Navigating Data Scarcity using Foundation Models: A Benchmark of Few-Shot and Zero-Shot Learning Approaches in Medical Imaging

Data scarcity is a major limiting factor for applying modern machine learning techniques to clinical tasks. Although sufficient data exists for some well-studied medical tasks, there remains a long tail of clinically relevant tasks with poor data availability. Recently, numerous foundation models have demonstrated high suitability for few-shot learning (FSL) and zero-shot learning (ZSL), potentially making them more accessible to practitioners. However, it remains unclear which foundation model performs best on FSL medical image analysis tasks and what the optimal methods are for learning from limited data. We conducted a comprehensive benchmark study of ZSL and FSL using 16 pretrained foundation models on 19 diverse medical imaging datasets. Our results indicate that BiomedCLIP, a model pretrained exclusively on medical data, performs best on average for very small training set sizes, while very large CLIP models pretrained on LAION-2B perform best with slightly more training samples. However, simply fine-tuning a ResNet-18 pretrained on ImageNet performs similarly with more than five training examples per class. Our findings also highlight the need for further research on foundation models specifically tailored for medical applications and the collection of more datasets to train these models.

Segmentation-guided MRI reconstruction for meaningfully diverse reconstructions

Inverse problems, such as accelerated MRI reconstruction, are ill-posed and an infinite amount of possible and plausible solutions exist. This may not only lead to uncertainty in the reconstructed image but also in downstream tasks such as semantic segmentation. This uncertainty, however, is mostly not analyzed in the literature, even though probabilistic reconstruction models are commonly used. These models can be prone to ignore plausible but unlikely solutions like rare pathologies. Building on MRI reconstruction approaches based on diffusion models, we add guidance to the diffusion process during inference, generating two meaningfully diverse reconstructions corresponding to an upper and lower bound segmentation. The reconstruction uncertainty can then be quantified by the difference between these bounds, which we coin the 'uncertainty boundary'. We analyzed the behavior of the upper and lower bound segmentations for a wide range of acceleration factors and found the uncertainty boundary to be both more reliable and more accurate compared to repeated sampling. Code is available at https://github.com/NikolasMorshuis/SGR

Conformal Performance Range Prediction for Segmentation Output Quality Control

Recent works have introduced methods to estimate segmentation performance without ground truth, relying solely on neural network softmax outputs. These techniques hold potential for intuitive output quality control. However, such performance estimates rely on calibrated softmax outputs, which is often not the case in modern neural networks. Moreover, the estimates do not take into account inherent uncertainty in segmentation tasks. These limitations may render precise performance predictions unattainable, restricting the practical applicability of performance estimation methods. To address these challenges, we develop a novel approach for predicting performance ranges with statistical guarantees of containing the ground truth with a user specified probability. Our method leverages sampling-based segmentation uncertainty estimation to derive heuristic performance ranges, and applies split conformal prediction to transform these estimates into rigorous prediction ranges that meet the desired guarantees. We demonstrate our approach on the FIVES retinal vessel segmentation dataset and compare five commonly used sampling-based uncertainty estimation techniques. Our results show that it is possible to achieve the desired coverage with small prediction ranges, highlighting the potential of performance range prediction as a valuable tool for output quality control.

PULPo: Probabilistic Unsupervised Laplacian Pyramid Registration

Deformable image registration is fundamental to many medical imaging applications. Registration is an inherently ambiguous task often admitting many viable solutions. While neural network-based registration techniques enable fast and accurate registration, the majority of existing approaches are not able to estimate uncertainty. Here, we present PULPo, a method for probabilistic deformable registration capable of uncertainty quantification. PULPo probabilistically models the distribution of deformation fields on different hierarchical levels combining them using Laplacian pyramids. This allows our method to model global as well as local aspects of the deformation field. We evaluate our method on two widely used neuroimaging datasets and find that it achieves high registration performance as well as substantially better calibrated uncertainty quantification compared to the current state-of-the-art.

Subgroup-Specific Risk-Controlled Dose Estimation in Radiotherapy

Cancer remains a leading cause of death, highlighting the importance of effective radiotherapy (RT). Magnetic resonance-guided linear accelerators (MR-Linacs) enable imaging during RT, allowing for inter-fraction, and perhaps even intra-fraction, adjustments of treatment plans. However, achieving this requires fast and accurate dose calculations. While Monte Carlo simulations offer accuracy, they are computationally intensive. Deep learning frameworks show promise, yet lack uncertainty quantification crucial for high-risk applications like RT. Risk-controlling prediction sets (RCPS) offer model-agnostic uncertainty quantification with mathematical guarantees. However, we show that naive application of RCPS may lead to only certain subgroups such as the image background being risk-controlled. In this work, we extend RCPS to provide prediction intervals with coverage guarantees for multiple subgroups with unknown subgroup membership at test time. We evaluate our algorithm on real clinical planing volumes from five different anatomical regions and show that our novel subgroup RCPS (SG-RCPS) algorithm leads to prediction intervals that jointly control the risk for multiple subgroups. In particular, our method controls the risk of the crucial voxels along the radiation beam significantly better than conventional RCPS.

Attri-Net: A Globally and Locally Inherently Interpretable Model for Multi-Label Classification Using Class-Specific Counterfactuals

Interpretability is crucial for machine learning algorithms in high-stakes medical applications. However, high-performing neural networks typically cannot explain their predictions. Post-hoc explanation methods provide a way to understand neural networks but have been shown to suffer from conceptual problems. Moreover, current research largely focuses on providing local explanations for individual samples rather than global explanations for the model itself. In this paper, we propose Attri-Net, an inherently interpretable model for multi-label classification that provides local and global explanations. Attri-Net first counterfactually generates class-specific attribution maps to highlight the disease evidence, then performs classification with logistic regression classifiers based solely on the attribution maps. Local explanations for each prediction can be obtained by interpreting the attribution maps weighted by the classifiers' weights. Global explanation of whole model can be obtained by jointly considering learned average representations of the attribution maps for each class (called the class centers) and the weights of the linear classifiers. To ensure the model is ``right for the right reason", we further introduce a mechanism to guide the model's explanations to align with human knowledge. Our comprehensive evaluations show that Attri-Net can generate high-quality explanations consistent with clinical knowledge while not sacrificing classification performance.

A comprehensive and easy-to-use multi-domain multi-task medical imaging meta-dataset

While the field of medical image analysis has undergone a transformative shift with the integration of machine learning techniques, the main challenge of these techniques is often the scarcity of large, diverse, and well-annotated datasets. Medical images vary in format, size, and other parameters and therefore require extensive preprocessing and standardization, for usage in machine learning. Addressing these challenges, we introduce the Medical Imaging Meta-Dataset (MedIMeta), a novel multi-domain, multi-task meta-dataset. MedIMeta contains 19 medical imaging datasets spanning 10 different domains and encompassing 54 distinct medical tasks, all of which are standardized to the same format and readily usable in PyTorch or other ML frameworks. We perform a technical validation of MedIMeta, demonstrating its utility through fully supervised and cross-domain few-shot learning baselines.

Unsupervised Anomaly Detection using Aggregated Normative Diffusion

Early detection of anomalies in medical images such as brain MRI is highly relevant for diagnosis and treatment of many conditions. Supervised machine learning methods are limited to a small number of pathologies where there is good availability of labeled data. In contrast, unsupervised anomaly detection (UAD) has the potential to identify a broader spectrum of anomalies by spotting deviations from normal patterns. Our research demonstrates that existing state-of-the-art UAD approaches do not generalise well to diverse types of anomalies in realistic multi-modal MR data. To overcome this, we introduce a new UAD method named Aggregated Normative Diffusion (ANDi). ANDi operates by aggregating differences between predicted denoising steps and ground truth backwards transitions in Denoising Diffusion Probabilistic Models (DDPMs) that have been trained on pyramidal Gaussian noise. We validate ANDi against three recent UAD baselines, and across three diverse brain MRI datasets. We show that ANDi, in some cases, substantially surpasses these baselines and shows increased robustness to varying types of anomalies. Particularly in detecting multiple sclerosis (MS) lesions, ANDi achieves improvements of up to 178% in terms of AUPRC.

Right for the Wrong Reason: Can Interpretable ML Techniques Detect Spurious Correlations?

While deep neural network models offer unmatched classification performance, they are prone to learning spurious correlations in the data. Such dependencies on confounding information can be difficult to detect using performance metrics if the test data comes from the same distribution as the training data. Interpretable ML methods such as post-hoc explanations or inherently interpretable classifiers promise to identify faulty model reasoning. However, there is mixed evidence whether many of these techniques are actually able to do so. In this paper, we propose a rigorous evaluation strategy to assess an explanation technique's ability to correctly identify spurious correlations. Using this strategy, we evaluate five post-hoc explanation techniques and one inherently interpretable method for their ability to detect three types of artificially added confounders in a chest x-ray diagnosis task. We find that the post-hoc technique SHAP, as well as the inherently interpretable Attri-Net provide the best performance and can be used to reliably identify faulty model behavior.

Uncertainty Estimation and Propagation in Accelerated MRI Reconstruction

MRI reconstruction techniques based on deep learning have led to unprecedented reconstruction quality especially in highly accelerated settings. However, deep learning techniques are also known to fail unexpectedly and hallucinate structures. This is particularly problematic if reconstructions are directly used for downstream tasks such as real-time treatment guidance or automated extraction of clinical paramters (e.g. via segmentation). Well-calibrated uncertainty quantification will be a key ingredient for safe use of this technology in clinical practice. In this paper we propose a novel probabilistic reconstruction technique (PHiRec) building on the idea of conditional hierarchical variational autoencoders. We demonstrate that our proposed method produces high-quality reconstructions as well as uncertainty quantification that is substantially better calibrated than several strong baselines. We furthermore demonstrate how uncertainties arising in the MR econstruction can be propagated to a downstream segmentation task, and show that PHiRec also allows well-calibrated estimation of segmentation uncertainties that originated in the MR reconstruction process.