Holger Roth

Ali Hatamizadeh, Ziyue Xu, Dong Yang et al.

Vision Transformers (ViT)s have recently become popular due to their outstanding modeling capabilities, in particular for capturing long-range information, and scalability to dataset and model sizes which has led to state-of-the-art performance in various computer vision and medical image analysis tasks. In this work, we introduce a unified framework consisting of two architectures, dubbed UNetFormer, with a 3D Swin Transformer-based encoder and Convolutional Neural Network (CNN) and transformer-based decoders. In the proposed model, the encoder is linked to the decoder via skip connections at five different resolutions with deep supervision. The design of proposed architecture allows for meeting a wide range of trade-off requirements between accuracy and computational cost. In addition, we present a methodology for self-supervised pre-training of the encoder backbone via learning to predict randomly masked volumetric tokens using contextual information of visible tokens. We pre-train our framework on a cohort of $5050$ CT images, gathered from publicly available CT datasets, and present a systematic investigation of various components such as masking ratio and patch size that affect the representation learning capability and performance of downstream tasks. We validate the effectiveness of our pre-training approach by fine-tuning and testing our model on liver and liver tumor segmentation task using the Medical Segmentation Decathlon (MSD) dataset and achieve state-of-the-art performance in terms of various segmentation metrics. To demonstrate its generalizability, we train and test the model on BraTS 21 dataset for brain tumor segmentation using MRI images and outperform other methods in terms of Dice score. Code: https://github.com/Project-MONAI/research-contributions

Hasan Kassem, Orion Banks, Omar Benjelloun et al.

Decentralized AI systems, such as federated learning, can play a critical role in further unlocking AI asset marketplaces (e.g., healthcare data marketplaces) thanks to increased asset privacy protection. Unlocking this big potential necessitates governance mechanisms that are transparent, scalable, and verifiable. However current governance approaches rely on bespoke, infrastructure-specific policies that hinder asset interoperability and trust among systems. We are proposing a Technical Policy Blueprint that encodes governance requirements as policy-as-code objects and separates asset policy verification from asset policy enforcement. In this architecture the Policy Engine verifies evidence (e.g., identities, signatures, payments, trusted-hardware attestations) and issues capability packages. Asset Guardians (e.g. data guardians, model guardians, computation guardians, etc.) enforce access or execution solely based on these capability packages. This core concept of decoupling policy processing from capabilities enables governance to evolve without reconfiguring AI infrastructure, thus creating an approach that is transparent, auditable, and resilient to change.

Ali Hatamizadeh, Hongxu Yin, Holger Roth et al.

In this work we demonstrate the vulnerability of vision transformers (ViTs) to gradient-based inversion attacks. During this attack, the original data batch is reconstructed given model weights and the corresponding gradients. We introduce a method, named GradViT, that optimizes random noise into naturally looking images via an iterative process. The optimization objective consists of (i) a loss on matching the gradients, (ii) image prior in the form of distance to batch-normalization statistics of a pretrained CNN model, and (iii) a total variation regularization on patches to guide correct recovery locations. We propose a unique loss scheduling function to overcome local minima during optimization. We evaluate GadViT on ImageNet1K and MS-Celeb-1M datasets, and observe unprecedentedly high fidelity and closeness to the original (hidden) data. During the analysis we find that vision transformers are significantly more vulnerable than previously studied CNNs due to the presence of the attention mechanism. Our method demonstrates new state-of-the-art results for gradient inversion in both qualitative and quantitative metrics. Project page at https://gradvit.github.io/.

An Xu, Wenqi Li, Pengfei Guo et al.

Cross-silo federated learning (FL) has attracted much attention in medical imaging analysis with deep learning in recent years as it can resolve the critical issues of insufficient data, data privacy, and training efficiency. However, there can be a generalization gap between the model trained from FL and the one from centralized training. This important issue comes from the non-iid data distribution of the local data in the participating clients and is well-known as client drift. In this work, we propose a novel training framework FedSM to avoid the client drift issue and successfully close the generalization gap compared with the centralized training for medical image segmentation tasks for the first time. We also propose a novel personalized FL objective formulation and a new method SoftPull to solve it in our proposed framework FedSM. We conduct rigorous theoretical analysis to guarantee its convergence for optimizing the non-convex smooth objective function. Real-world medical image segmentation experiments using deep FL validate the motivations and effectiveness of our proposed method.

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.

Pedro R. A. S. Bassi, Wenxuan Li, Yucheng Tang et al.

How can we test AI performance? This question seems trivial, but it isn't. Standard benchmarks often have problems such as in-distribution and small-size test sets, oversimplified metrics, unfair comparisons, and short-term outcome pressure. As a consequence, good performance on standard benchmarks does not guarantee success in real-world scenarios. To address these problems, we present Touchstone, a large-scale collaborative segmentation benchmark of 9 types of abdominal organs. This benchmark is based on 5,195 training CT scans from 76 hospitals around the world and 5,903 testing CT scans from 11 additional hospitals. This diverse test set enhances the statistical significance of benchmark results and rigorously evaluates AI algorithms across various out-of-distribution scenarios. We invited 14 inventors of 19 AI algorithms to train their algorithms, while our team, as a third party, independently evaluated these algorithms on three test sets. In addition, we also evaluated pre-existing AI frameworks--which, differing from algorithms, are more flexible and can support different algorithms--including MONAI from NVIDIA, nnU-Net from DKFZ, and numerous other open-source frameworks. We are committed to expanding this benchmark to encourage more innovation of AI algorithms for the medical domain.

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.

Ali Hatamizadeh, Vishwesh Nath, Yucheng Tang et al.

Semantic segmentation of brain tumors is a fundamental medical image analysis task involving multiple MRI imaging modalities that can assist clinicians in diagnosing the patient and successively studying the progression of the malignant entity. In recent years, Fully Convolutional Neural Networks (FCNNs) approaches have become the de facto standard for 3D medical image segmentation. The popular "U-shaped" network architecture has achieved state-of-the-art performance benchmarks on different 2D and 3D semantic segmentation tasks and across various imaging modalities. However, due to the limited kernel size of convolution layers in FCNNs, their performance of modeling long-range information is sub-optimal, and this can lead to deficiencies in the segmentation of tumors with variable sizes. On the other hand, transformer models have demonstrated excellent capabilities in capturing such long-range information in multiple domains, including natural language processing and computer vision. Inspired by the success of vision transformers and their variants, we propose a novel segmentation model termed Swin UNEt TRansformers (Swin UNETR). Specifically, the task of 3D brain tumor semantic segmentation is reformulated as a sequence to sequence prediction problem wherein multi-modal input data is projected into a 1D sequence of embedding and used as an input to a hierarchical Swin transformer as the encoder. The swin transformer encoder extracts features at five different resolutions by utilizing shifted windows for computing self-attention and is connected to an FCNN-based decoder at each resolution via skip connections. We have participated in BraTS 2021 segmentation challenge, and our proposed model ranks among the top-performing approaches in the validation phase. Code: https://monai.io/research/swin-unetr

Yucheng Tang, Dong Yang, Wenqi Li et al.

Vision Transformers (ViT)s have shown great performance in self-supervised learning of global and local representations that can be transferred to downstream applications. Inspired by these results, we introduce a novel self-supervised learning framework with tailored proxy tasks for medical image analysis. Specifically, we propose: (i) a new 3D transformer-based model, dubbed Swin UNEt TRansformers (Swin UNETR), with a hierarchical encoder for self-supervised pre-training; (ii) tailored proxy tasks for learning the underlying pattern of human anatomy. We demonstrate successful pre-training of the proposed model on 5,050 publicly available computed tomography (CT) images from various body organs. The effectiveness of our approach is validated by fine-tuning the pre-trained models on the Beyond the Cranial Vault (BTCV) Segmentation Challenge with 13 abdominal organs and segmentation tasks from the Medical Segmentation Decathlon (MSD) dataset. Our model is currently the state-of-the-art (i.e. ranked 1st) on the public test leaderboards of both MSD and BTCV datasets. Code: https://monai.io/research/swin-unetr

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.

Vishwesh Nath, Dong Yang, Ali Hatamizadeh et al.

Deep learning models for medical image segmentation are primarily data-driven. Models trained with more data lead to improved performance and generalizability. However, training is a computationally expensive process because multiple hyper-parameters need to be tested to find the optimal setting for best performance. In this work, we focus on accelerating the estimation of hyper-parameters by proposing two novel methodologies: proxy data and proxy networks. Both can be useful for estimating hyper-parameters more efficiently. We test the proposed techniques on CT and MR imaging modalities using well-known public datasets. In both cases using one dataset for building proxy data and another data source for external evaluation. For CT, the approach is tested on spleen segmentation with two datasets. The first dataset is from the medical segmentation decathlon (MSD), where the proxy data is constructed, the secondary dataset is utilized as an external validation dataset. Similarly, for MR, the approach is evaluated on prostate segmentation where the first dataset is from MSD and the second dataset is PROSTATEx. First, we show higher correlation to using full data for training when testing on the external validation set using smaller proxy data than a random selection of the proxy data. Second, we show that a high correlation exists for proxy networks when compared with the full network on validation Dice score. Third, we show that the proposed approach of utilizing a proxy network can speed up an AutoML framework for hyper-parameter search by 3.3x, and by 4.4x if proxy data and proxy network are utilized together.

Yingda Xia, Dong Yang, Wenqi Li et al.

Federated learning (FL) enables collaborative model training while preserving each participant's privacy, which is particularly beneficial to the medical field. FedAvg is a standard algorithm that uses fixed weights, often originating from the dataset sizes at each client, to aggregate the distributed learned models on a server during the FL process. However, non-identical data distribution across clients, known as the non-i.i.d problem in FL, could make this assumption for setting fixed aggregation weights sub-optimal. In this work, we design a new data-driven approach, namely Auto-FedAvg, where aggregation weights are dynamically adjusted, depending on data distributions across data silos and the current training progress of the models. We disentangle the parameter set into two parts, local model parameters and global aggregation parameters, and update them iteratively with a communication-efficient algorithm. We first show the validity of our approach by outperforming state-of-the-art FL methods for image recognition on a heterogeneous data split of CIFAR-10. Furthermore, we demonstrate our algorithm's effectiveness on two multi-institutional medical image analysis tasks, i.e., COVID-19 lesion segmentation in chest CT and pancreas segmentation in abdominal CT.

Yufan He, Dong Yang, Holger Roth et al.

Recently, neural architecture search (NAS) has been applied to automatically search high-performance networks for medical image segmentation. The NAS search space usually contains a network topology level (controlling connections among cells with different spatial scales) and a cell level (operations within each cell). Existing methods either require long searching time for large-scale 3D image datasets, or are limited to pre-defined topologies (such as U-shaped or single-path). In this work, we focus on three important aspects of NAS in 3D medical image segmentation: flexible multi-path network topology, high search efficiency, and budgeted GPU memory usage. A novel differentiable search framework is proposed to support fast gradient-based search within a highly flexible network topology search space. The discretization of the searched optimal continuous model in differentiable scheme may produce a sub-optimal final discrete model (discretization gap). Therefore, we propose a topology loss to alleviate this problem. In addition, the GPU memory usage for the searched 3D model is limited with budget constraints during search. Our Differentiable Network Topology Search scheme (DiNTS) is evaluated on the Medical Segmentation Decathlon (MSD) challenge, which contains ten challenging segmentation tasks. Our method achieves the state-of-the-art performance and the top ranking on the MSD challenge leaderboard.

Ali Hatamizadeh, Yucheng Tang, Vishwesh Nath et al.

Fully Convolutional Neural Networks (FCNNs) with contracting and expanding paths have shown prominence for the majority of medical image segmentation applications since the past decade. In FCNNs, the encoder plays an integral role by learning both global and local features and contextual representations which can be utilized for semantic output prediction by the decoder. Despite their success, the locality of convolutional layers in FCNNs, limits the capability of learning long-range spatial dependencies. Inspired by the recent success of transformers for Natural Language Processing (NLP) in long-range sequence learning, we reformulate the task of volumetric (3D) medical image segmentation as a sequence-to-sequence prediction problem. We introduce a novel architecture, dubbed as UNEt TRansformers (UNETR), that utilizes a transformer as the encoder to learn sequence representations of the input volume and effectively capture the global multi-scale information, while also following the successful "U-shaped" network design for the encoder and decoder. The transformer encoder is directly connected to a decoder via skip connections at different resolutions to compute the final semantic segmentation output. We have validated the performance of our method on the Multi Atlas Labeling Beyond The Cranial Vault (BTCV) dataset for multi-organ segmentation and the Medical Segmentation Decathlon (MSD) dataset for brain tumor and spleen segmentation tasks. Our benchmarks demonstrate new state-of-the-art performance on the BTCV leaderboard. Code: https://monai.io/research/unetr

Vikash Gupta1, Holger Roth, Varun Buch3 et al.

The training of deep learning models typically requires extensive data, which are not readily available as large well-curated medical-image datasets for development of artificial intelligence (AI) models applied in Radiology. Recognizing the potential for transfer learning (TL) to allow a fully trained model from one institution to be fine-tuned by another institution using a much small local dataset, this report describes the challenges, methodology, and benefits of TL within the context of developing an AI model for a basic use-case, segmentation of Left Ventricular Myocardium (LVM) on images from 4-dimensional coronary computed tomography angiography. Ultimately, our results from comparisons of LVM segmentation predicted by a model locally trained using random initialization, versus one training-enhanced by TL, showed that a use-case model initiated by TL can be developed with sparse labels with acceptable performance. This process reduces the time required to build a new model in the clinical environment at a different institution.

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.

Yingda Xia, Dong Yang, Zhiding Yu et al.

Although having achieved great success in medical image segmentation, deep learning-based approaches usually require large amounts of well-annotated data, which can be extremely expensive in the field of medical image analysis. Unlabeled data, on the other hand, is much easier to acquire. Semi-supervised learning and unsupervised domain adaptation both take the advantage of unlabeled data, and they are closely related to each other. In this paper, we propose uncertainty-aware multi-view co-training (UMCT), a unified framework that addresses these two tasks for volumetric medical image segmentation. Our framework is capable of efficiently utilizing unlabeled data for better performance. We firstly rotate and permute the 3D volumes into multiple views and train a 3D deep network on each view. We then apply co-training by enforcing multi-view consistency on unlabeled data, where an uncertainty estimation of each view is utilized to achieve accurate labeling. Experiments on the NIH pancreas segmentation dataset and a multi-organ segmentation dataset show state-of-the-art performance of the proposed framework on semi-supervised medical image segmentation. Under unsupervised domain adaptation settings, we validate the effectiveness of this work by adapting our multi-organ segmentation model to two pathological organs from the Medical Segmentation Decathlon Datasets. Additionally, we show that our UMCT-DA model can even effectively handle the challenging situation where labeled source data is inaccessible, demonstrating strong potentials for real-world applications.

Xiahai Zhuang, Jiahang Xu, Xinzhe Luo et al.

Accurate computing, analysis and modeling of the ventricles and myocardium from medical images are important, especially in the diagnosis and treatment management for patients suffering from myocardial infarction (MI). Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) provides an important protocol to visualize MI. However, automated segmentation of LGE CMR is still challenging, due to the indistinguishable boundaries, heterogeneous intensity distribution and complex enhancement patterns of pathological myocardium from LGE CMR. Furthermore, compared with the other sequences LGE CMR images with gold standard labels are particularly limited, which represents another obstacle for developing novel algorithms for automatic segmentation of LGE CMR. This paper presents the selective results from the Multi-Sequence Cardiac MR (MS-CMR) Segmentation challenge, in conjunction with MICCAI 2019. The challenge offered a data set of paired MS-CMR images, including auxiliary CMR sequences as well as LGE CMR, from 45 patients who underwent cardiomyopathy. It was aimed to develop new algorithms, as well as benchmark existing ones for LGE CMR segmentation and compare them objectively. In addition, the paired MS-CMR images could enable algorithms to combine the complementary information from the other sequences for the segmentation of LGE CMR. Nine representative works were selected for evaluation and comparisons, among which three methods are unsupervised methods and the other six are supervised. The results showed that the average performance of the nine methods was comparable to the inter-observer variations. The success of these methods was mainly attributed to the inclusion of the auxiliary sequences from the MS-CMR images, which provide important label information for the training of deep neural networks.

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.

Nicola Rieke, Jonny Hancox, Wenqi Li et al.

Data-driven Machine Learning has emerged as a promising approach for building accurate and robust statistical models from medical data, which is collected in huge volumes by modern healthcare systems. Existing medical data is not fully exploited by ML primarily because it sits in data silos and privacy concerns restrict access to this data. However, without access to sufficient data, ML will be prevented from reaching its full potential and, ultimately, from making the transition from research to clinical practice. This paper considers key factors contributing to this issue, explores how Federated Learning (FL) may provide a solution for the future of digital health and highlights the challenges and considerations that need to be addressed.

Qihang Yu, Dong Yang, Holger Roth et al.

3D convolution neural networks (CNN) have been proved very successful in parsing organs or tumours in 3D medical images, but it remains sophisticated and time-consuming to choose or design proper 3D networks given different task contexts. Recently, Neural Architecture Search (NAS) is proposed to solve this problem by searching for the best network architecture automatically. However, the inconsistency between search stage and deployment stage often exists in NAS algorithms due to memory constraints and large search space, which could become more serious when applying NAS to some memory and time consuming tasks, such as 3D medical image segmentation. In this paper, we propose coarse-to-fine neural architecture search (C2FNAS) to automatically search a 3D segmentation network from scratch without inconsistency on network size or input size. Specifically, we divide the search procedure into two stages: 1) the coarse stage, where we search the macro-level topology of the network, i.e. how each convolution module is connected to other modules; 2) the fine stage, where we search at micro-level for operations in each cell based on previous searched macro-level topology. The coarse-to-fine manner divides the search procedure into two consecutive stages and meanwhile resolves the inconsistency. We evaluate our method on 10 public datasets from Medical Segmentation Decalthon (MSD) challenge, and achieve state-of-the-art performance with the network searched using one dataset, which demonstrates the effectiveness and generalization of our searched models.

Jinzheng Cai, Yingda Xia, Dong Yang et al.

Automatic segmentation of abdomen organs using medical imaging has many potential applications in clinical workflows. Recently, the state-of-the-art performance for organ segmentation has been achieved by deep learning models, i.e., convolutional neural network (CNN). However, it is challenging to train the conventional CNN-based segmentation models that aware of the shape and topology of organs. In this work, we tackle this problem by introducing a novel end-to-end shape learning architecture -- organ point-network. It takes deep learning features as inputs and generates organ shape representations as points that located on organ surface. We later present a novel adversarial shape learning objective function to optimize the point-network to capture shape information better. We train the point-network together with a CNN-based segmentation model in a multi-task fashion so that the shared network parameters can benefit from both shape learning and segmentation tasks. We demonstrate our method with three challenging abdomen organs including liver, spleen, and pancreas. The point-network generates surface points with fine-grained details and it is found critical for improving organ segmentation. Consequently, the deep segmentation model is improved by the introduced shape learning as significantly better Dice scores are observed for spleen and pancreas segmentation.

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.

Andriy Myronenko, Dong Yang, Varun Buch et al.

We propose a 4D convolutional neural network (CNN) for the segmentation of retrospective ECG-gated cardiac CT, a series of single-channel volumetric data over time. While only a small subset of volumes in the temporal sequence is annotated, we define a sparse loss function on available labels to allow the network to leverage unlabeled images during training and generate a fully segmented sequence. We investigate the accuracy of the proposed 4D network to predict temporally consistent segmentations and compare with traditional 3D segmentation approaches. We demonstrate the feasibility of the 4D CNN and establish its performance on cardiac 4D CCTA.

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.

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.

Yingda Xia, Fengze Liu, Dong Yang et al.

While making a tremendous impact in various fields, deep neural networks usually require large amounts of labeled data for training which are expensive to collect in many applications, especially in the medical domain. Unlabeled data, on the other hand, is much more abundant. Semi-supervised learning techniques, such as co-training, could provide a powerful tool to leverage unlabeled data. In this paper, we propose a novel framework, uncertainty-aware multi-view co-training (UMCT), to address semi-supervised learning on 3D data, such as volumetric data from medical imaging. In our work, co-training is achieved by exploiting multi-viewpoint consistency of 3D data. We generate different views by rotating or permuting the 3D data and utilize asymmetrical 3D kernels to encourage diversified features in different sub-networks. In addition, we propose an uncertainty-weighted label fusion mechanism to estimate the reliability of each view's prediction with Bayesian deep learning. As one view requires the supervision from other views in co-training, our self-adaptive approach computes a confidence score for the prediction of each unlabeled sample in order to assign a reliable pseudo label. Thus, our approach can take advantage of unlabeled data during training. We show the effectiveness of our proposed semi-supervised method on several public datasets from medical image segmentation tasks (NIH pancreas & LiTS liver tumor dataset). Meanwhile, a fully-supervised method based on our approach achieved state-of-the-art performances on both the LiTS liver tumor segmentation and the Medical Segmentation Decathlon (MSD) challenge, demonstrating the robustness and value of our framework, even when fully supervised training is feasible.

Holger Roth, Masahiro Oda, Natsuki Shimizu et al.

Pancreas segmentation in computed tomography imaging has been historically difficult for automated methods because of the large shape and size variations between patients. In this work, we describe a custom-build 3D fully convolutional network (FCN) that can process a 3D image including the whole pancreas and produce an automatic segmentation. We investigate two variations of the 3D FCN architecture; one with concatenation and one with summation skip connections to the decoder part of the network. We evaluate our methods on a dataset from a clinical trial with gastric cancer patients, including 147 contrast enhanced abdominal CT scans acquired in the portal venous phase. Using the summation architecture, we achieve an average Dice score of 89.7 $\pm$ 3.8 (range [79.8, 94.8]) % in testing, achieving the new state-of-the-art performance in pancreas segmentation on this dataset.

Shuqing Chen, Holger Roth, Sabrina Dorn et al.

Automatic multi-organ segmentation of the dual energy computed tomography (DECT) data can be beneficial for biomedical research and clinical applications. However, it is a challenging task. Recent advances in deep learning showed the feasibility to use 3-D fully convolutional networks (FCN) for voxel-wise dense predictions in single energy computed tomography (SECT). In this paper, we proposed a 3D FCN based method for automatic multi-organ segmentation in DECT. The work was based on a cascaded FCN and a general model for the major organs trained on a large set of SECT data. We preprocessed the DECT data by using linear weighting and fine-tuned the model for the DECT data. The method was evaluated using 42 torso DECT data acquired with a clinical dual-source CT system. Four abdominal organs (liver, spleen, left and right kidneys) were evaluated. Cross-validation was tested. Effect of the weight on the accuracy was researched. In all the tests, we achieved an average Dice coefficient of 93% for the liver, 90% for the spleen, 91% for the right kidney and 89% for the left kidney, respectively. The results show our method is feasible and promising.

Ari Seff, Le Lu, Kevin M. Cherry et al.

Enlarged lymph nodes (LNs) can provide important information for cancer diagnosis, staging, and measuring treatment reactions, making automated detection a highly sought goal. In this paper, we propose a new algorithm representation of decomposing the LN detection problem into a set of 2D object detection subtasks on sampled CT slices, largely alleviating the curse of dimensionality issue. Our 2D detection can be effectively formulated as linear classification on a single image feature type of Histogram of Oriented Gradients (HOG), covering a moderate field-of-view of 45 by 45 voxels. We exploit both simple pooling and sparse linear fusion schemes to aggregate these 2D detection scores for the final 3D LN detection. In this manner, detection is more tractable and does not need to perform perfectly at instance level (as weak hypotheses) since our aggregation process will robustly harness collective information for LN detection. Two datasets (90 patients with 389 mediastinal LNs and 86 patients with 595 abdominal LNs) are used for validation. Cross-validation demonstrates 78.0% sensitivity at 6 false positives/volume (FP/vol.) (86.1% at 10 FP/vol.) and 73.1% sensitivity at 6 FP/vol. (87.2% at 10 FP/vol.), for the mediastinal and abdominal datasets respectively. Our results compare favorably to previous state-of-the-art methods.