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Deep learning has shown remarkable performance in medical image segmentation. However, despite its promise, deep learning has many challenges in practice due to its inability to effectively transition to unseen domains, caused by the inherent data distribution shift and the lack of manual annotations to guide domain adaptation. To tackle this problem, we present an unsupervised domain adaptation (UDA) method named AdaptDiff that enables a retinal vessel segmentation network trained on fundus photography (FP) to produce satisfactory results on unseen modalities (e.g., OCT-A) without any manual labels. For all our target domains, we first adopt a segmentation model trained on the source domain to create pseudo-labels. With these pseudo-labels, we train a conditional semantic diffusion probabilistic model to represent the target domain distribution. Experimentally, we show that even with low quality pseudo-labels, the diffusion model can still capture the conditional semantic information. Subsequently, we sample on the target domain with binary vessel masks from the source domain to get paired data, i.e., target domain synthetic images conditioned on the binary vessel map. Finally, we fine-tune the pre-trained segmentation network using the synthetic paired data to mitigate the domain gap. We assess the effectiveness of AdaptDiff on seven publicly available datasets across three distinct modalities. Our results demonstrate a significant improvement in segmentation performance across all unseen datasets. Our code is publicly available at https://github.com/DeweiHu/AdaptDiff.

We propose a novel framework for retinal feature point alignment, designed for learning cross-modality features to enhance matching and registration across multi-modality retinal images. Our model draws on the success of previous learning-based feature detection and description methods. To better leverage unlabeled data and constrain the model to reproduce relevant keypoints, we integrate a keypoint-based segmentation task. It is trained in a self-supervised manner by enforcing segmentation consistency between different augmentations of the same image. By incorporating a keypoint augmented self-supervised layer, we achieve robust feature extraction across modalities. Extensive evaluation on two public datasets and one in-house dataset demonstrates significant improvements in performance for modality-agnostic retinal feature alignment. Our code and model weights are publicly available at \url{https://github.com/MedICL-VU/RetinaIPA}.

In this paper, we present PRISM, a Promptable and Robust Interactive Segmentation Model, aiming for precise segmentation of 3D medical images. PRISM accepts various visual inputs, including points, boxes, and scribbles as sparse prompts, as well as masks as dense prompts. Specifically, PRISM is designed with four principles to achieve robustness: (1) Iterative learning. The model produces segmentations by using visual prompts from previous iterations to achieve progressive improvement. (2) Confidence learning. PRISM employs multiple segmentation heads per input image, each generating a continuous map and a confidence score to optimize predictions. (3) Corrective learning. Following each segmentation iteration, PRISM employs a shallow corrective refinement network to reassign mislabeled voxels. (4) Hybrid design. PRISM integrates hybrid encoders to better capture both the local and global information. Comprehensive validation of PRISM is conducted using four public datasets for tumor segmentation in the colon, pancreas, liver, and kidney, highlighting challenges caused by anatomical variations and ambiguous boundaries in accurate tumor identification. Compared to state-of-the-art methods, both with and without prompt engineering, PRISM significantly improves performance, achieving results that are close to human levels. The code is publicly available at https://github.com/MedICL-VU/PRISM.

High-resolution Optical Coherence Tomography (OCT) images are crucial for ophthalmology studies but are limited by their relatively narrow field of view (FoV). Image mosaicking is a technique for aligning multiple overlapping images to obtain a larger FoV. Current mosaicking pipelines often struggle with substantial noise and considerable displacement between the input sub-fields. In this paper, we propose a versatile pipeline for stitching multi-view OCT/OCTA \textit{en face} projection images. Our method combines the strengths of learning-based feature matching and robust pixel-based registration to align multiple images effectively. Furthermore, we advance the application of a trained foundational model, Segment Anything Model (SAM), to validate mosaicking results in an unsupervised manner. The efficacy of our pipeline is validated using an in-house dataset and a large public dataset, where our method shows superior performance in terms of both accuracy and computational efficiency. We also made our evaluation tool for image mosaicking and the corresponding pipeline publicly available at \url{https://github.com/MedICL-VU/OCT-mosaicking}., Comment: ISBI 2024 Oral

Interactive segmentation model leverages prompts from users to produce robust segmentation. This advancement is facilitated by prompt engineering, where interactive prompts serve as strong priors during test-time. However, this is an inherently subjective and hard-to-reproduce process. The variability in user expertise and inherently ambiguous boundaries in medical images can lead to inconsistent prompt selections, potentially affecting segmentation accuracy. This issue has not yet been extensively explored for medical imaging. In this paper, we assess the test-time variability for interactive medical image segmentation with diverse point prompts. For a given target region, the point is classified into three sub-regions: boundary, margin, and center. Our goal is to identify a straightforward and efficient approach for optimal prompt selection during test-time based on three considerations: (1) benefits of additional prompts, (2) effects of prompt placement, and (3) strategies for optimal prompt selection. We conduct extensive experiments on the public Medical Segmentation Decathlon dataset for challenging colon tumor segmentation task. We suggest an optimal strategy for prompt selection during test-time, supported by comprehensive results. The code is publicly available at https://github.com/MedICL-VU/variability

To address prevalent issues in medical imaging, such as data acquisition challenges and label availability, transfer learning from natural to medical image domains serves as a viable strategy to produce reliable segmentation results. However, several existing barriers between domains need to be broken down, including addressing contrast discrepancies, managing anatomical variability, and adapting 2D pretrained models for 3D segmentation tasks. In this paper, we propose ProMISe,a prompt-driven 3D medical image segmentation model using only a single point prompt to leverage knowledge from a pretrained 2D image foundation model. In particular, we use the pretrained vision transformer from the Segment Anything Model (SAM) and integrate lightweight adapters to extract depth-related (3D) spatial context without updating the pretrained weights. For robust results, a hybrid network with complementary encoders is designed, and a boundary-aware loss is proposed to achieve precise boundaries. We evaluate our model on two public datasets for colon and pancreas tumor segmentations, respectively. Compared to the state-of-the-art segmentation methods with and without prompt engineering, our proposed method achieves superior performance. The code is publicly available at https://github.com/MedICL-VU/ProMISe., Comment: updated acknowledgments and fixed typos

Deep models suffer from limited generalization capability to unseen domains, which has severely hindered their clinical applicability. Specifically for the retinal vessel segmentation task, although the model is supposed to learn the anatomy of the target, it can be distracted by confounding factors like intensity and contrast. We propose Meta learning on Anatomy-consistent Pseudo-modalities (MAP), a method that improves model generalizability by learning structural features. We first leverage a feature extraction network to generate three distinct pseudo-modalities that share the vessel structure of the original image. Next, we use the episodic learning paradigm by selecting one of the pseudo-modalities as the meta-train dataset, and perform meta-testing on a continuous augmented image space generated through Dirichlet mixup of the remaining pseudo-modalities. Further, we introduce two loss functions that facilitate the model's focus on shape information by clustering the latent vectors obtained from images featuring identical vasculature. We evaluate our model on seven public datasets of various retinal imaging modalities and we conclude that MAP has substantially better generalizability. Our code is publically available at https://github.com/DeweiHu/MAP.

The Segment Anything Model (SAM) is a recently developed all-range foundation model for image segmentation. It can use sparse manual prompts such as bounding boxes to generate pixel-level segmentation in natural images but struggles in medical images such as low-contrast, noisy ultrasound images. We propose a refined test-phase prompt augmentation technique designed to improve SAM's performance in medical image segmentation. The method couples multi-box prompt augmentation and an aleatoric uncertainty-based false-negative (FN) and false-positive (FP) correction (FNPC) strategy. We evaluate the method on two ultrasound datasets and show improvement in SAM's performance and robustness to inaccurate prompts, without the necessity for further training or tuning. Moreover, we present the Single-Slice-to-Volume (SS2V) method, enabling 3D pixel-level segmentation using only the bounding box annotation from a single 2D slice. Our results allow efficient use of SAM in even noisy, low-contrast medical images. The source code will be released soon.

Convolutional Neural Networks (CNNs) have exhibited strong performance in medical image segmentation tasks by capturing high-level (local) information, such as edges and textures. However, due to the limited field of view of convolution kernel, it is hard for CNNs to fully represent global information. Recently, transformers have shown good performance for medical image segmentation due to their ability to better model long-range dependencies. Nevertheless, transformers struggle to capture high-level spatial features as effectively as CNNs. A good segmentation model should learn a better representation from local and global features to be both precise and semantically accurate. In our previous work, we proposed CATS, which is a U-shaped segmentation network augmented with transformer encoder. In this work, we further extend this model and propose CATS v2 with hybrid encoders. Specifically, hybrid encoders consist of a CNN-based encoder path paralleled to a transformer path with a shifted window, which better leverage both local and global information to produce robust 3D medical image segmentation. We fuse the information from the convolutional encoder and the transformer at the skip connections of different resolutions to form the final segmentation. The proposed method is evaluated on three public challenge datasets: Beyond the Cranial Vault (BTCV), Cross-Modality Domain Adaptation (CrossMoDA) and task 5 of Medical Segmentation Decathlon (MSD-5), to segment abdominal organs, vestibular schwannoma (VS) and prostate, respectively. Compared with the state-of-the-art methods, our approach demonstrates superior performance in terms of higher Dice scores. Our code is publicly available at https://github.com/MedICL-VU/CATS.

Medical image segmentation is a critical task in medical image analysis. In recent years, deep learning based approaches have shown exceptional performance when trained on a fully-annotated dataset. However, data annotation is often a significant bottleneck, especially for 3D medical images. Active learning (AL) is a promising solution for efficient annotation but requires an initial set of labeled samples to start active selection. When the entire data pool is unlabeled, how do we select the samples to annotate as our initial set? This is also known as the cold-start AL, which permits only one chance to request annotations from experts without access to previously annotated data. Cold-start AL is highly relevant in many practical scenarios but has been under-explored, especially for 3D medical segmentation tasks requiring substantial annotation effort. In this paper, we present a benchmark named COLosSAL by evaluating six cold-start AL strategies on five 3D medical image segmentation tasks from the public Medical Segmentation Decathlon collection. We perform a thorough performance analysis and explore important open questions for cold-start AL, such as the impact of budget on different strategies. Our results show that cold-start AL is still an unsolved problem for 3D segmentation tasks but some important trends have been observed. The code repository, data partitions, and baseline results for the complete benchmark are publicly available at https://github.com/MedICL-VU/COLosSAL., Comment: Accepted by MICCAI 2023

Among the research efforts to segment the retinal vasculature from fundus images, deep learning models consistently achieve superior performance. However, this data-driven approach is very sensitive to domain shifts. For fundus images, such data distribution changes can easily be caused by variations in illumination conditions as well as the presence of disease-related features such as hemorrhages and drusen. Since the source domain may not include all possible types of pathological cases, a model that can robustly recognize vessels on unseen domains is desirable but remains elusive, despite many proposed segmentation networks of ever-increasing complexity. In this work, we propose a contrastive variational auto-encoder that can filter out irrelevant features and synthesize a latent image, named deep angiogram, representing only the retinal vessels. Then segmentation can be readily accomplished by thresholding the deep angiogram. The generalizability of the synthetic network is improved by the contrastive loss that makes the model less sensitive to variations of image contrast and noisy features. Compared to baseline deep segmentation networks, our model achieves higher segmentation performance via simple thresholding. Our experiments show that the model can generate stable angiograms on different target domains, providing excellent visualization of vessels and a non-invasive, safe alternative to fluorescein angiography., Comment: 5 pages, 4 figures, SPIE 2023

Due to the absence of a single standardized imaging protocol, domain shift between data acquired from different sites is an inherent property of medical images and has become a major obstacle for large-scale deployment of learning-based algorithms. For retinal vessel images, domain shift usually presents as the variation of intensity, contrast and resolution, while the basic tubular shape of vessels remains unaffected. Thus, taking advantage of such domain-invariant morphological features can greatly improve the generalizability of deep models. In this study, we propose a method named VesselMorph which generalizes the 2D retinal vessel segmentation task by synthesizing a shape-aware representation. Inspired by the traditional Frangi filter and the diffusion tensor imaging literature, we introduce a Hessian-based bipolar tensor field to depict the morphology of the vessels so that the shape information is taken into account. We map the intensity image and the tensor field to a latent space for feature extraction. Then we fuse the two latent representations via a weight-balancing trick and feed the result to a segmentation network. We evaluate on six public datasets of fundus and OCT angiography images from diverse patient populations. VesselMorph achieves superior generalization performance compared with competing methods in different domain shift scenarios.

Automated segmentation of multiple sclerosis (MS) lesions from MRI scans is important to quantify disease progression. In recent years, convolutional neural networks (CNNs) have shown top performance for this task when a large amount of labeled data is available. However, the accuracy of CNNs suffers when dealing with few and/or sparsely labeled datasets. A potential solution is to leverage the information available in large public datasets in conjunction with a target dataset which only has limited labeled data. In this paper, we propose a training framework, SSL2 (self-supervised-semi-supervised), for multi-modality MS lesion segmentation with limited supervision. We adopt self-supervised learning to leverage the knowledge from large public 3T datasets to tackle the limitations of a small 7T target dataset. To leverage the information from unlabeled 7T data, we also evaluate state-of-the-art semi-supervised methods for other limited annotation settings, such as small labeled training size and sparse annotations. We use the shifted-window (Swin) transformer1 as our backbone network. The effectiveness of self-supervised and semi-supervised training strategies is evaluated in our in-house 7T MRI dataset. The results indicate that each strategy improves lesion segmentation for both limited training data size and for sparse labeling scenarios. The combined overall framework further improves the performance substantially compared to either of its components alone. Our proposed framework thus provides a promising solution for future data/label-hungry 7T MS studies., Comment: Accepted at the International Society for Optics and Photonics - Medical Imaging (SPIE-MI) 2023

Recently, deep learning methods have achieved state-of-the-art performance in many medical image segmentation tasks. Many of these are based on convolutional neural networks (CNNs). For such methods, the encoder is the key part for global and local information extraction from input images; the extracted features are then passed to the decoder for predicting the segmentations. In contrast, several recent works show a superior performance with the use of transformers, which can better model long-range spatial dependencies and capture low-level details. However, transformer as sole encoder underperforms for some tasks where it cannot efficiently replace the convolution based encoder. In this paper, we propose a model with double encoders for 3D biomedical image segmentation. Our model is a U-shaped CNN augmented with an independent transformer encoder. We fuse the information from the convolutional encoder and the transformer, and pass it to the decoder to obtain the results. We evaluate our methods on three public datasets from three different challenges: BTCV, MoDA and Decathlon. Compared to the state-of-the-art models with and without transformers on each task, our proposed method obtains higher Dice scores across the board.

Multiple Sclerosis (MS) is a chronic neuroinflammatory disease and multi-modality MRIs are routinely used to monitor MS lesions. Many automatic MS lesion segmentation models have been developed and have reached human-level performance. However, most established methods assume the MRI modalities used during training are also available during testing, which is not guaranteed in clinical practice. Previously, a training strategy termed Modality Dropout (ModDrop) has been applied to MS lesion segmentation to achieve the state-of-the-art performance with missing modality. In this paper, we present a novel method dubbed ModDrop++ to train a unified network adaptive to an arbitrary number of input MRI sequences. ModDrop++ upgrades the main idea of ModDrop in two key ways. First, we devise a plug-and-play dynamic head and adopt a filter scaling strategy to improve the expressiveness of the network. Second, we design a co-training strategy to leverage the intra-subject relation between full modality and missing modality. Specifically, the intra-subject co-training strategy aims to guide the dynamic head to generate similar feature representations between the full- and missing-modality data from the same subject. We use two public MS datasets to show the superiority of ModDrop++. Source code and trained models are available at https://github.com/han-liu/ModDropPlusPlus., Comment: MICCAI 2022

Optical coherence tomography (OCT) is a prevalent non-invasive imaging method which provides high resolution volumetric visualization of retina. However, its inherent defect, the speckle noise, can seriously deteriorate the tissue visibility in OCT. Deep learning based approaches have been widely used for image restoration, but most of these require a noise-free reference image for supervision. In this study, we present a diffusion probabilistic model that is fully unsupervised to learn from noise instead of signal. A diffusion process is defined by adding a sequence of Gaussian noise to self-fused OCT b-scans. Then the reverse process of diffusion, modeled by a Markov chain, provides an adjustable level of denoising. Our experiment results demonstrate that our method can significantly improve the image quality with a simple working pipeline and a small amount of training data., Comment: SPIE medical imaging, 2022

Magnetic resonance images (MRIs) are widely used to quantify vestibular schwannoma and the cochlea. Recently, deep learning methods have shown state-of-the-art performance for segmenting these structures. However, training segmentation models may require manual labels in target domain, which is expensive and time-consuming. To overcome this problem, domain adaptation is an effective way to leverage information from source domain to obtain accurate segmentations without requiring manual labels in target domain. In this paper, we propose an unsupervised learning framework to segment the VS and cochlea. Our framework leverages information from contrast-enhanced T1-weighted (ceT1-w) MRIs and its labels, and produces segmentations for T2-weighted MRIs without any labels in the target domain. We first applied a generator to achieve image-to-image translation. Next, we ensemble outputs from an ensemble of different models to obtain final segmentations. To cope with MRIs from different sites/scanners, we applied various 'online' augmentations during training to better capture the geometric variability and the variability in image appearance and quality. Our method is easy to build and produces promising segmentations, with a mean Dice score of 0.7930 and 0.7432 for VS and cochlea respectively in the validation set.

Optical coherence tomography (OCT) is a non-invasive imaging technique widely used for ophthalmology. It can be extended to OCT angiography (OCT-A), which reveals the retinal vasculature with improved contrast. Recent deep learning algorithms produced promising vascular segmentation results; however, 3D retinal vessel segmentation remains difficult due to the lack of manually annotated training data. We propose a learning-based method that is only supervised by a self-synthesized modality named local intensity fusion (LIF). LIF is a capillary-enhanced volume computed directly from the input OCT-A. We then construct the local intensity fusion encoder (LIFE) to map a given OCT-A volume and its LIF counterpart to a shared latent space. The latent space of LIFE has the same dimensions as the input data and it contains features common to both modalities. By binarizing this latent space, we obtain a volumetric vessel segmentation. Our method is evaluated in a human fovea OCT-A and three zebrafish OCT-A volumes with manual labels. It yields a Dice score of 0.7736 on human data and 0.8594 +/- 0.0275 on zebrafish data, a dramatic improvement over existing unsupervised algorithms., Comment: Accepted by International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) 2021

Optical coherence tomography (OCT) is a prevalent imaging technique for retina. However, it is affected by multiplicative speckle noise that can degrade the visibility of essential anatomical structures, including blood vessels and tissue layers. Although averaging repeated B-scan frames can significantly improve the signal-to-noise-ratio (SNR), this requires longer acquisition time, which can introduce motion artifacts and cause discomfort to patients. In this study, we propose a learning-based method that exploits information from the single-frame noisy B-scan and a pseudo-modality that is created with the aid of the self-fusion method. The pseudo-modality provides good SNR for layers that are barely perceptible in the noisy B-scan but can over-smooth fine features such as small vessels. By using a fusion network, desired features from each modality can be combined, and the weight of their contribution is adjustable. Evaluated by intensity-based and structural metrics, the result shows that our method can effectively suppress the speckle noise and enhance the contrast between retina layers while the overall structure and small blood vessels are preserved. Compared to the single modality network, our method improves the structural similarity with low noise B-scan from 0.559 +\- 0.033 to 0.576 +\- 0.031., Comment: Accepted by International Workshop on Ophthalmic Medical Image Analysis (OMIA) 2020