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Delineating lesions and anatomical structure is important for image-guided interventions. Point-supervised medical image segmentation (PSS) has great potential to alleviate costly expert delineation labeling. However, due to the lack of precise size and boundary guidance, the effectiveness of PSS often falls short of expectations. Although recent vision foundational models, such as the medical segment anything model (MedSAM), have made significant advancements in bounding-box-prompted segmentation, it is not straightforward to utilize point annotation, and is prone to semantic ambiguity. In this preliminary study, we introduce an iterative framework to facilitate semantic-aware point-supervised MedSAM. Specifically, the semantic box-prompt generator (SBPG) module has the capacity to convert the point input into potential pseudo bounding box suggestions, which are explicitly refined by the prototype-based semantic similarity. This is then succeeded by a prompt-guided spatial refinement (PGSR) module that harnesses the exceptional generalizability of MedSAM to infer the segmentation mask, which also updates the box proposal seed in SBPG. Performance can be progressively improved with adequate iterations. We conducted an evaluation on BraTS2018 for the segmentation of whole brain tumors and demonstrated its superior performance compared to traditional PSS methods and on par with box-supervised methods., Comment: 2024 IEEE Nuclear Science Symposium and Medical Imaging Conference

Deep learning (DL) models for segmenting various anatomical structures have achieved great success via a static DL model that is trained in a single source domain. Yet, the static DL model is likely to perform poorly in a continually evolving environment, requiring appropriate model updates. In an incremental learning setting, we would expect that well-trained static models are updated, following continually evolving target domain data -- e.g., additional lesions or structures of interest -- collected from different sites, without catastrophic forgetting. This, however, poses challenges, due to distribution shifts, additional structures not seen during the initial model training, and the absence of training data in a source domain. To address these challenges, in this work, we seek to progressively evolve an ``off-the-shelf" trained segmentation model to diverse datasets with additional anatomical categories in a unified manner. Specifically, we first propose a divergence-aware dual-flow module with balanced rigidity and plasticity branches to decouple old and new tasks, which is guided by continuous batch renormalization. Then, a complementary pseudo-label training scheme with self-entropy regularized momentum MixUp decay is developed for adaptive network optimization. We evaluated our framework on a brain tumor segmentation task with continually changing target domains -- i.e., new MRI scanners/modalities with incremental structures. Our framework was able to well retain the discriminability of previously learned structures, hence enabling the realistic life-long segmentation model extension along with the widespread accumulation of big medical data., Comment: Early Accept to MICCAI 2023

Self-training is an important class of unsupervised domain adaptation (UDA) approaches that are used to mitigate the problem of domain shift, when applying knowledge learned from a labeled source domain to unlabeled and heterogeneous target domains. While self-training-based UDA has shown considerable promise on discriminative tasks, including classification and segmentation, through reliable pseudo-label filtering based on the maximum softmax probability, there is a paucity of prior work on self-training-based UDA for generative tasks, including image modality translation. To fill this gap, in this work, we seek to develop a generative self-training (GST) framework for domain adaptive image translation with continuous value prediction and regression objectives. Specifically, we quantify both aleatoric and epistemic uncertainties within our GST using variational Bayes learning to measure the reliability of synthesized data. We also introduce a self-attention scheme that de-emphasizes the background region to prevent it from dominating the training process. The adaptation is then carried out by an alternating optimization scheme with target domain supervision that focuses attention on the regions with reliable pseudo-labels. We evaluated our framework on two cross-scanner/center, inter-subject translation tasks, including tagged-to-cine magnetic resonance (MR) image translation and T1-weighted MR-to-fractional anisotropy translation. Extensive validations with unpaired target domain data showed that our GST yielded superior synthesis performance in comparison to adversarial training UDA methods., Comment: Accepted to Medical Image Analysis

Background: In medical imaging, images are usually treated as deterministic, while their uncertainties are largely underexplored. Purpose: This work aims at using deep learning to efficiently estimate posterior distributions of imaging parameters, which in turn can be used to derive the most probable parameters as well as their uncertainties. Methods: Our deep learning-based approaches are based on a variational Bayesian inference framework, which is implemented using two different deep neural networks based on conditional variational auto-encoder (CVAE), CVAE-dual-encoder and CVAE-dual-decoder. The conventional CVAE framework, i.e., CVAE-vanilla, can be regarded as a simplified case of these two neural networks. We applied these approaches to a simulation study of dynamic brain PET imaging using a reference region-based kinetic model. Results: In the simulation study, we estimated posterior distributions of PET kinetic parameters given a measurement of time-activity curve. Our proposed CVAE-dual-encoder and CVAE-dual-decoder yield results that are in good agreement with the asymptotically unbiased posterior distributions sampled by Markov Chain Monte Carlo (MCMC). The CVAE-vanilla can also be used for estimating posterior distributions, although it has an inferior performance to both CVAE-dual-encoder and CVAE-dual-decoder. Conclusions: We have evaluated the performance of our deep learning approaches for estimating posterior distributions in dynamic brain PET. Our deep learning approaches yield posterior distributions, which are in good agreement with unbiased distributions estimated by MCMC. All these neural networks have different characteristics and can be chosen by the user for specific applications. The proposed methods are general and can be adapted to other problems., Comment: Published in Medical Physics

Unsupervised domain adaptation (UDA) has been a vital protocol for migrating information learned from a labeled source domain to facilitate the implementation in an unlabeled heterogeneous target domain. Although UDA is typically jointly trained on data from both domains, accessing the labeled source domain data is often restricted, due to concerns over patient data privacy or intellectual property. To sidestep this, we propose "off-the-shelf (OS)" UDA (OSUDA), aimed at image segmentation, by adapting an OS segmentor trained in a source domain to a target domain, in the absence of source domain data in adaptation. Toward this goal, we aim to develop a novel batch-wise normalization (BN) statistics adaptation framework. In particular, we gradually adapt the domain-specific low-order BN statistics, e.g., mean and variance, through an exponential momentum decay strategy, while explicitly enforcing the consistency of the domain shareable high-order BN statistics, e.g., scaling and shifting factors, via our optimization objective. We also adaptively quantify the channel-wise transferability to gauge the importance of each channel, via both low-order statistics divergence and a scaling factor.~Furthermore, we incorporate unsupervised self-entropy minimization into our framework to boost performance alongside a novel queued, memory-consistent self-training strategy to utilize the reliable pseudo label for stable and efficient unsupervised adaptation. We evaluated our OSUDA-based framework on both cross-modality and cross-subtype brain tumor segmentation and cardiac MR to CT segmentation tasks. Our experimental results showed that our memory consistent OSUDA performs better than existing source-relaxed UDA methods and yields similar performance to UDA methods with source data., Comment: Published in Medical Image Analysis (extension of MICCAI paper)

Unsupervised domain adaptation (UDA) has been widely used to transfer knowledge from a labeled source domain to an unlabeled target domain to counter the difficulty of labeling in a new domain. The training of conventional solutions usually relies on the existence of both source and target domain data. However, privacy of the large-scale and well-labeled data in the source domain and trained model parameters can become the major concern of cross center/domain collaborations. In this work, to address this, we propose a practical solution to UDA for segmentation with a black-box segmentation model trained in the source domain only, rather than original source data or a white-box source model. Specifically, we resort to a knowledge distillation scheme with exponential mixup decay (EMD) to gradually learn target-specific representations. In addition, unsupervised entropy minimization is further applied to regularization of the target domain confidence. We evaluated our framework on the BraTS 2018 database, achieving performance on par with white-box source model adaptation approaches., Comment: SPIE Medical Imaging 2022: Image Processing

Unsupervised domain adaptation (UDA) has been successfully applied to transfer knowledge from a labeled source domain to target domains without their labels. Recently introduced transferable prototypical networks (TPN) further addresses class-wise conditional alignment. In TPN, while the closeness of class centers between source and target domains is explicitly enforced in a latent space, the underlying fine-grained subtype structure and the cross-domain within-class compactness have not been fully investigated. To counter this, we propose a new approach to adaptively perform a fine-grained subtype-aware alignment to improve performance in the target domain without the subtype label in both domains. The insight of our approach is that the unlabeled subtypes in a class have the local proximity within a subtype, while exhibiting disparate characteristics, because of different conditional and label shifts. Specifically, we propose to simultaneously enforce subtype-wise compactness and class-wise separation, by utilizing intermediate pseudo-labels. In addition, we systematically investigate various scenarios with and without prior knowledge of subtype numbers, and propose to exploit the underlying subtype structure. Furthermore, a dynamic queue framework is developed to evolve the subtype cluster centroids steadily using an alternative processing scheme. Experimental results, carried out with multi-view congenital heart disease data and VisDA and DomainNet, show the effectiveness and validity of our subtype-aware UDA, compared with state-of-the-art UDA methods., Comment: IEEE Transactions on Neural Networks and Learning Systems (TNNLS)

Deep learning has become the method of choice to tackle real-world problems in different domains, partly because of its ability to learn from data and achieve impressive performance on a wide range of applications. However, its success usually relies on two assumptions: (i) vast troves of labeled datasets are required for accurate model fitting, and (ii) training and testing data are independent and identically distributed. Its performance on unseen target domains, thus, is not guaranteed, especially when encountering out-of-distribution data at the adaptation stage. The performance drop on data in a target domain is a critical problem in deploying deep neural networks that are successfully trained on data in a source domain. Unsupervised domain adaptation (UDA) is proposed to counter this, by leveraging both labeled source domain data and unlabeled target domain data to carry out various tasks in the target domain. UDA has yielded promising results on natural image processing, video analysis, natural language processing, time-series data analysis, medical image analysis, etc. In this review, as a rapidly evolving topic, we provide a systematic comparison of its methods and applications. In addition, the connection of UDA with its closely related tasks, e.g., domain generalization and out-of-distribution detection, has also been discussed. Furthermore, deficiencies in current methods and possible promising directions are highlighted., Comment: APSIPA Transactions on Signal and Information Processing

Cycle reconstruction regularized adversarial training -- e.g., CycleGAN, DiscoGAN, and DualGAN -- has been widely used for image style transfer with unpaired training data. Several recent works, however, have shown that local distortions are frequent, and structural consistency cannot be guaranteed. Targeting this issue, prior works usually relied on additional segmentation or consistent feature extraction steps that are task-specific. To counter this, this work aims to learn a general add-on structural feature extractor, by explicitly enforcing the structural alignment between an input and its synthesized image. Specifically, we propose a novel input-output image patches self-training scheme to achieve a disentanglement of underlying anatomical structures and imaging modalities. The translator and structure encoder are updated, following an alternating training protocol. In addition, the information w.r.t. imaging modality can be eliminated with an asymmetric adversarial game. We train, validate, and test our network on 1,768, 416, and 1,560 unpaired subject-independent slices of tagged and cine magnetic resonance imaging from a total of twenty healthy subjects, respectively, demonstrating superior performance over competing methods., Comment: SPIE Medical Imaging: Image Processing (Oral presentation)

Lesions or organ boundaries visible through medical imaging data are often ambiguous, thus resulting in significant variations in multi-reader delineations, i.e., the source of aleatoric uncertainty. In particular, quantifying the inter-observer variability of manual annotations with Magnetic Resonance (MR) Imaging data plays a crucial role in establishing a reference standard for various diagnosis and treatment tasks. Most segmentation methods, however, simply model a mapping from an image to its single segmentation map and do not take the disagreement of annotators into consideration. In order to account for inter-observer variability, without sacrificing accuracy, we propose a novel variational inference framework to model the distribution of plausible segmentation maps, given a specific MR image, which explicitly represents the multi-reader variability. Specifically, we resort to a latent vector to encode the multi-reader variability and counteract the inherent information loss in the imaging data. Then, we apply a variational autoencoder network and optimize its evidence lower bound (ELBO) to efficiently approximate the distribution of the segmentation map, given an MR image. Experimental results, carried out with the QUBIQ brain growth MRI segmentation datasets with seven annotators, demonstrate the effectiveness of our approach., Comment: SPIE Medical Imaging 2022 (Oral)

Unsupervised domain adaptation (UDA) between two significantly disparate domains to learn high-level semantic alignment is a crucial yet challenging task.~To this end, in this work, we propose exploiting low-level edge information to facilitate the adaptation as a precursor task, which has a small cross-domain gap, compared with semantic segmentation.~The precise contour then provides spatial information to guide the semantic adaptation. More specifically, we propose a multi-task framework to learn a contouring adaptation network along with a semantic segmentation adaptation network, which takes both magnetic resonance imaging (MRI) slice and its initial edge map as input.~These two networks are jointly trained with source domain labels, and the feature and edge map level adversarial learning is carried out for cross-domain alignment. In addition, self-entropy minimization is incorporated to further enhance segmentation performance. We evaluated our framework on the BraTS2018 database for cross-modality segmentation of brain tumors, showing the validity and superiority of our approach, compared with competing methods., Comment: Accepted to ISBI 2022

In this work, we propose an adversarial unsupervised domain adaptation (UDA) approach with the inherent conditional and label shifts, in which we aim to align the distributions w.r.t. both $p(x|y)$ and $p(y)$. Since the label is inaccessible in the target domain, the conventional adversarial UDA assumes $p(y)$ is invariant across domains, and relies on aligning $p(x)$ as an alternative to the $p(x|y)$ alignment. To address this, we provide a thorough theoretical and empirical analysis of the conventional adversarial UDA methods under both conditional and label shifts, and propose a novel and practical alternative optimization scheme for adversarial UDA. Specifically, we infer the marginal $p(y)$ and align $p(x|y)$ iteratively in the training, and precisely align the posterior $p(y|x)$ in testing. Our experimental results demonstrate its effectiveness on both classification and segmentation UDA, and partial UDA., Comment: Accepted to ICCV 2021

In this work, we propose a domain generalization (DG) approach to learn on several labeled source domains and transfer knowledge to a target domain that is inaccessible in training. Considering the inherent conditional and label shifts, we would expect the alignment of $p(x|y)$ and $p(y)$. However, the widely used domain invariant feature learning (IFL) methods relies on aligning the marginal concept shift w.r.t. $p(x)$, which rests on an unrealistic assumption that $p(y)$ is invariant across domains. We thereby propose a novel variational Bayesian inference framework to enforce the conditional distribution alignment w.r.t. $p(x|y)$ via the prior distribution matching in a latent space, which also takes the marginal label shift w.r.t. $p(y)$ into consideration with the posterior alignment. Extensive experiments on various benchmarks demonstrate that our framework is robust to the label shift and the cross-domain accuracy is significantly improved, thereby achieving superior performance over the conventional IFL counterparts., Comment: 30th International Joint Conference on Artificial Intelligence (IJCAI) 2021

Assessment of cardiovascular disease (CVD) with cine magnetic resonance imaging (MRI) has been used to non-invasively evaluate detailed cardiac structure and function. Accurate segmentation of cardiac structures from cine MRI is a crucial step for early diagnosis and prognosis of CVD, and has been greatly improved with convolutional neural networks (CNN). There, however, are a number of limitations identified in CNN models, such as limited interpretability and high complexity, thus limiting their use in clinical practice. In this work, to address the limitations, we propose a lightweight and interpretable machine learning model, successive subspace learning with the subspace approximation with adjusted bias (Saab) transform, for accurate and efficient segmentation from cine MRI. Specifically, our segmentation framework is comprised of the following steps: (1) sequential expansion of near-to-far neighborhood at different resolutions; (2) channel-wise subspace approximation using the Saab transform for unsupervised dimension reduction; (3) class-wise entropy guided feature selection for supervised dimension reduction; (4) concatenation of features and pixel-wise classification with gradient boost; and (5) conditional random field for post-processing. Experimental results on the ACDC 2017 segmentation database, showed that our framework performed better than state-of-the-art U-Net models with 200$\times$ fewer parameters in delineating the left ventricle, right ventricle, and myocardium, thus showing its potential to be used in clinical practice., Comment: 43rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2021)

Unsupervised domain adaptation (UDA) aims to transfer knowledge learned from a labeled source domain to an unlabeled and unseen target domain, which is usually trained on data from both domains. Access to the source domain data at the adaptation stage, however, is often limited, due to data storage or privacy issues. To alleviate this, in this work, we target source free UDA for segmentation, and propose to adapt an ``off-the-shelf" segmentation model pre-trained in the source domain to the target domain, with an adaptive batch-wise normalization statistics adaptation framework. Specifically, the domain-specific low-order batch statistics, i.e., mean and variance, are gradually adapted with an exponential momentum decay scheme, while the consistency of domain shareable high-order batch statistics, i.e., scaling and shifting parameters, is explicitly enforced by our optimization objective. The transferability of each channel is adaptively measured first from which to balance the contribution of each channel. Moreover, the proposed source free UDA framework is orthogonal to unsupervised learning methods, e.g., self-entropy minimization, which can thus be simply added on top of our framework. Extensive experiments on the BraTS 2018 database show that our source free UDA framework outperformed existing source-relaxed UDA methods for the cross-subtype UDA segmentation task and yielded comparable results for the cross-modality UDA segmentation task, compared with a supervised UDA methods with the source data., Comment: To appear in MICCAI 2021

Self-training based unsupervised domain adaptation (UDA) has shown great potential to address the problem of domain shift, when applying a trained deep learning model in a source domain to unlabeled target domains. However, while the self-training UDA has demonstrated its effectiveness on discriminative tasks, such as classification and segmentation, via the reliable pseudo-label selection based on the softmax discrete histogram, the self-training UDA for generative tasks, such as image synthesis, is not fully investigated. In this work, we propose a novel generative self-training (GST) UDA framework with continuous value prediction and regression objective for cross-domain image synthesis. Specifically, we propose to filter the pseudo-label with an uncertainty mask, and quantify the predictive confidence of generated images with practical variational Bayes learning. The fast test-time adaptation is achieved by a round-based alternative optimization scheme. We validated our framework on the tagged-to-cine magnetic resonance imaging (MRI) synthesis problem, where datasets in the source and target domains were acquired from different scanners or centers. Extensive validations were carried out to verify our framework against popular adversarial training UDA methods. Results show that our GST, with tagged MRI of test subjects in new target domains, improved the synthesis quality by a large margin, compared with the adversarial training UDA methods., Comment: MICCAI 2021 (early accept <13%)

Recent advances in unsupervised domain adaptation (UDA) show that transferable prototypical learning presents a powerful means for class conditional alignment, which encourages the closeness of cross-domain class centroids. However, the cross-domain inner-class compactness and the underlying fine-grained subtype structure remained largely underexplored. In this work, we propose to adaptively carry out the fine-grained subtype-aware alignment by explicitly enforcing the class-wise separation and subtype-wise compactness with intermediate pseudo labels. Our key insight is that the unlabeled subtypes of a class can be divergent to one another with different conditional and label shifts, while inheriting the local proximity within a subtype. The cases of with or without the prior information on subtype numbers are investigated to discover the underlying subtype structure in an online fashion. The proposed subtype-aware dynamic UDA achieves promising results on medical diagnosis tasks., Comment: Accepted to AAAI 2021