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Humans effortlessly interpret images by parsing them into part-whole hierarchies; deep learning excels in learning multi-level feature spaces, but they often lack explicit coding of part-whole relations, a prominent property of medical imaging. To overcome this limitation, we introduce Adam-v2, a new self-supervised learning framework extending Adam [79] by explicitly incorporating part-whole hierarchies into its learning objectives through three key branches: (1) Localizability, acquiring discriminative representations to distinguish different anatomical patterns; (2) Composability, learning each anatomical structure in a parts-to-whole manner; and (3) Decomposability, comprehending each anatomical structure in a whole-to-parts manner. Experimental results across 10 tasks, compared to 11 baselines in zero-shot, few-shot transfer, and full fine-tuning settings, showcase Adam-v2's superior performance over large-scale medical models and existing SSL methods across diverse downstream tasks. The higher generality and robustness of Adam-v2's representations originate from its explicit construction of hierarchies for distinct anatomical structures from unlabeled medical images. Adam-v2 preserves a semantic balance of anatomical diversity and harmony in its embedding, yielding representations that are both generic and semantically meaningful, yet overlooked in existing SSL methods. All code and pretrained models are available at https://github.com/JLiangLab/Eden., Comment: Accepted at CVPR 2024 [main conference]

Deep learning nowadays offers expert-level and sometimes even super-expert-level performance, but achieving such performance demands massive annotated data for training (e.g., Google's proprietary CXR Foundation Model (CXR-FM) was trained on 821,544 labeled and mostly private chest X-rays (CXRs)). Numerous datasets are publicly available in medical imaging but individually small and heterogeneous in expert labels. We envision a powerful and robust foundation model that can be trained by aggregating numerous small public datasets. To realize this vision, we have developed Ark, a framework that accrues and reuses knowledge from heterogeneous expert annotations in various datasets. As a proof of concept, we have trained two Ark models on 335,484 and 704,363 CXRs, respectively, by merging several datasets including ChestX-ray14, CheXpert, MIMIC-II, and VinDr-CXR, evaluated them on a wide range of imaging tasks covering both classification and segmentation via fine-tuning, linear-probing, and gender-bias analysis, and demonstrated our Ark's superior and robust performance over the SOTA fully/self-supervised baselines and Google's proprietary CXR-FM. This enhanced performance is attributed to our simple yet powerful observation that aggregating numerous public datasets diversifies patient populations and accrues knowledge from diverse experts, yielding unprecedented performance yet saving annotation cost. With all codes and pretrained models released at GitHub.com/JLiangLab/Ark, we hope that Ark exerts an important impact on open science, as accruing and reusing knowledge from expert annotations in public datasets can potentially surpass the performance of proprietary models trained on unusually large data, inspiring many more researchers worldwide to share codes and datasets to build open foundation models, accelerate open science, and democratize deep learning for medical imaging., Comment: Best Paper Award Runner-Up at Medical Image Computing and Computer Assisted Intervention (MICCAI) 2023

Human anatomy is the foundation of medical imaging and boasts one striking characteristic: its hierarchy in nature, exhibiting two intrinsic properties: (1) locality: each anatomical structure is morphologically distinct from the others; and (2) compositionality: each anatomical structure is an integrated part of a larger whole. We envision a foundation model for medical imaging that is consciously and purposefully developed upon this foundation to gain the capability of "understanding" human anatomy and to possess the fundamental properties of medical imaging. As our first step in realizing this vision towards foundation models in medical imaging, we devise a novel self-supervised learning (SSL) strategy that exploits the hierarchical nature of human anatomy. Our extensive experiments demonstrate that the SSL pretrained model, derived from our training strategy, not only outperforms state-of-the-art (SOTA) fully/self-supervised baselines but also enhances annotation efficiency, offering potential few-shot segmentation capabilities with performance improvements ranging from 9% to 30% for segmentation tasks compared to SSL baselines. This performance is attributed to the significance of anatomy comprehension via our learning strategy, which encapsulates the intrinsic attributes of anatomical structures-locality and compositionality-within the embedding space, yet overlooked in existing SSL methods. All code and pretrained models are available at https://github.com/JLiangLab/Eden., Comment: International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2023)---Domain Adaptation and Representation Transfer

Discriminative learning, restorative learning, and adversarial learning have proven beneficial for self-supervised learning schemes in computer vision and medical imaging. Existing efforts, however, omit their synergistic effects on each other in a ternary setup, which, we envision, can significantly benefit deep semantic representation learning. To realize this vision, we have developed DiRA, the first framework that unites discriminative, restorative, and adversarial learning in a unified manner to collaboratively glean complementary visual information from unlabeled medical images for fine-grained semantic representation learning. Our extensive experiments demonstrate that DiRA (1) encourages collaborative learning among three learning ingredients, resulting in more generalizable representation across organs, diseases, and modalities; (2) outperforms fully supervised ImageNet models and increases robustness in small data regimes, reducing annotation cost across multiple medical imaging applications; (3) learns fine-grained semantic representation, facilitating accurate lesion localization with only image-level annotation; and (4) enhances state-of-the-art restorative approaches, revealing that DiRA is a general mechanism for united representation learning. All code and pre-trained models are available at https: //github.com/JLiangLab/DiRA., Comment: Accepted at CVPR 2022 [main conference]

Recently, self-supervised instance discrimination methods have achieved significant success in learning visual representations from unlabeled photographic images. However, given the marked differences between photographic and medical images, the efficacy of instance-based objectives, focusing on learning the most discriminative global features in the image (i.e., wheels in bicycle), remains unknown in medical imaging. Our preliminary analysis showed that high global similarity of medical images in terms of anatomy hampers instance discrimination methods for capturing a set of distinct features, negatively impacting their performance on medical downstream tasks. To alleviate this limitation, we have developed a simple yet effective self-supervised framework, called Context-Aware instance Discrimination (CAiD). CAiD aims to improve instance discrimination learning by providing finer and more discriminative information encoded from a diverse local context of unlabeled medical images. We conduct a systematic analysis to investigate the utility of the learned features from a three-pronged perspective: (i) generalizability and transferability, (ii) separability in the embedding space, and (iii) reusability. Our extensive experiments demonstrate that CAiD (1) enriches representations learned from existing instance discrimination methods; (2) delivers more discriminative features by adequately capturing finer contextual information from individual medial images; and (3) improves reusability of low/mid-level features compared to standard instance discriminative methods. As open science, all codes and pre-trained models are available on our GitHub page: https://github.com/JLiangLab/CAiD., Comment: Accepted at MIDL 2022 [main conference]

Pulmonary embolism (PE) represents a thrombus ("blood clot"), usually originating from a lower extremity vein, that travels to the blood vessels in the lung, causing vascular obstruction and in some patients, death. This disorder is commonly diagnosed using CT pulmonary angiography (CTPA). Deep learning holds great promise for the computer-aided CTPA diagnosis (CAD) of PE. However, numerous competing methods for a given task in the deep learning literature exist, causing great confusion regarding the development of a CAD PE system. To address this confusion, we present a comprehensive analysis of competing deep learning methods applicable to PE diagnosis using CTPA at the both image and exam levels. At the image level, we compare convolutional neural networks (CNNs) with vision transformers, and contrast self-supervised learning (SSL) with supervised learning, followed by an evaluation of transfer learning compared with training from scratch. At the exam level, we focus on comparing conventional classification (CC) with multiple instance learning (MIL). Our extensive experiments consistently show: (1) transfer learning consistently boosts performance despite differences between natural images and CT scans, (2) transfer learning with SSL surpasses its supervised counterparts; (3) CNNs outperform vision transformers, which otherwise show satisfactory performance; and (4) CC is, surprisingly, superior to MIL. Compared with the state of the art, our optimal approach provides an AUC gain of 0.2\% and 1.05\% for image-level and exam-level, respectively.

Transfer learning from supervised ImageNet models has been frequently used in medical image analysis. Yet, no large-scale evaluation has been conducted to benchmark the efficacy of newly-developed pre-training techniques for medical image analysis, leaving several important questions unanswered. As the first step in this direction, we conduct a systematic study on the transferability of models pre-trained on iNat2021, the most recent large-scale fine-grained dataset, and 14 top self-supervised ImageNet models on 7 diverse medical tasks in comparison with the supervised ImageNet model. Furthermore, we present a practical approach to bridge the domain gap between natural and medical images by continually (pre-)training supervised ImageNet models on medical images. Our comprehensive evaluation yields new insights: (1) pre-trained models on fine-grained data yield distinctive local representations that are more suitable for medical segmentation tasks, (2) self-supervised ImageNet models learn holistic features more effectively than supervised ImageNet models, and (3) continual pre-training can bridge the domain gap between natural and medical images. We hope that this large-scale open evaluation of transfer learning can direct the future research of deep learning for medical imaging. As open science, all codes and pre-trained models are available on our GitHub page https://github.com/JLiangLab/BenchmarkTransferLearning., Comment: International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2021); Domain Adaptation and Representation Transfer (DART)

This paper introduces a new concept called "transferable visual words" (TransVW), aiming to achieve annotation efficiency for deep learning in medical image analysis. Medical imaging--focusing on particular parts of the body for defined clinical purposes--generates images of great similarity in anatomy across patients and yields sophisticated anatomical patterns across images, which are associated with rich semantics about human anatomy and which are natural visual words. We show that these visual words can be automatically harvested according to anatomical consistency via self-discovery, and that the self-discovered visual words can serve as strong yet free supervision signals for deep models to learn semantics-enriched generic image representation via self-supervision (self-classification and self-restoration). Our extensive experiments demonstrate the annotation efficiency of TransVW by offering higher performance and faster convergence with reduced annotation cost in several applications. Our TransVW has several important advantages, including (1) TransVW is a fully autodidactic scheme, which exploits the semantics of visual words for self-supervised learning, requiring no expert annotation; (2) visual word learning is an add-on strategy, which complements existing self-supervised methods, boosting their performance; and (3) the learned image representation is semantics-enriched models, which have proven to be more robust and generalizable, saving annotation efforts for a variety of applications through transfer learning. Our code, pre-trained models, and curated visual words are available at https://github.com/JLiangLab/TransVW., Comment: Journal version of arXiv:2007.06959, accepted by IEEE Transactions on Medical Imaging (TMI)

Medical images are naturally associated with rich semantics about the human anatomy, reflected in an abundance of recurring anatomical patterns, offering unique potential to foster deep semantic representation learning and yield semantically more powerful models for different medical applications. But how exactly such strong yet free semantics embedded in medical images can be harnessed for self-supervised learning remains largely unexplored. To this end, we train deep models to learn semantically enriched visual representation by self-discovery, self-classification, and self-restoration of the anatomy underneath medical images, resulting in a semantics-enriched, general-purpose, pre-trained 3D model, named Semantic Genesis. We examine our Semantic Genesis with all the publicly-available pre-trained models, by either self-supervision or fully supervision, on the six distinct target tasks, covering both classification and segmentation in various medical modalities (i.e.,CT, MRI, and X-ray). Our extensive experiments demonstrate that Semantic Genesis significantly exceeds all of its 3D counterparts as well as the de facto ImageNet-based transfer learning in 2D. This performance is attributed to our novel self-supervised learning framework, encouraging deep models to learn compelling semantic representation from abundant anatomical patterns resulting from consistent anatomies embedded in medical images. Code and pre-trained Semantic Genesis are available at https://github.com/JLiangLab/SemanticGenesis ., Comment: International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2020)

Transfer learning from natural images to medical images has been established as one of the most practical paradigms in deep learning for medical image analysis. To fit this paradigm, however, 3D imaging tasks in the most prominent imaging modalities (e.g., CT and MRI) have to be reformulated and solved in 2D, losing rich 3D anatomical information, thereby inevitably compromising its performance. To overcome this limitation, we have built a set of models, called Generic Autodidactic Models, nicknamed Models Genesis, because they are created ex nihilo (with no manual labeling), self-taught (learnt by self-supervision), and generic (served as source models for generating application-specific target models). Our extensive experiments demonstrate that our Models Genesis significantly outperform learning from scratch and existing pre-trained 3D models in all five target 3D applications covering both segmentation and classification. More importantly, learning a model from scratch simply in 3D may not necessarily yield performance better than transfer learning from ImageNet in 2D, but our Models Genesis consistently top any 2D/2.5D approaches including fine-tuning the models pre-trained from ImageNet as well as fine-tuning the 2D versions of our Models Genesis, confirming the importance of 3D anatomical information and significance of Models Genesis for 3D medical imaging. This performance is attributed to our unified self-supervised learning framework, built on a simple yet powerful observation: the sophisticated and recurrent anatomy in medical images can serve as strong yet free supervision signals for deep models to learn common anatomical representation automatically via self-supervision. As open science, all codes and pre-trained Models Genesis are available at https://github.com/MrGiovanni/ModelsGenesis., Comment: Journal version of arXiv:1908.06912, accepted by Medical Image Analysis

Rationale: Computer aided detection (CAD) algorithms for Pulmonary Embolism (PE) algorithms have been shown to increase radiologists' sensitivity with a small increase in specificity. However, CAD for PE has not been adopted into clinical practice, likely because of the high number of false positives current CAD software produces. Objective: To generate a database of annotated computed tomography pulmonary angiographies, use it to compare the sensitivity and false positive rate of current algorithms and to develop new methods that improve such metrics. Methods: 91 Computed tomography pulmonary angiography scans were annotated by at least one radiologist by segmenting all pulmonary emboli visible on the study. 20 annotated CTPAs were open to the public in the form of a medical image analysis challenge. 20 more were kept for evaluation purposes. 51 were made available post-challenge. 8 submissions, 6 of them novel, were evaluated on the 20 evaluation CTPAs. Performance was measured as per embolus sensitivity vs. false positives per scan curve. Results: The best algorithms achieved a per-embolus sensitivity of 75% at 2 false positives per scan (fps) or of 70% at 1 fps, outperforming the state of the art. Deep learning approaches outperformed traditional machine learning ones, and their performance improved with the number of training cases. Significance: Through this work and challenge we have improved the state-of-the art of computer aided detection algorithms for pulmonary embolism. An open database and an evaluation benchmark for such algorithms have been generated, easing the development of further improvements. Implications on clinical practice will need further research., Comment: 8 pages, 3 figures

Transfer learning from natural image to medical image has established as one of the most practical paradigms in deep learning for medical image analysis. However, to fit this paradigm, 3D imaging tasks in the most prominent imaging modalities (e.g., CT and MRI) have to be reformulated and solved in 2D, losing rich 3D anatomical information and inevitably compromising the performance. To overcome this limitation, we have built a set of models, called Generic Autodidactic Models, nicknamed Models Genesis, because they are created ex nihilo (with no manual labeling), self-taught (learned by self-supervision), and generic (served as source models for generating application-specific target models). Our extensive experiments demonstrate that our Models Genesis significantly outperform learning from scratch in all five target 3D applications covering both segmentation and classification. More importantly, learning a model from scratch simply in 3D may not necessarily yield performance better than transfer learning from ImageNet in 2D, but our Models Genesis consistently top any 2D approaches including fine-tuning the models pre-trained from ImageNet as well as fine-tuning the 2D versions of our Models Genesis, confirming the importance of 3D anatomical information and significance of our Models Genesis for 3D medical imaging. This performance is attributed to our unified self-supervised learning framework, built on a simple yet powerful observation: the sophisticated yet recurrent anatomy in medical images can serve as strong supervision signals for deep models to learn common anatomical representation automatically via self-supervision. As open science, all pre-trained Models Genesis are available at https://github.com/MrGiovanni/ModelsGenesis., Comment: International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI)

Generative adversarial networks (GANs) have ushered in a revolution in image-to-image translation. The development and proliferation of GANs raises an interesting question: can we train a GAN to remove an object, if present, from an image while otherwise preserving the image? Specifically, can a GAN "virtually heal" anyone by turning his medical image, with an unknown health status (diseased or healthy), into a healthy one, so that diseased regions could be revealed by subtracting those two images? Such a task requires a GAN to identify a minimal subset of target pixels for domain translation, an ability that we call fixed-point translation, which no GAN is equipped with yet. Therefore, we propose a new GAN, called Fixed-Point GAN, trained by (1) supervising same-domain translation through a conditional identity loss, and (2) regularizing cross-domain translation through revised adversarial, domain classification, and cycle consistency loss. Based on fixed-point translation, we further derive a novel framework for disease detection and localization using only image-level annotation. Qualitative and quantitative evaluations demonstrate that the proposed method outperforms the state of the art in multi-domain image-to-image translation and that it surpasses predominant weakly-supervised localization methods in both disease detection and localization. Implementation is available at https://github.com/jlianglab/Fixed-Point-GAN.

The splendid success of convolutional neural networks (CNNs) in computer vision is largely attributable to the availability of massive annotated datasets, such as ImageNet and Places. However, in medical imaging, it is challenging to create such large annotated datasets, as annotating medical images is not only tedious, laborious, and time consuming, but it also demands costly, specialty-oriented skills, which are not easily accessible. To dramatically reduce annotation cost, this paper presents a novel method to naturally integrate active learning and transfer learning (fine-tuning) into a single framework, which starts directly with a pre-trained CNN to seek "worthy" samples for annotation and gradually enhances the (fine-tuned) CNN via continual fine-tuning. We have evaluated our method using three distinct medical imaging applications, demonstrating that it can reduce annotation efforts by at least half compared with random selection.

Training a deep convolutional neural network (CNN) from scratch is difficult because it requires a large amount of labeled training data and a great deal of expertise to ensure proper convergence. A promising alternative is to fine-tune a CNN that has been pre-trained using, for instance, a large set of labeled natural images. However, the substantial differences between natural and medical images may advise against such knowledge transfer. In this paper, we seek to answer the following central question in the context of medical image analysis: \emph{Can the use of pre-trained deep CNNs with sufficient fine-tuning eliminate the need for training a deep CNN from scratch?} To address this question, we considered 4 distinct medical imaging applications in 3 specialties (radiology, cardiology, and gastroenterology) involving classification, detection, and segmentation from 3 different imaging modalities, and investigated how the performance of deep CNNs trained from scratch compared with the pre-trained CNNs fine-tuned in a layer-wise manner. Our experiments consistently demonstrated that (1) the use of a pre-trained CNN with adequate fine-tuning outperformed or, in the worst case, performed as well as a CNN trained from scratch; (2) fine-tuned CNNs were more robust to the size of training sets than CNNs trained from scratch; (3) neither shallow tuning nor deep tuning was the optimal choice for a particular application; and (4) our layer-wise fine-tuning scheme could offer a practical way to reach the best performance for the application at hand based on the amount of available data.