Ziyue Xu

Yufan He, Pengfei Guo, Yucheng Tang et al.

Since the release of Segment Anything 2 (SAM2), the medical imaging community has been actively evaluating its performance for 3D medical image segmentation. However, different studies have employed varying evaluation pipelines, resulting in conflicting outcomes that obscure a clear understanding of SAM2's capabilities and potential applications. We shortly review existing benchmarks and point out that the SAM2 paper clearly outlines a zero-shot evaluation pipeline, which simulates user clicks iteratively for up to eight iterations. We reproduced this interactive annotation simulation on 3D CT datasets and provided the results and code~\url{https://github.com/Project-MONAI/VISTA}. Our findings reveal that directly applying SAM2 on 3D medical imaging in a zero-shot manner is far from satisfactory. It is prone to generating false positives when foreground objects disappear, and annotating more slices cannot fully offset this tendency. For smaller single-connected objects like kidney and aorta, SAM2 performs reasonably well but for most organs it is still far behind state-of-the-art 3D annotation methods. More research and innovation are needed for 3D medical imaging community to use SAM2 correctly.

Pengfei Guo, Can Zhao, Dong Yang et al.

Medical imaging analysis faces challenges such as data scarcity, high annotation costs, and privacy concerns. This paper introduces the Medical AI for Synthetic Imaging (MAISI), an innovative approach using the diffusion model to generate synthetic 3D computed tomography (CT) images to address those challenges. MAISI leverages the foundation volume compression network and the latent diffusion model to produce high-resolution CT images (up to a landmark volume dimension of 512 x 512 x 768 ) with flexible volume dimensions and voxel spacing. By incorporating ControlNet, MAISI can process organ segmentation, including 127 anatomical structures, as additional conditions and enables the generation of accurately annotated synthetic images that can be used for various downstream tasks. Our experiment results show that MAISI's capabilities in generating realistic, anatomically accurate images for diverse regions and conditions reveal its promising potential to mitigate challenges using synthetic data.

Jeya Maria Jose Valanarasu, Yucheng Tang, Dong Yang et al.

Harnessing the power of pre-training on large-scale datasets like ImageNet forms a fundamental building block for the progress of representation learning-driven solutions in computer vision. Medical images are inherently different from natural images as they are acquired in the form of many modalities (CT, MR, PET, Ultrasound etc.) and contain granulated information like tissue, lesion, organs etc. These characteristics of medical images require special attention towards learning features representative of local context. In this work, we focus on designing an effective pre-training framework for 3D radiology images. First, we propose a new masking strategy called local masking where the masking is performed across channel embeddings instead of tokens to improve the learning of local feature representations. We combine this with classical low-level perturbations like adding noise and downsampling to further enable low-level representation learning. To this end, we introduce Disruptive Autoencoders, a pre-training framework that attempts to reconstruct the original image from disruptions created by a combination of local masking and low-level perturbations. Additionally, we also devise a cross-modal contrastive loss (CMCL) to accommodate the pre-training of multiple modalities in a single framework. We curate a large-scale dataset to enable pre-training of 3D medical radiology images (MRI and CT). The proposed pre-training framework is tested across multiple downstream tasks and achieves state-of-the-art performance. Notably, our proposed method tops the public test leaderboard of BTCV multi-organ segmentation challenge.

Yucheng Tang, Yufan He, Vishwesh Nath et al.

In digital pathology, the traditional method for deep learning-based image segmentation typically involves a two-stage process: initially segmenting high-resolution whole slide images (WSI) into smaller patches (e.g., 256x256, 512x512, 1024x1024) and subsequently reconstructing them to their original scale. This method often struggles to capture the complex details and vast scope of WSIs. In this paper, we propose the holistic histopathology (HoloHisto) segmentation method to achieve end-to-end segmentation on gigapixel WSIs, whose maximum resolution is above 80,000$\times$70,000 pixels. HoloHisto fundamentally shifts the paradigm of WSI segmentation to an end-to-end learning fashion with 1) a large (4K) resolution base patch for elevated visual information inclusion and efficient processing, and 2) a novel sequential tokenization mechanism to properly model the contextual relationships and efficiently model the rich information from the 4K input. To our best knowledge, HoloHisto presents the first holistic approach for gigapixel resolution WSI segmentation, supporting direct I/O of complete WSI and their corresponding gigapixel masks. Under the HoloHisto platform, we unveil a random 4K sampler that transcends ultra-high resolution, delivering 31 and 10 times more pixels than standard 2D and 3D patches, respectively, for advancing computational capabilities. To facilitate efficient 4K resolution dense prediction, we leverage sequential tokenization, utilizing a pre-trained image tokenizer to group image features into a discrete token grid. To assess the performance, our team curated a new kidney pathology image segmentation (KPIs) dataset with WSI-level glomeruli segmentation from whole mouse kidneys. From the results, HoloHisto-4K delivers remarkable performance gains over previous state-of-the-art models.

Wentao Zhu, Can Zhao, Wenqi Li et al.

Deep Learning (DL) models are becoming larger, because the increase in model size might offer significant accuracy gain. To enable the training of large deep networks, data parallelism and model parallelism are two well-known approaches for parallel training. However, data parallelism does not help reduce memory footprint per device. In this work, we introduce Large deep 3D ConvNets with Automated Model Parallelism (LAMP) and investigate the impact of both input's and deep 3D ConvNets' size on segmentation accuracy. Through automated model parallelism, it is feasible to train large deep 3D ConvNets with a large input patch, even the whole image. Extensive experiments demonstrate that, facilitated by the automated model parallelism, the segmentation accuracy can be improved through increasing model size and input context size, and large input yields significant inference speedup compared with sliding window of small patches in the inference. Code is available\footnote{https://monai.io/research/lamp-automated-model-parallelism}.

Vishwesh Nath, Wenqi Li, Dong Yang et al.

Generalist vision language models (VLMs) have made significant strides in computer vision, but they fall short in specialized fields like healthcare, where expert knowledge is essential. In traditional computer vision tasks, creative or approximate answers may be acceptable, but in healthcare, precision is paramount.Current large multimodal models like Gemini and GPT-4o are insufficient for medical tasks due to their reliance on memorized internet knowledge rather than the nuanced expertise required in healthcare. VLMs are usually trained in three stages: vision pre-training, vision-language pre-training, and instruction fine-tuning (IFT). IFT has been typically applied using a mixture of generic and healthcare data. In contrast, we propose that for medical VLMs, a fourth stage of specialized IFT is necessary, which focuses on medical data and includes information from domain expert models. Domain expert models developed for medical use are crucial because they are specifically trained for certain clinical tasks, e.g. to detect tumors and classify abnormalities through segmentation and classification, which learn fine-grained features of medical data$-$features that are often too intricate for a VLM to capture effectively especially in radiology. This paper introduces a new framework, VILA-M3, for medical VLMs that utilizes domain knowledge via expert models. Through our experiments, we show an improved state-of-the-art (SOTA) performance with an average improvement of ~9% over the prior SOTA model Med-Gemini and ~6% over models trained on the specific tasks. Our approach emphasizes the importance of domain expertise in creating precise, reliable VLMs for medical applications.

Hongyi Pan, Ziliang Hong, Gorkem Durak et al.

Accurate classification of Intraductal Papillary Mucinous Neoplasms (IPMN) is essential for identifying high-risk cases that require timely intervention. In this study, we develop a federated learning framework for multi-center IPMN classification utilizing a comprehensive pancreas MRI dataset. This dataset includes 652 T1-weighted and 655 T2-weighted MRI images, accompanied by corresponding IPMN risk scores from 7 leading medical institutions, making it the largest and most diverse dataset for IPMN classification to date. We assess the performance of DenseNet-121 in both centralized and federated settings for training on distributed data. Our results demonstrate that the federated learning approach achieves high classification accuracy comparable to centralized learning while ensuring data privacy across institutions. This work marks a significant advancement in collaborative IPMN classification, facilitating secure and high-accuracy model training across multiple centers.

Hongyi Pan, Gorkem Durak, Zheyuan Zhang et al.

Federated learning (FL) enables collaborative model training across institutions without sharing sensitive data, making it an attractive solution for medical imaging tasks. However, traditional FL methods, such as Federated Averaging (FedAvg), face difficulties in generalizing across domains due to variations in imaging protocols and patient demographics across institutions. This challenge is particularly evident in pancreas MRI segmentation, where anatomical variability and imaging artifacts significantly impact performance. In this paper, we conduct a comprehensive evaluation of FL algorithms for pancreas MRI segmentation and introduce a novel approach that incorporates adaptive aggregation weights. By dynamically adjusting the contribution of each client during model aggregation, our method accounts for domain-specific differences and improves generalization across heterogeneous datasets. Experimental results demonstrate that our approach enhances segmentation accuracy and reduces the impact of domain shift compared to conventional FL methods while maintaining privacy-preserving capabilities. Significant performance improvements are observed across multiple hospitals (centers).

Ziyue Xu, Mingfeng Xu, Tianchi Liao et al.

Recently, the success of large models has demonstrated the importance of scaling up model size. This has spurred interest in exploring collaborative training of large-scale models from federated learning perspective. Due to computational constraints, many institutions struggle to train a large-scale model locally. Thus, training a larger global model using only smaller local models has become an important scenario (i.e., the \textbf{small-to-large scenario}). Although recent device-heterogeneity federated learning approaches have started to explore this area, they face limitations in fully covering the parameter space of the global model. In this paper, we propose a method called \textbf{FedBRB} (\underline{B}lock-wise \underline{R}olling and weighted \underline{B}roadcast) based on the block concept. FedBRB can uses small local models to train all blocks of the large global model, and broadcasts the trained parameters to the entire space for faster information interaction. Experiments demonstrate FedBRB yields substantial performance gains, achieving state-of-the-art results in this scenario. Moreover, FedBRB using only minimal local models can even surpass baselines using larger local models.

Hongyi Pan, Ziliang Hong, Gorkem Durak et al.

Federated learning (FL) has emerged as a promising paradigm for collaboratively training deep learning models across institutions without exchanging sensitive medical data. However, its effectiveness is often hindered by limited data availability and non-independent, identically distributed data across participating clients, which can degrade model performance and generalization. To address these challenges, we propose a generative AI based data augmentation framework that integrates synthetic image sharing into the federated training process for breast cancer diagnosis via ultrasound images. Specifically, we train two simple class-specific Deep Convolutional Generative Adversarial Networks: one for benign and one for malignant lesions. We then simulate a realistic FL setting using three publicly available breast ultrasound image datasets: BUSI, BUS-BRA, and UDIAT. FedAvg and FedProx are adopted as baseline FL algorithms. Experimental results show that incorporating a suitable number of synthetic images improved the average AUC from 0.9206 to 0.9237 for FedAvg and from 0.9429 to 0.9538 for FedProx. We also note that excessive use of synthetic data reduced performance, underscoring the importance of maintaining a balanced ratio of real and synthetic samples. Our findings highlight the potential of generative AI based data augmentation to enhance FL results in the breast ultrasound image classification task.

Bin Sun, Jingyi Zhou, Jianan Mu et al.

In traditional EDA flows, layout-level performance metrics are only obtainable after placement and routing, hindering global optimization at earlier stages. Although some neural-network-based solutions predict layout-level performance directly from netlists, they often face generalization challenges due to the black-box heuristics of commercial placement-and-routing tools, which create disparate data across designs. To this end, we propose ParaGate, a three-step cross-stage prediction framework that infers layout-level timing and power from netlists. First, we propose a two-phase transfer-learning approach to predict parasitic parameters, pre-training on mid-scale circuits and fine-tuning on larger ones to capture extreme conditions. Next, we rely on EDA tools for timing analysis, offloading the long-path numerical reasoning. Finally, ParaGate performs global calibration using subgraph features. Experiments show that ParaGate achieves strong generalization with minimal fine-tuning data: on openE906, its arrival-time R2 from 0.119 to 0.897. These results demonstrate that ParaGate could provide guidance for global optimization in the synthesis and placement stages.

Dong Yang, Andriy Myronenko, Xiaosong Wang et al.

Lesion segmentation in medical imaging has been an important topic in clinical research. Researchers have proposed various detection and segmentation algorithms to address this task. Recently, deep learning-based approaches have significantly improved the performance over conventional methods. However, most state-of-the-art deep learning methods require the manual design of multiple network components and training strategies. In this paper, we propose a new automated machine learning algorithm, T-AutoML, which not only searches for the best neural architecture, but also finds the best combination of hyper-parameters and data augmentation strategies simultaneously. The proposed method utilizes the modern transformer model, which is introduced to adapt to the dynamic length of the search space embedding and can significantly improve the ability of the search. We validate T-AutoML on several large-scale public lesion segmentation data-sets and achieve state-of-the-art performance.

Andriy Myronenko, Ziyue Xu, Dong Yang et al.

Multiple instance learning (MIL) is a key algorithm for classification of whole slide images (WSI). Histology WSIs can have billions of pixels, which create enormous computational and annotation challenges. Typically, such images are divided into a set of patches (a bag of instances), where only bag-level class labels are provided. Deep learning based MIL methods calculate instance features using convolutional neural network (CNN). Our proposed approach is also deep learning based, with the following two contributions: Firstly, we propose to explicitly account for dependencies between instances during training by embedding self-attention Transformer blocks to capture dependencies between instances. For example, a tumor grade may depend on the presence of several particular patterns at different locations in WSI, which requires to account for dependencies between patches. Secondly, we propose an instance-wise loss function based on instance pseudo-labels. We compare the proposed algorithm to multiple baseline methods, evaluate it on the PANDA challenge dataset, the largest publicly available WSI dataset with over 11K images, and demonstrate state-of-the-art results.

Riddhish Bhalodia, Ali Hatamizadeh, Leo Tam et al.

Localization and characterization of diseases like pneumonia are primary steps in a clinical pipeline, facilitating detailed clinical diagnosis and subsequent treatment planning. Additionally, such location annotated datasets can provide a pathway for deep learning models to be used for downstream tasks. However, acquiring quality annotations is expensive on human resources and usually requires domain expertise. On the other hand, medical reports contain a plethora of information both about pneumonia characteristics and its location. In this paper, we propose a novel weakly-supervised attention-driven deep learning model that leverages encoded information in medical reports during training to facilitate better localization. Our model also performs classification of attributes that are associated to pneumonia and extracted from medical reports for supervision. Both the classification and localization are trained in conjunction and once trained, the model can be utilized for both the localization and characterization of pneumonia using only the input image. In this paper, we explore and analyze the model using chest X-ray datasets and demonstrate qualitatively and quantitatively that the introduction of textual information improves pneumonia localization. We showcase quantitative results on two datasets, MIMIC-CXR and Chest X-ray-8, and we also showcase severity characterization on the COVID-19 dataset.

Holger R. Roth, Dong Yang, Wenqi Li et al.

Building robust deep learning-based models requires diverse training data, ideally from several sources. However, these datasets cannot be combined easily because of patient privacy concerns or regulatory hurdles, especially if medical data is involved. Federated learning (FL) is a way to train machine learning models without the need for centralized datasets. Each FL client trains on their local data while only sharing model parameters with a global server that aggregates the parameters from all clients. At the same time, each client's data can exhibit differences and inconsistencies due to the local variation in the patient population, imaging equipment, and acquisition protocols. Hence, the federated learned models should be able to adapt to the local particularities of a client's data. In this work, we combine FL with an AutoML technique based on local neural architecture search by training a "supernet". Furthermore, we propose an adaptation scheme to allow for personalized model architectures at each FL client's site. The proposed method is evaluated on four different datasets from 3D prostate MRI and shown to improve the local models' performance after adaptation through selecting an optimal path through the AutoML supernet.

Chuan Chen, Weibo Hu, Ziyue Xu et al.

Graph data are ubiquitous in the real world. Graph learning (GL) tries to mine and analyze graph data so that valuable information can be discovered. Existing GL methods are designed for centralized scenarios. However, in practical scenarios, graph data are usually distributed in different organizations, i.e., the curse of isolated data islands. To address this problem, we incorporate federated learning into GL and propose a general Federated Graph Learning framework FedGL, which is capable of obtaining a high-quality global graph model while protecting data privacy by discovering the global self-supervision information during the federated training. Concretely, we propose to upload the prediction results and node embeddings to the server for discovering the global pseudo label and global pseudo graph, which are distributed to each client to enrich the training labels and complement the graph structure respectively, thereby improving the quality of each local model. Moreover, the global self-supervision enables the information of each client to flow and share in a privacy-preserving manner, thus alleviating the heterogeneity and utilizing the complementarity of graph data among different clients. Finally, experimental results show that FedGL significantly outperforms baselines on four widely used graph datasets.

Xiaosong Wang, Ziyue Xu, Leo Tam et al.

Pre-trained models, e.g., from ImageNet, have proven to be effective in boosting the performance of many downstream applications. It is too demanding to acquire large-scale annotations to build such models for medical imaging. Meanwhile, there are numerous clinical data (in the form of images and text reports) stored in the hospital information systems. The paired image-text data from the same patient study could be utilized for the pre-training task in a weakly supervised manner. However, the integrity, accessibility, and amount of such raw data vary across different institutes, e.g., paired vs. unpaired (image-only or text-only). In this work, we introduce an image-text pre-training framework that can learn from these raw data with mixed data inputs, i.e., paired image-text data, a mixture of paired and unpaired data. The unpaired data can be sourced from one or multiple institutes (e.g., images from one institute coupled with texts from another). Specifically, we propose a transformer-based training framework for jointly learning the representation of both the image and text data. In addition to the existing masked language modeling, multi-scale masked vision modeling is introduced as a self-supervised training task for image patch regeneration. We not only demonstrate the feasibility of pre-training across mixed data inputs but also illustrate the benefits of adopting such pre-trained models in 3 chest X-ray applications, i.e., classification, retrieval, and image regeneration. Superior results are reported in comparison to prior art using MIMIC-CXR, NIH14-CXR, and OpenI-CXR datasets.

Dong Yang, Ziyue Xu, Wenqi Li et al.

The recent outbreak of COVID-19 has led to urgent needs for reliable diagnosis and management of SARS-CoV-2 infection. As a complimentary tool, chest CT has been shown to be able to reveal visual patterns characteristic for COVID-19, which has definite value at several stages during the disease course. To facilitate CT analysis, recent efforts have focused on computer-aided characterization and diagnosis, which has shown promising results. However, domain shift of data across clinical data centers poses a serious challenge when deploying learning-based models. In this work, we attempt to find a solution for this challenge via federated and semi-supervised learning. A multi-national database consisting of 1704 scans from three countries is adopted to study the performance gap, when training a model with one dataset and applying it to another. Expert radiologists manually delineated 945 scans for COVID-19 findings. In handling the variability in both the data and annotations, a novel federated semi-supervised learning technique is proposed to fully utilize all available data (with or without annotations). Federated learning avoids the need for sensitive data-sharing, which makes it favorable for institutions and nations with strict regulatory policy on data privacy. Moreover, semi-supervision potentially reduces the annotation burden under a distributed setting. The proposed framework is shown to be effective compared to fully supervised scenarios with conventional data sharing instead of model weight sharing.

Holger R Roth, Dong Yang, Ziyue Xu et al.

Medical image annotation is a major hurdle for developing precise and robust machine learning models. Annotation is expensive, time-consuming, and often requires expert knowledge, particularly in the medical field. Here, we suggest using minimal user interaction in the form of extreme point clicks to train a segmentation model which, in effect, can be used to speed up medical image annotation. An initial segmentation is generated based on the extreme points utilizing the random walker algorithm. This initial segmentation is then used as a noisy supervision signal to train a fully convolutional network that can segment the organ of interest, based on the provided user clicks. Through experimentation on several medical imaging datasets, we show that the predictions of the network can be refined using several rounds of training with the prediction from the same weakly annotated data. Further improvements are shown utilizing the clicked points within a custom-designed loss and attention mechanism. Our approach has the potential to speed up the process of generating new training datasets for the development of new machine learning and deep learning-based models for, but not exclusively, medical image analysis.

Xiaosong Wang, Ziyue Xu, Dong Yang et al.

Current deep learning paradigms largely benefit from the tremendous amount of annotated data. However, the quality of the annotations often varies among labelers. Multi-observer studies have been conducted to study these annotation variances (by labeling the same data for multiple times) and its effects on critical applications like medical image analysis. This process indeed adds an extra burden to the already tedious annotation work that usually requires professional training and expertise in the specific domains. On the other hand, automated annotation methods based on NLP algorithms have recently shown promise as a reasonable alternative, relying on the existing diagnostic reports of those images that are widely available in the clinical system. Compared to human labelers, different algorithms provide labels with varying qualities that are even noisier. In this paper, we show how noisy annotations (e.g., from different algorithm-based labelers) can be utilized together and mutually benefit the learning of classification tasks. Specifically, the concept of attention-on-label is introduced to sample better label sets on-the-fly as the training data. A meta-training based label-sampling module is designed to attend the labels that benefit the model learning the most through additional back-propagation processes. We apply the attention-on-label scheme on the classification task of a synthetic noisy CIFAR-10 dataset to prove the concept, and then demonstrate superior results (3-5% increase on average in multiple disease classification AUCs) on the chest x-ray images from a hospital-scale dataset (MIMIC-CXR) and hand-labeled dataset (OpenI) in comparison to regular training paradigms.

Bowen Chen, Huan Ling, Xiaohui Zeng et al.

Manually labeling video datasets for segmentation tasks is extremely time consuming. In this paper, we introduce ScribbleBox, a novel interactive framework for annotating object instances with masks in videos. In particular, we split annotation into two steps: annotating objects with tracked boxes, and labeling masks inside these tracks. We introduce automation and interaction in both steps. Box tracks are annotated efficiently by approximating the trajectory using a parametric curve with a small number of control points which the annotator can interactively correct. Our approach tolerates a modest amount of noise in the box placements, thus typically only a few clicks are needed to annotate tracked boxes to a sufficient accuracy. Segmentation masks are corrected via scribbles which are efficiently propagated through time. We show significant performance gains in annotation efficiency over past work. We show that our ScribbleBox approach reaches 88.92% J&F on DAVIS2017 with 9.14 clicks per box track, and 4 frames of scribble annotation.

Hoo-Chang Shin, Alvin Ihsani, Ziyue Xu et al.

Positron Emission Tomography (PET) is now regarded as the gold standard for the diagnosis of Alzheimer's Disease (AD). However, PET imaging can be prohibitive in terms of cost and planning, and is also among the imaging techniques with the highest dosage of radiation. Magnetic Resonance Imaging (MRI), in contrast, is more widely available and provides more flexibility when setting the desired image resolution. Unfortunately, the diagnosis of AD using MRI is difficult due to the very subtle physiological differences between healthy and AD subjects visible on MRI. As a result, many attempts have been made to synthesize PET images from MR images using generative adversarial networks (GANs) in the interest of enabling the diagnosis of AD from MR. Existing work on PET synthesis from MRI has largely focused on Conditional GANs, where MR images are used to generate PET images and subsequently used for AD diagnosis. There is no end-to-end training goal. This paper proposes an alternative approach to the aforementioned, where AD diagnosis is incorporated in the GAN training objective to achieve the best AD classification performance. Different GAN lossesare fine-tuned based on the discriminator performance, and the overall training is stabilized. The proposed network architecture and training regime show state-of-the-art performance for three- and four- class AD classification tasks.

Dong Yang, Holger Roth, Ziyue Xu et al.

Deep neural network (DNN) based approaches have been widely investigated and deployed in medical image analysis. For example, fully convolutional neural networks (FCN) achieve the state-of-the-art performance in several applications of 2D/3D medical image segmentation. Even the baseline neural network models (U-Net, V-Net, etc.) have been proven to be very effective and efficient when the training process is set up properly. Nevertheless, to fully exploit the potentials of neural networks, we propose an automated searching approach for the optimal training strategy with reinforcement learning. The proposed approach can be utilized for tuning hyper-parameters, and selecting necessary data augmentation with certain probabilities. The proposed approach is validated on several tasks of 3D medical image segmentation. The performance of the baseline model is boosted after searching, and it can achieve comparable accuracy to other manually-tuned state-of-the-art segmentation approaches.

Dong Yang, Holger Roth, Xiaosong Wang et al.

Object segmentation plays an important role in the modern medical image analysis, which benefits clinical study, disease diagnosis, and surgery planning. Given the various modalities of medical images, the automated or semi-automated segmentation approaches have been used to identify and parse organs, bones, tumors, and other regions-of-interest (ROI). However, these contemporary segmentation approaches tend to fail to predict the boundary areas of ROI, because of the fuzzy appearance contrast caused during the imaging procedure. To further improve the segmentation quality of boundary areas, we propose a boundary enhancement loss to enforce additional constraints on optimizing machine learning models. The proposed loss function is light-weighted and easy to implement without any pre- or post-processing. Our experimental results validate that our loss function are better than, or at least comparable to, other state-of-the-art loss functions in terms of segmentation accuracy.

Rodney LaLonde, Ziyue Xu, Ismail Irmakci et al.

Our work expands the use of capsule networks to the task of object segmentation for the first time in the literature. This is made possible via the introduction of locally-constrained routing and transformation matrix sharing, which reduces the parameter/memory burden and allows for the segmentation of objects at large resolutions. To compensate for the loss of global information in constraining the routing, we propose the concept of "deconvolutional" capsules to create a deep encoder-decoder style network, called SegCaps. We extend the masked reconstruction regularization to the task of segmentation and perform thorough ablation experiments on each component of our method. The proposed convolutional-deconvolutional capsule network, SegCaps, shows state-of-the-art results while using a fraction of the parameters of popular segmentation networks. To validate our proposed method, we perform experiments segmenting pathological lungs from clinical and pre-clinical thoracic computed tomography (CT) scans and segmenting muscle and adipose (fat) tissue from magnetic resonance imaging (MRI) scans of human subjects' thighs. Notably, our experiments in lung segmentation represent the largest-scale study in pathological lung segmentation in the literature, where we conduct experiments across five extremely challenging datasets, containing both clinical and pre-clinical subjects, and nearly 2000 computed-tomography scans. Our newly developed segmentation platform outperforms other methods across all datasets while utilizing less than 5% of the parameters in the popular U-Net for biomedical image segmentation. Further, we demonstrate capsules' ability to generalize to unseen rotations/reflections on natural images.

Yixiao Zhang, Xiaosong Wang, Ziyue Xu et al.

Automatic radiology report generation has been an attracting research problem towards computer-aided diagnosis to alleviate the workload of doctors in recent years. Deep learning techniques for natural image captioning are successfully adapted to generating radiology reports. However, radiology image reporting is different from the natural image captioning task in two aspects: 1) the accuracy of positive disease keyword mentions is critical in radiology image reporting in comparison to the equivalent importance of every single word in a natural image caption; 2) the evaluation of reporting quality should focus more on matching the disease keywords and their associated attributes instead of counting the occurrence of N-gram. Based on these concerns, we propose to utilize a pre-constructed graph embedding module (modeled with a graph convolutional neural network) on multiple disease findings to assist the generation of reports in this work. The incorporation of knowledge graph allows for dedicated feature learning for each disease finding and the relationship modeling between them. In addition, we proposed a new evaluation metric for radiology image reporting with the assistance of the same composed graph. Experimental results demonstrate the superior performance of the methods integrated with the proposed graph embedding module on a publicly accessible dataset (IU-RR) of chest radiographs compared with previous approaches using both the conventional evaluation metrics commonly adopted for image captioning and our proposed ones.

Wentao Zhu, Andriy Myronenko, Ziyue Xu et al.

Registration is a fundamental task in medical image analysis which can be applied to several tasks including image segmentation, intra-operative tracking, multi-modal image alignment, and motion analysis. Popular registration tools such as ANTs and NiftyReg optimize an objective function for each pair of images from scratch which is time-consuming for large images with complicated deformation. Facilitated by the rapid progress of deep learning, learning-based approaches such as VoxelMorph have been emerging for image registration. These approaches can achieve competitive performance in a fraction of a second on advanced GPUs. In this work, we construct a neural registration framework, called NeurReg, with a hybrid loss of displacement fields and data similarity, which substantially improves the current state-of-the-art of registrations. Within the framework, we simulate various transformations by a registration simulator which generates fixed image and displacement field ground truth for training. Furthermore, we design three segmentation frameworks based on the proposed registration framework: 1) atlas-based segmentation, 2) joint learning of both segmentation and registration tasks, and 3) multi-task learning with atlas-based segmentation as an intermediate feature. Extensive experimental results validate the effectiveness of the proposed NeurReg framework based on various metrics: the endpoint error (EPE) of the predicted displacement field, mean square error (MSE), normalized local cross-correlation (NLCC), mutual information (MI), Dice coefficient, uncertainty estimation, and the interpretability of the segmentation. The proposed NeurReg improves registration accuracy with fast inference speed, which can greatly accelerate related medical image analysis tasks.

Holger Roth, Wentao Zhu, Dong Yang et al.

In this work, we attempt the segmentation of cardiac structures in late gadolinium-enhanced (LGE) magnetic resonance images (MRI) using only minimal supervision in a two-step approach. In the first step, we register a small set of five LGE cardiac magnetic resonance (CMR) images with ground truth labels to a set of 40 target LGE CMR images without annotation. Each manually annotated ground truth provides labels of the myocardium and the left ventricle (LV) and right ventricle (RV) cavities, which are used as atlases. After multi-atlas label fusion by majority voting, we possess noisy labels for each of the targeted LGE images. A second set of manual labels exists for 30 patients of the target LGE CMR images, but are annotated on different MRI sequences (bSSFP and T2-weighted). Again, we use multi-atlas label fusion with a consistency constraint to further refine our noisy labels if additional annotations in other modalities are available for a given patient. In the second step, we train a deep convolutional network for semantic segmentation on the target data while using data augmentation techniques to avoid over-fitting to the noisy labels. After inference and simple post-processing, we achieve our final segmentation for the targeted LGE CMR images, resulting in an average Dice of 0.890, 0.780, and 0.844 for LV cavity, LV myocardium, and RV cavity, respectively.

Holger Roth, Ling Zhang, Dong Yang et al.

Annotation of medical images has been a major bottleneck for the development of accurate and robust machine learning models. Annotation is costly and time-consuming and typically requires expert knowledge, especially in the medical domain. Here, we propose to use minimal user interaction in the form of extreme point clicks in order to train a segmentation model that can, in turn, be used to speed up the annotation of medical images. We use extreme points in each dimension of a 3D medical image to constrain an initial segmentation based on the random walker algorithm. This segmentation is then used as a weak supervisory signal to train a fully convolutional network that can segment the organ of interest based on the provided user clicks. We show that the network's predictions can be refined through several iterations of training and prediction using the same weakly annotated data. Ultimately, our method has the potential to speed up the generation process of new training datasets for the development of new machine learning and deep learning-based models for, but not exclusively, medical image analysis.

Ziyue Xu, Xiaosong Wang, Hoo-Chang Shin et al.

Radiogenomic map linking image features and gene expression profiles is useful for noninvasively identifying molecular properties of a particular type of disease. Conventionally, such map is produced in three separate steps: 1) gene-clustering to "metagenes", 2) image feature extraction, and 3) statistical correlation between metagenes and image features. Each step is independently performed and relies on arbitrary measurements. In this work, we investigate the potential of an end-to-end method fusing gene data with image features to generate synthetic image and learn radiogenomic map simultaneously. To achieve this goal, we develop a generative adversarial network (GAN) conditioned on both background images and gene expression profiles, synthesizing the corresponding image. Image and gene features are fused at different scales to ensure the realism and quality of the synthesized image. We tested our method on non-small cell lung cancer (NSCLC) dataset. Results demonstrate that the proposed method produces realistic synthetic images, and provides a promising way to find gene-image relationship in a holistic end-to-end manner.

Ling Zhang, Xiaosong Wang, Dong Yang et al.

Recent advances in deep learning for medical image segmentation demonstrate expert-level accuracy. However, in clinically realistic environments, such methods have marginal performance due to differences in image domains, including different imaging protocols, device vendors and patient populations. Here we consider the problem of domain generalization, when a model is trained once, and its performance generalizes to unseen domains. Intuitively, within a specific medical imaging modality the domain differences are smaller relative to natural images domain variability. We rethink data augmentation for medical 3D images and propose a deep stacked transformations (DST) approach for domain generalization. Specifically, a series of n stacked transformations are applied to each image in each mini-batch during network training to account for the contribution of domain-specific shifts in medical images. We comprehensively evaluate our method on three tasks: segmentation of whole prostate from 3D MRI, left atrial from 3D MRI, and left ventricle from 3D ultrasound. We demonstrate that when trained on a small source dataset, (i) on average, DST models on unseen datasets degrade only by 11% (Dice score change), compared to the conventional augmentation (degrading 39%) and CycleGAN-based domain adaptation method (degrading 25%); (ii) when evaluation on the same domain, DST is also better albeit only marginally. (iii) When training on large-sized data, DST on unseen domains reaches performance of state-of-the-art fully supervised models. These findings establish a strong benchmark for the study of domain generalization in medical imaging, and can be generalized to the design of robust deep segmentation models for clinical deployment.

Hugo J. Kuijf, J. Matthijs Biesbroek, Jeroen de Bresser et al.

Quantification of cerebral white matter hyperintensities (WMH) of presumed vascular origin is of key importance in many neurological research studies. Currently, measurements are often still obtained from manual segmentations on brain MR images, which is a laborious procedure. Automatic WMH segmentation methods exist, but a standardized comparison of the performance of such methods is lacking. We organized a scientific challenge, in which developers could evaluate their method on a standardized multi-center/-scanner image dataset, giving an objective comparison: the WMH Segmentation Challenge (https://wmh.isi.uu.nl/). Sixty T1+FLAIR images from three MR scanners were released with manual WMH segmentations for training. A test set of 110 images from five MR scanners was used for evaluation. Segmentation methods had to be containerized and submitted to the challenge organizers. Five evaluation metrics were used to rank the methods: (1) Dice similarity coefficient, (2) modified Hausdorff distance (95th percentile), (3) absolute log-transformed volume difference, (4) sensitivity for detecting individual lesions, and (5) F1-score for individual lesions. Additionally, methods were ranked on their inter-scanner robustness. Twenty participants submitted their method for evaluation. This paper provides a detailed analysis of the results. In brief, there is a cluster of four methods that rank significantly better than the other methods, with one clear winner. The inter-scanner robustness ranking shows that not all methods generalize to unseen scanners. The challenge remains open for future submissions and provides a public platform for method evaluation.

Tomas Sakinis, Fausto Milletari, Holger Roth et al.

Image segmentation plays an essential role in medicine for both diagnostic and interventional tasks. Segmentation approaches are either manual, semi-automated or fully-automated. Manual segmentation offers full control over the quality of the results, but is tedious, time consuming and prone to operator bias. Fully automated methods require no human effort, but often deliver sub-optimal results without providing users with the means to make corrections. Semi-automated approaches keep users in control of the results by providing means for interaction, but the main challenge is to offer a good trade-off between precision and required interaction. In this paper we present a deep learning (DL) based semi-automated segmentation approach that aims to be a "smart" interactive tool for region of interest delineation in medical images. We demonstrate its use for segmenting multiple organs on computed tomography (CT) of the abdomen. Our approach solves some of the most pressing clinical challenges: (i) it requires only one to a few user clicks to deliver excellent 2D segmentations in a fast and reliable fashion; (ii) it can generalize to previously unseen structures and "corner cases"; (iii) it delivers results that can be corrected quickly in a smart and intuitive way up to an arbitrary degree of precision chosen by the user and (iv) ensures high accuracy. We present our approach and compare it to other techniques and previous work to show the advantages brought by our method.

Dakai Jin, Ziyue Xu, Youbao Tang et al.

Data availability plays a critical role for the performance of deep learning systems. This challenge is especially acute within the medical image domain, particularly when pathologies are involved, due to two factors: 1) limited number of cases, and 2) large variations in location, scale, and appearance. In this work, we investigate whether augmenting a dataset with artificially generated lung nodules can improve the robustness of the progressive holistically nested network (P-HNN) model for pathological lung segmentation of CT scans. To achieve this goal, we develop a 3D generative adversarial network (GAN) that effectively learns lung nodule property distributions in 3D space. In order to embed the nodules within their background context, we condition the GAN based on a volume of interest whose central part containing the nodule has been erased. To further improve realism and blending with the background, we propose a novel multi-mask reconstruction loss. We train our method on over 1000 nodules from the LIDC dataset. Qualitative results demonstrate the effectiveness of our method compared to the state-of-art. We then use our GAN to generate simulated training images where nodules lie on the lung border, which are cases where the published P-HNN model struggles. Qualitative and quantitative results demonstrate that armed with these simulated images, the P-HNN model learns to better segment lung regions under these challenging situations. As a result, our system provides a promising means to help overcome the data paucity that commonly afflicts medical imaging.

Dakai Jin, Ziyue Xu, Adam P. Harrison et al.

Segmentation and quantification of white matter hyperintensities (WMHs) are of great importance in studying and understanding various neurological and geriatric disorders. Although automatic methods have been proposed for WMH segmentation on magnetic resonance imaging (MRI), manual corrections are often necessary to achieve clinically practical results. Major challenges for WMH segmentation stem from their inhomogeneous MRI intensities, random location and size distributions, and MRI noise. The presence of other brain anatomies or diseases with enhanced intensities adds further difficulties. To cope with these challenges, we present a specifically designed fully convolutional neural network (FCN) with residual connections to segment WMHs by using combined T1 and fluid-attenuated inversion recovery (FLAIR) images. Our customized FCN is designed to be straightforward and generalizable, providing efficient end-to-end training due to its enhanced information propagation. We tested our method on the open WMH Segmentation Challenge MICCAI2017 dataset, and, despite our method's relative simplicity, results show that it performs amongst the leading techniques across five metrics. More importantly, our method achieves the best score for hausdorff distance and average volume difference in testing datasets from two MRI scanners that were not included in training, demonstrating better generalization ability of our proposed method over its competitors.

Mingchen Gao, Ziyue Xu, Le Lu et al.

Accurately predicting and detecting interstitial lung disease (ILD) patterns given any computed tomography (CT) slice without any pre-processing prerequisites, such as manually delineated regions of interest (ROIs), is a clinically desirable, yet challenging goal. The majority of existing work relies on manually-provided ILD ROIs to extract sampled 2D image patches from CT slices and, from there, performs patch-based ILD categorization. Acquiring manual ROIs is labor intensive and serves as a bottleneck towards fully-automated CT imaging ILD screening over large-scale populations. Furthermore, despite the considerable high frequency of more than one ILD pattern on a single CT slice, previous works are only designed to detect one ILD pattern per slice or patch. To tackle these two critical challenges, we present multi-label deep convolutional neural networks (CNNs) for detecting ILDs from holistic CT slices (instead of ROIs or sub-images). Conventional single-labeled CNN models can be augmented to cope with the possible presence of multiple ILD pattern labels, via 1) continuous-valued deep regression based robust norm loss functions or 2) a categorical objective as the sum of element-wise binary logistic losses. Our methods are evaluated and validated using a publicly available database of 658 patient CT scans under five-fold cross-validation, achieving promising performance on detecting four major ILD patterns: Ground Glass, Reticular, Honeycomb, and Emphysema. We also investigate the effectiveness of a CNN activation-based deep-feature encoding scheme using Fisher vector encoding, which treats ILD detection as spatially-unordered deep texture classification.

Mario Buty, Ziyue Xu, Mingchen Gao et al.

Computed tomography imaging is a standard modality for detecting and assessing lung cancer. In order to evaluate the malignancy of lung nodules, clinical practice often involves expert qualitative ratings on several criteria describing a nodule's appearance and shape. Translating these features for computer-aided diagnostics is challenging due to their subjective nature and the difficulties in gaining a complete description. In this paper, we propose a computerized approach to quantitatively evaluate both appearance distinctions and 3D surface variations. Nodule shape was modeled and parameterized using spherical harmonics, and appearance features were extracted using deep convolutional neural networks. Both sets of features were combined to estimate the nodule malignancy using a random forest classifier. The proposed algorithm was tested on the publicly available Lung Image Database Consortium dataset, achieving high accuracy. By providing lung nodule characterization, this method can provide a robust alternative reference opinion for lung cancer diagnosis.

Hoo-Chang Shin, Holger R. Roth, Mingchen Gao et al.

Remarkable progress has been made in image recognition, primarily due to the availability of large-scale annotated datasets and the revival of deep CNN. CNNs enable learning data-driven, highly representative, layered hierarchical image features from sufficient training data. However, obtaining datasets as comprehensively annotated as ImageNet in the medical imaging domain remains a challenge. There are currently three major techniques that successfully employ CNNs to medical image classification: training the CNN from scratch, using off-the-shelf pre-trained CNN features, and conducting unsupervised CNN pre-training with supervised fine-tuning. Another effective method is transfer learning, i.e., fine-tuning CNN models pre-trained from natural image dataset to medical image tasks. In this paper, we exploit three important, but previously understudied factors of employing deep convolutional neural networks to computer-aided detection problems. We first explore and evaluate different CNN architectures. The studied models contain 5 thousand to 160 million parameters, and vary in numbers of layers. We then evaluate the influence of dataset scale and spatial image context on performance. Finally, we examine when and why transfer learning from pre-trained ImageNet (via fine-tuning) can be useful. We study two specific computer-aided detection (CADe) problems, namely thoraco-abdominal lymph node (LN) detection and interstitial lung disease (ILD) classification. We achieve the state-of-the-art performance on the mediastinal LN detection, with 85% sensitivity at 3 false positive per patient, and report the first five-fold cross-validation classification results on predicting axial CT slices with ILD categories. Our extensive empirical evaluation, CNN model analysis and valuable insights can be extended to the design of high performance CAD systems for other medical imaging tasks.