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Pulmonary embolism (PE) is a life-threatening condition where rapid and accurate diagnosis is imperative yet difficult due to predominantly atypical symptomatology. Computed tomography pulmonary angiography (CTPA) is acknowledged as the gold standard imaging tool in clinics, yet it can be contraindicated for emergency department (ED) patients and represents an onerous procedure, thus necessitating PE identification through non-contrast CT (NCT) scans. In this work, we explore the feasibility of applying a deep-learning approach to NCT scans for PE identification. We propose a novel Cross-Phase Mutual learNing framework (CPMN) that fosters knowledge transfer from CTPA to NCT, while concurrently conducting embolism segmentation and abnormality classification in a multi-task manner. The proposed CPMN leverages the Inter-Feature Alignment (IFA) strategy that enhances spatial contiguity and mutual learning between the dual-pathway network, while the Intra-Feature Discrepancy (IFD) strategy can facilitate precise segmentation of PE against complex backgrounds for single-pathway networks. For a comprehensive assessment of the proposed approach, a large-scale dual-phase dataset containing 334 PE patients and 1,105 normal subjects has been established. Experimental results demonstrate that CPMN achieves the leading identification performance, which is 95.4\% and 99.6\% in patient-level sensitivity and specificity on NCT scans, indicating the potential of our approach as an economical, accessible, and precise tool for PE identification in clinical practice., Comment: Early accept by MICCAI 2024

Chest pain symptoms are highly prevalent in emergency departments (EDs), where acute aortic syndrome (AAS) is a catastrophic cardiovascular emergency with a high fatality rate, especially when timely and accurate treatment is not administered. However, current triage practices in the ED can cause up to approximately half of patients with AAS to have an initially missed diagnosis or be misdiagnosed as having other acute chest pain conditions. Subsequently, these AAS patients will undergo clinically inaccurate or suboptimal differential diagnosis. Fortunately, even under these suboptimal protocols, nearly all these patients underwent non-contrast CT covering the aorta anatomy at the early stage of differential diagnosis. In this study, we developed an artificial intelligence model (DeepAAS) using non-contrast CT, which is highly accurate for identifying AAS and provides interpretable results to assist in clinical decision-making. Performance was assessed in two major phases: a multi-center retrospective study (n = 20,750) and an exploration in real-world emergency scenarios (n = 137,525). In the multi-center cohort, DeepAAS achieved a mean area under the receiver operating characteristic curve of 0.958 (95% CI 0.950-0.967). In the real-world cohort, DeepAAS detected 109 AAS patients with misguided initial suspicion, achieving 92.6% (95% CI 76.2%-97.5%) in mean sensitivity and 99.2% (95% CI 99.1%-99.3%) in mean specificity. Our AI model performed well on non-contrast CT at all applicable early stages of differential diagnosis workflows, effectively reduced the overall missed diagnosis and misdiagnosis rate from 48.8% to 4.8% and shortened the diagnosis time for patients with misguided initial suspicion from an average of 681.8 (74-11,820) mins to 68.5 (23-195) mins. DeepAAS could effectively fill the gap in the current clinical workflow without requiring additional tests.

The absence of adequately sufficient expert-level tumor annotations hinders the effectiveness of supervised learning based opportunistic cancer screening on medical imaging. Clinical reports (that are rich in descriptive textual details) can offer a "free lunch'' supervision information and provide tumor location as a type of weak label to cope with screening tasks, thus saving human labeling workloads, if properly leveraged. However, predicting cancer only using such weak labels can be very changeling since tumors are usually presented in small anatomical regions compared to the whole 3D medical scans. Weakly semi-supervised learning (WSSL) utilizes a limited set of voxel-level tumor annotations and incorporates alongside a substantial number of medical images that have only off-the-shelf clinical reports, which may strike a good balance between minimizing expert annotation workload and optimizing screening efficacy. In this paper, we propose a novel text-guided learning method to achieve highly accurate cancer detection results. Through integrating diagnostic and tumor location text prompts into the text encoder of a vision-language model (VLM), optimization of weakly supervised learning can be effectively performed in the latent space of VLM, thereby enhancing the stability of training. Our approach can leverage clinical knowledge by large-scale pre-trained VLM to enhance generalization ability, and produce reliable pseudo tumor masks to improve cancer detection. Our extensive quantitative experimental results on a large-scale cancer dataset, including 1,651 unique patients, validate that our approach can reduce human annotation efforts by at least 70% while maintaining comparable cancer detection accuracy to competing fully supervised methods (AUC value 0.961 versus 0.966).

Radiologists highly desire fully automated versatile AI for medical imaging interpretation. However, the lack of extensively annotated large-scale multi-disease datasets has hindered the achievement of this goal. In this paper, we explore the feasibility of leveraging language as a naturally high-quality supervision for chest CT imaging. In light of the limited availability of image-report pairs, we bootstrap the understanding of 3D chest CT images by distilling chest-related diagnostic knowledge from an extensively pre-trained 2D X-ray expert model. Specifically, we propose a language-guided retrieval method to match each 3D CT image with its semantically closest 2D X-ray image, and perform pair-wise and semantic relation knowledge distillation. Subsequently, we use contrastive learning to align images and reports within the same patient while distinguishing them from the other patients. However, the challenge arises when patients have similar semantic diagnoses, such as healthy patients, potentially confusing if treated as negatives. We introduce a robust contrastive learning that identifies and corrects these false negatives. We train our model with over 12,000 pairs of chest CT images and radiology reports. Extensive experiments across multiple scenarios, including zero-shot learning, report generation, and fine-tuning processes, demonstrate the model's feasibility in interpreting chest CT images., Comment: Accepted by CVPR 2024

In the realm of medical 3D data, such as CT and MRI images, prevalent anisotropic resolution is characterized by high intra-slice but diminished inter-slice resolution. The lowered resolution between adjacent slices poses challenges, hindering optimal viewing experiences and impeding the development of robust downstream analysis algorithms. Various volumetric super-resolution algorithms aim to surmount these challenges, enhancing inter-slice resolution and overall 3D medical imaging quality. However, existing approaches confront inherent challenges: 1) often tailored to specific upsampling factors, lacking flexibility for diverse clinical scenarios; 2) newly generated slices frequently suffer from over-smoothing, degrading fine details, and leading to inter-slice inconsistency. In response, this study presents CycleINR, a novel enhanced Implicit Neural Representation model for 3D medical data volumetric super-resolution. Leveraging the continuity of the learned implicit function, the CycleINR model can achieve results with arbitrary up-sampling rates, eliminating the need for separate training. Additionally, we enhance the grid sampling in CycleINR with a local attention mechanism and mitigate over-smoothing by integrating cycle-consistent loss. We introduce a new metric, Slice-wise Noise Level Inconsistency (SNLI), to quantitatively assess inter-slice noise level inconsistency. The effectiveness of our approach is demonstrated through image quality evaluations on an in-house dataset and a downstream task analysis on the Medical Segmentation Decathlon liver tumor dataset., Comment: CVPR accepted paper

Segment anything model (SAM) demonstrates strong generalization ability on natural image segmentation. However, its direct adaption in medical image segmentation tasks shows significant performance drops with inferior accuracy and unstable results. It may also requires an excessive number of prompt points to obtain a reasonable accuracy. For segmenting 3D radiological CT or MRI scans, a 2D SAM model has to separately handle hundreds of 2D slices. Although quite a few studies explore adapting SAM into medical image volumes, the efficiency of 2D adaption methods is unsatisfactory and 3D adaptation methods only capable of segmenting specific organs/tumors. In this work, we propose a comprehensive and scalable 3D SAM model for whole-body CT segmentation, named CT-SAM3D. Instead of adapting SAM, we propose a 3D promptable segmentation model using a (nearly) fully labeled CT dataset. To train CT-SAM3D effectively, ensuring the model's accurate responses to higher-dimensional spatial prompts is crucial, and 3D patch-wise training is required due to GPU memory constraints. For this purpose, we propose two key technical developments: 1) a progressively and spatially aligned prompt encoding method to effectively encode click prompts in local 3D space; and 2) a cross-patch prompt learning scheme to capture more 3D spatial context, which is beneficial for reducing the editing workloads when interactively prompting on large organs. CT-SAM3D is trained and validated using a curated dataset of 1204 CT scans containing 107 whole-body anatomies, reporting significantly better quantitative performance against all previous SAM-derived models by a large margin with much fewer click prompts. Our model can handle segmenting unseen organ as well. Code, data, and our 3D interactive segmentation tool with quasi-real-time responses will be made publicly available.

Establishing dense anatomical correspondence across distinct imaging modalities is a foundational yet challenging procedure for numerous medical image analysis studies and image-guided radiotherapy. Existing multi-modality image registration algorithms rely on statistical-based similarity measures or local structural image representations. However, the former is sensitive to locally varying noise, while the latter is not discriminative enough to cope with complex anatomical structures in multimodal scans, causing ambiguity in determining the anatomical correspondence across scans with different modalities. In this paper, we propose a modality-agnostic structural representation learning method, which leverages Deep Neighbourhood Self-similarity (DNS) and anatomy-aware contrastive learning to learn discriminative and contrast-invariance deep structural image representations (DSIR) without the need for anatomical delineations or pre-aligned training images. We evaluate our method on multiphase CT, abdomen MR-CT, and brain MR T1w-T2w registration. Comprehensive results demonstrate that our method is superior to the conventional local structural representation and statistical-based similarity measures in terms of discriminability and accuracy., Comment: Accepted by CVPR2024

Estimating displacement vector field via a cost volume computed in the feature space has shown great success in image registration, but it suffers excessive computation burdens. Moreover, existing feature descriptors only extract local features incapable of representing the global semantic information, which is especially important for solving large transformations. To address the discussed issues, we propose SAMConvex, a fast coarse-to-fine discrete optimization method for CT registration that includes a decoupled convex optimization procedure to obtain deformation fields based on a self-supervised anatomical embedding (SAM) feature extractor that captures both local and global information. To be specific, SAMConvex extracts per-voxel features and builds 6D correlation volumes based on SAM features, and iteratively updates a flow field by performing lookups on the correlation volumes with a coarse-to-fine scheme. SAMConvex outperforms the state-of-the-art learning-based methods and optimization-based methods over two inter-patient registration datasets (Abdomen CT and HeadNeck CT) and one intra-patient registration dataset (Lung CT). Moreover, as an optimization-based method, SAMConvex only takes $\sim2$s ($\sim5s$ with instance optimization) for one paired images.

Radiotherapists require accurate registration of MR/CT images to effectively use information from both modalities. In a typical registration pipeline, rigid or affine transformations are applied to roughly align the fixed and moving images before proceeding with the deformation step. While recent learning-based methods have shown promising results in the rigid/affine step, these methods often require images with similar field-of-view (FOV) for successful alignment. As a result, aligning images with different FOVs remains a challenging task. Self-supervised landmark detection methods like self-supervised Anatomical eMbedding (SAM) have emerged as a useful tool for mapping and cropping images to similar FOVs. However, these methods are currently limited to intra-modality use only. To address this limitation and enable cross-modality matching, we propose a new approach called Cross-SAM. Our approach utilizes a novel iterative process that alternates between embedding learning and CT-MRI registration. We start by applying aggressive contrast augmentation on both CT and MRI images to train a SAM model. We then use this SAM to identify corresponding regions on paired images using robust grid-points matching, followed by a point-set based affine/rigid registration, and a deformable fine-tuning step to produce registered paired images. We use these registered pairs to enhance the matching ability of SAM, which is then processed iteratively. We use the final model for cross-modality matching tasks. We evaluated our approach on two CT-MRI affine registration datasets and found that Cross-SAM achieved robust affine registration on both datasets, significantly outperforming other methods and achieving state-of-the-art performance.

State-of-the-art deep learning-based registration methods employ three different learning strategies: supervised learning, which requires costly manual annotations, unsupervised learning, which heavily relies on hand-crafted similarity metrics designed by domain experts, or learning from synthetic data, which introduces a domain shift. To overcome the limitations of these strategies, we propose a novel self-supervised learning paradigm for unsupervised registration, relying on self-training. Our idea is based on two key insights. Feature-based differentiable optimizers 1) perform reasonable registration even from random features and 2) stabilize the training of the preceding feature extraction network on noisy labels. Consequently, we propose cyclical self-training, where pseudo labels are initialized as the displacement fields inferred from random features and cyclically updated based on more and more expressive features from the learning feature extractor, yielding a self-reinforcement effect. We evaluate the method for abdomen and lung registration, consistently surpassing metric-based supervision and outperforming diverse state-of-the-art competitors. Source code is available at https://github.com/multimodallearning/reg-cyclical-self-train., Comment: accepted at MICCAI 2023

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.

Registration of pre-operative and follow-up brain MRI scans is challenging due to the large variation of tissue appearance and missing correspondences in tumour recurrence regions caused by tumour mass effect. Although recent deep learning-based deformable registration methods have achieved remarkable success in various medical applications, most of them are not capable of registering images with pathologies. In this paper, we propose a 3-step registration pipeline for pre-operative and follow-up brain MRI scans that consists of 1) a multi-level affine registration, 2) a conditional deep Laplacian pyramid image registration network (cLapIRN) with forward-backward consistency constraint, and 3) a non-linear instance optimization method. We apply the method to the Brain Tumor Sequence Registration (BraTS-Reg) Challenge. Our method achieves accurate and robust registration of brain MRI scans with pathologies, which achieves a median absolute error of 1.64 mm and 88\% of successful registration rate in the validation set of BraTS-Reg challenge. Our method ranks 1st place in the 2022 MICCAI BraTS-Reg challenge., Comment: BraTS-Reg workshop

Registration of pre-operative and post-recurrence brain images is often needed to evaluate the effectiveness of brain gliomas treatment. While recent deep learning-based deformable registration methods have achieved remarkable success with healthy brain images, most of them would be unable to accurately align images with pathologies due to the absent correspondences in the reference image. In this paper, we propose a deep learning-based deformable registration method that jointly estimates regions with absent correspondence and bidirectional deformation fields. A forward-backward consistency constraint is used to aid in the localization of the resection and recurrence region from voxels with absence correspondences in the two images. Results on 3D clinical data from the BraTS-Reg challenge demonstrate our method can improve image alignment compared to traditional and deep learning-based registration approaches with or without cost function masking strategy. The source code is available at https://github.com/cwmok/DIRAC., Comment: Accepted by MICCAI2022

Affine registration is indispensable in a comprehensive medical image registration pipeline. However, only a few studies focus on fast and robust affine registration algorithms. Most of these studies utilize convolutional neural networks (CNNs) to learn joint affine and non-parametric registration, while the standalone performance of the affine subnetwork is less explored. Moreover, existing CNN-based affine registration approaches focus either on the local misalignment or the global orientation and position of the input to predict the affine transformation matrix, which are sensitive to spatial initialization and exhibit limited generalizability apart from the training dataset. In this paper, we present a fast and robust learning-based algorithm, Coarse-to-Fine Vision Transformer (C2FViT), for 3D affine medical image registration. Our method naturally leverages the global connectivity and locality of the convolutional vision transformer and the multi-resolution strategy to learn the global affine registration. We evaluate our method on 3D brain atlas registration and template-matching normalization. Comprehensive results demonstrate that our method is superior to the existing CNNs-based affine registration methods in terms of registration accuracy, robustness and generalizability while preserving the runtime advantage of the learning-based methods. The source code is available at https://github.com/cwmok/C2FViT., Comment: Accepted by CVPR2022

Registration of longitudinal brain MRI scans containing pathologies is challenging due to dramatic changes in tissue appearance. Although there has been progress in developing general-purpose medical image registration techniques, they have not yet attained the requisite precision and reliability for this task, highlighting its inherent complexity. Here we describe the Brain Tumor Sequence Registration (BraTS-Reg) challenge, as the first public benchmark environment for deformable registration algorithms focusing on estimating correspondences between pre-operative and follow-up scans of the same patient diagnosed with a diffuse brain glioma. The BraTS-Reg data comprise de-identified multi-institutional multi-parametric MRI (mpMRI) scans, curated for size and resolution according to a canonical anatomical template, and divided into training, validation, and testing sets. Clinical experts annotated ground truth (GT) landmark points of anatomical locations distinct across the temporal domain. Quantitative evaluation and ranking were based on the Median Euclidean Error (MEE), Robustness, and the determinant of the Jacobian of the displacement field. The top-ranked methodologies yielded similar performance across all evaluation metrics and shared several methodological commonalities, including pre-alignment, deep neural networks, inverse consistency analysis, and test-time instance optimization per-case basis as a post-processing step. The top-ranked method attained the MEE at or below that of the inter-rater variability for approximately 60% of the evaluated landmarks, underscoring the scope for further accuracy and robustness improvements, especially relative to human experts. The aim of BraTS-Reg is to continue to serve as an active resource for research, with the data and online evaluation tools accessible at https://bratsreg.github.io/.

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration data set for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state-of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.

Recent deep learning-based methods have shown promising results and runtime advantages in deformable image registration. However, analyzing the effects of hyperparameters and searching for optimal regularization parameters prove to be too prohibitive in deep learning-based methods. This is because it involves training a substantial number of separate models with distinct hyperparameter values. In this paper, we propose a conditional image registration method and a new self-supervised learning paradigm for deep deformable image registration. By learning the conditional features that are correlated with the regularization hyperparameter, we demonstrate that optimal solutions with arbitrary hyperparameters can be captured by a single deep convolutional neural network. In addition, the smoothness of the resulting deformation field can be manipulated with arbitrary strength of smoothness regularization during inference. Extensive experiments on a large-scale brain MRI dataset show that our proposed method enables the precise control of the smoothness of the deformation field without sacrificing the runtime advantage or registration accuracy., Comment: Early accepted by MICCAI2021

Deep learning-based methods have recently demonstrated promising results in deformable image registration for a wide range of medical image analysis tasks. However, existing deep learning-based methods are usually limited to small deformation settings, and desirable properties of the transformation including bijective mapping and topology preservation are often being ignored by these approaches. In this paper, we propose a deep Laplacian Pyramid Image Registration Network, which can solve the image registration optimization problem in a coarse-to-fine fashion within the space of diffeomorphic maps. Extensive quantitative and qualitative evaluations on two MR brain scan datasets show that our method outperforms the existing methods by a significant margin while maintaining desirable diffeomorphic properties and promising registration speed., Comment: Paper accepted by MICCAI 2020

Diffeomorphic deformable image registration is crucial in many medical image studies, as it offers unique, special properties including topology preservation and invertibility of the transformation. Recent deep learning-based deformable image registration methods achieve fast image registration by leveraging a convolutional neural network (CNN) to learn the spatial transformation from the synthetic ground truth or the similarity metric. However, these approaches often ignore the topology preservation of the transformation and the smoothness of the transformation which is enforced by a global smoothing energy function alone. Moreover, deep learning-based approaches often estimate the displacement field directly, which cannot guarantee the existence of the inverse transformation. In this paper, we present a novel, efficient unsupervised symmetric image registration method which maximizes the similarity between images within the space of diffeomorphic maps and estimates both forward and inverse transformations simultaneously. We evaluate our method on 3D image registration with a large scale brain image dataset. Our method achieves state-of-the-art registration accuracy and running time while maintaining desirable diffeomorphic properties., Comment: Accepted to CVPR 2020

There is a common belief that the successful training of deep neural networks requires many annotated training samples, which are often expensive and difficult to obtain especially in the biomedical imaging field. While it is often easy for researchers to use data augmentation to expand the size of training sets, constructing and generating generic augmented data that is able to teach the network the desired invariance and robustness properties using traditional data augmentation techniques is challenging in practice. In this paper, we propose a novel automatic data augmentation method that uses generative adversarial networks to learn augmentations that enable machine learning based method to learn the available annotated samples more efficiently. The architecture consists of a coarse-to-fine generator to capture the manifold of the training sets and generate generic augmented data. In our experiments, we show the efficacy of our approach on a Magnetic Resonance Imaging (MRI) image, achieving improvements of 3.5% Dice coefficient on the BRATS15 Challenge dataset as compared to traditional augmentation approaches. Also, our proposed method successfully boosts a common segmentation network to reach the state-of-the-art performance on the BRATS15 Challenge.