Unsupervised anomaly detection and segmentation methods train a model to learn the training distribution as 'normal'. In the testing phase, they identify patterns that deviate from this normal distribution as 'anomalies'. To learn the 'normal' distribution, prevailing methods corrupt the images and train a model to reconstruct them. During testing, the model attempts to reconstruct corrupted inputs based on the learned 'normal' distribution. Deviations from this distribution lead to high reconstruction errors, which indicate potential anomalies. However, corrupting an input image inevitably causes information loss even in normal regions, leading to suboptimal reconstruction and an increased risk of false positives. To alleviate this, we propose IterMask3D, an iterative spatial mask-refining strategy designed for 3D brain MRI. We iteratively spatially mask areas of the image as corruption and reconstruct them, then shrink the mask based on reconstruction error. This process iteratively unmasks 'normal' areas to the model, whose information further guides reconstruction of 'normal' patterns under the mask to be reconstructed accurately, reducing false positives. In addition, to achieve better reconstruction performance, we also propose using high-frequency image content as additional structural information to guide the reconstruction of the masked area. Extensive experiments on the detection of both synthetic and real-world imaging artifacts, as well as segmentation of various pathological lesions across multiple MRI sequences, consistently demonstrate the effectiveness of our proposed method. Code is available at https://github.com/ZiyunLiang/IterMask3D.

Large Vision-Language Models (VLMs), possessing millions or billions of parameters, typically require large text and image datasets for effective fine-tuning. However, collecting data from various sites, especially in healthcare, is challenging due to strict privacy regulations. An alternative is to fine-tune these foundation models on end-user devices, such as in medical clinics and hospitals, without sending data to a server. These local clients typically have limited computing power and small datasets, which are not enough for fully fine-tuning large VLMs on their own. A naive solution to these scenarios is to leverage parameter-efficient fine-tuning (PEFT) strategies such as adapters and apply federated learning (FL) algorithms to combine the learned adapter weights, thereby respecting the resource limitations and data privacy of the clients. However, this approach does not fully leverage the knowledge from multiple adapters trained on diverse data distributions and for diverse tasks. The adapters are adversely impacted by data heterogeneity and task heterogeneity across clients resulting in sub-optimal convergence. To this end, we propose a novel framework called FedPIA that improves upon the naive combinations of FL and PEFT by introducing Permutation and Integration of the local Adapters in the server and global Adapters in the clients exploiting Wasserstein barycenters for improved blending of client-specific and client-agnostic knowledge. This layerwise permutation helps to bridge the gap in the parameter space of local and global adapters before integration. We conduct over 2000 client-level experiments utilizing 48 medical image datasets across five different medical vision-language FL task settings encompassing visual question answering as well as image and report-based multi-label disease detection. Our experiments involving diverse client settings, ten different modalities, and two VLM backbones demonstrate that FedPIA consistently outperforms the state-of-the-art PEFT-FL baselines.

Federated Learning (FL) in healthcare ensures patient privacy by allowing hospitals to collaboratively train machine learning models while keeping sensitive medical data secure and localized. Most existing research in FL has concentrated on unimodal scenarios, where all healthcare institutes share the same type of data. However, in real-world healthcare situations, some clients may have access to multiple types of data pertaining to the same disease. Multimodal Federated Learning (MMFL) utilizes multiple modalities to build a more powerful FL model than its unimodal counterpart. However, the impact of missing modality in different clients, called modality incongruity, has been greatly overlooked. This paper, for the first time, analyses the impact of modality incongruity and reveals its connection with data heterogeneity across participating clients. We particularly inspect whether incongruent MMFL with unimodal and multimodal clients is more beneficial than unimodal FL. Furthermore, we examine three potential routes of addressing this issue. Firstly, we study the effectiveness of various self-attention mechanisms towards incongruity-agnostic information fusion in MMFL. Secondly, we introduce a modality imputation network (MIN) pre-trained in a multimodal client for modality translation in unimodal clients and investigate its potential towards mitigating the missing modality problem. Thirdly, we introduce several client-level and server-level regularization techniques including Modality-aware knowledge Distillation (MAD) and Leave-one-out teacher (LOOT) towards mitigating modality incongruity effects. Experiments are conducted with Chest X-Ray and radiology reports under several MMFL settings on two publicly available real-world datasets, MIMIC-CXR and Open-I.

Effective training of large Vision-Language Models (VLMs) on resource-constrained client devices in Federated Learning (FL) requires the usage of parameter-efficient finetuning (PEFT) strategies. To this end, we demonstrate the impact of two factors viz., client-specific layer importance score that selects the most important VLM layers for finetuning and inter-client layer diversity score that encourages diverse layer selection across clients for optimal VLM layer selection. We first theoretically motivate and leverage the principal eigenvalue magnitude of layerwise Neural Tangent Kernels and show its effectiveness as client-specific layer importance score. Next, we propose a novel layer updating strategy dubbed F3OCUS that jointly optimizes the layer importance and diversity factors by employing a data-free, multi-objective, meta-heuristic optimization on the server. We explore 5 different meta-heuristic algorithms and compare their effectiveness for selecting model layers and adapter layers towards PEFT-FL. Furthermore, we release a new MedVQA-FL dataset involving overall 707,962 VQA triplets and 9 modality-specific clients and utilize it to train and evaluate our method. Overall, we conduct more than 10,000 client-level experiments on 6 Vision-Language FL task settings involving 58 medical image datasets and 4 different VLM architectures of varying sizes to demonstrate the effectiveness of the proposed method. Project Page: https://pramitsaha.github.io/FOCUS/

Medical image segmentation data inherently contain uncertainty. This can stem from both imperfect image quality and variability in labeling preferences on ambiguous pixels, which depend on annotator expertise and the clinical context of the annotations. For instance, a boundary pixel might be labeled as tumor in diagnosis to avoid under-estimation of severity, but as normal tissue in radiotherapy to prevent damage to sensitive structures. As segmentation preferences vary across downstream applications, it is often desirable for an image segmentation model to offer user-adaptable predictions rather than a fixed output. While prior uncertainty-aware and interactive methods offer adaptability, they are inefficient at test time: uncertainty-aware models require users to choose from numerous similar outputs, while interactive models demand significant user input through click or box prompts to refine segmentation. To address these challenges, we propose \textbf{SPA}, a new \textbf{S}egmentation \textbf{P}reference \textbf{A}lignment framework that efficiently adapts to diverse test-time preferences with minimal human interaction. By presenting users with a select few, distinct segmentation candidates that best capture uncertainties, it reduces the user workload to reach the preferred segmentation. To accommodate user preference, we introduce a probabilistic mechanism that leverages user feedback to adapt a model's segmentation preference. The proposed framework is evaluated on several medical image segmentation tasks: color fundus images, lung lesion and kidney CT scans, MRI scans of brain and prostate. SPA shows 1) a significant reduction in user time and effort compared to existing interactive segmentation approaches, 2) strong adaptability based on human feedback, and 3) state-of-the-art image segmentation performance across different imaging modalities and semantic labels.

Safe deployment of machine learning (ML) models in safety-critical domains such as medical imaging requires detecting inputs with characteristics not seen during training, known as out-of-distribution (OOD) detection, to prevent unreliable predictions. Effective OOD detection after deployment could benefit from access to the training data, enabling direct comparison between test samples and the training data distribution to identify differences. State-of-the-art OOD detection methods, however, either discard the training data after deployment or assume that test samples and training data are centrally stored together, an assumption that rarely holds in real-world settings. This is because shipping the training data with the deployed model is usually impossible due to the size of training databases, as well as proprietary or privacy constraints. We introduce the Isolation Network, an OOD detection framework that quantifies the difficulty of separating a target test sample from the training data by solving a binary classification task. We then propose Decentralized Isolation Networks (DIsoN), which enables the comparison of training and test data when data-sharing is impossible, by exchanging only model parameters between the remote computational nodes of training and deployment. We further extend DIsoN with class-conditioning, comparing a target sample solely with training data of its predicted class. We evaluate DIsoN on four medical imaging datasets (dermatology, chest X-ray, breast ultrasound, histopathology) across 12 OOD detection tasks. DIsoN performs favorably against existing methods while respecting data-privacy. This decentralized OOD detection framework opens the way for a new type of service that ML developers could provide along with their models: providing remote, secure utilization of their training data for OOD detection services. Code available at: https://github.com/FelixWag/DIsoN

Segmentation models for brain lesions in MRI are commonly developed for a specific disease and trained on data with a predefined set of MRI modalities. Such models cannot segment the disease using data with a different set of MRI modalities, nor can they segment other types of diseases. Moreover, this training paradigm prevents a model from using the advantages of learning from heterogeneous databases that may contain scans and segmentation labels for different brain pathologies and diverse sets of MRI modalities. Additionally, the confidentiality of patient data often prevents central data aggregation, necessitating a decentralized approach. Is it feasible to use Federated Learning (FL) to train a single model on client databases that contain scans and labels of different brain pathologies and diverse sets of MRI modalities? We demonstrate promising results by combining appropriate, simple, and practical modifications to the model and training strategy: Designing a model with input channels that cover the whole set of modalities available across clients, training with random modality drop, and exploring the effects of feature normalization methods. Evaluation on 7 brain MRI databases with 5 different diseases shows that this FL framework can train a single model that achieves very promising results in segmenting all disease types seen during training. Importantly, it can segment these diseases in new databases that contain sets of modalities different from those in training clients. These results demonstrate, for the first time, the feasibility and effectiveness of using FL to train a single 3D segmentation model on decentralised data with diverse brain diseases and MRI modalities, a necessary step towards leveraging heterogeneous real-world databases. Code: https://github.com/FelixWag/FedUniBrain

This paper presents an effective and general data augmentation framework for medical image segmentation. We adopt a computationally efficient and data-efficient gradient-based meta-learning scheme to explicitly align the distribution of training and validation data which is used as a proxy for unseen test data. We improve the current data augmentation strategies with two core designs. First, we learn class-specific training-time data augmentation (TRA) effectively increasing the heterogeneity within the training subsets and tackling the class imbalance common in segmentation. Second, we jointly optimize TRA and test-time data augmentation (TEA), which are closely connected as both aim to align the training and test data distribution but were so far considered separately in previous works. We demonstrate the effectiveness of our method on four medical image segmentation tasks across different scenarios with two state-of-the-art segmentation models, DeepMedic and nnU-Net. Extensive experimentation shows that the proposed data augmentation framework can significantly and consistently improve the segmentation performance when compared to existing solutions. Code is publicly available at https://github.com/ZerojumpLine/JCSAugment.

Background samples provide key contextual information for segmenting regions of interest (ROIs). However, they always cover a diverse set of structures, causing difficulties for the segmentation model to learn good decision boundaries with high sensitivity and precision. The issue concerns the highly heterogeneous nature of the background class, resulting in multi-modal distributions. Empirically, we find that neural networks trained with heterogeneous background struggle to map the corresponding contextual samples to compact clusters in feature space. As a result, the distribution over background logit activations may shift across the decision boundary, leading to systematic over-segmentation across different datasets and tasks. In this study, we propose context label learning (CoLab) to improve the context representations by decomposing the background class into several subclasses. Specifically, we train an auxiliary network as a task generator, along with the primary segmentation model, to automatically generate context labels that positively affect the ROI segmentation accuracy. Extensive experiments are conducted on several challenging segmentation tasks and datasets. The results demonstrate that CoLab can guide the segmentation model to map the logits of background samples away from the decision boundary, resulting in significantly improved segmentation accuracy. Code is available at https://github.com/ZerojumpLine/CoLab.

Class imbalance poses a challenge for developing unbiased, accurate predictive models. In particular, in image segmentation neural networks may overfit to the foreground samples from small structures, which are often heavily under-represented in the training set, leading to poor generalization. In this study, we provide new insights on the problem of overfitting under class imbalance by inspecting the network behavior. We find empirically that when training with limited data and strong class imbalance, at test time the distribution of logit activations may shift across the decision boundary, while samples of the well-represented class seem unaffected. This bias leads to a systematic under-segmentation of small structures. This phenomenon is consistently observed for different databases, tasks and network architectures. To tackle this problem, we introduce new asymmetric variants of popular loss functions and regularization techniques including a large margin loss, focal loss, adversarial training, mixup and data augmentation, which are explicitly designed to counter logit shift of the under-represented classes. Extensive experiments are conducted on several challenging segmentation tasks. Our results demonstrate that the proposed modifications to the objective function can lead to significantly improved segmentation accuracy compared to baselines and alternative approaches.

In image segmentation, there is often more than one plausible solution for a given input. In medical imaging, for example, experts will often disagree about the exact location of object boundaries. Estimating this inherent uncertainty and predicting multiple plausible hypotheses is of great interest in many applications, yet this ability is lacking in most current deep learning methods. In this paper, we introduce stochastic segmentation networks (SSNs), an efficient probabilistic method for modelling aleatoric uncertainty with any image segmentation network architecture. In contrast to approaches that produce pixel-wise estimates, SSNs model joint distributions over entire label maps and thus can generate multiple spatially coherent hypotheses for a single image. By using a low-rank multivariate normal distribution over the logit space to model the probability of the label map given the image, we obtain a spatially consistent probability distribution that can be efficiently computed by a neural network without any changes to the underlying architecture. We tested our method on the segmentation of real-world medical data, including lung nodules in 2D CT and brain tumours in 3D multimodal MRI scans. SSNs outperform state-of-the-art for modelling correlated uncertainty in ambiguous images while being much simpler, more flexible, and more efficient.

Quantification of anatomical shape changes currently relies on scalar global indexes which are largely insensitive to regional or asymmetric modifications. Accurate assessment of pathology-driven anatomical remodeling is a crucial step for the diagnosis and treatment of many conditions. Deep learning approaches have recently achieved wide success in the analysis of medical images, but they lack interpretability in the feature extraction and decision processes. In this work, we propose a new interpretable deep learning model for shape analysis. In particular, we exploit deep generative networks to model a population of anatomical segmentations through a hierarchy of conditional latent variables. At the highest level of this hierarchy, a two-dimensional latent space is simultaneously optimised to discriminate distinct clinical conditions, enabling the direct visualisation of the classification space. Moreover, the anatomical variability encoded by this discriminative latent space can be visualised in the segmentation space thanks to the generative properties of the model, making the classification task transparent. This approach yielded high accuracy in the categorisation of healthy and remodelled left ventricles when tested on unseen segmentations from our own multi-centre dataset as well as in an external validation set, and on hippocampi from healthy controls and patients with Alzheimer's disease when tested on ADNI data. More importantly, it enabled the visualisation in three-dimensions of both global and regional anatomical features which better discriminate between the conditions under exam. The proposed approach scales effectively to large populations, facilitating high-throughput analysis of normal anatomy and pathology in large-scale studies of volumetric imaging.

Generalization capability to unseen domains is crucial for machine learning models when deploying to real-world conditions. We investigate the challenging problem of domain generalization, i.e., training a model on multi-domain source data such that it can directly generalize to target domains with unknown statistics. We adopt a model-agnostic learning paradigm with gradient-based meta-train and meta-test procedures to expose the optimization to domain shift. Further, we introduce two complementary losses which explicitly regularize the semantic structure of the feature space. Globally, we align a derived soft confusion matrix to preserve general knowledge of inter-class relationships. Locally, we promote domain-independent class-specific cohesion and separation of sample features with a metric-learning component. The effectiveness of our method is demonstrated with new state-of-the-art results on two common object recognition benchmarks. Our method also shows consistent improvement on a medical image segmentation task.

We present a novel cost function for semi-supervised learning of neural networks that encourages compact clustering of the latent space to facilitate separation. The key idea is to dynamically create a graph over embeddings of labeled and unlabeled samples of a training batch to capture underlying structure in feature space, and use label propagation to estimate its high and low density regions. We then devise a cost function based on Markov chains on the graph that regularizes the latent space to form a single compact cluster per class, while avoiding to disturb existing clusters during optimization. We evaluate our approach on three benchmarks and compare to state-of-the art with promising results. Our approach combines the benefits of graph-based regularization with efficient, inductive inference, does not require modifications to a network architecture, and can thus be easily applied to existing networks to enable an effective use of unlabeled data.

Incorporation of prior knowledge about organ shape and location is key to improve performance of image analysis approaches. In particular, priors can be useful in cases where images are corrupted and contain artefacts due to limitations in image acquisition. The highly constrained nature of anatomical objects can be well captured with learning-based techniques. However, in most recent and promising techniques such as CNN-based segmentation it is not obvious how to incorporate such prior knowledge. State-of-the-art methods operate as pixel-wise classifiers where the training objectives do not incorporate the structure and inter-dependencies of the output. To overcome this limitation, we propose a generic training strategy that incorporates anatomical prior knowledge into CNNs through a new regularisation model, which is trained end-to-end. The new framework encourages models to follow the global anatomical properties of the underlying anatomy (e.g. shape, label structure) via learnt non-linear representations of the shape. We show that the proposed approach can be easily adapted to different analysis tasks (e.g. image enhancement, segmentation) and improve the prediction accuracy of the state-of-the-art models. The applicability of our approach is shown on multi-modal cardiac data sets and public benchmarks. In addition, we demonstrate how the learnt deep models of 3-D shapes can be interpreted and used as biomarkers for classification of cardiac pathologies.

We propose a dual pathway, 11-layers deep, three-dimensional Convolutional Neural Network for the challenging task of brain lesion segmentation. The devised architecture is the result of an in-depth analysis of the limitations of current networks proposed for similar applications. To overcome the computational burden of processing 3D medical scans, we have devised an efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data. Further, we analyze the development of deeper, thus more discriminative 3D CNNs. In order to incorporate both local and larger contextual information, we employ a dual pathway architecture that processes the input images at multiple scales simultaneously. For post-processing of the network's soft segmentation, we use a 3D fully connected Conditional Random Field which effectively removes false positives. Our pipeline is extensively evaluated on three challenging tasks of lesion segmentation in multi-channel MRI patient data with traumatic brain injuries, brain tumours, and ischemic stroke. We improve on the state-of-the-art for all three applications, with top ranking performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is computationally efficient, which allows its adoption in a variety of research and clinical settings. The source code of our implementation is made publicly available.

Identifying and interpreting fetal standard scan planes during 2-D ultrasound mid-pregnancy examinations are highly complex tasks, which require years of training. Apart from guiding the probe to the correct location, it can be equally difficult for a non-expert to identify relevant structures within the image. Automatic image processing can provide tools to help experienced as well as inexperienced operators with these tasks. In this paper, we propose a novel method based on convolutional neural networks, which can automatically detect 13 fetal standard views in freehand 2-D ultrasound data as well as provide a localization of the fetal structures via a bounding box. An important contribution is that the network learns to localize the target anatomy using weak supervision based on image-level labels only. The network architecture is designed to operate in real-time while providing optimal output for the localization task. We present results for real-time annotation, retrospective frame retrieval from saved videos, and localization on a very large and challenging dataset consisting of images and video recordings of full clinical anomaly screenings. We found that the proposed method achieved an average F1-score of 0.798 in a realistic classification experiment modeling real-time detection, and obtained a 90.09% accuracy for retrospective frame retrieval. Moreover, an accuracy of 77.8% was achieved on the localization task.

In this paper, we propose DeepCut, a method to obtain pixelwise object segmentations given an image dataset labelled weak annotations, in our case bounding boxes. It extends the approach of the well-known GrabCut [1] method to include machine learning by training a neural network classifier from bounding box annotations. We formulate the problem as an energy minimisation problem over a densely-connected conditional random field and iteratively update the training targets to obtain pixelwise object segmentations. Additionally, we propose variants of the DeepCut method and compare those to a naïve approach to CNN training under weak supervision. We test its applicability to solve brain and lung segmentation problems on a challenging fetal magnetic resonance dataset and obtain encouraging results in terms of accuracy.

When integrating computational tools, such as automatic segmentation, into clinical practice, it is of utmost importance to be able to assess the level of accuracy on new data and, in particular, to detect when an automatic method fails. However, this is difficult to achieve due to the absence of ground truth. Segmentation accuracy on clinical data might be different from what is found through cross validation, because validation data are often used during incremental method development, which can lead to overfitting and unrealistic performance expectations. Before deployment, performance is quantified using different metrics, for which the predicted segmentation is compared with a reference segmentation, often obtained manually by an expert. But little is known about the real performance after deployment when a reference is unavailable. In this paper, we introduce the concept of reverse classification accuracy (RCA) as a framework for predicting the performance of a segmentation method on new data. In RCA, we take the predicted segmentation from a new image to train a reverse classifier, which is evaluated on a set of reference images with available ground truth. The hypothesis is that if the predicted segmentation is of good quality, then the reverse classifier will perform well on at least some of the reference images. We validate our approach on multi-organ segmentation with different classifiers and segmentation methods. Our results indicate that it is indeed possible to predict the quality of individual segmentations, in the absence of ground truth. Thus, RCA is ideal for integration into automatic processing pipelines in clinical routine and as a part of large-scale image analysis studies.

3D cardiac MR imaging enables accurate analysis of cardiac morphology and physiology. However, due to the requirements for long acquisition and breath-hold, the clinical routine is still dominated by multi-slice 2D imaging, which hamper the visualization of anatomy and quantitative measurements as relatively thick slices are acquired. As a solution, we propose a novel image super-resolution (SR) approach that is based on a residual convolutional neural network (CNN) model. It reconstructs high resolution 3D volumes from 2D image stacks for more accurate image analysis. The proposed model allows the use of multiple input data acquired from different viewing planes for improved performance. Experimental results on 1233 cardiac short and long-axis MR image stacks show that the CNN model outperforms state-of-the-art SR methods in terms of image quality while being computationally efficient. Also, we show that image segmentation and motion tracking benefits more from SR-CNN when it is used as an initial upscaling method than conventional interpolation methods for the subsequent analysis.