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Le Lu

Publications and source records attributed to Le Lu.

At least 109 records · Page 6Linked to original sources

Knowledge Distillation with Adaptive Asymmetric Label Sharpening for Semi-supervised Fracture Detection in Chest X-rays

Exploiting available medical records to train high performance computer-aided diagnosis (CAD) models via the semi-supervised learning (SSL) setting is emerging to tackle the prohibitively high labor costs involved in large-scale medical image annotations. Despite the extensive attentions received on SSL, previous methods failed to 1) account for the low disease prevalence in medical records and 2) utilize the image-level diagnosis indicated from the medical records. Both issues are unique to SSL for CAD models. In this work, we propose a new knowledge distillation method that effectively exploits large-scale image-level labels extracted from the medical records, augmented with limited expert annotated region-level labels, to train a rib and clavicle fracture CAD model for chest X-ray (CXR). Our method leverages the teacher-student model paradigm and features a novel adaptive asymmetric label sharpening (AALS) algorithm to address the label imbalance problem that specially exists in medical domain. Our approach is extensively evaluated on all CXR (N = 65,845) from the trauma registry of anonymous hospital over a period of 9 years (2008-2016), on the most common rib and clavicle fractures. The experiment results demonstrate that our method achieves the state-of-the-art fracture detection performance, i.e., an area under receiver operating characteristic curve (AUROC) of 0.9318 and a free-response receiver operating characteristic (FROC) score of 0.8914 on the rib fractures, significantly outperforming previous approaches by an AUROC gap of 1.63% and an FROC improvement by 3.74%. Consistent performance gains are also observed for clavicle fracture detection.

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TransUNet: Transformers Make Strong Encoders for Medical Image Segmentation

Medical image segmentation is an essential prerequisite for developing healthcare systems, especially for disease diagnosis and treatment planning. On various medical image segmentation tasks, the u-shaped architecture, also known as U-Net, has become the de-facto standard and achieved tremendous success. However, due to the intrinsic locality of convolution operations, U-Net generally demonstrates limitations in explicitly modeling long-range dependency. Transformers, designed for sequence-to-sequence prediction, have emerged as alternative architectures with innate global self-attention mechanisms, but can result in limited localization abilities due to insufficient low-level details. In this paper, we propose TransUNet, which merits both Transformers and U-Net, as a strong alternative for medical image segmentation. On one hand, the Transformer encodes tokenized image patches from a convolution neural network (CNN) feature map as the input sequence for extracting global contexts. On the other hand, the decoder upsamples the encoded features which are then combined with the high-resolution CNN feature maps to enable precise localization. We argue that Transformers can serve as strong encoders for medical image segmentation tasks, with the combination of U-Net to enhance finer details by recovering localized spatial information. TransUNet achieves superior performances to various competing methods on different medical applications including multi-organ segmentation and cardiac segmentation. Code and models are available at https://github.com/Beckschen/TransUNet.

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A New Window Loss Function for Bone Fracture Detection and Localization in X-ray Images with Point-based Annotation

Object detection methods are widely adopted for computer-aided diagnosis using medical images. Anomalous findings are usually treated as objects that are described by bounding boxes. Yet, many pathological findings, e.g., bone fractures, cannot be clearly defined by bounding boxes, owing to considerable instance, shape and boundary ambiguities. This makes bounding box annotations, and their associated losses, highly ill-suited. In this work, we propose a new bone fracture detection method for X-ray images, based on a labor effective and flexible annotation scheme suitable for abnormal findings with no clear object-level spatial extents or boundaries. Our method employs a simple, intuitive, and informative point-based annotation protocol to mark localized pathology information. To address the uncertainty in the fracture scales annotated via point(s), we convert the annotations into pixel-wise supervision that uses lower and upper bounds with positive, negative, and uncertain regions. A novel Window Loss is subsequently proposed to only penalize the predictions outside of the uncertain regions. Our method has been extensively evaluated on 4410 pelvic X-ray images of unique patients. Experiments demonstrate that our method outperforms previous state-of-the-art image classification and object detection baselines by healthy margins, with an AUROC of 0.983 and FROC score of 89.6%.

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Learning from Multiple Datasets with Heterogeneous and Partial Labels for Universal Lesion Detection in CT

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.

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Automatic Vertebra Localization and Identification in CT by Spine Rectification and Anatomically-constrained Optimization

Accurate vertebra localization and identification are required in many clinical applications of spine disorder diagnosis and surgery planning. However, significant challenges are posed in this task by highly varying pathologies (such as vertebral compression fracture, scoliosis, and vertebral fixation) and imaging conditions (such as limited field of view and metal streak artifacts). This paper proposes a robust and accurate method that effectively exploits the anatomical knowledge of the spine to facilitate vertebra localization and identification. A key point localization model is trained to produce activation maps of vertebra centers. They are then re-sampled along the spine centerline to produce spine-rectified activation maps, which are further aggregated into 1-D activation signals. Following this, an anatomically-constrained optimization module is introduced to jointly search for the optimal vertebra centers under a soft constraint that regulates the distance between vertebrae and a hard constraint on the consecutive vertebra indices. When being evaluated on a major public benchmark of 302 highly pathological CT images, the proposed method reports the state of the art identification (id.) rate of 97.4%, and outperforms the best competing method of 94.7% id. rate by reducing the relative id. error rate by half.

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Interactive Radiotherapy Target Delineation with 3D-Fused Context Propagation

Gross tumor volume (GTV) delineation on tomography medical imaging is crucial for radiotherapy planning and cancer diagnosis. Convolutional neural networks (CNNs) has been predominated on automatic 3D medical segmentation tasks, including contouring the radiotherapy target given 3D CT volume. While CNNs may provide feasible outcome, in clinical scenario, double-check and prediction refinement by experts is still necessary because of CNNs' inconsistent performance on unexpected patient cases. To provide experts an efficient way to modify the CNN predictions without retrain the model, we propose 3D-fused context propagation, which propagates any edited slice to the whole 3D volume. By considering the high-level feature maps, the radiation oncologists would only required to edit few slices to guide the correction and refine the whole prediction volume. Specifically, we leverage the backpropagation for activation technique to convey the user editing information backwardly to the latent space and generate new prediction based on the updated and original feature. During the interaction, our proposed approach reuses the extant extracted features and does not alter the existing 3D CNN model architectures, avoiding the perturbation on other predictions. The proposed method is evaluated on two published radiotherapy target contouring datasets of nasopharyngeal and esophageal cancer. The experimental results demonstrate that our proposed method is able to further effectively improve the existing segmentation prediction from different model architectures given oncologists' interactive inputs.

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3D Graph Anatomy Geometry-Integrated Network for Pancreatic Mass Segmentation, Diagnosis, and Quantitative Patient Management

The pancreatic disease taxonomy includes ten types of masses (tumors or cysts)[20,8]. Previous work focuses on developing segmentation or classification methods only for certain mass types. Differential diagnosis of all mass types is clinically highly desirable [20] but has not been investigated using an automated image understanding approach. We exploit the feasibility to distinguish pancreatic ductal adenocarcinoma (PDAC) from the nine other nonPDAC masses using multi-phase CT imaging. Both image appearance and the 3D organ-mass geometry relationship are critical. We propose a holistic segmentation-mesh-classification network (SMCN) to provide patient-level diagnosis, by fully utilizing the geometry and location information, which is accomplished by combining the anatomical structure and the semantic detection-by-segmentation network. SMCN learns the pancreas and mass segmentation task and builds an anatomical correspondence-aware organ mesh model by progressively deforming a pancreas prototype on the raw segmentation mask (i.e., mask-to-mesh). A new graph-based residual convolutional network (Graph-ResNet), whose nodes fuse the information of the mesh model and feature vectors extracted from the segmentation network, is developed to produce the patient-level differential classification results. Extensive experiments on 661 patients' CT scans (five phases per patient) show that SMCN can improve the mass segmentation and detection accuracy compared to the strong baseline method nnUNet (e.g., for nonPDAC, Dice: 0.611 vs. 0.478; detection rate: 89% vs. 70%), achieve similar sensitivity and specificity in differentiating PDAC and nonPDAC as expert radiologists (i.e., 94% and 90%), and obtain results comparable to a multimodality test [20] that combines clinical, imaging, and molecular testing for clinical management of patients.

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Contour Transformer Network for One-shot Segmentation of Anatomical Structures

Accurate segmentation of anatomical structures is vital for medical image analysis. The state-of-the-art accuracy is typically achieved by supervised learning methods, where gathering the requisite expert-labeled image annotations in a scalable manner remains a main obstacle. Therefore, annotation-efficient methods that permit to produce accurate anatomical structure segmentation are highly desirable. In this work, we present Contour Transformer Network (CTN), a one-shot anatomy segmentation method with a naturally built-in human-in-the-loop mechanism. We formulate anatomy segmentation as a contour evolution process and model the evolution behavior by graph convolutional networks (GCNs). Training the CTN model requires only one labeled image exemplar and leverages additional unlabeled data through newly introduced loss functions that measure the global shape and appearance consistency of contours. On segmentation tasks of four different anatomies, we demonstrate that our one-shot learning method significantly outperforms non-learning-based methods and performs competitively to the state-of-the-art fully supervised deep learning methods. With minimal human-in-the-loop editing feedback, the segmentation performance can be further improved to surpass the fully supervised methods.

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Lesion Harvester: Iteratively Mining Unlabeled Lesions and Hard-Negative Examples at Scale

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.

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User-Guided Domain Adaptation for Rapid Annotation from User Interactions: A Study on Pathological Liver Segmentation

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.

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Harvesting, Detecting, and Characterizing Liver Lesions from Large-scale Multi-phase CT Data via Deep Dynamic Texture Learning

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.

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Deep Volumetric Universal Lesion Detection using Light-Weight Pseudo 3D Convolution and Surface Point Regression

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.

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Lymph Node Gross Tumor Volume Detection in Oncology Imaging via Relationship Learning Using Graph Neural Network

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.

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Lymph Node Gross Tumor Volume Detection and Segmentation via Distance-based Gating using 3D CT/PET Imaging in Radiotherapy

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).

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DeepPrognosis: Preoperative Prediction of Pancreatic Cancer Survival and Surgical Margin via Contrast-Enhanced CT Imaging

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and carries a dismal prognosis. Surgery remains the best chance of a potential cure for patients who are eligible for initial resection of PDAC. However, outcomes vary significantly even among the resected patients of the same stage and received similar treatments. Accurate preoperative prognosis of resectable PDACs for personalized treatment is thus highly desired. Nevertheless, there are no automated methods yet to fully exploit the contrast-enhanced computed tomography (CE-CT) imaging for PDAC. Tumor attenuation changes across different CT phases can reflect the tumor internal stromal fractions and vascularization of individual tumors that may impact the clinical outcomes. In this work, we propose a novel deep neural network for the survival prediction of resectable PDAC patients, named as 3D Contrast-Enhanced Convolutional Long Short-Term Memory network(CE-ConvLSTM), which can derive the tumor attenuation signatures or patterns from CE-CT imaging studies. We present a multi-task CNN to accomplish both tasks of outcome and margin prediction where the network benefits from learning the tumor resection margin related features to improve survival prediction. The proposed framework can improve the prediction performances compared with existing state-of-the-art survival analysis approaches. The tumor signature built from our model has evidently added values to be combined with the existing clinical staging system.

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Robust Pancreatic Ductal Adenocarcinoma Segmentation with Multi-Institutional Multi-Phase Partially-Annotated CT Scans

Accurate and automated tumor segmentation is highly desired since it has the great potential to increase the efficiency and reproducibility of computing more complete tumor measurements and imaging biomarkers, comparing to (often partial) human measurements. This is probably the only viable means to enable the large-scale clinical oncology patient studies that utilize medical imaging. Deep learning approaches have shown robust segmentation performances for certain types of tumors, e.g., brain tumors in MRI imaging, when a training dataset with plenty of pixel-level fully-annotated tumor images is available. However, more than often, we are facing the challenge that only (very) limited annotations are feasible to acquire, especially for hard tumors. Pancreatic ductal adenocarcinoma (PDAC) segmentation is one of the most challenging tumor segmentation tasks, yet critically important for clinical needs. Previous work on PDAC segmentation is limited to the moderate amounts of annotated patient images (n<300) from venous or venous+arterial phase CT scans. Based on a new self-learning framework, we propose to train the PDAC segmentation model using a much larger quantity of patients (n~=1,000), with a mix of annotated and un-annotated venous or multi-phase CT images. Pseudo annotations are generated by combining two teacher models with different PDAC segmentation specialties on unannotated images, and can be further refined by a teaching assistant model that identifies associated vessels around the pancreas. A student model is trained on both manual and pseudo annotated multi-phase images. Experiment results show that our proposed method provides an absolute improvement of 6.3% Dice score over the strong baseline of nnUNet trained on annotated images, achieving the performance (Dice = 0.71) similar to the inter-observer variability between radiologists.

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Reliable Liver Fibrosis Assessment from Ultrasound using Global Hetero-Image Fusion and View-Specific Parameterization

Ultrasound (US) is a critical modality for diagnosing liver fibrosis. Unfortunately, assessment is very subjective, motivating automated approaches. We introduce a principled deep convolutional neural network (CNN) workflow that incorporates several innovations. First, to avoid overfitting on non-relevant image features, we force the network to focus on a clinical region of interest (ROI), encompassing the liver parenchyma and upper border. Second, we introduce global heteroimage fusion (GHIF), which allows the CNN to fuse features from any arbitrary number of images in a study, increasing its versatility and flexibility. Finally, we use 'style'-based view-specific parameterization (VSP) to tailor the CNN processing for different viewpoints of the liver, while keeping the majority of parameters the same across views. Experiments on a dataset of 610 patient studies (6979 images) demonstrate that our pipeline can contribute roughly 7% and 22% improvements in partial area under the curve and recall at 90% precision, respectively, over conventional classifiers, validating our approach to this crucial problem.

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Anatomy-Aware Siamese Network: Exploiting Semantic Asymmetry for Accurate Pelvic Fracture Detection in X-ray Images

Visual cues of enforcing bilaterally symmetric anatomies as normal findings are widely used in clinical practice to disambiguate subtle abnormalities from medical images. So far, inadequate research attention has been received on effectively emulating this practice in CAD methods. In this work, we exploit semantic anatomical symmetry or asymmetry analysis in a complex CAD scenario, i.e., anterior pelvic fracture detection in trauma PXRs, where semantically pathological (refer to as fracture) and non-pathological (e.g., pose) asymmetries both occur. Visually subtle yet pathologically critical fracture sites can be missed even by experienced clinicians, when limited diagnosis time is permitted in emergency care. We propose a novel fracture detection framework that builds upon a Siamese network enhanced with a spatial transformer layer to holistically analyze symmetric image features. Image features are spatially formatted to encode bilaterally symmetric anatomies. A new contrastive feature learning component in our Siamese network is designed to optimize the deep image features being more salient corresponding to the underlying semantic asymmetries (caused by pelvic fracture occurrences). Our proposed method have been extensively evaluated on 2,359 PXRs from unique patients (the largest study to-date), and report an area under ROC curve score of 0.9771. This is the highest among state-of-the-art fracture detection methods, with improved clinical indications.

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