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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., Comment: Accepted as an oral presentation in MICCAI 2024 2nd International Workshop on Foundation Models for General Medical AI

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, Comment: Accepted at DGM4MICCAI 2024

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., Comment: Accepted as an oral presentation at MICCAI UNSURE 2024

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., Comment: Accepted as full paper to MICCAI 2024

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., Comment: This work was accepted as a full paper at MICCAI 2024

We demonstrate transport in 2D arrays of multiterminal $\varphi_0$-junctions. When applying an in-plane magnetic field we observe nonreciprocal vortex depinning currents, induced by a ratchet-like pinning potential. The ratchet effect is explained as a consequence of spontaneous supercurrents that arise in the presence of next-nearest neighbor Josephson couplings. Tuning the density of vortices to commensurate values of the frustration parameter results in an enhancement of the ratchet effect. In addition, we find a surprising sign reversal of the ratchet effect near frustration 1/3., Comment: 15 pages, 11 Figures

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., Comment: Extension of paper: Inherently Interpretable Multi-Label Classification Using Class-Specific Counterfactuals (Sun et al., MIDL 2023)

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.

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.

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.

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., Comment: Accepted to MICCAI 2023

Distribution shifts remain a fundamental problem for the safe application of machine learning systems. If undetected, they may impact the real-world performance of such systems or will at least render original performance claims invalid. In this paper, we focus on the detection of subgroup shifts, a type of distribution shift that can occur when subgroups have a different prevalence during validation compared to the deployment setting. For example, algorithms developed on data from various acquisition settings may be predominantly applied in hospitals with lower quality data acquisition, leading to an inadvertent performance drop. We formulate subgroup shift detection in the framework of statistical hypothesis testing and show that recent state-of-the-art statistical tests can be effectively applied to subgroup shift detection on medical imaging data. We provide synthetic experiments as well as extensive evaluation on clinically meaningful subgroup shifts on histopathology as well as retinal fundus images. We conclude that classifier-based subgroup shift detection tests could be a particularly useful tool for post-market surveillance of deployed ML systems., Comment: Under review

Interpretability is essential for machine learning algorithms in high-stakes application fields such as medical image analysis. However, high-performing black-box neural networks do not provide explanations for their predictions, which can lead to mistrust and suboptimal human-ML collaboration. Post-hoc explanation techniques, which are widely used in practice, have been shown to suffer from severe conceptual problems. Furthermore, as we show in this paper, current explanation techniques do not perform adequately in the multi-label scenario, in which multiple medical findings may co-occur in a single image. We propose Attri-Net, an inherently interpretable model for multi-label classification. Attri-Net is a powerful classifier that provides transparent, trustworthy, and human-understandable explanations. The model first generates class-specific attribution maps based on counterfactuals to identify which image regions correspond to certain medical findings. Then a simple logistic regression classifier is used to make predictions based solely on these attribution maps. We compare Attri-Net to five post-hoc explanation techniques and one inherently interpretable classifier on three chest X-ray datasets. We find that Attri-Net produces high-quality multi-label explanations consistent with clinical knowledge and has comparable classification performance to state-of-the-art classification models., Comment: Accepted to MIDL 2023

Understanding the interactions of different cell types inside the immune tumor microenvironment (iTME) is crucial for the development of immunotherapy treatments as well as for predicting their outcomes. Highly multiplexed tissue imaging (HMTI) technologies offer a tool which can capture cell properties of tissue samples by measuring expression of various proteins and storing them in separate image channels. HMTI technologies can be used to gain insights into the iTME and in particular how the iTME differs for different patient outcome groups of interest (e.g., treatment responders vs. non-responders). Understanding the systematic differences in the iTME of different patient outcome groups is crucial for developing better treatments and personalising existing treatments. However, such analyses are inherently limited by the fact that any two tissue samples vary due to a large number of factors unrelated to the outcome. Here, we present CF-HistoGAN, a machine learning framework that employs generative adversarial networks (GANs) to create artificial counterfactual tissue samples that resemble the original tissue samples as closely as possible but capture the characteristics of a different patient outcome group. Specifically, we learn to "translate" HMTI samples from one patient group to create artificial paired samples. We show that this approach allows to directly study the effects of different patient outcomes on the iTMEs of individual tissue samples. We demonstrate that CF-HistoGAN can be employed as an explorative tool for understanding iTME effects on the pixel level. Moreover, we show that our method can be used to identify statistically significant differences in the expression of different proteins between patient groups with greater sensitivity compared to conventional approaches.

Generative modeling of 3D brain MRIs presents difficulties in achieving high visual fidelity while ensuring sufficient coverage of the data distribution. In this work, we propose to address this challenge with composable, multiscale morphological transformations in a variational autoencoder (VAE) framework. These transformations are applied to a chosen reference brain image to generate MRI volumes, equipping the model with strong anatomical inductive biases. We structure the VAE latent space in a way such that the model covers the data distribution sufficiently well. We show substantial performance improvements in FID while retaining comparable, or superior, reconstruction quality compared to prior work based on VAEs and generative adversarial networks (GANs)., Comment: Accepted to the NeurIPS 2022 Workshop on Medical Imaging meets NeurIPS

The recent discovery of intrinsic supercurrent diode effect, and its prompt observation in a rich variety of systems, has shown that nonreciprocal supercurrents naturally emerge when both space- and time-inversion symmetries are broken. In Josephson junctions, nonreciprocal supercurrent can be conveniently described in terms of spin-split Andreev states. Here, we demonstrate a sign reversal of the supercurrent diode effect, in both its AC and DC manifestations. In particular, the AC diode effect -- i.e., the asymmetry of the Josephson inductance as a function of the supercurrent -- allows us to probe the current-phase relation near equilibrium. Using a minimal theoretical model, we can then link the sign reversal of the AC diode effect to the so-called 0-$\pi$-like transition, a predicted, but still elusive feature of multi-channel junctions. Our results demonstrate the potential of inductance measurements as sensitive probes of the fundamental properties of unconventional Josephson junctions., Comment: 13 pages, 6 figures

Deep Learning (DL) methods have shown promising results for solving ill-posed inverse problems such as MR image reconstruction from undersampled $k$-space data. However, these approaches currently have no guarantees for reconstruction quality and the reliability of such algorithms is only poorly understood. Adversarial attacks offer a valuable tool to understand possible failure modes and worst case performance of DL-based reconstruction algorithms. In this paper we describe adversarial attacks on multi-coil $k$-space measurements and evaluate them on the recently proposed E2E-VarNet and a simpler UNet-based model. In contrast to prior work, the attacks are targeted to specifically alter diagnostically relevant regions. Using two realistic attack models (adversarial $k$-space noise and adversarial rotations) we are able to show that current state-of-the-art DL-based reconstruction algorithms are indeed sensitive to such perturbations to a degree where relevant diagnostic information may be lost. Surprisingly, in our experiments the UNet and the more sophisticated E2E-VarNet were similarly sensitive to such attacks. Our findings add further to the evidence that caution must be exercised as DL-based methods move closer to clinical practice., Comment: Accepted at the MICCAI-2022 workshop: Machine Learning for Medical Image Reconstruction

Biomechanical and clinical gait research observes muscles and tendons in limbs to study their functions and behaviour. Therefore, movements of distinct anatomical landmarks, such as muscle-tendon junctions, are frequently measured. We propose a reliable and time efficient machine-learning approach to track these junctions in ultrasound videos and support clinical biomechanists in gait analysis. In order to facilitate this process, a method based on deep-learning was introduced. We gathered an extensive dataset, covering 3 functional movements, 2 muscles, collected on 123 healthy and 38 impaired subjects with 3 different ultrasound systems, and providing a total of 66864 annotated ultrasound images in our network training. Furthermore, we used data collected across independent laboratories and curated by researchers with varying levels of experience. For the evaluation of our method a diverse test-set was selected that is independently verified by four specialists. We show that our model achieves similar performance scores to the four human specialists in identifying the muscle-tendon junction position. Our method provides time-efficient tracking of muscle-tendon junctions, with prediction times of up to 0.078 seconds per frame (approx. 100 times faster than manual labeling). All our codes, trained models and test-set were made publicly available and our model is provided as a free-to-use online service on https://deepmtj.org/., Comment: in IEEE Transactions on Biomedical Engineering

Most of 2D superconductors are of type II, i.e., they are penetrated by quantized vortices when exposed to out-of-plane magnetic fields. In presence of a supercurrent, a Lorentz-like force acts on the vortices, leading to drift and dissipation. The current-induced vortex motion is impeded by pinning at defects, enabling the use of superconductors to generate high magnetic fields without dissipation. Usually, the pinning strength decreases upon any type of pair-breaking. Here we show that in Rashba superconductors the application of an in-plane field leads, instead, to an unexpected enhancement of pinning. When rotating the in-plane component of the field with respect to the current direction, the vortex inductance turns out to be highly anisotropic. We explain this phenomenon as a manifestation of Lifshitz invariant terms in the Ginzburg-Landau free energy, which are enabled by inversion and time-reversal symmetry breaking and lead to an elliptic squeezing of vortex cores. Our experiment provides access to a fundamental property of Rashba superconductors and offers an entirely new approach to vortex manipulation., Comment: 23 pages, 9 figures

Simultaneous breaking of inversion- and time-reversal symmetry in Josephson junction leads to a possible violation of the $I(\varphi)=-I(-\varphi)$ equality for the current-phase relation. This is known as anomalous Josephson effect and it produces a phase shift $\varphi_0$ in sinusoidal current-phase relations. In ballistic Josephson junctions with non-sinusoidal current phase relation the observed phenomenology is much richer, including the supercurrent diode effect and the magnetochiral anisotropy of Josephson inductance. In this work, we present measurements of both effects on arrays of Josephson junctions defined on epitaxial Al/InAs heterostructures. We show that the orientation of the current with respect to the lattice affects the magnetochiral anisotropy, possibly as the result of a finite Dresselhaus component. In addition, we show that the two-fold symmetry of the Josephson inductance reflects in the activation energy for phase slips., Comment: 9 pages, 4 figures

Nonreciprocal transport refers to charge transfer processes that are sensitive to the bias polarity. Until recently, nonreciprocal transport was studied only in dissipative systems, where the nonreciprocal quantity is the resistance. Recent experiments have, however, demonstrated nonreciprocal supercurrent leading to the observation of a supercurrent diode effect in Rashba superconductors, opening the vision of dissipationless electronics. Here we report on a supercurrent diode effect in NbSe$_2$ constrictions obtained by patterning NbSe$_2$ flakes with both even and odd layer number. The observed rectification is driven by valley-Zeeman spin-orbit interaction. We demonstrate a rectification efficiency as large as 60%, considerably larger than the efficiency of devices based on Rashba superconductors. In agreement with recent theory for superconducting transition metal dichalcogenides, we show that the effect is driven by an out-of-plane magnetic field component. Remarkably, we find that the effect becomes field-asymmetric in the presence of an additional in-plane field component transverse to the current direction. Supercurrent diodes offer a further degree of freedom in designing superconducting quantum electronics with the high degree of integrability offered by van der Waals materials., Comment: 18 pages, 12 figures

Transport is called nonreciprocal when not only the sign, but also the absolute value of the current, depends on the polarity of the applied voltage. It requires simultaneously broken inversion and time-reversal symmetries, e.g., by the interplay of spin-orbit coupling and magnetic field. So far, observation of nonreciprocity was always tied to resistivity, and dissipationless nonreciprocal circuit elements were elusive. Here, we engineer fully superconducting nonreciprocal devices based on highly-transparent Josephson junctions fabricated on InAs quantum wells. We demonstrate supercurrent rectification far below the transition temperature. By measuring Josephson inductance, we can link nonreciprocal supercurrent to the asymmetry of the current-phase relation, and directly derive the supercurrent magnetochiral anisotropy coefficient for the first time. A semi-quantitative model well explains the main features of our experimental data. Nonreciprocal Josephson junctions have the potential to become for superconducting circuits what $pn$-junctions are for traditional electronics, opening the way to novel nondissipative circuit elements., Comment: 16 pages, 11 figures