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Arterial blood pressure (ABP) holds substantial promise for proactive cardiovascular health management. Notwithstanding its potential, the invasive nature of ABP measurements confines their utility primarily to clinical environments, limiting their applicability for continuous monitoring beyond medical facilities. The conversion of photoplethysmography (PPG) signals into ABP equivalents has garnered significant attention due to its potential in revolutionizing cardiovascular disease management. Recent strides in PPG-to-ABP prediction encompass the integration of generative and discriminative models. Despite these advances, the efficacy of these models is curtailed by the latent space shift predicament, stemming from alterations in PPG data distribution across disparate hardware and individuals, potentially leading to distorted ABP waveforms. To tackle this problem, we present an innovative solution named the Latent Space Constraint Transformer (LSCT), leveraging a quantized codebook to yield robust latent spaces by employing multiple discretizing bases. To facilitate improved reconstruction, the Correlation-boosted Attention Module (CAM) is introduced to systematically query pertinent bases on a global scale. Furthermore, to enhance expressive capacity, we propose the Multi-Spectrum Enhancement Knowledge (MSEK), which fosters local information flow within the channels of latent code and provides additional embedding for reconstruction. Through comprehensive experimentation on both publicly available datasets and a private downstream task dataset, the proposed approach demonstrates noteworthy performance enhancements compared to existing methods. Extensive ablation studies further substantiate the effectiveness of each introduced module., Comment: Accepted by AAAI-2024, main track

Protein representation learning has primarily benefited from the remarkable development of language models (LMs). Accordingly, pre-trained protein models also suffer from a problem in LMs: a lack of factual knowledge. The recent solution models the relationships between protein and associated knowledge terms as the knowledge encoding objective. However, it fails to explore the relationships at a more granular level, i.e., the token level. To mitigate this, we propose Knowledge-exploited Auto-encoder for Protein (KeAP), which performs token-level knowledge graph exploration for protein representation learning. In practice, non-masked amino acids iteratively query the associated knowledge tokens to extract and integrate helpful information for restoring masked amino acids via attention. We show that KeAP can consistently outperform the previous counterpart on 9 representative downstream applications, sometimes surpassing it by large margins. These results suggest that KeAP provides an alternative yet effective way to perform knowledge enhanced protein representation learning., Comment: Camera ready atICLR 2023. Code and models are available at https://github.com/RL4M/KeAP

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Medical image classification has been widely adopted in medical image analysis. However, due to the difficulty of collecting and labeling data in the medical area, medical image datasets are usually highly-imbalanced. To address this problem, previous works utilized class samples as prior for re-weighting or re-sampling but the feature representation is usually still not discriminative enough. In this paper, we adopt the contrastive learning to tackle the long-tailed medical imbalance problem. Specifically, we first propose the category prototype and adversarial proto-instance to generate representative contrastive pairs. Then, the prototype recalibration strategy is proposed to address the highly imbalanced data distribution. Finally, a unified proto-loss is designed to train our framework. The overall framework, namely as Prototype-aware Contrastive learning (ProCo), is unified as a single-stage pipeline in an end-to-end manner to alleviate the imbalanced problem in medical image classification, which is also a distinct progress than existing works as they follow the traditional two-stage pipeline. Extensive experiments on two highly-imbalanced medical image classification datasets demonstrate that our method outperforms the existing state-of-the-art methods by a large margin., Comment: Accept to MICCAI 2022. Zhixiong Yang and Junwen Pan contributed equally to this work

Answer grounding aims to reveal the visual evidence for visual question answering (VQA), which entails highlighting relevant positions in the image when answering questions about images. Previous attempts typically tackle this problem using pretrained object detectors, but without the flexibility for objects not in the predefined vocabulary. However, these black-box methods solely concentrate on the linguistic generation, ignoring the visual interpretability. In this paper, we propose Dual Visual-Linguistic Interaction (DaVI), a novel unified end-to-end framework with the capability for both linguistic answering and visual grounding. DaVI innovatively introduces two visual-linguistic interaction mechanisms: 1) visual-based linguistic encoder that understands questions incorporated with visual features and produces linguistic-oriented evidence for further answer decoding, and 2) linguistic-based visual decoder that focuses visual features on the evidence-related regions for answer grounding. This way, our approach ranked the 1st place in the answer grounding track of 2022 VizWiz Grand Challenge., Comment: Accepted to CVPR 2022 VizWiz Workshop

Due to the lack of properly annotated medical data, exploring the generalization capability of the deep model is becoming a public concern. Zero-shot learning (ZSL) has emerged in recent years to equip the deep model with the ability to recognize unseen classes. However, existing studies mainly focus on natural images, which utilize linguistic models to extract auxiliary information for ZSL. It is impractical to apply the natural image ZSL solutions directly to medical images, since the medical terminology is very domain-specific, and it is not easy to acquire linguistic models for the medical terminology. In this work, we propose a new paradigm of ZSL specifically for medical images utilizing cross-modality information. We make three main contributions with the proposed paradigm. First, we extract the prior knowledge about the segmentation targets, called relation prototypes, from the prior model and then propose a cross-modality adaptation module to inherit the prototypes to the zero-shot model. Second, we propose a relation prototype awareness module to make the zero-shot model aware of information contained in the prototypes. Last but not least, we develop an inheritance attention module to recalibrate the relation prototypes to enhance the inheritance process. The proposed framework is evaluated on two public cross-modality datasets including a cardiac dataset and an abdominal dataset. Extensive experiments show that the proposed framework significantly outperforms the state of the arts., Comment: IEEE TMI

Due to the lack of expertise for medical image annotation, the investigation of label-efficient methodology for medical image segmentation becomes a heated topic. Recent progresses focus on the efficient utilization of weak annotations together with few strongly-annotated labels so as to achieve comparable segmentation performance in many unprofessional scenarios. However, these approaches only concentrate on the supervision inconsistency between strongly- and weakly-annotated instances but ignore the instance inconsistency inside the weakly-annotated instances, which inevitably leads to performance degradation. To address this problem, we propose a novel label-efficient hybrid-supervised framework, which considers each weakly-annotated instance individually and learns its weight guided by the gradient direction of the strongly-annotated instances, so that the high-quality prior in the strongly-annotated instances is better exploited and the weakly-annotated instances are depicted more precisely. Specially, our designed dynamic instance indicator (DII) realizes the above objectives, and is adapted to our dynamic co-regularization (DCR) framework further to alleviate the erroneous accumulation from distortions of weak annotations. Extensive experiments on two hybrid-supervised medical segmentation datasets demonstrate that with only 10% strong labels, the proposed framework can leverage the weak labels efficiently and achieve competitive performance against the 100% strong-label supervised scenario., Comment: Accepted to AAAI 2022

With the rapid development of artificial intelligence (AI) in medical image processing, deep learning in color fundus photography (CFP) analysis is also evolving. Although there are some open-source, labeled datasets of CFPs in the ophthalmology community, large-scale datasets for screening only have labels of disease categories, and datasets with annotations of fundus structures are usually small in size. In addition, labeling standards are not uniform across datasets, and there is no clear information on the acquisition device. Here we release a multi-annotation, multi-quality, and multi-device color fundus image dataset for glaucoma analysis on an original challenge -- Retinal Fundus Glaucoma Challenge 2nd Edition (REFUGE2). The REFUGE2 dataset contains 2000 color fundus images with annotations of glaucoma classification, optic disc/cup segmentation, as well as fovea localization. Meanwhile, the REFUGE2 challenge sets three sub-tasks of automatic glaucoma diagnosis and fundus structure analysis and provides an online evaluation framework. Based on the characteristics of multi-device and multi-quality data, some methods with strong generalizations are provided in the challenge to make the predictions more robust. This shows that REFUGE2 brings attention to the characteristics of real-world multi-domain data, bridging the gap between scientific research and clinical application., Comment: 29 pages, 21 figures

Unsupervised domain adaption has proven to be an effective approach for alleviating the intensive workload of manual annotation by aligning the synthetic source-domain data and the real-world target-domain samples. Unfortunately, mapping the target-domain distribution to the source-domain unconditionally may distort the essential structural information of the target-domain data. To this end, we firstly propose to introduce a novel multi-anchor based active learning strategy to assist domain adaptation regarding the semantic segmentation task. By innovatively adopting multiple anchors instead of a single centroid, the source domain can be better characterized as a multimodal distribution, thus more representative and complimentary samples are selected from the target domain. With little workload to manually annotate these active samples, the distortion of the target-domain distribution can be effectively alleviated, resulting in a large performance gain. The multi-anchor strategy is additionally employed to model the target-distribution. By regularizing the latent representation of the target samples compact around multiple anchors through a novel soft alignment loss, more precise segmentation can be achieved. Extensive experiments are conducted on public datasets to demonstrate that the proposed approach outperforms state-of-the-art methods significantly, along with thorough ablation study to verify the effectiveness of each component., Comment: ICCV 2021 Oral

Domain shift happens in cross-domain scenarios commonly because of the wide gaps between different domains: when applying a deep learning model well-trained in one domain to another target domain, the model usually performs poorly. To tackle this problem, unsupervised domain adaptation (UDA) techniques are proposed to bridge the gap between different domains, for the purpose of improving model performance without annotation in the target domain. Particularly, UDA has a great value for multimodal medical image analysis, where annotation difficulty is a practical concern. However, most existing UDA methods can only achieve satisfactory improvements in one adaptation direction (e.g., MRI to CT), but often perform poorly in the other (CT to MRI), limiting their practical usage. In this paper, we propose a bidirectional UDA (BiUDA) framework based on disentangled representation learning for equally competent two-way UDA performances. This framework employs a unified domain-aware pattern encoder which not only can adaptively encode images in different domains through a domain controller, but also improve model efficiency by eliminating redundant parameters. Furthermore, to avoid distortion of contents and patterns of input images during the adaptation process, a content-pattern consistency loss is introduced. Additionally, for better UDA segmentation performance, a label consistency strategy is proposed to provide extra supervision by recomposing target-domain-styled images and corresponding source-domain annotations. Comparison experiments and ablation studies conducted on two public datasets demonstrate the superiority of our BiUDA framework to current state-of-the-art UDA methods and the effectiveness of its novel designs. By successfully addressing two-way adaptations, our BiUDA framework offers a flexible solution of UDA techniques to the real-world scenario., Comment: IPMI 2021

Accuracy segmentation of brain structures could be helpful for glioma and radiotherapy planning. However, due to the visual and anatomical differences between different modalities, the accurate segmentation of brain structures becomes challenging. To address this problem, we first construct a residual block based U-shape network with a deep encoder and shallow decoder, which can trade off the framework performance and efficiency. Then, we introduce the Tversky loss to address the issue of the class imbalance between different foreground and the background classes. Finally, a model ensemble strategy is utilized to remove outliers and further boost performance.

Retinal artery/vein (A/V) classification lays the foundation for the quantitative analysis of retinal vessels, which is associated with potential risks of various cardiovascular and cerebral diseases. The topological connection relationship, which has been proved effective in improving the A/V classification performance for the conventional graph based method, has not been exploited by the deep learning based method. In this paper, we propose a Topology Ranking Generative Adversarial Network (TR-GAN) to improve the topology connectivity of the segmented arteries and veins, and further to boost the A/V classification performance. A topology ranking discriminator based on ordinal regression is proposed to rank the topological connectivity level of the ground-truth, the generated A/V mask and the intentionally shuffled mask. The ranking loss is further back-propagated to the generator to generate better connected A/V masks. In addition, a topology preserving module with triplet loss is also proposed to extract the high-level topological features and further to narrow the feature distance between the predicted A/V mask and the ground-truth. The proposed framework effectively increases the topological connectivity of the predicted A/V masks and achieves state-of-the-art A/V classification performance on the publicly available AV-DRIVE dataset.

Medical images are generally labeled by multiple experts before the final ground-truth labels are determined. Consensus or disagreement among experts regarding individual images reflects the gradeability and difficulty levels of the image. However, when being used for model training, only the final ground-truth label is utilized, while the critical information contained in the raw multi-rater gradings regarding the image being an easy/hard case is discarded. In this paper, we aim to take advantage of the raw multi-rater gradings to improve the deep learning model performance for the glaucoma classification task. Specifically, a multi-branch model structure is proposed to predict the most sensitive, most specifical and a balanced fused result for the input images. In order to encourage the sensitivity branch and specificity branch to generate consistent results for consensus labels and opposite results for disagreement labels, a consensus loss is proposed to constrain the output of the two branches. Meanwhile, the consistency/inconsistency between the prediction results of the two branches implies the image being an easy/hard case, which is further utilized to encourage the balanced fusion branch to concentrate more on the hard cases. Compared with models trained only with the final ground-truth labels, the proposed method using multi-rater consensus information has achieved superior performance, and it is also able to estimate the difficulty levels of individual input images when making the prediction.

Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness among Asian people. Early detection of PACG is essential, so as to provide timely treatment and minimize the vision loss. In the clinical practice, PACG is diagnosed by analyzing the angle between the cornea and iris with anterior segment optical coherence tomography (AS-OCT). The rapid development of deep learning technologies provides the feasibility of building a computer-aided system for the fast and accurate segmentation of cornea and iris tissues. However, the application of deep learning methods in the medical imaging field is still restricted by the lack of enough fully-annotated samples. In this paper, we propose a novel framework to segment the target tissues accurately for the AS-OCT images, by using the combination of weakly-annotated images (majority) and fully-annotated images (minority). The proposed framework consists of two models which provide reliable guidance for each other. In addition, uncertainty guided strategies are adopted to increase the accuracy and stability of the guidance. Detailed experiments on the publicly available AGE dataset demonstrate that the proposed framework outperforms the state-of-the-art semi-/weakly-supervised methods and has a comparable performance as the fully-supervised method. Therefore, the proposed method is demonstrated to be effective in exploiting information contained in the weakly-annotated images and has the capability to substantively relieve the annotation workload., Comment: MICCAI 2020

In deep learning era, pretrained models play an important role in medical image analysis, in which ImageNet pretraining has been widely adopted as the best way. However, it is undeniable that there exists an obvious domain gap between natural images and medical images. To bridge this gap, we propose a new pretraining method which learns from 700k radiographs given no manual annotations. We call our method as Comparing to Learn (C2L) because it learns robust features by comparing different image representations. To verify the effectiveness of C2L, we conduct comprehensive ablation studies and evaluate it on different tasks and datasets. The experimental results on radiographs show that C2L can outperform ImageNet pretraining and previous state-of-the-art approaches significantly. Code and models are available., Comment: MICCAI 2020 early accept; Code and pretrained models available at http://github.com/funnyzhou/C2L_MICCAI2020

Angle closure glaucoma (ACG) is a more aggressive disease than open-angle glaucoma, where the abnormal anatomical structures of the anterior chamber angle (ACA) may cause an elevated intraocular pressure and gradually lead to glaucomatous optic neuropathy and eventually to visual impairment and blindness. Anterior Segment Optical Coherence Tomography (AS-OCT) imaging provides a fast and contactless way to discriminate angle closure from open angle. Although many medical image analysis algorithms have been developed for glaucoma diagnosis, only a few studies have focused on AS-OCT imaging. In particular, there is no public AS-OCT dataset available for evaluating the existing methods in a uniform way, which limits progress in the development of automated techniques for angle closure detection and assessment. To address this, we organized the Angle closure Glaucoma Evaluation challenge (AGE), held in conjunction with MICCAI 2019. The AGE challenge consisted of two tasks: scleral spur localization and angle closure classification. For this challenge, we released a large dataset of 4800 annotated AS-OCT images from 199 patients, and also proposed an evaluation framework to benchmark and compare different models. During the AGE challenge, over 200 teams registered online, and more than 1100 results were submitted for online evaluation. Finally, eight teams participated in the onsite challenge. In this paper, we summarize these eight onsite challenge methods and analyze their corresponding results for the two tasks. We further discuss limitations and future directions. In the AGE challenge, the top-performing approach had an average Euclidean Distance of 10 pixels (10um) in scleral spur localization, while in the task of angle closure classification, all the algorithms achieved satisfactory performances, with two best obtaining an accuracy rate of 100%., Comment: Accepted to Medical Image Analysis (MedIA). AGE Challenge website at: https://age.grand-challenge.org

Segmentation of cardiac images, particularly late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) widely used for visualizing diseased cardiac structures, is a crucial first step for clinical diagnosis and treatment. However, direct segmentation of LGE-MRIs is challenging due to its attenuated contrast. Since most clinical studies have relied on manual and labor-intensive approaches, automatic methods are of high interest, particularly optimized machine learning approaches. To address this, we organized the "2018 Left Atrium Segmentation Challenge" using 154 3D LGE-MRIs, currently the world's largest cardiac LGE-MRI dataset, and associated labels of the left atrium segmented by three medical experts, ultimately attracting the participation of 27 international teams. In this paper, extensive analysis of the submitted algorithms using technical and biological metrics was performed by undergoing subgroup analysis and conducting hyper-parameter analysis, offering an overall picture of the major design choices of convolutional neural networks (CNNs) and practical considerations for achieving state-of-the-art left atrium segmentation. Results show the top method achieved a dice score of 93.2% and a mean surface to a surface distance of 0.7 mm, significantly outperforming prior state-of-the-art. Particularly, our analysis demonstrated that double, sequentially used CNNs, in which a first CNN is used for automatic region-of-interest localization and a subsequent CNN is used for refined regional segmentation, achieved far superior results than traditional methods and pipelines containing single CNNs. This large-scale benchmarking study makes a significant step towards much-improved segmentation methods for cardiac LGE-MRIs, and will serve as an important benchmark for evaluating and comparing the future works in the field.

Primary angle-closure disease (PACD) is a severe retinal disease, which might cause irreversible vision loss. In clinic, accurate identification of angle-closure and localization of the scleral spur's position on anterior segment optical coherence tomography (AS-OCT) is essential for the diagnosis of PACD. However, manual delineation might confine in low accuracy and low efficiency. In this paper, we propose an efficient and accurate end-to-end architecture for angle-closure classification and scleral spur localization. Specifically, we utilize a revised ResNet152 as our backbone to improve the accuracy of the angle-closure identification. For scleral spur localization, we adopt EfficientNet as encoder because of its powerful feature extraction potential. By combining the skip-connect module and pyramid pooling module, the network is able to collect semantic cues in feature maps from multiple dimensions and scales. Afterward, we propose a novel keypoint registration loss to constrain the model's attention to the intensity and location of the scleral spur area. Several experiments are extensively conducted to evaluate our method on the angle-closure glaucoma evaluation (AGE) Challenge dataset. The results show that our proposed architecture ranks the first place of the classification task on the test dataset and achieves the average Euclidean distance error of 12.00 pixels in the scleral spur localization task., Comment: The third place in angle-closure glaucoma evaluation (AGE) Challenge, MICCAI 2019

Automatic and accurate segmentation for retinal and choroidal layers of Optical Coherence Tomography (OCT) is crucial for detection of various ocular diseases. However, because of the variations in different equipments, OCT data obtained from different manufacturers might encounter appearance discrepancy, which could lead to performance fluctuation to a deep neural network. In this paper, we propose an uncertainty-guided domain alignment method to aim at alleviating this problem to transfer discriminative knowledge across distinct domains. We disign a novel uncertainty-guided cross-entropy loss for boosting the performance over areas with high uncertainty. An uncertainty-guided curriculum transfer strategy is developed for the self-training (ST), which regards uncertainty as efficient and effective guidance to optimize the learning process in target domain. Adversarial learning with feature recalibration module (FRM) is applied to transfer informative knowledge from the domain feature spaces adaptively. The experiments on two OCT datasets show that the proposed methods can obtain significant segmentation improvements compared with the baseline models.

Knowledge of whole heart anatomy is a prerequisite for many clinical applications. Whole heart segmentation (WHS), which delineates substructures of the heart, can be very valuable for modeling and analysis of the anatomy and functions of the heart. However, automating this segmentation can be arduous due to the large variation of the heart shape, and different image qualities of the clinical data. To achieve this goal, a set of training data is generally needed for constructing priors or for training. In addition, it is difficult to perform comparisons between different methods, largely due to differences in the datasets and evaluation metrics used. This manuscript presents the methodologies and evaluation results for the WHS algorithms selected from the submissions to the Multi-Modality Whole Heart Segmentation (MM-WHS) challenge, in conjunction with MICCAI 2017. The challenge provides 120 three-dimensional cardiac images covering the whole heart, including 60 CT and 60 MRI volumes, all acquired in clinical environments with manual delineation. Ten algorithms for CT data and eleven algorithms for MRI data, submitted from twelve groups, have been evaluated. The results show that many of the deep learning (DL) based methods achieved high accuracy, even though the number of training datasets was limited. A number of them also reported poor results in the blinded evaluation, probably due to overfitting in their training. The conventional algorithms, mainly based on multi-atlas segmentation, demonstrated robust and stable performance, even though the accuracy is not as good as the best DL method in CT segmentation. The challenge, including the provision of the annotated training data and the blinded evaluation for submitted algorithms on the test data, continues as an ongoing benchmarking resource via its homepage (\url{www.sdspeople.fudan.edu.cn/zhuangxiahai/0/mmwhs/})., Comment: 14 pages, 7 figures, sumitted to Medical Image Analysis

Accurately segmenting left atrium in MR volume can benefit the ablation procedure of atrial fibrillation. Traditional automated solutions often fail in relieving experts from the labor-intensive manual labeling. In this paper, we propose a deep neural network based solution for automated left atrium segmentation in gadolinium-enhanced MR volumes with promising performance. We firstly argue that, for this volumetric segmentation task, networks in 2D fashion can present great superiorities in time efficiency and segmentation accuracy than networks with 3D fashion. Considering the highly varying shape of atrium and the branchy structure of associated pulmonary veins, we propose to adopt a pyramid module to collect semantic cues in feature maps from multiple scales for fine-grained segmentation. Also, to promote our network in classifying the hard examples, we propose an Online Hard Negative Example Mining strategy to identify voxels in slices with low classification certainties and penalize the wrong predictions on them. Finally, we devise a competitive training scheme to further boost the generalization ability of networks. Extensively verified on 20 testing volumes, our proposed framework achieves an average Dice of 92.83% in segmenting the left atria and pulmonary veins., Comment: 9 pages, 4 figures. MICCAI Workshop on STACOM 2018