E2-MIL: An explainable and evidential multiple instance learning framework for whole slide image classification.

Multiple instance learning (MIL)-based methods have been widely adopted to process the whole slide image (WSI) in the field of computational pathology. Due to the sparse slide-level supervision, these methods usually lack good localization on the tumor regions, leading to poor interpretability. Moreover, they lack robust uncertainty estimation of prediction results, leading to poor reliability. To solve the above two limitations, we propose an explainable and evidential multiple instance learning (E2-MIL) framework for whole slide image classification. E2-MIL is mainly composed of three modules: a detail-aware attention distillation module (DAM), a structure-aware attention refined module (SRM), and an uncertainty-aware instance classifier (UIC). Specifically, DAM helps the global network locate more detail-aware positive instances by utilizing the complementary sub-bags to learn detailed attention knowledge from the local network. In addition, a masked self-guidance loss is also introduced to help bridge the gap between the slide-level labels and instance-level classification tasks. SRM generates a structure-aware attention map that locates the entire tumor region structure by effectively modeling the spatial relations between clustering instances. Moreover, UIC provides accurate instance-level classification results and robust predictive uncertainty estimation to improve the model reliability based on subjective logic theory. Extensive experiments on three large multi-center subtyping datasets demonstrate both slide-level and instance-level performance superiority of E2-MIL.

Say No to Freeloader: Protecting Intellectual Property of Your Deep Model.

Model intellectual property (IP) protection has attracted growing attention as science and technology advancements stem from human intellectual labor and computational expenses. Ensuring IP safety for trainers and owners is of utmost importance, particularly in domains where ownership verification and applicability authorization are required. A notable approach to safeguarding model IP involves proactively preventing the use of well-trained models of authorized domains from unauthorized domains. In this paper, we introduce a novel Compact Un-transferable Pyramid Isolation Domain (CUPI-Domain) which serves as a barrier against illegal transfers from authorized to unauthorized domains. Drawing inspiration from human transitive inference and learning abilities, the CUPI-Domain is designed to obstruct cross-domain transfers by emphasizing the distinctive style features of the authorized domain. This emphasis leads to failure in recognizing irrelevant private style features on unauthorized domains. To this end, we propose novel CUPI-Domain generators, which select features from both authorized and CUPI-Domain as anchors. Then, we fuse the style features and semantic features of these anchors to generate labeled and style-rich CUPI-Domain. Additionally, we design external Domain-Information Memory Banks (DIMB) for storing and updating labeled pyramid features to obtain stable domain class features and domain class-wise style features. Based on the proposed whole method, the novel style and discriminative loss functions are designed to effectively enhance the distinction in style and discriminative features between authorized and unauthorized domains, respectively. Moreover, we provide two solutions for utilizing CUPI-Domain based on whether the unauthorized domain is known: target-specified CUPI-Domain and target-free CUPI-Domain. By conducting comprehensive experiments on various public datasets, we validate the effectiveness of our proposed CUPI-Domain approach with different backbone models. The results highlight that our method offers an efficient model intellectual property protection solution.

Iterative feedback-based models for image and video polyp segmentation.

Accurate segmentation of polyps in colonoscopy images has gained significant attention in recent years, given its crucial role in automated colorectal cancer diagnosis. Many existing deep learning-based methods follow a one-stage processing pipeline, often involving feature fusion across different levels or utilizing boundary-related attention mechanisms. Drawing on the success of applying Iterative Feedback Units (IFU) in image polyp segmentation, this paper proposes FlowICBNet by extending the IFU to the domain of video polyp segmentation. By harnessing the unique capabilities of IFU to propagate and refine past segmentation results, our method proves effective in mitigating challenges linked to the inherent limitations of endoscopic imaging, notably the presence of frequent camera shake and frame defocusing. Furthermore, in FlowICBNet, we introduce two pivotal modules: Reference Frame Selection (RFS) and Flow Guided Warping (FGW). These modules play a crucial role in filtering and selecting the most suitable historical reference frames for the task at hand. The experimental results on a large video polyp segmentation dataset demonstrate that our method can significantly outperform state-of-the-art methods by notable margins achieving an average metrics improvement of 7.5% on SUN-SEG-Easy and 7.4% on SUN-SEG-Hard. Our code is available at https://github.com/eraserNut/ICBNet.

Bilateral Supervision Network for Semi-Supervised Medical Image Segmentation.

Massive high-quality annotated data is required by fully-supervised learning, which is difficult to obtain for image segmentation since the pixel-level annotation is expensive, especially for medical image segmentation tasks that need domain knowledge. As an alternative solution, semi-supervised learning (SSL) can effectively alleviate the dependence on the annotated samples by leveraging abundant unlabeled samples. Among the SSL methods, mean-teacher (MT) is the most popular one. However, in MT, teacher model's weights are completely determined by student model's weights, which will lead to the training bottleneck at the late training stages. Besides, only pixel-wise consistency is applied for unlabeled data, which ignores the category information and is susceptible to noise. In this paper, we propose a bilateral supervision network with bilateral exponential moving average (bilateral-EMA), named BSNet to overcome these issues. On the one hand, both the student and teacher models are trained on labeled data, and then their weights are updated with the bilateral-EMA, and thus the two models can learn from each other. On the other hand, pseudo labels are used to perform bilateral supervision for unlabeled data. Moreover, for enhancing the supervision, we adopt adversarial learning to enforce the network generate more reliable pseudo labels for unlabeled data. We conduct extensive experiments on three datasets to evaluate the proposed BSNet, and results show that BSNet can improve the semi-supervised segmentation performance by a large margin and surpass other state-of-the-art SSL methods.

Orthogonal Subspace Representation for Generative Adversarial Networks.

Disentanglement learning aims to separate explanatory factors of variation so that different attributes of the data can be well characterized and isolated, which promotes efficient inference for downstream tasks. Mainstream disentanglement approaches based on generative adversarial networks (GANs) learn interpretable data representation. However, most typical GAN-based works lack the discussion of the latent subspace, causing insufficient consideration of the variation of independent factors. Although some recent research analyzes the latent space on pretrained GANs for image editing, they do not emphasize learning representation directly from the subspace perspective. Appropriate subspace properties could facilitate corresponding feature representation learning to satisfy the independent variation requirements of the obtained explanatory factors, which is crucial for better disentanglement. In this work, we propose a unified framework for ensuring disentanglement, which fully investigates latent subspace learning (SL) in GAN. The novel GAN-based architecture explores orthogonal subspace representation (OSR) on vanilla GAN, named OSRGAN. To guide a subspace with strong correlation, less redundancy, and robust distinguishability, our OSR includes three stages, self-latent-aware, orthogonal subspace-aware, and structure representation-aware, respectively. First, the self-latent-aware stage promotes the latent subspace strongly correlated with the data space to discover interpretable factors, but with poor independence of variation. Second, the following orthogonal subspace-aware stage adaptively learns some 1-D linear subspace spanned by a set of orthogonal bases in the latent space. There is less redundancy between them, expressing the corresponding independence. Third, the structure representation-aware stage aligns the projection on the orthogonal subspace and the latent variables. Accordingly, feature representation in each linear subspace can be distinguishable, enhancing the independent expression of interpretable factors. In addition, we design an alternating optimization step, achieving a tradeoff training of OSRGAN on different properties. Despite it strictly constrains orthogonality, the loss weight coefficient of distinguishability induced by orthogonality could be adjusted and balanced with correlation constraint. To elucidate, this tradeoff training prevents our OSRGAN from overemphasizing any property and damaging the expressiveness of the feature representation. It takes into account both interpretable factors and their independent variation characteristics. Meanwhile, alternating optimization could keep the cost and efficiency of forward inference unchanged and will not burden the computational complexity. In theory, we clarify the significance of OSR, which brings better independence of factors, along with interpretability as correlation could converge to a high range faster. Moreover, through the convergence behavior analysis, including the objective functions under different constraints and the evaluation curve with iterations, our model demonstrates enhanced stability and definitely converges toward a higher peak for disentanglement. To depict the performance in downstream tasks, we compared the state-of-the-art GAN-based and even VAE-based approaches on different datasets. Our OSRGAN achieves higher disentanglement scores on FactorVAE, SAP, MIG, and VP metrics. All the experimental results illustrate that our novel GAN-based framework has considerable advantages on disentanglement.

Reliable segmentation of multiple lesions from medical images.

BACKGROUND: Focusing on the complicated pathological features, such as blurred boundaries, severe scale differences between symptoms, and background noise interference, we aim to enhance the reliability of multiple lesions joint segmentation from medical images. PURPOSE: Propose a novel reliable multi-scale wavelet-enhanced transformer network, which can provide accurate segmentation results with reliability assessment. METHODS: Focusing on enhancing the model's capability to capture intricate pathological features in medical images, this work introduces a novel segmentation backbone. The backbone integrates a wavelet-enhanced feature extractor network and incorporates a multi-scale transformer module developed within the scope of this work. Simultaneously, to enhance the reliability of segmentation outcomes, a novel uncertainty segmentation head is proposed. This segmentation head is rooted in the SL, contributing to the generation of final segmentation results along with an associated overall uncertainty evaluation score map. RESULTS: Comprehensive experiments are conducted on the public database of AI-Challenge 2018 for retinal edema lesions segmentation and the segmentation of Thoracic Organs at Risk in CT images. The experimental results highlight the superior segmentation accuracy and heightened reliability achieved by the proposed method in comparison to other state-of-the-art segmentation approaches. CONCLUSIONS: Unlike previous segmentation methods, the proposed approach can produce reliable segmentation results with an estimated uncertainty and higher accuracy, enhancing the overall reliability of the model. The code will be release on https://github.com/LooKing9218/ReMultiSeg.

Instrument-Tissue Interaction Detection Framework for Surgical Video Understanding.

Instrument-tissue interaction detection task, which helps understand surgical activities, is vital for constructing computer-assisted surgery systems but with many challenges. Firstly, most models represent instrument-tissue interaction in a coarse-grained way which only focuses on classification and lacks the ability to automatically detect instruments and tissues. Secondly, existing works do not fully consider relations between intra- and inter-frame of instruments and tissues. In the paper, we propose to represent instrument-tissue interaction as 〈 instrument class, instrument bounding box, tissue class, tissue bounding box, action class 〉 quintuple and present an Instrument-Tissue Interaction Detection Network (ITIDNet) to detect the quintuple for surgery videos understanding. Specifically, we propose a Snippet Consecutive Feature (SCF) Layer to enhance features by modeling relationships of proposals in the current frame using global context information in the video snippet. We also propose a Spatial Corresponding Attention (SCA) Layer to incorporate features of proposals between adjacent frames through spatial encoding. To reason relationships between instruments and tissues, a Temporal Graph (TG) Layer is proposed with intra-frame connections to exploit relationships between instruments and tissues in the same frame and inter-frame connections to model the temporal information for the same instance. For evaluation, we build a cataract surgery video (PhacoQ) dataset and a cholecystectomy surgery video (CholecQ) dataset. Experimental results demonstrate the promising performance of our model, which outperforms other state-of-the-art models on both datasets.

Exploring Separable Attention for Multi-Contrast MR Image Super-Resolution.

Super-resolving the magnetic resonance (MR) image of a target contrast under the guidance of the corresponding auxiliary contrast, which provides additional anatomical information, is a new and effective solution for fast MR imaging. However, current multi-contrast super-resolution (SR) methods tend to concatenate different contrasts directly, ignoring their relationships in different clues, e.g., in the high-and low-intensity regions. In this study, we propose a separable attention network (comprising high-intensity priority (HP) attention and low-intensity separation (LS) attention), named SANet. Our SANet could explore the areas of high-and low-intensity regions in the "forward" and "reverse" directions with the help of the auxiliary contrast while learning clearer anatomical structure and edge information for the SR of a target-contrast MR image. SANet provides three appealing benefits: First, it is the first model to explore a separable attention mechanism that uses the auxiliary contrast to predict the high-and low-intensity regions, diverting more attention to refining any uncertain details between these regions and correcting the fine areas in the reconstructed results. Second, a multistage integration module is proposed to learn the response of multi-contrast fusion at multiple stages, get the dependency between the fused representations, and boost their representation ability. Third, extensive experiments with various state-of-the-art multi-contrast SR methods on fastMRI and clinical in vivo datasets demonstrate the superiority of our model. The code is released at https://github.com/chunmeifeng/SANet.

EM-Trans: Edge-Aware Multimodal Transformer for RGB-D Salient Object Detection.

RGB-D salient object detection (SOD) has gained tremendous attention in recent years. In particular, transformer has been employed and shown great potential. However, existing transformer models usually overlook the vital edge information, which is a major issue restricting the further improvement of SOD accuracy. To this end, we propose a novel edge-aware RGB-D SOD transformer, called, which explicitly models the edge information in a dual-band decomposition framework. Specifically, we employ two parallel decoder networks to learn the high-frequency edge and low-frequency body features from the low-and high-level features extracted from a two-steam multimodal backbone network, respectively. Next, we propose a cross-attention complementarity exploration module to enrich the edge/body features by exploiting the multimodal complementarity information. The refined features are then fed into our proposed color-hint guided fusion module for enhancing the depth feature and fusing the multimodal features. Finally, the resulting features are fused using our deeply supervised progressive fusion module, which progressively integrates edge and body features for predicting saliency maps. Our model explicitly considers the edge information for accurate RGB-D SOD, overcoming the limitations of existing methods and effectively improving the performance. Extensive experiments on benchmark datasets demonstrate that is an effective RGB-D SOD framework that outperforms the current state-of-the-art models, both quantitatively and qualitatively. A further extension to RGB-T SOD demonstrates the promising potential of our model in various kinds of multimodal SOD tasks.

Diverse Data Generation for Retinal Layer Segmentation with Potential Structure Modelling.

Accurate retinal layer segmentation on optical coherence tomography (OCT) images is hampered by the challenges of collecting OCT images with diverse pathological characterization and balanced distribution. Current generative models can produce high-realistic images and corresponding labels without quantitative limitations by fitting distributions of real collected data. Nevertheless, the diversity of their generated data is still limited due to the inherent imbalance of training data. To address these issues, we propose an image-label pair generation framework that generates diverse and balanced potential data from imbalanced real samples. Specifically, the framework first generates diverse layer masks, and then generates plausible OCT images corresponding to these layer masks using two customized diffusion probabilistic models respectively. To learn from imbalanced data and facilitate balanced generation, we introduce pathological-related conditions to guide the generation processes. To enhance the diversity of the generated image-label pairs, we propose a potential structure modeling technique that transfers the knowledge of diverse sub-structures from lowly- or non-pathological samples to highly pathological samples. We conducted extensive experiments on two public datasets for retinal layer segmentation. Firstly, our method generates OCT images with higher image quality and diversity compared to other generative methods. Furthermore, based on the extensive training with the generated OCT images, downstream retinal layer segmentation tasks demonstrate improved results. The code is publicly available at: https://github.com/nicetomeetu21/GenPSM.

Edge-Guided Contrastive Adaptation Network for Arteriovenous Nicking Classification Using Synthetic Data.

Retinal arteriovenous nicking (AVN) manifests as a reduced venular caliber of an arteriovenous crossing. AVNs are signs of many systemic, particularly cardiovascular diseases. Studies have shown that people with AVN are twice as likely to have a stroke. However, AVN classification faces two challenges. One is the lack of data, especially AVNs compared to the normal arteriovenous (AV) crossings. The other is the significant intra-class variations and minute inter-class differences. AVNs may look different in shape, scale, pose, and color. On the other hand, the AVN could be different from the normal AV crossing only by slight thinning of the vein. To address these challenges, first, we develop a data synthesis method to generate AV crossings, including normal and AVNs. Second, to mitigate the domain shift between the synthetic and real data, an edge-guided unsupervised domain adaptation network is designed to guide the transfer of domain invariant information. Third, a semantic contrastive learning branch (SCLB) is introduced and a set of semantically related images, as a semantic triplet, are input to the network simultaneously to guide the network to focus on the subtle differences in venular width and to ignore the differences in appearance. These strategies effectively mitigate the lack of data, domain shift between synthetic and real data, and significant intra- but minute inter-class differences. Extensive experiments have been performed to demonstrate the outstanding performance of the proposed method.

Enhancing and Adapting in the Clinic: Source-Free Unsupervised Domain Adaptation for Medical Image Enhancement.

Medical imaging provides many valuable clues involving anatomical structure and pathological characteristics. However, image degradation is a common issue in clinical practice, which can adversely impact the observation and diagnosis by physicians and algorithms. Although extensive enhancement models have been developed, these models require a well pre-training before deployment, while failing to take advantage of the potential value of inference data after deployment. In this paper, we raise an algorithm for source-free unsupervised domain adaptive medical image enhancement (SAME), which adapts and optimizes enhancement models using test data in the inference phase. A structure-preserving enhancement network is first constructed to learn a robust source model from synthesized training data. Then a teacher-student model is initialized with the source model and conducts source-free unsupervised domain adaptation (SFUDA) by knowledge distillation with the test data. Additionally, a pseudo-label picker is developed to boost the knowledge distillation of enhancement tasks. Experiments were implemented on ten datasets from three medical image modalities to validate the advantage of the proposed algorithm, and setting analysis and ablation studies were also carried out to interpret the effectiveness of SAME. The remarkable enhancement performance and benefits for downstream tasks demonstrate the potential and generalizability of SAME. The code is available at https://github.com/liamheng/Annotation-free-Medical-Image-Enhancement.

MR2-Net: Retinal OCTA Image Stitching via Multi-Scale Representation Learning and Dynamic Location Guidance.

Optical coherence tomography angiography (OCTA) plays a crucial role in quantifying and analyzing retinal vascular diseases. However, the limited field of view (FOV) inherent in most commercial OCTA imaging systems poses a significant challenge for clinicians, restricting the possibility to analyze larger retinal regions of high resolution. Automatic stitching of OCTA scans in adjacent regions may provide a promising solution to extend the region of interest. However, commonly-used stitching algorithms face difficulties in achieving effective alignment due to noise, artifacts and dense vasculature present in OCTA images. To address these challenges, we propose a novel retinal OCTA image stitching network, named MR2-Net, which integrates multi-scale representation learning and dynamic location guidance. In the first stage, an image registration network with a progressive multi-resolution feature fusion is proposed to derive deep semantic information effectively. Additionally, we introduce a dynamic guidance strategy to locate the foveal avascular zone (FAZ) and constrain registration errors in overlapping vascular regions. In the second stage, an image fusion network based on multiple mask constraints and adjacent image aggregation (AIA) strategies is developed to further eliminate the artifacts in the overlapping areas of stitched images, thereby achieving precise vessel alignment. To validate the effectiveness of our method, we conduct a series of experiments on two delicately constructed datasets, i.e., OPTOVUE-OCTA and SVision-OCTA. Experimental results demonstrate that our method outperforms other image stitching methods and effectively generates high-quality wide-field OCTA images, achieving a structural similarity index (SSIM) score of 0.8264 and 0.8014 on the two datasets, respectively.

Open Fundus Photograph Dataset with Pathologic Myopia Recognition and Anatomical Structure Annotation.

Pathologic myopia (PM) is a common blinding retinal degeneration suffered by highly myopic population. Early screening of this condition can reduce the damage caused by the associated fundus lesions and therefore prevent vision loss. Automated diagnostic tools based on artificial intelligence methods can benefit this process by aiding clinicians to identify disease signs or to screen mass populations using color fundus photographs as inputs. This paper provides insights about PALM, our open fundus imaging dataset for pathological myopia recognition and anatomical structure annotation. Our databases comprises 1200 images with associated labels for the pathologic myopia category and manual annotations of the optic disc, the position of the fovea and delineations of lesions such as patchy retinal atrophy (including peripapillary atrophy) and retinal detachment. In addition, this paper elaborates on other details such as the labeling process used to construct the database, the quality and characteristics of the samples and provides other relevant usage notes.

Confidence-aware multi-modality learning for eye disease screening.

Multi-modal ophthalmic image classification plays a key role in diagnosing eye diseases, as it integrates information from different sources to complement their respective performances. However, recent improvements have mainly focused on accuracy, often neglecting the importance of confidence and robustness in predictions for diverse modalities. In this study, we propose a novel multi-modality evidential fusion pipeline for eye disease screening. It provides a measure of confidence for each modality and elegantly integrates the multi-modality information using a multi-distribution fusion perspective. Specifically, our method first utilizes normal inverse gamma prior distributions over pre-trained models to learn both aleatoric and epistemic uncertainty for uni-modality. Then, the normal inverse gamma distribution is analyzed as the Student's t distribution. Furthermore, within a confidence-aware fusion framework, we propose a mixture of Student's t distributions to effectively integrate different modalities, imparting the model with heavy-tailed properties and enhancing its robustness and reliability. More importantly, the confidence-aware multi-modality ranking regularization term induces the model to more reasonably rank the noisy single-modal and fused-modal confidence, leading to improved reliability and accuracy. Experimental results on both public and internal datasets demonstrate that our model excels in robustness, particularly in challenging scenarios involving Gaussian noise and modality missing conditions. Moreover, our model exhibits strong generalization capabilities to out-of-distribution data, underscoring its potential as a promising solution for multimodal eye disease screening.

Structure and Intensity Unbiased Translation for 2D Medical Image Segmentation.

Data distribution gaps often pose significant challenges to the use of deep segmentation models. However, retraining models for each distribution is expensive and time-consuming. In clinical contexts, device-embedded algorithms and networks, typically unretrainable and unaccessable post-manufacture, exacerbate this issue. Generative translation methods offer a solution to mitigate the gap by transferring data across domains. However, existing methods mainly focus on intensity distributions while ignoring the gaps due to structure disparities. In this paper, we formulate a new image-to-image translation task to reduce structural gaps. We propose a simple, yet powerful Structure-Unbiased Adversarial (SUA) network which accounts for both intensity and structural differences between the training and test sets for segmentation. It consists of a spatial transformation block followed by an intensity distribution rendering module. The spatial transformation block is proposed to reduce the structural gaps between the two images. The intensity distribution rendering module then renders the deformed structure to an image with the target intensity distribution. Experimental results show that the proposed SUA method has the capability to transfer both intensity distribution and structural content between multiple pairs of datasets and is superior to prior arts in closing the gaps for improving segmentation.

Deep segmentation of OCTA for evaluation and association of changes of retinal microvasculature with Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Optical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature and is suggested as a potential tool in the early detection of retinal microvascular changes in Alzheimer's Disease (AD). We developed a standardised OCTA analysis framework and compared their extracted parameters among controls and AD/mild cognitive impairment (MCI) in a cross-section study. METHODS: We defined and extracted geometrical parameters of retinal microvasculature at different retinal layers and in the foveal avascular zone (FAZ) from segmented OCTA images obtained using well-validated state-of-the-art deep learning models. We studied these parameters in 158 subjects (62 healthy control, 55 AD and 41 MCI) using logistic regression to determine their potential in predicting the status of our subjects. RESULTS: In the AD group, there was a significant decrease in vessel area and length densities in the inner vascular complexes (IVC) compared with controls. The number of vascular bifurcations in AD is also significantly lower than that of healthy people. The MCI group demonstrated a decrease in vascular area, length densities, vascular fractal dimension and the number of bifurcations in both the superficial vascular complexes (SVC) and the IVC compared with controls. A larger vascular tortuosity in the IVC, and a larger roundness of FAZ in the SVC, can also be observed in MCI compared with controls. CONCLUSION: Our study demonstrates the applicability of OCTA for the diagnosis of AD and MCI, and provides a standard tool for future clinical service and research. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of AD and MCI.

Unsupervised spatially embedded deep representation of spatial transcriptomics.

Optimal integration of transcriptomics data and associated spatial information is essential towards fully exploiting spatial transcriptomics to dissect tissue heterogeneity and map out inter-cellular communications. We present SEDR, which uses a deep autoencoder coupled with a masked self-supervised learning mechanism to construct a low-dimensional latent representation of gene expression, which is then simultaneously embedded with the corresponding spatial information through a variational graph autoencoder. SEDR achieved higher clustering performance on manually annotated 10 × Visium datasets and better scalability on high-resolution spatial transcriptomics datasets than existing methods. Additionally, we show SEDR's ability to impute and denoise gene expression (URL: https://github.com/JinmiaoChenLab/SEDR/ ).

Geometric Correspondence-Based Multimodal Learning for Ophthalmic Image Analysis.

Color fundus photography (CFP) and Optical coherence tomography (OCT) images are two of the most widely used modalities in the clinical diagnosis and management of retinal diseases. Despite the widespread use of multimodal imaging in clinical practice, few methods for automated diagnosis of eye diseases utilize correlated and complementary information from multiple modalities effectively. This paper explores how to leverage the information from CFP and OCT images to improve the automated diagnosis of retinal diseases. We propose a novel multimodal learning method, named geometric correspondence-based multimodal learning network (GeCoM-Net), to achieve the fusion of CFP and OCT images. Specifically, inspired by clinical observations, we consider the geometric correspondence between the OCT slice and the CFP region to learn the correlated features of the two modalities for robust fusion. Furthermore, we design a new feature selection strategy to extract discriminative OCT representations by automatically selecting the important feature maps from OCT slices. Unlike the existing multimodal learning methods, GeCoM-Net is the first method that formulates the geometric relationships between the OCT slice and the corresponding region of the CFP image explicitly for CFP and OCT fusion. Experiments have been conducted on a large-scale private dataset and a publicly available dataset to evaluate the effectiveness of GeCoM-Net for diagnosing diabetic macular edema (DME), impaired visual acuity (VA) and glaucoma. The empirical results show that our method outperforms the current state-of-the-art multimodal learning methods by improving the AUROC score 0.4%, 1.9% and 2.9% for DME, VA and glaucoma detection, respectively.

Crystalline lens nuclear age prediction as a new biomarker of nucleus degeneration.

BACKGROUND: The crystalline lens is a transparent structure of the eye to focus light on the retina. It becomes muddy, hard and dense with increasing age, which makes the crystalline lens gradually lose its function. We aim to develop a nuclear age predictor to reflect the degeneration of the crystalline lens nucleus. METHODS: First we trained and internally validated the nuclear age predictor with a deep-learning algorithm, using 12 904 anterior segment optical coherence tomography (AS-OCT) images from four diverse Asian and American cohorts: Zhongshan Ophthalmic Center with Machine0 (ZOM0), Tomey Corporation (TOMEY), University of California San Francisco and the Chinese University of Hong Kong. External testing was done on three independent datasets: Tokyo University (TU), ZOM1 and Shenzhen People's Hospital (SPH). We also demonstrate the possibility of detecting nuclear cataracts (NCs) from the nuclear age gap. FINDINGS: In the internal validation dataset, the nuclear age could be predicted with a mean absolute error (MAE) of 2.570 years (95% CI 1.886 to 2.863). Across the three external testing datasets, the algorithm achieved MAEs of 4.261 years (95% CI 3.391 to 5.094) in TU, 3.920 years (95% CI 3.332 to 4.637) in ZOM1-NonCata and 4.380 years (95% CI 3.730 to 5.061) in SPH-NonCata. The MAEs for NC eyes were 8.490 years (95% CI 7.219 to 9.766) in ZOM1-NC and 9.998 years (95% CI 5.673 to 14.642) in SPH-NC. The nuclear age gap outperformed both ophthalmologists in detecting NCs, with areas under the receiver operating characteristic curves of 0.853 years (95% CI 0.787 to 0.917) in ZOM1 and 0.909 years (95% CI 0.828 to 0.978) in SPH. INTERPRETATION: The nuclear age predictor shows good performance, validating the feasibility of using AS-OCT images as an effective screening tool for nucleus degeneration. Our work also demonstrates the potential use of the nuclear age gap to detect NCs.