Weakly Supervised Universal Fracture Detection in Pelvic X-rays

Hip and pelvic fractures are serious injuries with life-threatening complications. However, diagnostic errors of fractures in pelvic X-rays (PXRs) are very common, driving the demand for computer-aided diagnosis (CAD) solutions. A major challenge lies in the fact that fractures are localized patterns that require localized analyses. Unfortunately, the PXRs residing in hospital picture archiving and communication system do not typically specify region of interests. In this paper, we propose a two-stage hip and pelvic fracture detection method that executes localized fracture classification using weakly supervised ROI mining. The first stage uses a large capacity fully-convolutional network, i.e., deep with high levels of abstraction, in a multiple instance learning setting to automatically mine probable true positive and definite hard negative ROIs from the whole PXR in the training data. The second stage trains a smaller capacity model, i.e., shallower and more generalizable, with the mined ROIs to perform localized analyses to classify fractures. During inference, our method detects hip and pelvic fractures in one pass by chaining the probability outputs of the two stages together. We evaluate our method on 4 410 PXRs, reporting an area under the ROC curve value of 0.975, the highest among state-of-the-art fracture detection methods. Moreover, we show that our two-stage approach can perform comparably to human physicians (even outperforming emergency physicians and surgeons), in a preliminary reader study of 23 readers.

Deep Esophageal Clinical Target Volume Delineation using Encoded 3D Spatial Context of Tumors, Lymph Nodes, and Organs At Risk

Clinical target volume (CTV) delineation from radiotherapy computed tomography (RTCT) images is used to define the treatment areas containing the gross tumor volume (GTV) and/or sub-clinical malignant disease for radiotherapy (RT). High intra- and inter-user variability makes this a particularly difficult task for esophageal cancer. This motivates automated solutions, which is the aim of our work. Because CTV delineation is highly context-dependent--it must encompass the GTV and regional lymph nodes (LNs) while also avoiding excessive exposure to the organs at risk (OARs)--we formulate it as a deep contextual appearance-based problem using encoded spatial contexts of these anatomical structures. This allows the deep network to better learn from and emulate the margin- and appearance-based delineation performed by human physicians. Additionally, we develop domain-specific data augmentation to inject robustness to our system. Finally, we show that a simple 3D progressive holistically nested network (PHNN), which avoids computationally heavy decoding paths while still aggregating features at different levels of context, can outperform more complicated networks. Cross-validated experiments on a dataset of 135 esophageal cancer patients demonstrate that our encoded spatial context approach can produce concrete performance improvements, with an average Dice score of 83.9% and an average surface distance of 4.2 mm, representing improvements of 3.8% and 2.4 mm, respectively, over the state-of-the-art approach.

Accurate Esophageal Gross Tumor Volume Segmentation in PET/CT using Two-Stream Chained 3D Deep Network Fusion

Gross tumor volume (GTV) segmentation is a critical step in esophageal cancer radiotherapy treatment planning. Inconsistencies across oncologists and prohibitive labor costs motivate automated approaches for this task. However, leading approaches are only applied to radiotherapy computed tomography (RTCT) images taken prior to treatment. This limits the performance as RTCT suffers from low contrast between the esophagus, tumor, and surrounding tissues. In this paper, we aim to exploit both RTCT and positron emission tomography (PET) imaging modalities to facilitate more accurate GTV segmentation. By utilizing PET, we emulate medical professionals who frequently delineate GTV boundaries through observation of the RTCT images obtained after prescribing radiotherapy and PET/CT images acquired earlier for cancer staging. To take advantage of both modalities, we present a two-stream chained segmentation approach that effectively fuses the CT and PET modalities via early and late 3D deep-network-based fusion. Furthermore, to effect the fusion and segmentation we propose a simple yet effective progressive semantically nested network (PSNN) model that outperforms more complicated models. Extensive 5-fold cross-validation on 110 esophageal cancer patients, the largest analysis to date, demonstrates that both the proposed two-stream chained segmentation pipeline and the PSNN model can significantly improve the quantitative performance over the previous state-of-the-art work by 11% in absolute Dice score (DSC) (from 0.654 to 0.764) and, at the same time, reducing the Hausdorff distance from 129 mm to 47 mm.

Attention-Guided Curriculum Learning for Weakly Supervised Classification and Localization of Thoracic Diseases on Chest Radiographs

In this work, we exploit the task of joint classification and weakly supervised localization of thoracic diseases from chest radiographs, with only image-level disease labels coupled with disease severity-level (DSL) information of a subset. A convolutional neural network (CNN) based attention-guided curriculum learning (AGCL) framework is presented, which leverages the severity-level attributes mined from radiology reports. Images in order of difficulty (grouped by different severity-levels) are fed to CNN to boost the learning gradually. In addition, highly confident samples (measured by classification probabilities) and their corresponding class-conditional heatmaps (generated by the CNN) are extracted and further fed into the AGCL framework to guide the learning of more distinctive convolutional features in the next iteration. A two-path network architecture is designed to regress the heatmaps from selected seed samples in addition to the original classification task. The joint learning scheme can improve the classification and localization performance along with more seed samples for the next iteration. We demonstrate the effectiveness of this iterative refinement framework via extensive experimental evaluations on the publicly available ChestXray14 dataset. AGCL achieves over 5.7\% (averaged over 14 diseases) increase in classification AUC and 7%/11% increases in Recall/Precision for the localization task compared to the state of the art.

CT Image Enhancement Using Stacked Generative Adversarial Networks and Transfer Learning for Lesion Segmentation Improvement

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.

Iterative Attention Mining for Weakly Supervised Thoracic Disease Pattern Localization in Chest X-Rays

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.

Accurate Weakly-Supervised Deep Lesion Segmentation using Large-Scale Clinical Annotations: Slice-Propagated 3D Mask Generation from 2D RECIST

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.

Semi-Automatic RECIST Labeling on CT Scans with Cascaded Convolutional Neural Networks

Response evaluation criteria in solid tumors (RECIST) is the standard measurement for tumor extent to evaluate treatment responses in cancer patients. As such, RECIST annotations must be accurate. However, RECIST annotations manually labeled by radiologists require professional knowledge and are time-consuming, subjective, and prone to inconsistency among different observers. To alleviate these problems, we propose a cascaded convolutional neural network based method to semi-automatically label RECIST annotations and drastically reduce annotation time. The proposed method consists of two stages: lesion region normalization and RECIST estimation. We employ the spatial transformer network (STN) for lesion region normalization, where a localization network is designed to predict the lesion region and the transformation parameters with a multi-task learning strategy. For RECIST estimation, we adapt the stacked hourglass network (SHN), introducing a relationship constraint loss to improve the estimation precision. STN and SHN can both be learned in an end-to-end fashion. We train our system on the DeepLesion dataset, obtaining a consensus model trained on RECIST annotations performed by multiple radiologists over a multi-year period. Importantly, when judged against the inter-reader variability of two additional radiologist raters, our system performs more stably and with less variability, suggesting that RECIST annotations can be reliably obtained with reduced labor and time.

CT-Realistic Lung Nodule Simulation from 3D Conditional Generative Adversarial Networks for Robust Lung Segmentation

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

White matter hyperintensity segmentation from T1 and FLAIR images using fully convolutional neural networks enhanced with residual connections

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