Zhuotun Zhu

Dazhou Guo, Jia Ge, Xianghua Ye et al.

Accurate organ at risk (OAR) segmentation is critical to reduce the radiotherapy post-treatment complications. Consensus guidelines recommend a set of more than 40 OARs in the head and neck (H&N) region, however, due to the predictable prohibitive labor-cost of this task, most institutions choose a substantially simplified protocol by delineating a smaller subset of OARs and neglecting the dose distributions associated with other OARs. In this work we propose a novel, automated and highly effective stratified OAR segmentation (SOARS) system using deep learning to precisely delineate a comprehensive set of 42 H&N OARs. SOARS stratifies 42 OARs into anchor, mid-level, and small & hard subcategories, with specifically derived neural network architectures for each category by neural architecture search (NAS) principles. We built SOARS models using 176 training patients in an internal institution and independently evaluated on 1327 external patients across six different institutions. It consistently outperformed other state-of-the-art methods by at least 3-5% in Dice score for each institutional evaluation (up to 36% relative error reduction in other metrics). More importantly, extensive multi-user studies evidently demonstrated that 98% of the SOARS predictions need only very minor or no revisions for direct clinical acceptance (saving 90% radiation oncologists workload), and their segmentation and dosimetric accuracy are within or smaller than the inter-user variation. These findings confirmed the strong clinical applicability of SOARS for the OAR delineation process in H&N cancer radiotherapy workflows, with improved efficiency, comprehensiveness, and quality.

Yingwei Li, Zhuotun Zhu, Yuyin Zhou et al.

Although deep neural networks have been a dominant method for many 2D vision tasks, it is still challenging to apply them to 3D tasks, such as medical image segmentation, due to the limited amount of annotated 3D data and limited computational resources. In this chapter, by rethinking the strategy to apply 3D Convolutional Neural Networks to segment medical images, we propose a novel 3D-based coarse-to-fine framework to efficiently tackle these challenges. The proposed 3D-based framework outperforms their 2D counterparts by a large margin since it can leverage the rich spatial information along all three axes. We further analyze the threat of adversarial attacks on the proposed framework and show how to defense against the attack. We conduct experiments on three datasets, the NIH pancreas dataset, the JHMI pancreas dataset and the JHMI pathological cyst dataset, where the first two and the last one contain healthy and pathological pancreases respectively, and achieve the current state-of-the-art in terms of Dice-Sorensen Coefficient (DSC) on all of them. Especially, on the NIH pancreas segmentation dataset, we outperform the previous best by an average of over $2\%$, and the worst case is improved by $7\%$ to reach almost $70\%$, which indicates the reliability of our framework in clinical applications.

Chun-Hung Chao, Zhuotun Zhu, Dazhou Guo et al.

Determining the spread of GTV$_{LN}$ is essential in defining the respective resection or irradiating regions for the downstream workflows of surgical resection and radiotherapy for many cancers. Different from the more common enlarged lymph node (LN), GTV$_{LN}$ also includes smaller ones if associated with high positron emission tomography signals and/or any metastasis signs in CT. This is a daunting task. In this work, we propose a unified LN appearance and inter-LN relationship learning framework to detect the true GTV$_{LN}$. This is motivated by the prior clinical knowledge that LNs form a connected lymphatic system, and the spread of cancer cells among LNs often follows certain pathways. Specifically, we first utilize a 3D convolutional neural network with ROI-pooling to extract the GTV$_{LN}$'s instance-wise appearance features. Next, we introduce a graph neural network to further model the inter-LN relationships where the global LN-tumor spatial priors are included in the learning process. This leads to an end-to-end trainable network to detect by classifying GTV$_{LN}$. We operate our model on a set of GTV$_{LN}$ candidates generated by a preliminary 1st-stage method, which has a sensitivity of $>85\%$ at the cost of high false positive (FP) ($>15$ FPs per patient). We validate our approach on a radiotherapy dataset with 142 paired PET/RTCT scans containing the chest and upper abdominal body parts. The proposed method significantly improves over the state-of-the-art (SOTA) LN classification method by $5.5\%$ and $13.1\%$ in F1 score and the averaged sensitivity value at $2, 3, 4, 6$ FPs per patient, respectively.

Zhuotun Zhu, Dakai Jin, Ke Yan et al.

Finding, identifying and segmenting suspicious cancer metastasized lymph nodes from 3D multi-modality imaging is a clinical task of paramount importance. In radiotherapy, they are referred to as Lymph Node Gross Tumor Volume (GTVLN). Determining and delineating the spread of GTVLN is essential in defining the corresponding resection and irradiating regions for the downstream workflows of surgical resection and radiotherapy of various cancers. In this work, we propose an effective distance-based gating approach to simulate and simplify the high-level reasoning protocols conducted by radiation oncologists, in a divide-and-conquer manner. GTVLN is divided into two subgroups of tumor-proximal and tumor-distal, respectively, by means of binary or soft distance gating. This is motivated by the observation that each category can have distinct though overlapping distributions of appearance, size and other LN characteristics. A novel multi-branch detection-by-segmentation network is trained with each branch specializing on learning one GTVLN category features, and outputs from multi-branch are fused in inference. The proposed method is evaluated on an in-house dataset of $141$ esophageal cancer patients with both PET and CT imaging modalities. Our results validate significant improvements on the mean recall from $72.5\%$ to $78.2\%$, as compared to previous state-of-the-art work. The highest achieved GTVLN recall of $82.5\%$ at $20\%$ precision is clinically relevant and valuable since human observers tend to have low sensitivity (around $80\%$ for the most experienced radiation oncologists, as reported by literature).

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.

Zhuotun Zhu, Ke Yan, Dakai Jin et al.

Finding and identifying scatteredly-distributed, small, and critically important objects in 3D oncology images is very challenging. We focus on the detection and segmentation of oncology-significant (or suspicious cancer metastasized) lymph nodes (OSLNs), which has not been studied before as a computational task. Determining and delineating the spread of OSLNs is essential in defining the corresponding resection/irradiating regions for the downstream workflows of surgical resection and radiotherapy of various cancers. For patients who are treated with radiotherapy, this task is performed by experienced radiation oncologists that involves high-level reasoning on whether LNs are metastasized, which is subject to high inter-observer variations. In this work, we propose a divide-and-conquer decision stratification approach that divides OSLNs into tumor-proximal and tumor-distal categories. This is motivated by the observation that each category has its own different underlying distributions in appearance, size and other characteristics. Two separate detection-by-segmentation networks are trained per category and fused. To further reduce false positives (FP), we present a novel global-local network (GLNet) that combines high-level lesion characteristics with features learned from localized 3D image patches. Our method is evaluated on a dataset of 141 esophageal cancer patients with PET and CT modalities (the largest to-date). Our results significantly improve the recall from $45\%$ to $67\%$ at $3$ FPs per patient as compared to previous state-of-the-art methods. The highest achieved OSLN recall of $0.828$ is clinically relevant and valuable.

Dazhou Guo, Dakai Jin, Zhuotun Zhu et al.

OAR segmentation is a critical step in radiotherapy of head and neck (H&N) cancer, where inconsistencies across radiation oncologists and prohibitive labor costs motivate automated approaches. However, leading methods using standard fully convolutional network workflows that are challenged when the number of OARs becomes large, e.g. > 40. For such scenarios, insights can be gained from the stratification approaches seen in manual clinical OAR delineation. This is the goal of our work, where we introduce stratified organ at risk segmentation (SOARS), an approach that stratifies OARs into anchor, mid-level, and small & hard (S&H) categories. SOARS stratifies across two dimensions. The first dimension is that distinct processing pipelines are used for each OAR category. In particular, inspired by clinical practices, anchor OARs are used to guide the mid-level and S&H categories. The second dimension is that distinct network architectures are used to manage the significant contrast, size, and anatomy variations between different OARs. We use differentiable neural architecture search (NAS), allowing the network to choose among 2D, 3D or Pseudo-3D convolutions. Extensive 4-fold cross-validation on 142 H&N cancer patients with 42 manually labeled OARs, the most comprehensive OAR dataset to date, demonstrates that both pipeline- and NAS-stratification significantly improves quantitative performance over the state-of-the-art (from 69.52% to 73.68% in absolute Dice scores). Thus, SOARS provides a powerful and principled means to manage the highly complex segmentation space of OARs.

Zhuotun Zhu, Yongyi Lu, Wei Shen et al.

This work presents comprehensive results to detect in the early stage the pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, which are the second common type of pancreatic cancer, by checking the abdominal CT scans. To the best of our knowledge, this task has not been studied before as a computational task. To provide radiologists with tumor locations, we adopt a segmentation framework to classify CT volumes by checking if at least a sufficient number of voxels is segmented as tumors. To quantitatively analyze our method, we collect and voxelwisely label a new abdominal CT dataset containing $376$ cases with both arterial and venous phases available for each case, in which $228$ cases were diagnosed with PNETs while the remaining $148$ cases are normal, which is currently the largest dataset for PNETs to the best of our knowledge. In order to incorporate rich knowledge of radiologists to our framework, we annotate dilated pancreatic duct as well, which is regarded as the sign of high risk for pancreatic cancer. Quantitatively, our approach outperforms state-of-the-art segmentation networks and achieves a sensitivity of $89.47\%$ at a specificity of $81.08\%$, which indicates a potential direction to achieve a clinical impact related to cancer diagnosis by earlier tumor detection.

Zhuotun Zhu, Chenxi Liu, Dong Yang et al.

Deep learning algorithms, in particular 2D and 3D fully convolutional neural networks (FCNs), have rapidly become the mainstream methodology for volumetric medical image segmentation. However, 2D convolutions cannot fully leverage the rich spatial information along the third axis, while 3D convolutions suffer from the demanding computation and high GPU memory consumption. In this paper, we propose to automatically search the network architecture tailoring to volumetric medical image segmentation problem. Concretely, we formulate the structure learning as differentiable neural architecture search, and let the network itself choose between 2D, 3D or Pseudo-3D (P3D) convolutions at each layer. We evaluate our method on 3 public datasets, i.e., the NIH Pancreas dataset, the Lung and Pancreas dataset from the Medical Segmentation Decathlon (MSD) Challenge. Our method, named V-NAS, consistently outperforms other state-of-the-arts on the segmentation task of both normal organ (NIH Pancreas) and abnormal organs (MSD Lung tumors and MSD Pancreas tumors), which shows the power of chosen architecture. Moreover, the searched architecture on one dataset can be well generalized to other datasets, which demonstrates the robustness and practical use of our proposed 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.

Zhuotun Zhu, Yingda Xia, Lingxi Xie et al.

We propose an intuitive approach of detecting pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, by checking abdominal CT scans. Our idea is named multi-scale segmentation-for-classification, which classifies volumes by checking if at least a sufficient number of voxels is segmented as tumors, by which we can provide radiologists with tumor locations. In order to deal with tumors with different scales, we train and test our volumetric segmentation networks with multi-scale inputs in a coarse-to-fine flowchart. A post-processing module is used to filter out outliers and reduce false alarms. We collect a new dataset containing 439 CT scans, in which 136 cases were diagnosed with PDAC and 303 cases are normal, which is the largest set for PDAC tumors to the best of our knowledge. To offer the best trade-off between sensitivity and specificity, our proposed framework reports a sensitivity of 94.1% at a specificity of 98.5%, which demonstrates the potential to make a clinical impact.

Yingda Xia, Lingxi Xie, Fengze Liu et al.

There has been a debate on whether to use 2D or 3D deep neural networks for volumetric organ segmentation. Both 2D and 3D models have their advantages and disadvantages. In this paper, we present an alternative framework, which trains 2D networks on different viewpoints for segmentation, and builds a 3D Volumetric Fusion Net (VFN) to fuse the 2D segmentation results. VFN is relatively shallow and contains much fewer parameters than most 3D networks, making our framework more efficient at integrating 3D information for segmentation. We train and test the segmentation and fusion modules individually, and propose a novel strategy, named cross-cross-augmentation, to make full use of the limited training data. We evaluate our framework on several challenging abdominal organs, and verify its superiority in segmentation accuracy and stability over existing 2D and 3D approaches.

Zhuotun Zhu, Yingda Xia, Wei Shen et al.

In this paper, we adopt 3D Convolutional Neural Networks to segment volumetric medical images. Although deep neural networks have been proven to be very effective on many 2D vision tasks, it is still challenging to apply them to 3D tasks due to the limited amount of annotated 3D data and limited computational resources. We propose a novel 3D-based coarse-to-fine framework to effectively and efficiently tackle these challenges. The proposed 3D-based framework outperforms the 2D counterpart to a large margin since it can leverage the rich spatial infor- mation along all three axes. We conduct experiments on two datasets which include healthy and pathological pancreases respectively, and achieve the current state-of-the-art in terms of Dice-Sørensen Coefficient (DSC). On the NIH pancreas segmentation dataset, we outperform the previous best by an average of over 2%, and the worst case is improved by 7% to reach almost 70%, which indicates the reliability of our framework in clinical applications.

Zhuotun Zhu, Lingxi Xie, Alan L. Yuille

While recent deep neural networks have achieved a promising performance on object recognition, they rely implicitly on the visual contents of the whole image. In this paper, we train deep neural net- works on the foreground (object) and background (context) regions of images respectively. Consider- ing human recognition in the same situations, net- works trained on the pure background without ob- jects achieves highly reasonable recognition performance that beats humans by a large margin if only given context. However, humans still outperform networks with pure object available, which indicates networks and human beings have different mechanisms in understanding an image. Furthermore, we straightforwardly combine multiple trained networks to explore different visual cues learned by different networks. Experiments show that useful visual hints can be explicitly learned separately and then combined to achieve higher performance, which verifies the advantages of the proposed framework.

Hanqiang Song, Zhuotun Zhu, Xinggang Wang

Multi-instance learning (MIL) has a wide range of applications due to its distinctive characteristics. Although many state-of-the-art algorithms have achieved decent performances, a plurality of existing methods solve the problem only in instance level rather than excavating relations among bags. In this paper, we propose an efficient algorithm to describe each bag by a corresponding feature vector via comparing it with other bags. In other words, the crucial information of a bag is extracted from the similarity between that bag and other reference bags. In addition, we apply extensions of Hausdorff distance to representing the similarity, to a certain extent, overcoming the key challenge of MIL problem, the ambiguity of instances' labels in positive bags. Experimental results on benchmarks and text categorization tasks show that the proposed method outperforms the previous state-of-the-art by a large margin.

Xinggang Wang, Zhuotun Zhu, Cong Yao et al.

Multiple-instance learning (MIL) has served as an important tool for a wide range of vision applications, for instance, image classification, object detection, and visual tracking. In this paper, we propose a novel method to solve the classical MIL problem, named relaxed multiple-instance SVM (RMI-SVM). We treat the positiveness of instance as a continuous variable, use Noisy-OR model to enforce the MIL constraints, and jointly optimize the bag label and instance label in a unified framework. The optimization problem can be efficiently solved using stochastic gradient decent. The extensive experiments demonstrate that RMI-SVM consistently achieves superior performance on various benchmarks for MIL. Moreover, we simply applied RMI-SVM to a challenging vision task, common object discovery. The state-of-the-art results of object discovery on Pascal VOC datasets further confirm the advantages of the proposed method.

Zhuotun Zhu, Xinggang Wang, Song Bai et al.

We study the problem of how to build a deep learning representation for 3D shape. Deep learning has shown to be very effective in variety of visual applications, such as image classification and object detection. However, it has not been successfully applied to 3D shape recognition. This is because 3D shape has complex structure in 3D space and there are limited number of 3D shapes for feature learning. To address these problems, we project 3D shapes into 2D space and use autoencoder for feature learning on the 2D images. High accuracy 3D shape retrieval performance is obtained by aggregating the features learned on 2D images. In addition, we show the proposed deep learning feature is complementary to conventional local image descriptors. By combing the global deep learning representation and the local descriptor representation, our method can obtain the state-of-the-art performance on 3D shape retrieval benchmarks.