dependencies between the outcomes. In the case of continuous outcomes, our model is essentially a nonparametric version of seemingly unrelated regression. Likewise, our proposal for binary outcomes is a nonparametric generalisation of the multivariate probit model. We give suggestions for easily interpretable prior distributions, which allow specification of both informative and uninformative priors. We provide detailed discussions of MCMC sampling methods to conduct posterior inference. Our methods are implemented in the R package "subart". We showcase their performance through extensive simulation experiments and an application to an empirical case study from health economics. By also accommodating propensity scores in a manner befitting a causal analysis, we find substantial evidence for a novel trauma care intervention's cost-effectiveness.

Reliable uncertainty quantification (UQ) is essential when employing large language models (LLMs) in high-risk domains such as clinical question answering (QA). In this work, we evaluate uncertainty estimation methods for clinical QA focusing, for the first time, on eleven clinical specialties and six question types, and across ten open-source LLMs (general-purpose, biomedical, and reasoning models). We analyze score-based UQ methods, present a case study introducing a novel lightweight method based on behavioral features derived from reasoning-oriented models, and examine conformal prediction as a complementary set-based approach. Our findings reveal that uncertainty reliability is not a monolithic property, but one that depends on clinical specialty and question type due to shifts in calibration and discrimination. Our results highlight the need to select or ensemble models based on their distinct, complementary strengths and clinical use.

Estimated brain age from magnetic resonance image (MRI) and its deviation from chronological age can provide early insights into potential neurodegenerative diseases, supporting early detection and implementation of prevention strategies. Diffusion MRI (dMRI), a widely used modality for brain age estimation, presents an opportunity to build an earlier biomarker for neurodegenerative disease prediction because it captures subtle microstructural changes that precede more perceptible macrostructural changes. However, the coexistence of macro- and micro-structural information in dMRI raises the question of whether current dMRI-based brain age estimation models are leveraging the intended microstructural information or if they inadvertently rely on the macrostructural information. To develop a microstructure-specific brain age, we propose a method for brain age identification from dMRI that minimizes the model's use of macrostructural information by non-rigidly registering all images to a standard template. Imaging data from 13,398 participants across 12 datasets were used for the training and evaluation. We compare our brain age models, trained with and without macrostructural information minimized, with an architecturally similar T1-weighted (T1w) MRI-based brain age model and two state-of-the-art T1w MRI-based brain age models that primarily use macrostructural information. We observe difference between our dMRI-based brain age and T1w MRI-based brain age across stages of neurodegeneration, with dMRI-based brain age being older than T1w MRI-based brain age in participants transitioning from cognitively normal (CN) to mild cognitive impairment (MCI), but younger in participants already diagnosed with Alzheimer's disease (AD). Approximately 4 years before MCI diagnosis, dMRI-based brain age yields better performance than T1w MRI-based brain ages in predicting transition from CN to MCI.

The reconstruction kernel in computed tomography (CT) generation determines the texture of the image. Consistency in reconstruction kernels is important as the underlying CT texture can impact measurements during quantitative image analysis. Harmonization (i.e., kernel conversion) minimizes differences in measurements due to inconsistent reconstruction kernels. Existing methods investigate harmonization of CT scans in single or multiple manufacturers. However, these methods require paired scans of hard and soft reconstruction kernels that are spatially and anatomically aligned. Additionally, a large number of models need to be trained across different kernel pairs within manufacturers. In this study, we adopt an unpaired image translation approach to investigate harmonization between and across reconstruction kernels from different manufacturers by constructing a multipath cycle generative adversarial network (GAN). We use hard and soft reconstruction kernels from the Siemens and GE vendors from the National Lung Screening Trial dataset. We use 50 scans from each reconstruction kernel and train a multipath cycle GAN. To evaluate the effect of harmonization on the reconstruction kernels, we harmonize 50 scans each from Siemens hard kernel, GE soft kernel and GE hard kernel to a reference Siemens soft kernel (B30f) and evaluate percent emphysema. We fit a linear model by considering the age, smoking status, sex and vendor and perform an analysis of variance (ANOVA) on the emphysema scores. Our approach minimizes differences in emphysema measurement and highlights the impact of age, sex, smoking status and vendor on emphysema quantification.

This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the ADNI (334 AD, 520 CN). Trained classifiers were subsequently applied to predict conversion to AD in ADNI MCI patients (231 converters, 628 non-converters) and in the independent Health-RI Parelsnoer data set. From this multi-center study representing a tertiary memory clinic population, we included 199 AD patients, 139 participants with subjective cognitive decline, 48 MCI patients converting to dementia, and 91 MCI patients who did not convert to dementia. AD-CN classification based on modulated GM maps resulted in a similar AUC for SVM (0.940) and CNN (0.933). Application to conversion prediction in MCI yielded significantly higher performance for SVM (0.756) than for CNN (0.742). In external validation, performance was slightly decreased. For AD-CN, it again gave similar AUCs for SVM (0.896) and CNN (0.876). For prediction in MCI, performances decreased for both SVM (0.665) and CNN (0.702). Both with SVM and CNN, classification based on modulated GM maps significantly outperformed classification based on minimally processed images. Deep and conventional classifiers performed equally well for AD classification and their performance decreased only slightly when applied to the external cohort. We expect that this work on external validation contributes towards translation of machine learning to clinical practice.

Prediction models are popular in medical research and practice. By predicting an outcome of interest for specific patients, these models may help inform difficult treatment decisions, and are often hailed as the poster children for personalized, data-driven healthcare. We show however, that using prediction models for decision making can lead to harmful decisions, even when the predictions exhibit good discrimination after deployment. These models are harmful self-fulfilling prophecies: their deployment harms a group of patients but the worse outcome of these patients does not invalidate the predictive power of the model. Our main result is a formal characterization of a set of such prediction models. Next we show that models that are well calibrated before and after deployment are useless for decision making as they made no change in the data distribution. These results point to the need to revise standard practices for validation, deployment and evaluation of prediction models that are used in medical decisions.

Spitz tumors are diagnostically challenging due to overlap in atypical histological features with conventional melanomas. We investigated to what extent AI models, using histological and/or clinical features, can: (1) distinguish Spitz tumors from conventional melanomas; (2) predict the underlying genetic aberration of Spitz tumors; and (3) predict the diagnostic category of Spitz tumors. The AI models were developed and validated using a dataset of 393 Spitz tumors and 379 conventional melanomas. Predictive performance was measured using the AUROC and the accuracy. The performance of the AI models was compared with that of four experienced pathologists in a reader study. Moreover, a simulation experiment was conducted to investigate the impact of implementing AI-based recommendations for ancillary diagnostic testing on the workflow of the pathology department. The best AI model based on UNI features reached an AUROC of 0.95 and an accuracy of 0.86 in differentiating Spitz tumors from conventional melanomas. The genetic aberration was predicted with an accuracy of 0.55 compared to 0.25 for randomly guessing. The diagnostic category was predicted with an accuracy of 0.51, where random chance-level accuracy equaled 0.33. On all three tasks, the AI models performed better than the four pathologists, although differences were not statistically significant for most individual comparisons. Based on the simulation experiment, implementing AI-based recommendations for ancillary diagnostic testing could reduce material costs, turnaround times, and examinations. In conclusion, the AI models achieved a strong predictive performance in distinguishing between Spitz tumors and conventional melanomas. On the more challenging tasks of predicting the genetic aberration and the diagnostic category of Spitz tumors, the AI models performed better than random chance.

Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural MRI data has become an important task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest. The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 years for cognitively normal participants and MAE of 6.62 years for cognitively impaired participants, while the second method achieves MAE of 4.69 years for cognitively normal participants and MAE of 4.96 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.

Quantification of cardiac motion with cine Cardiac Magnetic Resonance Imaging (CMRI) is an integral part of arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Yet, the expert evaluation of motion abnormalities with CMRI is a challenging task. To automatically assess cardiac motion, we register CMRIs from different time points of the cardiac cycle using Implicit Neural Representations (INRs) and perform a biomechanically informed regularization inspired by the myocardial incompressibility assumption. To enhance the registration performance, our method first rectifies the inter-slice misalignment inherent to CMRI by performing a rigid registration guided by the long-axis views, and then increases the through-plane resolution using an unsupervised deep learning super-resolution approach. Finally, we propose to synergically combine information from short-axis and 4-chamber long-axis views, along with an initialization to incorporate information from multiple cardiac time points. Thereafter, to quantify cardiac motion, we calculate global and segmental strain over a cardiac cycle and compute the peak strain. The evaluation of the method is performed on a dataset of cine CMRI scans from 47 ARVC patients and 67 controls. Our results show that inter-slice alignment and generation of super-resolved volumes combined with joint analysis of the two cardiac views, notably improves registration performance. Furthermore, the proposed initialization yields more physiologically plausible registrations. The significant differences in the peak strain, discerned between the ARVC patients and healthy controls suggest that automated motion quantification methods may assist in diagnosis and provide further understanding of disease-specific alterations of cardiac motion.

Graph Neural Networks (GNNs) have emerged as a powerful tool to learn from graph-structured data. A paramount example of such data is the brain, which operates as a network, from the micro-scale of neurons, to the macro-scale of regions. This organization deemed GNNs a natural tool of choice to model brain activity, and have consequently attracted a lot of attention in the neuroimaging community. Yet, the advantage of adopting these models over conventional methods has not yet been assessed in a systematic way to gauge if GNNs are capable of leveraging the underlying structure of the data to improve learning. In this work, we study and evaluate the performance of five popular GNN architectures in diagnosing major depression disorder and autism spectrum disorder in two multi-site clinical datasets, and sex classification on the UKBioBank, from functional brain scans under a general uniform framework. Our results show that GNNs fail to outperform kernel-based and structure-agnostic deep learning models, in which 1D CNNs outperform the other methods in all scenarios. We highlight that creating optimal graph structures for functional brain data is a major bottleneck hindering the performance of GNNs, where existing works use arbitrary measures to define the edges resulting in noisy graphs. We therefore propose to integrate graph diffusion into existing architectures and show that it can alleviate this problem and improve their performance. Our results call for increased moderation and rigorous validation when evaluating graph methods and advocate for more data-centeric approaches in developing GNNs for functional neuroimaging applications.

Single subject prediction of brain disorders from neuroimaging data has gained increasing attention in recent years. Yet, for some heterogeneous disorders such as major depression disorder (MDD) and autism spectrum disorder (ASD), the performance of prediction models on large-scale multi-site datasets remains poor. We present a two-stage framework to improve the diagnosis of heterogeneous psychiatric disorders from resting-state functional magnetic resonance imaging (rs-fMRI). First, we propose a self-supervised mask prediction task on data from healthy individuals that can exploit differences between healthy controls and patients in clinical datasets. Next, we train a supervised classifier on the learned discriminative representations. To model rs-fMRI data, we develop Graph-S4; an extension to the recently proposed state-space model S4 to graph settings where the underlying graph structure is not known in advance. We show that combining the framework and Graph-S4 can significantly improve the diagnostic performance of neuroimaging-based single subject prediction models of MDD and ASD on three open-source multi-center rs-fMRI clinical datasets.