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Retinal fundus photography is significant in diagnosing and monitoring retinal diseases. However, systemic imperfections and operator/patient-related factors can hinder the acquisition of high-quality retinal images. Previous efforts in retinal image enhancement primarily relied on GANs, which are limited by the trade-off between training stability and output diversity. In contrast, the Schr\"odinger Bridge (SB), offers a more stable solution by utilizing Optimal Transport (OT) theory to model a stochastic differential equation (SDE) between two arbitrary distributions. This allows SB to effectively transform low-quality retinal images into their high-quality counterparts. In this work, we leverage the SB framework to propose an image-to-image translation pipeline for retinal image enhancement. Additionally, previous methods often fail to capture fine structural details, such as blood vessels. To address this, we enhance our pipeline by introducing Dynamic Snake Convolution, whose tortuous receptive field can better preserve tubular structures. We name the resulting retinal fundus image enhancement framework the Context-aware Unpaired Neural Schr\"{o}dinger Bridge (CUNSB-RFIE). To the best of our knowledge, this is the first endeavor to use the SB approach for retinal image enhancement. Experimental results on a large-scale dataset demonstrate the advantage of the proposed method compared to several state-of-the-art supervised and unsupervised methods in terms of image quality and performance on downstream tasks.The code is available at https://github.com/Retinal-Research/CUNSB-RFIE .

Convolutional neural networks are widely used in various segmentation tasks in medical images. However, they are challenged to learn global features adaptively due to the inherent locality of convolutional operations. In contrast, MLP Mixers are proposed as a backbone to learn global information across channels with low complexity. However, they cannot capture spatial features efficiently. Additionally, they lack effective mechanisms to fuse and mix features adaptively. To tackle these limitations, we propose a novel Dynamic Decomposed Mixer module. It is designed to employ novel Mixers to extract features and aggregate information across different spatial locations and channels. Additionally, it employs novel dynamic mixing mechanisms to model inter-dependencies between channel and spatial feature representations and to fuse them adaptively. Subsequently, we incorporate it into a U-shaped Transformer-based architecture to generate a novel network, termed the Dynamic Decomposed MLP Mixer. We evaluated it for medical image segmentation on two datasets, and it achieved superior segmentation performance than other state-of-the-art methods., Comment: 5 pages, 2 figures

Retinal fundus photography offers a non-invasive way to diagnose and monitor a variety of retinal diseases, but is prone to inherent quality glitches arising from systemic imperfections or operator/patient-related factors. However, high-quality retinal images are crucial for carrying out accurate diagnoses and automated analyses. The fundus image enhancement is typically formulated as a distribution alignment problem, by finding a one-to-one mapping between a low-quality image and its high-quality counterpart. This paper proposes a context-informed optimal transport (OT) learning framework for tackling unpaired fundus image enhancement. In contrast to standard generative image enhancement methods, which struggle with handling contextual information (e.g., over-tampered local structures and unwanted artifacts), the proposed context-aware OT learning paradigm better preserves local structures and minimizes unwanted artifacts. Leveraging deep contextual features, we derive the proposed context-aware OT using the earth mover's distance and show that the proposed context-OT has a solid theoretical guarantee. Experimental results on a large-scale dataset demonstrate the superiority of the proposed method over several state-of-the-art supervised and unsupervised methods in terms of signal-to-noise ratio, structural similarity index, as well as two downstream tasks. The code is available at \url{https://github.com/Retinal-Research/Contextual-OT}.

Survival analysis models time-to-event distributions with censorship. Recently, deep survival models using neural networks have dominated due to their representational power and state-of-the-art performance. However, their "black-box" nature hinders interpretability, which is crucial in real-world applications. In contrast, "white-box" tree-based survival models offer better interpretability but struggle to converge to global optima due to greedy expansion. In this paper, we bridge the gap between previous deep survival models and traditional tree-based survival models through deep rectified linear unit (ReLU) networks. We show that a deliberately constructed deep ReLU network (SurvReLU) can harness the interpretability of tree-based structures with the representational power of deep survival models. Empirical studies on both simulated and real survival benchmark datasets show the effectiveness of the proposed SurvReLU in terms of performance and interoperability. The code is available at \href{https://github.com/xs018/SurvReLU}{\color{magenta}{ https://github.com/xs018/SurvReLU}}.

Detecting retinal image analysis, particularly the geometrical features of branching points, plays an essential role in diagnosing eye diseases. However, existing methods used for this purpose often are coarse-level and lack fine-grained analysis for efficient annotation. To mitigate these issues, this paper proposes a novel method for detecting retinal branching angles using a self-configured image processing technique. Additionally, we offer an open-source annotation tool and a benchmark dataset comprising 40 images annotated with retinal branching angles. Our methodology for retinal branching angle detection and calculation is detailed, followed by a benchmark analysis comparing our method with previous approaches. The results indicate that our method is robust under various conditions with high accuracy and efficiency, which offers a valuable instrument for ophthalmic research and clinical applications.

Multiple instance learning (MIL) stands as a powerful approach in weakly supervised learning, regularly employed in histological whole slide image (WSI) classification for detecting tumorous lesions. However, existing mainstream MIL methods focus on modeling correlation between instances while overlooking the inherent diversity among instances. However, few MIL methods have aimed at diversity modeling, which empirically show inferior performance but with a high computational cost. To bridge this gap, we propose a novel MIL aggregation method based on diverse global representation (DGR-MIL), by modeling diversity among instances through a set of global vectors that serve as a summary of all instances. First, we turn the instance correlation into the similarity between instance embeddings and the predefined global vectors through a cross-attention mechanism. This stems from the fact that similar instance embeddings typically would result in a higher correlation with a certain global vector. Second, we propose two mechanisms to enforce the diversity among the global vectors to be more descriptive of the entire bag: (i) positive instance alignment and (ii) a novel, efficient, and theoretically guaranteed diversification learning paradigm. Specifically, the positive instance alignment module encourages the global vectors to align with the center of positive instances (e.g., instances containing tumors in WSI). To further diversify the global representations, we propose a novel diversification learning paradigm leveraging the determinantal point process. The proposed model outperforms the state-of-the-art MIL aggregation models by a substantial margin on the CAMELYON-16 and the TCGA-lung cancer datasets. The code is available at \url{https://github.com/ChongQingNoSubway/DGR-MIL}., Comment: Accepted to ECCV 2024

Since its introduction, UNet has been leading a variety of medical image segmentation tasks. Although numerous follow-up studies have also been dedicated to improving the performance of standard UNet, few have conducted in-depth analyses of the underlying interest pattern of UNet in medical image segmentation. In this paper, we explore the patterns learned in a UNet and observe two important factors that potentially affect its performance: (i) irrelative feature learned caused by asymmetric supervision; (ii) feature redundancy in the feature map. To this end, we propose to balance the supervision between encoder and decoder and reduce the redundant information in the UNet. Specifically, we use the feature map that contains the most semantic information (i.e., the last layer of the decoder) to provide additional supervision to other blocks to provide additional supervision and reduce feature redundancy by leveraging feature distillation. The proposed method can be easily integrated into existing UNet architecture in a plug-and-play fashion with negligible computational cost. The experimental results suggest that the proposed method consistently improves the performance of standard UNets on four medical image segmentation datasets. The code is available at \url{https://github.com/ChongQingNoSubway/SelfReg-UNet}, Comment: Accepted as a conference paper to 2024 MICCAI

Deep neural networks, including transformers and convolutional neural networks, have significantly improved multivariate time series classification (MTSC). However, these methods often rely on supervised learning, which does not fully account for the sparsity and locality of patterns in time series data (e.g., diseases-related anomalous points in ECG). To address this challenge, we formally reformulate MTSC as a weakly supervised problem, introducing a novel multiple-instance learning (MIL) framework for better localization of patterns of interest and modeling time dependencies within time series. Our novel approach, TimeMIL, formulates the temporal correlation and ordering within a time-aware MIL pooling, leveraging a tokenized transformer with a specialized learnable wavelet positional token. The proposed method surpassed 26 recent state-of-the-art methods, underscoring the effectiveness of the weakly supervised TimeMIL in MTSC. The code will be available at https://github.com/xiwenc1/TimeMIL., Comment: Accepted by ICML2024

Inverse imaging problems (IIPs) arise in various applications, with the main objective of reconstructing an image from its compressed measurements. This problem is often ill-posed for being under-determined with multiple interchangeably consistent solutions. The best solution inherently depends on prior knowledge or assumptions, such as the sparsity of the image. Furthermore, the reconstruction process for most IIPs relies significantly on the imaging (i.e. forward model) parameters, which might not be fully known, or the measurement device may undergo calibration drifts. These uncertainties in the forward model create substantial challenges, where inaccurate reconstructions usually happen when the postulated parameters of the forward model do not fully match the actual ones. In this work, we devoted to tackling accurate reconstruction under the context of a set of possible forward model parameters that exist. Here, we propose a novel Moment-Aggregation (MA) framework that is compatible with the popular IIP solution by using a neural network prior. Specifically, our method can reconstruct the signal by considering all candidate parameters of the forward model simultaneously during the update of the neural network. We theoretically demonstrate the convergence of the MA framework, which has a similar complexity with reconstruction under the known forward model parameters. Proof-of-concept experiments demonstrate that the proposed MA achieves performance comparable to the forward model with the known precise parameter in reconstruction across both compressive sensing and phase retrieval applications, with a PSNR gap of 0.17 to 1.94 over various datasets, including MNIST, X-ray, Glas, and MoNuseg. This highlights our method's significant potential in reconstruction under an uncertain forward model., Comment: Accepted by PBDL-CVPR 2024

In the past decades, deep neural networks, particularly convolutional neural networks, have achieved state-of-the-art performance in a variety of medical image segmentation tasks. Recently, the introduction of the vision transformer (ViT) has significantly altered the landscape of deep segmentation models. There has been a growing focus on ViTs, driven by their excellent performance and scalability. However, we argue that the current design of the vision transformer-based UNet (ViT-UNet) segmentation models may not effectively handle the heterogeneous appearance (e.g., varying shapes and sizes) of objects of interest in medical image segmentation tasks. To tackle this challenge, we present a structured approach to introduce spatially dynamic components to the ViT-UNet. This adaptation enables the model to effectively capture features of target objects with diverse appearances. This is achieved by three main components: \textbf{(i)} deformable patch embedding; \textbf{(ii)} spatially dynamic multi-head attention; \textbf{(iii)} deformable positional encoding. These components were integrated into a novel architecture, termed AgileFormer. AgileFormer is a spatially agile ViT-UNet designed for medical image segmentation. Experiments in three segmentation tasks using publicly available datasets demonstrated the effectiveness of the proposed method. The code is available at \href{https://github.com/sotiraslab/AgileFormer}{https://github.com/sotiraslab/AgileFormer}.

Hierarchical transformers have achieved significant success in medical image segmentation due to their large receptive field and capabilities of effectively leveraging global long-range contextual information. Convolutional neural networks (CNNs) can also deliver a large receptive field by using large kernels, enabling them to achieve competitive performance with fewer model parameters. However, CNNs incorporated with large convolutional kernels remain constrained in adaptively capturing multi-scale features from organs with large variations in shape and size due to the employment of fixed-sized kernels. Additionally, they are unable to utilize global contextual information efficiently. To address these limitations, we propose Dynamic Large Kernel (DLK) and Dynamic Feature Fusion (DFF) modules. The DLK module employs multiple large kernels with varying kernel sizes and dilation rates to capture multi-scale features. Subsequently, a dynamic selection mechanism is utilized to adaptively highlight the most important spatial features based on global information. Additionally, the DFF module is proposed to adaptively fuse multi-scale local feature maps based on their global information. We integrate DLK and DFF in a hierarchical transformer architecture to develop a novel architecture, termed D-Net. D-Net is able to effectively utilize a multi-scale large receptive field and adaptively harness global contextual information. Extensive experimental results demonstrate that D-Net outperforms other state-of-the-art models in the two volumetric segmentation tasks, including abdominal multi-organ segmentation and multi-modality brain tumor segmentation. Our code is available at https://github.com/sotiraslab/DLK., Comment: 12 pages, 4 figures, 2 tables

Multiple Instance Learning (MIL) has been widely used in weakly supervised whole slide image (WSI) classification. Typical MIL methods include a feature embedding part, which embeds the instances into features via a pre-trained feature extractor, and an MIL aggregator that combines instance embeddings into predictions. Most efforts have typically focused on improving these parts. This involves refining the feature embeddings through self-supervised pre-training as well as modeling the correlations between instances separately. In this paper, we proposed a sparsely coding MIL (SC-MIL) method that addresses those two aspects at the same time by leveraging sparse dictionary learning. The sparse dictionary learning captures the similarities of instances by expressing them as sparse linear combinations of atoms in an over-complete dictionary. In addition, imposing sparsity improves instance feature embeddings by suppressing irrelevant instances while retaining the most relevant ones. To make the conventional sparse coding algorithm compatible with deep learning, we unrolled it into a sparsely coded module leveraging deep unrolling. The proposed SC module can be incorporated into any existing MIL framework in a plug-and-play manner with an acceptable computational cost. The experimental results on multiple datasets demonstrated that the proposed SC module could substantially boost the performance of state-of-the-art MIL methods. The codes are available at \href{https://github.com/sotiraslab/SCMIL.git}{https://github.com/sotiraslab/SCMIL.git}.

Survival analysis is a statistical method employed to scrutinize the duration until a specific event of interest transpires, known as time-to-event information characterized by censorship. Recently, deep learning-based methods have dominated this field due to their representational capacity and state-of-the-art performance. However, the black-box nature of the deep neural network hinders its interpretability, which is desired in real-world survival applications but has been largely neglected by previous works. In contrast, conventional tree-based methods are advantageous with respect to interpretability, while consistently grappling with an inability to approximate the global optima due to greedy expansion. In this paper, we leverage the strengths of both neural networks and tree-based methods, capitalizing on their ability to approximate intricate functions while maintaining interpretability. To this end, we propose a Neural Survival Oblique Tree (NSOTree) for survival analysis. Specifically, the NSOTree was derived from the ReLU network and can be easily incorporated into existing survival models in a plug-and-play fashion. Evaluations on both simulated and real survival datasets demonstrated the effectiveness of the proposed method in terms of performance and interpretability., Comment: 12 pages

Multiple instance learning (MIL) was a weakly supervised learning approach that sought to assign binary class labels to collections of instances known as bags. However, due to their weak supervision nature, the MIL methods were susceptible to overfitting and required assistance in developing comprehensive representations of target instances. While regularization typically effectively combated overfitting, its integration with the MIL model has been frequently overlooked in prior studies. Meanwhile, current regularization methods for MIL have shown limitations in their capacity to uncover a diverse array of representations. In this study, we delve into the realm of regularization within the MIL model, presenting a novel approach in the form of a Progressive Dropout Layer (PDL). We aim to not only address overfitting but also empower the MIL model in uncovering intricate and impactful feature representations. The proposed method was orthogonal to existing MIL methods and could be easily integrated into them to boost performance. Our extensive evaluation across a range of MIL benchmark datasets demonstrated that the incorporation of the PDL into multiple MIL methods not only elevated their classification performance but also augmented their potential for weakly-supervised feature localizations., Comment: The code is available in https://github.com/ChongQingNoSubway/PDL

Over the past few decades, convolutional neural networks (CNNs) have been at the forefront of the detection and tracking of various retinal diseases (RD). Despite their success, the emergence of vision transformers (ViT) in the 2020s has shifted the trajectory of RD model development. The leading-edge performance of ViT-based models in RD can be largely credited to their scalability-their ability to improve as more parameters are added. As a result, ViT-based models tend to outshine traditional CNNs in RD applications, albeit at the cost of increased data and computational demands. ViTs also differ from CNNs in their approach to processing images, working with patches rather than local regions, which can complicate the precise localization of small, variably presented lesions in RD. In our study, we revisited and updated the architecture of a CNN model, specifically MobileNet, to enhance its utility in RD diagnostics. We found that an optimized MobileNet, through selective modifications, can surpass ViT-based models in various RD benchmarks, including diabetic retinopathy grading, detection of multiple fundus diseases, and classification of diabetic macular edema. The code is available at https://github.com/Retinal-Research/NN-MOBILENET, Comment: Accepted as a conference paper to 2024 CVPRW

Learning rich data representations from unlabeled data is a key challenge towards applying deep learning algorithms in downstream tasks. Several variants of variational autoencoders (VAEs) have been proposed to learn compact data representations by encoding high-dimensional data in a lower dimensional space. Two main classes of VAEs methods may be distinguished depending on the characteristics of the meta-priors that are enforced in the representation learning step. The first class of methods derives a continuous encoding by assuming a static prior distribution in the latent space. The second class of methods learns instead a discrete latent representation using vector quantization (VQ) along with a codebook. However, both classes of methods suffer from certain challenges, which may lead to suboptimal image reconstruction results. The first class suffers from posterior collapse, whereas the second class suffers from codebook collapse. To address these challenges, we introduce a new VAE variant, termed sparse coding-based VAE with learned ISTA (SC-VAE), which integrates sparse coding within variational autoencoder framework. The proposed method learns sparse data representations that consist of a linear combination of a small number of predetermined orthogonal atoms. The sparse coding problem is solved using a learnable version of the iterative shrinkage thresholding algorithm (ISTA). Experiments on two image datasets demonstrate that our model achieves improved image reconstruction results compared to state-of-the-art methods. Moreover, we demonstrate that the use of learned sparse code vectors allows us to perform downstream tasks like image generation and unsupervised image segmentation through clustering image patches., Comment: 21 pages, 23 figures, and 4 tables

Convolutional neural networks (CNN) have been broadly studied on images, videos, graphs, and triangular meshes. However, it has seldom been studied on tetrahedral meshes. Given the merits of using volumetric meshes in applications like brain image analysis, we introduce a novel interpretable graph CNN framework for the tetrahedral mesh structure. Inspired by ChebyNet, our model exploits the volumetric Laplace-Beltrami Operator (LBO) to define filters over commonly used graph Laplacian which lacks the Riemannian metric information of 3D manifolds. For pooling adaptation, we introduce new objective functions for localized minimum cuts in the Graclus algorithm based on the LBO. We employ a piece-wise constant approximation scheme that uses the clustering assignment matrix to estimate the LBO on sampled meshes after each pooling. Finally, adapting the Gradient-weighted Class Activation Mapping algorithm for tetrahedral meshes, we use the obtained heatmaps to visualize discovered regions-of-interest as biomarkers. We demonstrate the effectiveness of our model on cortical tetrahedral meshes from patients with Alzheimer's disease, as there is scientific evidence showing the correlation of cortical thickness to neurodegenerative disease progression. Our results show the superiority of our LBO-based convolution layer and adapted pooling over the conventionally used unitary cortical thickness, graph Laplacian, and point cloud representation., Comment: Accepted as a conference paper to Information Processing in Medical Imaging (IPMI 2023) conference

Non-mydriatic retinal color fundus photography (CFP) is widely available due to the advantage of not requiring pupillary dilation, however, is prone to poor quality due to operators, systemic imperfections, or patient-related causes. Optimal retinal image quality is mandated for accurate medical diagnoses and automated analyses. Herein, we leveraged the Optimal Transport (OT) theory to propose an unpaired image-to-image translation scheme for mapping low-quality retinal CFPs to high-quality counterparts. Furthermore, to improve the flexibility, robustness, and applicability of our image enhancement pipeline in the clinical practice, we generalized a state-of-the-art model-based image reconstruction method, regularization by denoising, by plugging in priors learned by our OT-guided image-to-image translation network. We named it as regularization by enhancing (RE). We validated the integrated framework, OTRE, on three publicly available retinal image datasets by assessing the quality after enhancement and their performance on various downstream tasks, including diabetic retinopathy grading, vessel segmentation, and diabetic lesion segmentation. The experimental results demonstrated the superiority of our proposed framework over some state-of-the-art unsupervised competitors and a state-of-the-art supervised method., Comment: Accepted as a conference paper to The 28th biennial international conference on Information Processing in Medical Imaging (IPMI 2023)

Real-world non-mydriatic retinal fundus photography is prone to artifacts, imperfections and low-quality when certain ocular or systemic co-morbidities exist. Artifacts may result in inaccuracy or ambiguity in clinical diagnoses. In this paper, we proposed a simple but effective end-to-end framework for enhancing poor-quality retinal fundus images. Leveraging the optimal transport theory, we proposed an unpaired image-to-image translation scheme for transporting low-quality images to their high-quality counterparts. We theoretically proved that a Generative Adversarial Networks (GAN) model with a generator and discriminator is sufficient for this task. Furthermore, to mitigate the inconsistency of information between the low-quality images and their enhancements, an information consistency mechanism was proposed to maximally maintain structural consistency (optical discs, blood vessels, lesions) between the source and enhanced domains. Extensive experiments were conducted on the EyeQ dataset to demonstrate the superiority of our proposed method perceptually and quantitatively., Comment: Accepted as a conference paper to 20th IEEE International Symposium on Biomedical Imaging(ISBI 2023)

Lesion appearance is a crucial clue for medical providers to distinguish referable diabetic retinopathy (rDR) from non-referable DR. Most existing large-scale DR datasets contain only image-level labels rather than pixel-based annotations. This motivates us to develop algorithms to classify rDR and segment lesions via image-level labels. This paper leverages self-supervised equivariant learning and attention-based multi-instance learning (MIL) to tackle this problem. MIL is an effective strategy to differentiate positive and negative instances, helping us discard background regions (negative instances) while localizing lesion regions (positive ones). However, MIL only provides coarse lesion localization and cannot distinguish lesions located across adjacent patches. Conversely, a self-supervised equivariant attention mechanism (SEAM) generates a segmentation-level class activation map (CAM) that can guide patch extraction of lesions more accurately. Our work aims at integrating both methods to improve rDR classification accuracy. We conduct extensive validation experiments on the Eyepacs dataset, achieving an area under the receiver operating characteristic curve (AU ROC) of 0.958, outperforming current state-of-the-art algorithms., Comment: 7 pages, 2 tables, 3 figures. 18th International Symposium on Medical Information Processing and Analysis