Jinzheng Cai

Ke Yan, Jinzheng Cai, Youjing Zheng et al.

Large-scale datasets with high-quality labels are desired for training accurate deep learning models. However, due to the annotation cost, datasets in medical imaging are often either partially-labeled or small. For example, DeepLesion is such a large-scale CT image dataset with lesions of various types, but it also has many unlabeled lesions (missing annotations). When training a lesion detector on a partially-labeled dataset, the missing annotations will generate incorrect negative signals and degrade the performance. Besides DeepLesion, there are several small single-type datasets, such as LUNA for lung nodules and LiTS for liver tumors. These datasets have heterogeneous label scopes, i.e., different lesion types are labeled in different datasets with other types ignored. In this work, we aim to develop a universal lesion detection algorithm to detect a variety of lesions. The problem of heterogeneous and partial labels is tackled. First, we build a simple yet effective lesion detection framework named Lesion ENSemble (LENS). LENS can efficiently learn from multiple heterogeneous lesion datasets in a multi-task fashion and leverage their synergy by proposal fusion. Next, we propose strategies to mine missing annotations from partially-labeled datasets by exploiting clinical prior knowledge and cross-dataset knowledge transfer. Finally, we train our framework on four public lesion datasets and evaluate it on 800 manually-labeled sub-volumes in DeepLesion. Our method brings a relative improvement of 49% compared to the current state-of-the-art approach in the metric of average sensitivity. We have publicly released our manual 3D annotations of DeepLesion in https://github.com/viggin/DeepLesion_manual_test_set.

Jinzheng Cai, Adam P. Harrison, Youjing Zheng et al.

Acquiring large-scale medical image data, necessary for training machine learning algorithms, is frequently intractable, due to prohibitive expert-driven annotation costs. Recent datasets extracted from hospital archives, e.g., DeepLesion, have begun to address this problem. However, these are often incompletely or noisily labeled, e.g., DeepLesion leaves over 50% of its lesions unlabeled. Thus, effective methods to harvest missing annotations are critical for continued progress in medical image analysis. This is the goal of our work, where we develop a powerful system to harvest missing lesions from the DeepLesion dataset at high precision. Accepting the need for some degree of expert labor to achieve high fidelity, we exploit a small fully-labeled subset of medical image volumes and use it to intelligently mine annotations from the remainder. To do this, we chain together a highly sensitive lesion proposal generator and a very selective lesion proposal classifier. While our framework is generic, we optimize our performance by proposing a 3D contextual lesion proposal generator and by using a multi-view multi-scale lesion proposal classifier. These produce harvested and hard-negative proposals, which we then re-use to finetune our proposal generator by using a novel hard negative suppression loss, continuing this process until no extra lesions are found. Extensive experimental analysis demonstrates that our method can harvest an additional 9,805 lesions while keeping precision above 90%. To demonstrate the benefits of our approach, we show that lesion detectors trained on our harvested lesions can significantly outperform the same variants only trained on the original annotations, with boost of average precision of 7% to 10%. We open source our annotations at https://github.com/JimmyCai91/DeepLesionAnnotation.

Chi-Tung Cheng, Jinzheng Cai, Wei Teng et al.

Hepatocellular carcinoma (HCC) can be potentially discovered from abdominal computed tomography (CT) studies under varied clinical scenarios, e.g., fully dynamic contrast enhanced (DCE) studies, non-contrast (NC) plus venous phase (VP) abdominal studies, or NC-only studies. We develop a flexible three-dimensional deep algorithm, called hetero-phase volumetric detection (HPVD), that can accept any combination of contrast-phase inputs and with adjustable sensitivity depending on the clinical purpose. We trained HPVD on 771 DCE CT scans to detect HCCs and tested on external 164 positives and 206 controls, respectively. We compare performance against six clinical readers, including two radiologists, two hepato-pancreatico-biliary (HPB) surgeons, and two hepatologists. The area under curve (AUC) of the localization receiver operating characteristic (LROC) for NC-only, NC plus VP, and full DCE CT yielded 0.71, 0.81, 0.89 respectively. At a high sensitivity operating point of 80% on DCE CT, HPVD achieved 97% specificity, which is comparable to measured physician performance. We also demonstrate performance improvements over more typical and less flexible non hetero-phase detectors. Thus, we demonstrate that a single deep learning algorithm can be effectively applied to diverse HCC detection clinical scenarios.

Youbao Tang, Ke Yan, Jinzheng Cai et al.

Measuring lesion size is an important step to assess tumor growth and monitor disease progression and therapy response in oncology image analysis. Although it is tedious and highly time-consuming, radiologists have to work on this task by using RECIST criteria (Response Evaluation Criteria In Solid Tumors) routinely and manually. Even though lesion segmentation may be the more accurate and clinically more valuable means, physicians can not manually segment lesions as now since much more heavy laboring will be required. In this paper, we present a prior-guided dual-path network (PDNet) to segment common types of lesions throughout the whole body and predict their RECIST diameters accurately and automatically. Similar to [1], a click guidance from radiologists is the only requirement. There are two key characteristics in PDNet: 1) Learning lesion-specific attention matrices in parallel from the click prior information by the proposed prior encoder, named click-driven attention; 2) Aggregating the extracted multi-scale features comprehensively by introducing top-down and bottom-up connections in the proposed decoder, named dual-path connection. Experiments show the superiority of our proposed PDNet in lesion segmentation and RECIST diameter prediction using the DeepLesion dataset and an external test set. PDNet learns comprehensive and representative deep image features for our tasks and produces more accurate results on both lesion segmentation and RECIST diameter prediction.

Youbao Tang, Jinzheng Cai, Ke Yan et al.

Accurately segmenting a variety of clinically significant lesions from whole body computed tomography (CT) scans is a critical task on precision oncology imaging, denoted as universal lesion segmentation (ULS). Manual annotation is the current clinical practice, being highly time-consuming and inconsistent on tumor's longitudinal assessment. Effectively training an automatic segmentation model is desirable but relies heavily on a large number of pixel-wise labelled data. Existing weakly-supervised segmentation approaches often struggle with regions nearby the lesion boundaries. In this paper, we present a novel weakly-supervised universal lesion segmentation method by building an attention enhanced model based on the High-Resolution Network (HRNet), named AHRNet, and propose a regional level set (RLS) loss for optimizing lesion boundary delineation. AHRNet provides advanced high-resolution deep image features by involving a decoder, dual-attention and scale attention mechanisms, which are crucial to performing accurate lesion segmentation. RLS can optimize the model reliably and effectively in a weakly-supervised fashion, forcing the segmentation close to lesion boundary. Extensive experimental results demonstrate that our method achieves the best performance on the publicly large-scale DeepLesion dataset and a hold-out test set.

Bolin Lai, Yuhsuan Wu, Xiaoyu Bai et al.

Using radiological scans to identify liver tumors is crucial for proper patient treatment. This is highly challenging, as top radiologists only achieve F1 scores of roughly 80% (hepatocellular carcinoma (HCC) vs. others) with only moderate inter-rater agreement, even when using multi-phase magnetic resonance (MR) imagery. Thus, there is great impetus for computer-aided diagnosis (CAD) solutions. A critical challenge is to robustly parse a 3D MR volume to localize diagnosable regions of interest (ROI), especially for edge cases. In this paper, we break down this problem using a key-slice parser (KSP), which emulates physician workflows by first identifying key slices and then localizing their corresponding key ROIs. To achieve robustness, the KSP also uses curve-parsing and detection confidence re-weighting. We evaluate our approach on the largest multi-phase MR liver lesion test dataset to date (430 biopsy-confirmed patients). Experiments demonstrate that our KSP can localize diagnosable ROIs with high reliability: 87% patients have an average 3D overlap of >= 40% with the ground truth compared to only 79% using the best tested detector. When coupled with a classifier, we achieve an HCC vs. others F1 score of 0.801, providing a fully-automated CAD performance comparable to top human physicians.

Jinzheng Cai, Youbao Tang, Ke Yan et al.

Monitoring treatment response in longitudinal studies plays an important role in clinical practice. Accurately identifying lesions across serial imaging follow-up is the core to the monitoring procedure. Typically this incorporates both image and anatomical considerations. However, matching lesions manually is labor-intensive and time-consuming. In this work, we present deep lesion tracker (DLT), a deep learning approach that uses both appearance- and anatomical-based signals. To incorporate anatomical constraints, we propose an anatomical signal encoder, which prevents lesions being matched with visually similar but spurious regions. In addition, we present a new formulation for Siamese networks that avoids the heavy computational loads of 3D cross-correlation. To present our network with greater varieties of images, we also propose a self-supervised learning (SSL) strategy to train trackers with unpaired images, overcoming barriers to data collection. To train and evaluate our tracker, we introduce and release the first lesion tracking benchmark, consisting of 3891 lesion pairs from the public DeepLesion database. The proposed method, DLT, locates lesion centers with a mean error distance of 7 mm. This is 5% better than a leading registration algorithm while running 14 times faster on whole CT volumes. We demonstrate even greater improvements over detector or similarity-learning alternatives. DLT also generalizes well on an external clinical test set of 100 longitudinal studies, achieving 88% accuracy. Finally, we plug DLT into an automatic tumor monitoring workflow where it leads to an accuracy of 85% in assessing lesion treatment responses, which is only 0.46% lower than the accuracy of manual inputs.

Ke Yan, Jinzheng Cai, Dakai Jin et al.

Radiological images such as computed tomography (CT) and X-rays render anatomy with intrinsic structures. Being able to reliably locate the same anatomical structure across varying images is a fundamental task in medical image analysis. In principle it is possible to use landmark detection or semantic segmentation for this task, but to work well these require large numbers of labeled data for each anatomical structure and sub-structure of interest. A more universal approach would learn the intrinsic structure from unlabeled images. We introduce such an approach, called Self-supervised Anatomical eMbedding (SAM). SAM generates semantic embeddings for each image pixel that describes its anatomical location or body part. To produce such embeddings, we propose a pixel-level contrastive learning framework. A coarse-to-fine strategy ensures both global and local anatomical information are encoded. Negative sample selection strategies are designed to enhance the embedding's discriminability. Using SAM, one can label any point of interest on a template image and then locate the same body part in other images by simple nearest neighbor searching. We demonstrate the effectiveness of SAM in multiple tasks with 2D and 3D image modalities. On a chest CT dataset with 19 landmarks, SAM outperforms widely-used registration algorithms while only taking 0.23 seconds for inference. On two X-ray datasets, SAM, with only one labeled template image, surpasses supervised methods trained on 50 labeled images. We also apply SAM on whole-body follow-up lesion matching in CT and obtain an accuracy of 91%. SAM can also be applied for improving image registration and initializing CNN weights.

Ashwin Raju, Zhanghexuan Ji, Chi Tung Cheng et al.

Mask-based annotation of medical images, especially for 3D data, is a bottleneck in developing reliable machine learning models. Using minimal-labor user interactions (UIs) to guide the annotation is promising, but challenges remain on best harmonizing the mask prediction with the UIs. To address this, we propose the user-guided domain adaptation (UGDA) framework, which uses prediction-based adversarial domain adaptation (PADA) to model the combined distribution of UIs and mask predictions. The UIs are then used as anchors to guide and align the mask prediction. Importantly, UGDA can both learn from unlabelled data and also model the high-level semantic meaning behind different UIs. We test UGDA on annotating pathological livers using a clinically comprehensive dataset of 927 patient studies. Using only extreme-point UIs, we achieve a mean (worst-case) performance of 96.1%(94.9%), compared to 93.0% (87.0%) for deep extreme points (DEXTR). Furthermore, we also show UGDA can retain this state-of-the-art performance even when only seeing a fraction of available UIs, demonstrating an ability for robust and reliable UI-guided segmentation with extremely minimal labor demands.

Jinzheng Cai, Ke Yan, Chi-Tung Cheng et al.

Identifying, measuring and reporting lesions accurately and comprehensively from patient CT scans are important yet time-consuming procedures for physicians. Computer-aided lesion/significant-findings detection techniques are at the core of medical imaging, which remain very challenging due to the tremendously large variability of lesion appearance, location and size distributions in 3D imaging. In this work, we propose a novel deep anchor-free one-stage VULD framework that incorporates (1) P3DC operators to recycle the architectural configurations and pre-trained weights from the off-the-shelf 2D networks, especially ones with large capacities to cope with data variance, and (2) a new SPR method to effectively regress the 3D lesion spatial extents by pinpointing their representative key points on lesion surfaces. Experimental validations are first conducted on the public large-scale NIH DeepLesion dataset where our proposed method delivers new state-of-the-art quantitative performance. We also test VULD on our in-house dataset for liver tumor detection. VULD generalizes well in both large-scale and small-sized tumor datasets in CT imaging.

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.

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.

Yuankai Huo, Jinzheng Cai, Chi-Tung Cheng et al.

Non-invasive radiological-based lesion characterization and identification, e.g., to differentiate cancer subtypes, has long been a major aim to enhance oncological diagnosis and treatment procedures. Here we study a specific population of human subjects, with the hope of reducing the need for invasive surgical biopsies of liver cancer patients, which can cause many harmful side-effects. To this end, we propose a fully-automated and multi-stage liver tumor characterization framework designed for dynamic contrast computed tomography (CT). Our system comprises four sequential processes of tumor proposal detection, tumor harvesting, primary tumor site selection, and deep texture-based tumor characterization. Our main contributions are that, (1) we propose a 3D non-isotropic anchor-free detection method for liver lesions; (2) we present and validate spatially adaptivedeep texture (SaDT) learning, which allows for more precise characterization of liver lesions; (3) using a semi-automatic process, we bootstrap off of 200 gold standard annotations to curate another 1001 patients. Experimental evaluations demonstrate that our new data curation strategy, combined with the SaDT deep dynamic texture analysis, can effectively improve the mean F1 scores by >8.6% compared with baselines, in differentiating four major liver lesion types. Our F1 score of (hepatocellular carcinoma versus remaining subclasses) is 0.763, which is higher than reported human observer performance using dynamic CT and comparable to an advanced magnetic resonance imagery protocol. Apart from demonstrating the benefits of our data curation approach and physician-inspired workflow, these results also indicate that analyzing texture features, instead of standard object-based analysis, is a promising strategy for lesion differentiation.

Ke Yan, Jinzheng Cai, Adam P. Harrison et al.

Lesion detection is an important problem within medical imaging analysis. Most previous work focuses on detecting and segmenting a specialized category of lesions (e.g., lung nodules). However, in clinical practice, radiologists are responsible for finding all possible types of anomalies. The task of universal lesion detection (ULD) was proposed to address this challenge by detecting a large variety of lesions from the whole body. There are multiple heterogeneously labeled datasets with varying label completeness: DeepLesion, the largest dataset of 32,735 annotated lesions of various types, but with even more missing annotation instances; and several fully-labeled single-type lesion datasets, such as LUNA for lung nodules and LiTS for liver tumors. In this work, we propose a novel framework to leverage all these datasets together to improve the performance of ULD. First, we learn a multi-head multi-task lesion detector using all datasets and generate lesion proposals on DeepLesion. Second, missing annotations in DeepLesion are retrieved by a new method of embedding matching that exploits clinical prior knowledge. Last, we discover suspicious but unannotated lesions using knowledge transfer from single-type lesion detectors. In this way, reliable positive and negative regions are obtained from partially-labeled and unlabeled images, which are effectively utilized to train ULD. To assess the clinically realistic protocol of 3D volumetric ULD, we fully annotated 1071 CT sub-volumes in DeepLesion. Our method outperforms the current state-of-the-art approach by 29% in the metric of average sensitivity.

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.

Ashwin Raju, Chi-Tung Cheng, Yunakai Huo et al.

In medical imaging, organ/pathology segmentation models trained on current publicly available and fully-annotated datasets usually do not well-represent the heterogeneous modalities, phases, pathologies, and clinical scenarios encountered in real environments. On the other hand, there are tremendous amounts of unlabelled patient imaging scans stored by many modern clinical centers. In this work, we present a novel segmentation strategy, co-heterogenous and adaptive segmentation (CHASe), which only requires a small labeled cohort of single phase imaging data to adapt to any unlabeled cohort of heterogenous multi-phase data with possibly new clinical scenarios and pathologies. To do this, we propose a versatile framework that fuses appearance based semi-supervision, mask based adversarial domain adaptation, and pseudo-labeling. We also introduce co-heterogeneous training, which is a novel integration of co-training and hetero modality learning. We have evaluated CHASe using a clinically comprehensive and challenging dataset of multi-phase computed tomography (CT) imaging studies (1147 patients and 4577 3D volumes). Compared to previous state-of-the-art baselines, CHASe can further improve pathological liver mask Dice-Sorensen coefficients by ranges of $4.2\% \sim 9.4\%$, depending on the phase combinations: e.g., from $84.6\%$ to $94.0\%$ on non-contrast CTs.

Fengze Liu, Jinzheng Cai, Yuankai Huo et al.

Multi-modal image registration is a challenging problem that is also an important clinical task for many real applications and scenarios. As a first step in analysis, deformable registration among different image modalities is often required in order to provide complementary visual information. During registration, semantic information is key to match homologous points and pixels. Nevertheless, many conventional registration methods are incapable in capturing high-level semantic anatomical dense correspondences. In this work, we propose a novel multi-task learning system, JSSR, based on an end-to-end 3D convolutional neural network that is composed of a generator, a registration and a segmentation component. The system is optimized to satisfy the implicit constraints between different tasks in an unsupervised manner. It first synthesizes the source domain images into the target domain, then an intra-modal registration is applied on the synthesized images and target images. The segmentation module are then applied on the synthesized and target images, providing additional cues based on semantic correspondences. The supervision from another fully-annotated dataset is used to regularize the segmentation. We extensively evaluate JSSR on a large-scale medical image dataset containing 1,485 patient CT imaging studies of four different contrast phases (i.e., 5,940 3D CT scans with pathological livers) on the registration, segmentation and synthesis tasks. The performance is improved after joint training on the registration and segmentation tasks by 0.9% and 1.9% respectively compared to a highly competitive and accurate deep learning baseline. The registration also consistently outperforms conventional state-of-the-art multi-modal registration methods.

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.

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.

Youbao Tang, Jinzheng Cai, Le Lu et al.

Automated lesion segmentation from computed tomography (CT) is an important and challenging task in medical image analysis. While many advancements have been made, there is room for continued improvements. One hurdle is that CT images can exhibit high noise and low contrast, particularly in lower dosages. To address this, we focus on a preprocessing method for CT images that uses stacked generative adversarial networks (SGAN) approach. The first GAN reduces the noise in the CT image and the second GAN generates a higher resolution image with enhanced boundaries and high contrast. To make up for the absence of high quality CT images, we detail how to synthesize a large number of low- and high-quality natural images and use transfer learning with progressively larger amounts of CT images. We apply both the classic GrabCut method and the modern holistically nested network (HNN) to lesion segmentation, testing whether SGAN can yield improved lesion segmentation. Experimental results on the DeepLesion dataset demonstrate that the SGAN enhancements alone can push GrabCut performance over HNN trained on original images. We also demonstrate that HNN + SGAN performs best compared against four other enhancement methods, including when using only a single GAN.

Jinzheng Cai, Le Lu, Adam P. Harrison et al.

Given image labels as the only supervisory signal, we focus on harvesting, or mining, thoracic disease localizations from chest X-ray images. Harvesting such localizations from existing datasets allows for the creation of improved data sources for computer-aided diagnosis and retrospective analyses. We train a convolutional neural network (CNN) for image classification and propose an attention mining (AM) strategy to improve the model's sensitivity or saliency to disease patterns. The intuition of AM is that once the most salient disease area is blocked or hidden from the CNN model, it will pay attention to alternative image regions, while still attempting to make correct predictions. However, the model requires to be properly constrained during AM, otherwise, it may overfit to uncorrelated image parts and forget the valuable knowledge that it has learned from the original image classification task. To alleviate such side effects, we then design a knowledge preservation (KP) loss, which minimizes the discrepancy between responses for X-ray images from the original and the updated networks. Furthermore, we modify the CNN model to include multi-scale aggregation (MSA), improving its localization ability on small-scale disease findings, e.g., lung nodules. We experimentally validate our method on the publicly-available ChestX-ray14 dataset, outperforming a class activation map (CAM)-based approach, and demonstrating the value of our novel framework for mining disease locations.

Jinzheng Cai, Youbao Tang, Le Lu et al.

Volumetric lesion segmentation from computed tomography (CT) images is a powerful means to precisely assess multiple time-point lesion/tumor changes. However, because manual 3D segmentation is prohibitively time consuming, current practices rely on an imprecise surrogate called response evaluation criteria in solid tumors (RECIST). Despite their coarseness, RECIST markers are commonly found in current hospital picture and archiving systems (PACS), meaning they can provide a potentially powerful, yet extraordinarily challenging, source of weak supervision for full 3D segmentation. Toward this end, we introduce a convolutional neural network (CNN) based weakly supervised slice-propagated segmentation (WSSS) method to 1) generate the initial lesion segmentation on the axial RECIST-slice; 2) learn the data distribution on RECIST-slices; 3) extrapolate to segment the whole lesion slice by slice to finally obtain a volumetric segmentation. To validate the proposed method, we first test its performance on a fully annotated lymph node dataset, where WSSS performs comparably to its fully supervised counterparts. We then test on a comprehensive lesion dataset with 32,735 RECIST marks, where we report a mean Dice score of 92% on RECIST-marked slices and 76% on the entire 3D volumes.

Jinzheng Cai, Le Lu, Fuyong Xing et al.

Automatic pancreas segmentation in radiology images, eg., computed tomography (CT) and magnetic resonance imaging (MRI), is frequently required by computer-aided screening, diagnosis, and quantitative assessment. Yet pancreas is a challenging abdominal organ to segment due to the high inter-patient anatomical variability in both shape and volume metrics. Recently, convolutional neural networks (CNNs) have demonstrated promising performance on accurate segmentation of pancreas. However, the CNN-based method often suffers from segmentation discontinuity for reasons such as noisy image quality and blurry pancreatic boundary. From this point, we propose to introduce recurrent neural networks (RNNs) to address the problem of spatial non-smoothness of inter-slice pancreas segmentation across adjacent image slices. To inference initial segmentation, we first train a 2D CNN sub-network, where we modify its network architecture with deep-supervision and multi-scale feature map aggregation so that it can be trained from scratch with small-sized training data and presents superior performance than transferred models. Thereafter, the successive CNN outputs are processed by another RNN sub-network, which refines the consistency of segmented shapes. More specifically, the RNN sub-network consists convolutional long short-term memory (CLSTM) units in both top-down and bottom-up directions, which regularizes the segmentation of an image by integrating predictions of its neighboring slices. We train the stacked CNN-RNN model end-to-end and perform quantitative evaluations on both CT and MRI images.

Jinzheng Cai, Youbao Tang, Le Lu et al.

Volumetric lesion segmentation via medical imaging is a powerful means to precisely assess multiple time-point lesion/tumor changes. Because manual 3D segmentation is prohibitively time consuming and requires radiological experience, current practices rely on an imprecise surrogate called response evaluation criteria in solid tumors (RECIST). Despite their coarseness, RECIST marks are commonly found in current hospital picture and archiving systems (PACS), meaning they can provide a potentially powerful, yet extraordinarily challenging, source of weak supervision for full 3D segmentation. Toward this end, we introduce a convolutional neural network based weakly supervised self-paced segmentation (WSSS) method to 1) generate the initial lesion segmentation on the axial RECIST-slice; 2) learn the data distribution on RECIST-slices; 3) adapt to segment the whole volume slice by slice to finally obtain a volumetric segmentation. In addition, we explore how super-resolution images (2~5 times beyond the physical CT imaging), generated from a proposed stacked generative adversarial network, can aid the WSSS performance. We employ the DeepLesion dataset, a comprehensive CT-image lesion dataset of 32,735 PACS-bookmarked findings, which include lesions, tumors, and lymph nodes of varying sizes, categories, body regions and surrounding contexts. These are drawn from 10,594 studies of 4,459 patients. We also validate on a lymph-node dataset, where 3D ground truth masks are available for all images. For the DeepLesion dataset, we report mean Dice coefficients of 93% on RECIST-slices and 76% in 3D lesion volumes. We further validate using a subjective user study, where an experienced radiologist accepted our WSSS-generated lesion segmentation results with a high probability of 92.4%.

Jinzheng Cai, Le Lu, Yuanpu Xie et al.

Deep neural networks have demonstrated very promising performance on accurate segmentation of challenging organs (e.g., pancreas) in abdominal CT and MRI scans. The current deep learning approaches conduct pancreas segmentation by processing sequences of 2D image slices independently through deep, dense per-pixel masking for each image, without explicitly enforcing spatial consistency constraint on segmentation of successive slices. We propose a new convolutional/recurrent neural network architecture to address the contextual learning and segmentation consistency problem. A deep convolutional sub-network is first designed and pre-trained from scratch. The output layer of this network module is then connected to recurrent layers and can be fine-tuned for contextual learning, in an end-to-end manner. Our recurrent sub-network is a type of Long short-term memory (LSTM) network that performs segmentation on an image by integrating its neighboring slice segmentation predictions, in the form of a dependent sequence processing. Additionally, a novel segmentation-direct loss function (named Jaccard Loss) is proposed and deep networks are trained to optimize Jaccard Index (JI) directly. Extensive experiments are conducted to validate our proposed deep models, on quantitative pancreas segmentation using both CT and MRI scans. Our method outperforms the state-of-the-art work on CT [11] and MRI pancreas segmentation [1], respectively.