Xianghua Ye

Lin Tian, Zi Li, Fengze Liu et al. · harvard

Image registration is a fundamental medical image analysis task. Ideally, registration should focus on aligning semantically corresponding voxels, i.e., the same anatomical locations. However, existing methods often optimize similarity measures computed directly on intensities or on hand-crafted features, which lack anatomical semantic information. These similarity measures may lead to sub-optimal solutions where large deformations, complex anatomical differences, or cross-modality imagery exist. In this work, we introduce a fast and accurate method for unsupervised 3D medical image registration building on top of a Self-supervised Anatomical eMbedding (SAM) algorithm, which is capable of computing dense anatomical correspondences between two images at the voxel level. We name our approach SAM-Enhanced registration (SAME++), which decomposes image registration into four steps: affine transformation, coarse deformation, deep non-parametric transformation, and instance optimization. Using SAM embeddings, we enhance these steps by finding more coherent correspondence and providing features with better semantic guidance. We extensively evaluated SAME++ using more than 50 labeled organs on three challenging inter-subject registration tasks of different body parts. As a complete registration framework, SAME++ markedly outperforms leading methods by $4.2\%$ - $8.2\%$ in terms of Dice score while being orders of magnitude faster than numerical optimization-based methods. Code is available at \url{https://github.com/alibaba-damo-academy/same}.

Zi Li, Lin Tian, Tony C. W. Mok et al. · harvard

Estimating displacement vector field via a cost volume computed in the feature space has shown great success in image registration, but it suffers excessive computation burdens. Moreover, existing feature descriptors only extract local features incapable of representing the global semantic information, which is especially important for solving large transformations. To address the discussed issues, we propose SAMConvex, a fast coarse-to-fine discrete optimization method for CT registration that includes a decoupled convex optimization procedure to obtain deformation fields based on a self-supervised anatomical embedding (SAM) feature extractor that captures both local and global information. To be specific, SAMConvex extracts per-voxel features and builds 6D correlation volumes based on SAM features, and iteratively updates a flow field by performing lookups on the correlation volumes with a coarse-to-fine scheme. SAMConvex outperforms the state-of-the-art learning-based methods and optimization-based methods over two inter-patient registration datasets (Abdomen CT and HeadNeck CT) and one intra-patient registration dataset (Lung CT). Moreover, as an optimization-based method, SAMConvex only takes $\sim2$s ($\sim5s$ with instance optimization) for one paired images.

Jieneng Chen, Yingda Xia, Jiawen Yao et al.

Human readers or radiologists routinely perform full-body multi-organ multi-disease detection and diagnosis in clinical practice, while most medical AI systems are built to focus on single organs with a narrow list of a few diseases. This might severely limit AI's clinical adoption. A certain number of AI models need to be assembled non-trivially to match the diagnostic process of a human reading a CT scan. In this paper, we construct a Unified Tumor Transformer (CancerUniT) model to jointly detect tumor existence & location and diagnose tumor characteristics for eight major cancers in CT scans. CancerUniT is a query-based Mask Transformer model with the output of multi-tumor prediction. We decouple the object queries into organ queries, tumor detection queries and tumor diagnosis queries, and further establish hierarchical relationships among the three groups. This clinically-inspired architecture effectively assists inter- and intra-organ representation learning of tumors and facilitates the resolution of these complex, anatomically related multi-organ cancer image reading tasks. CancerUniT is trained end-to-end using a curated large-scale CT images of 10,042 patients including eight major types of cancers and occurring non-cancer tumors (all are pathology-confirmed with 3D tumor masks annotated by radiologists). On the test set of 631 patients, CancerUniT has demonstrated strong performance under a set of clinically relevant evaluation metrics, substantially outperforming both multi-disease methods and an assembly of eight single-organ expert models in tumor detection, segmentation, and diagnosis. This moves one step closer towards a universal high performance cancer screening tool.

Jianpeng Zhang, Xianghua Ye, Jianfeng Zhang et al.

Lung cancer is a leading cause of death worldwide and early screening is critical for improving survival outcomes. In clinical practice, the contextual structure of nodules and the accumulated experience of radiologists are the two core elements related to the accuracy of identification of benign and malignant nodules. Contextual information provides comprehensive information about nodules such as location, shape, and peripheral vessels, and experienced radiologists can search for clues from previous cases as a reference to enrich the basis of decision-making. In this paper, we propose a radiologist-inspired method to simulate the diagnostic process of radiologists, which is composed of context parsing and prototype recalling modules. The context parsing module first segments the context structure of nodules and then aggregates contextual information for a more comprehensive understanding of the nodule. The prototype recalling module utilizes prototype-based learning to condense previously learned cases as prototypes for comparative analysis, which is updated online in a momentum way during training. Building on the two modules, our method leverages both the intrinsic characteristics of the nodules and the external knowledge accumulated from other nodules to achieve a sound diagnosis. To meet the needs of both low-dose and noncontrast screening, we collect a large-scale dataset of 12,852 and 4,029 nodules from low-dose and noncontrast CTs respectively, each with pathology- or follow-up-confirmed labels. Experiments on several datasets demonstrate that our method achieves advanced screening performance on both low-dose and noncontrast scenarios.

Xiaoyu Bai, Fan Bai, Xiaofei Huo et al.

Radiotherapists require accurate registration of MR/CT images to effectively use information from both modalities. In a typical registration pipeline, rigid or affine transformations are applied to roughly align the fixed and moving images before proceeding with the deformation step. While recent learning-based methods have shown promising results in the rigid/affine step, these methods often require images with similar field-of-view (FOV) for successful alignment. As a result, aligning images with different FOVs remains a challenging task. Self-supervised landmark detection methods like self-supervised Anatomical eMbedding (SAM) have emerged as a useful tool for mapping and cropping images to similar FOVs. However, these methods are currently limited to intra-modality use only. To address this limitation and enable cross-modality matching, we propose a new approach called Cross-SAM. Our approach utilizes a novel iterative process that alternates between embedding learning and CT-MRI registration. We start by applying aggressive contrast augmentation on both CT and MRI images to train a SAM model. We then use this SAM to identify corresponding regions on paired images using robust grid-points matching, followed by a point-set based affine/rigid registration, and a deformable fine-tuning step to produce registered paired images. We use these registered pairs to enhance the matching ability of SAM, which is then processed iteratively. We use the final model for cross-modality matching tasks. We evaluated our approach on two CT-MRI affine registration datasets and found that Cross-SAM achieved robust affine registration on both datasets, significantly outperforming other methods and achieving state-of-the-art performance.

Zhanghexuan Ji, Dazhou Guo, Puyang Wang et al.

Deep learning empowers the mainstream medical image segmentation methods. Nevertheless current deep segmentation approaches are not capable of efficiently and effectively adapting and updating the trained models when new incremental segmentation classes (along with new training datasets or not) are required to be added. In real clinical environment, it can be preferred that segmentation models could be dynamically extended to segment new organs/tumors without the (re-)access to previous training datasets due to obstacles of patient privacy and data storage. This process can be viewed as a continual semantic segmentation (CSS) problem, being understudied for multi-organ segmentation. In this work, we propose a new architectural CSS learning framework to learn a single deep segmentation model for segmenting a total of 143 whole-body organs. Using the encoder/decoder network structure, we demonstrate that a continually-trained then frozen encoder coupled with incrementally-added decoders can extract and preserve sufficiently representative image features for new classes to be subsequently and validly segmented. To maintain a single network model complexity, we trim each decoder progressively using neural architecture search and teacher-student based knowledge distillation. To incorporate with both healthy and pathological organs appearing in different datasets, a novel anomaly-aware and confidence learning module is proposed to merge the overlapped organ predictions, originated from different decoders. Trained and validated on 3D CT scans of 2500+ patients from four datasets, our single network can segment total 143 whole-body organs with very high accuracy, closely reaching the upper bound performance level by training four separate segmentation models (i.e., one model per dataset/task).

Puyang Wang, Dazhou Guo, Dandan Zheng et al.

Intrathoracic airway segmentation in computed tomography (CT) is a prerequisite for various respiratory disease analyses such as chronic obstructive pulmonary disease (COPD), asthma and lung cancer. Unlike other organs with simpler shapes or topology, the airway's complex tree structure imposes an unbearable burden to generate the "ground truth" label (up to 7 or 3 hours of manual or semi-automatic annotation on each case). Most of the existing airway datasets are incompletely labeled/annotated, thus limiting the completeness of computer-segmented airway. In this paper, we propose a new anatomy-aware multi-class airway segmentation method enhanced by topology-guided iterative self-learning. Based on the natural airway anatomy, we formulate a simple yet highly effective anatomy-aware multi-class segmentation task to intuitively handle the severe intra-class imbalance of the airway. To solve the incomplete labeling issue, we propose a tailored self-iterative learning scheme to segment toward the complete airway tree. For generating pseudo-labels to achieve higher sensitivity , we introduce a novel breakage attention map and design a topology-guided pseudo-label refinement method by iteratively connecting breaking branches commonly existed from initial pseudo-labels. Extensive experiments have been conducted on four datasets including two public challenges. The proposed method ranked 1st in both EXACT'09 challenge using average score and ATM'22 challenge on weighted average score. In a public BAS dataset and a private lung cancer dataset, our method significantly improves previous leading approaches by extracting at least (absolute) 7.5% more detected tree length and 4.0% more tree branches, while maintaining similar precision.

Ke Yan, Dakai Jin, Dazhou Guo et al.

Finding abnormal lymph nodes in radiological images is highly important for various medical tasks such as cancer metastasis staging and radiotherapy planning. Lymph nodes (LNs) are small glands scattered throughout the body. They are grouped or defined to various LN stations according to their anatomical locations. The CT imaging appearance and context of LNs in different stations vary significantly, posing challenges for automated detection, especially for pathological LNs. Motivated by this observation, we propose a novel end-to-end framework to improve LN detection performance by leveraging their station information. We design a multi-head detector and make each head focus on differentiating the LN and non-LN structures of certain stations. Pseudo station labels are generated by an LN station classifier as a form of multi-task learning during training, so we do not need another explicit LN station prediction model during inference. Our algorithm is evaluated on 82 patients with lung cancer and 91 patients with esophageal cancer. The proposed implicit station stratification method improves the detection sensitivity of thoracic lymph nodes from 65.1% to 71.4% and from 80.3% to 85.5% at 2 false positives per patient on the two datasets, respectively, which significantly outperforms various existing state-of-the-art baseline techniques such as nnUNet, nnDetection and LENS.

Weiwei Cao, Jianpeng Zhang, Zhongyi Shui et al.

Vision-language pre-training (VLP) has great potential for developing multifunctional and general medical diagnostic capabilities. However, aligning medical images with a low signal-to-noise ratio (SNR) to reports with a high SNR presents a semantic density gap, leading to visual alignment bias. In this paper, we propose boosting vision semantic density to improve alignment effectiveness. On one hand, we enhance visual semantics through disease-level vision contrastive learning, which strengthens the model's ability to differentiate between normal and abnormal samples for each anatomical structure. On the other hand, we introduce an anatomical normality modeling method to model the distribution of normal samples for each anatomy, leveraging VQ-VAE for reconstructing normal vision embeddings in the latent space. This process amplifies abnormal signals by leveraging distribution shifts in abnormal samples, enhancing the model's perception and discrimination of abnormal attributes. The enhanced visual representation effectively captures the diagnostic-relevant semantics, facilitating more efficient and accurate alignment with the diagnostic report. We conduct extensive experiments on two chest CT datasets, CT-RATE and Rad-ChestCT, and an abdominal CT dataset, MedVL-CT69K, and comprehensively evaluate the diagnosis performance across multiple tasks in the chest and abdominal CT scenarios, achieving state-of-the-art zero-shot performance. Notably, our method achieved an average AUC of 84.9% across 54 diseases in 15 organs, significantly surpassing existing methods. Additionally, we demonstrate the superior transfer learning capabilities of our pre-trained model. Code is available at https://github.com/alibaba-damo-academy/ViSD-Boost.

Zhongyi Shui, Jianpeng Zhang, Weiwei Cao et al.

Artificial intelligence (AI) shows great potential in assisting radiologists to improve the efficiency and accuracy of medical image interpretation and diagnosis. However, a versatile AI model requires large-scale data and comprehensive annotations, which are often impractical in medical settings. Recent studies leverage radiology reports as a naturally high-quality supervision for medical images, using contrastive language-image pre-training (CLIP) to develop language-informed models for radiological image interpretation. Nonetheless, these approaches typically contrast entire images with reports, neglecting the local associations between imaging regions and report sentences, which may undermine model performance and interoperability. In this paper, we propose a fine-grained vision-language model (fVLM) for anatomy-level CT image interpretation. Specifically, we explicitly match anatomical regions of CT images with corresponding descriptions in radiology reports and perform contrastive pre-training for each anatomy individually. Fine-grained alignment, however, faces considerable false-negative challenges, mainly from the abundance of anatomy-level healthy samples and similarly diseased abnormalities. To tackle this issue, we propose identifying false negatives of both normal and abnormal samples and calibrating contrastive learning from patient-level to disease-aware pairing. We curated the largest CT dataset to date, comprising imaging and report data from 69,086 patients, and conducted a comprehensive evaluation of 54 major and important disease diagnosis tasks across 15 main anatomies. Experimental results demonstrate the substantial potential of fVLM in versatile medical image interpretation. In the zero-shot classification task, we achieved an average AUC of 81.3% on 54 diagnosis tasks, surpassing CLIP and supervised methods by 12.9% and 8.0%, respectively.

Weiwei Cao, Jianpeng Zhang, Yingda Xia et al.

Radiologists highly desire fully automated versatile AI for medical imaging interpretation. However, the lack of extensively annotated large-scale multi-disease datasets has hindered the achievement of this goal. In this paper, we explore the feasibility of leveraging language as a naturally high-quality supervision for chest CT imaging. In light of the limited availability of image-report pairs, we bootstrap the understanding of 3D chest CT images by distilling chest-related diagnostic knowledge from an extensively pre-trained 2D X-ray expert model. Specifically, we propose a language-guided retrieval method to match each 3D CT image with its semantically closest 2D X-ray image, and perform pair-wise and semantic relation knowledge distillation. Subsequently, we use contrastive learning to align images and reports within the same patient while distinguishing them from the other patients. However, the challenge arises when patients have similar semantic diagnoses, such as healthy patients, potentially confusing if treated as negatives. We introduce a robust contrastive learning that identifies and corrects these false negatives. We train our model with over 12,000 pairs of chest CT images and radiology reports. Extensive experiments across multiple scenarios, including zero-shot learning, report generation, and fine-tuning processes, demonstrate the model's feasibility in interpreting chest CT images.

Zi Li, Jianpeng Zhang, Tai Ma et al.

Learning-based medical image registration has achieved performance parity with conventional methods while demonstrating a substantial advantage in computational efficiency. However, learning-based registration approaches lack generalizability across diverse clinical scenarios, requiring the laborious development of multiple isolated networks for specific registration tasks, e.g., inter-/intra-subject registration or organ-specific alignment. % To overcome this limitation, we propose \textbf{UniReg}, the first interactive foundation model for medical image registration, which combines the precision advantages of task-specific learning methods with the generalization of traditional optimization methods. Our key innovation is a unified framework for diverse registration scenarios, achieved through a conditional deformation field estimation within a unified registration model. This is realized through a dynamic learning paradigm that explicitly encodes: (1) anatomical structure priors, (2) registration type constraints (inter/intra-subject), and (3) instance-specific features, enabling the generation of scenario-optimal deformation fields. % Through comprehensive experiments encompassing $90$ anatomical structures at different body regions, our UniReg model demonstrates comparable performance with contemporary state-of-the-art methodologies while achieving ~50\% reduction in required training iterations relative to the conventional learning-based paradigm. This optimization contributes to a significant reduction in computational resources, such as training time. Code and model will be available.

Yirui Wang, Qinji Yu, Ke Yan et al.

Lymph node (LN) assessment is a critical, indispensable yet very challenging task in the routine clinical workflow of radiology and oncology. Accurate LN analysis is essential for cancer diagnosis, staging, and treatment planning. Finding scatteredly distributed, low-contrast clinically relevant LNs in 3D CT is difficult even for experienced physicians under high inter-observer variations. Previous automatic LN detection works typically yield limited recall and high false positives (FPs) due to adjacent anatomies with similar image intensities, shapes, or textures (vessels, muscles, esophagus, etc). In this work, we propose a new LN DEtection TRansformer, named LN-DETR, to achieve more accurate performance. By enhancing the 2D backbone with a multi-scale 2.5D feature fusion to incorporate 3D context explicitly, more importantly, we make two main contributions to improve the representation quality of LN queries. 1) Considering that LN boundaries are often unclear, an IoU prediction head and a location debiased query selection are proposed to select LN queries of higher localization accuracy as the decoder query's initialization. 2) To reduce FPs, query contrastive learning is employed to explicitly reinforce LN queries towards their best-matched ground-truth queries over unmatched query predictions. Trained and tested on 3D CT scans of 1067 patients (with 10,000+ labeled LNs) via combining seven LN datasets from different body parts (neck, chest, and abdomen) and pathologies/cancers, our method significantly improves the performance of previous leading methods by > 4-5% average recall at the same FP rates in both internal and external testing. We further evaluate on the universal lesion detection task using NIH DeepLesion benchmark, and our method achieves the top performance of 88.46% averaged recall across 0.5 to 4 FPs per image, compared with other leading reported results.

Dazhou Guo, Zhanghexuan Ji, Yanzhou Su et al.

Precision medicine in the quantitative management of chronic diseases and oncology would be greatly improved if the Computed Tomography (CT) scan of any patient could be segmented, parsed and analyzed in a precise and detailed way. However, there is no such fully annotated CT dataset with all anatomies delineated for training because of the exceptionally high manual cost, the need for specialized clinical expertise, and the time required to finish the task. To this end, we proposed a novel continual learning-driven CT model that can segment complete anatomies presented using dozens of previously partially labeled datasets, dynamically expanding its capacity to segment new ones without compromising previously learned organ knowledge. Existing multi-dataset approaches are not able to dynamically segment new anatomies without catastrophic forgetting and would encounter optimization difficulty or infeasibility when segmenting hundreds of anatomies across the whole range of body regions. Our single unified CT segmentation model, CL-Net, can highly accurately segment a clinically comprehensive set of 235 fine-grained whole-body anatomies. Composed of a universal encoder, multiple optimized and pruned decoders, CL-Net is developed using 13,952 CT scans from 20 public and 16 private high-quality partially labeled CT datasets of various vendors, different contrast phases, and pathologies. Extensive evaluation demonstrates that CL-Net consistently outperforms the upper limit of an ensemble of 36 specialist nnUNets trained per dataset with the complexity of 5% model size and significantly surpasses the segmentation accuracy of recent leading Segment Anything-style medical image foundation models by large margins. Our continual learning-driven CL-Net model would lay a solid foundation to facilitate many downstream tasks of oncology and chronic diseases using the most widely adopted CT imaging.

Runze Wang, Zeli Chen, Zhiyun Song et al.

To reduce radiation exposure and improve the diagnostic efficacy of low-dose computed tomography (LDCT), numerous deep learning-based denoising methods have been developed to mitigate noise and artifacts. However, most of these approaches ignore the anatomical semantics of human tissues, which may potentially result in suboptimal denoising outcomes. To address this problem, we propose ALDEN, an anatomy-aware LDCT denoising method that integrates semantic features of pretrained vision models (PVMs) with adversarial and contrastive learning. Specifically, we introduce an anatomy-aware discriminator that dynamically fuses hierarchical semantic features from reference normal-dose CT (NDCT) via cross-attention mechanisms, enabling tissue-specific realism evaluation in the discriminator. In addition, we propose a semantic-guided contrastive learning module that enforces anatomical consistency by contrasting PVM-derived features from LDCT, denoised CT and NDCT, preserving tissue-specific patterns through positive pairs and suppressing artifacts via dual negative pairs. Extensive experiments conducted on two LDCT denoising datasets reveal that ALDEN achieves the state-of-the-art performance, offering superior anatomy preservation and substantially reducing over-smoothing issue of previous work. Further validation on a downstream multi-organ segmentation task (encompassing 117 anatomical structures) affirms the model's ability to maintain anatomical awareness.

Qinji Yu, Yirui Wang, Ke Yan et al.

Lymph node (LN) assessment is an essential task in the routine radiology workflow, providing valuable insights for cancer staging, treatment planning and beyond. Identifying scatteredly-distributed and low-contrast LNs in 3D CT scans is highly challenging, even for experienced clinicians. Previous lesion and LN detection methods demonstrate effectiveness of 2.5D approaches (i.e, using 2D network with multi-slice inputs), leveraging pretrained 2D model weights and showing improved accuracy as compared to separate 2D or 3D detectors. However, slice-based 2.5D detectors do not explicitly model inter-slice consistency for LN as a 3D object, requiring heuristic post-merging steps to generate final 3D LN instances, which can involve tuning a set of parameters for each dataset. In this work, we formulate 3D LN detection as a tracking task and propose LN-Tracker, a novel LN tracking transformer, for joint end-to-end detection and 3D instance association. Built upon DETR-based detector, LN-Tracker decouples transformer decoder's query into the track and detection groups, where the track query autoregressively follows previously tracked LN instances along the z-axis of a CT scan. We design a new transformer decoder with masked attention module to align track query's content to the context of current slice, meanwhile preserving detection query's high accuracy in current slice. An inter-slice similarity loss is introduced to encourage cohesive LN association between slices. Extensive evaluation on four lymph node datasets shows LN-Tracker's superior performance, with at least 2.7% gain in average sensitivity when compared to other top 3D/2.5D detectors. Further validation on public lung nodule and prostate tumor detection tasks confirms the generalizability of LN-Tracker as it achieves top performance on both tasks.

Zi Li, Ying Chen, Zeli Chen et al.

In the radiation therapy of nasopharyngeal carcinoma (NPC), clinicians typically delineate the gross tumor volume (GTV) using non-contrast planning computed tomography to ensure accurate radiation dose delivery. However, the low contrast between tumors and adjacent normal tissues necessitates that radiation oncologists manually delineate the tumors, often relying on diagnostic MRI for guidance. % In this study, we propose a novel approach to directly segment NPC gross tumors on non-contrast planning CT images, circumventing potential registration errors when aligning MRI or MRI-derived tumor masks to planning CT. To address the low contrast issues between tumors and adjacent normal structures in planning CT, we introduce a 3D Semantic Asymmetry Tumor segmentation (SATs) method. Specifically, we posit that a healthy nasopharyngeal region is characteristically bilaterally symmetric, whereas the emergence of nasopharyngeal carcinoma disrupts this symmetry. Then, we propose a Siamese contrastive learning segmentation framework that minimizes the voxel-wise distance between original and flipped areas without tumor and encourages a larger distance between original and flipped areas with tumor. Thus, our approach enhances the sensitivity of features to semantic asymmetries. % Extensive experiments demonstrate that the proposed SATs achieves the leading NPC GTV segmentation performance in both internal and external testing, \emph{e.g.}, with at least 2\% absolute Dice score improvement and 12\% average distance error reduction when compared to other state-of-the-art methods in the external testing.

Xiaoyu Bai, Fan Bai, Xiaofei Huo et al.

Identifying specific anatomical structures (\textit{e.g.}, lesions or landmarks) in medical images plays a fundamental role in medical image analysis. Exemplar-based landmark detection methods are receiving increasing attention since they can detect arbitrary anatomical points in inference while do not need landmark annotations in training. They use self-supervised learning to acquire a discriminative embedding for each voxel within the image. These approaches can identify corresponding landmarks through nearest neighbor matching and has demonstrated promising results across various tasks. However, current methods still face challenges in: (1) differentiating voxels with similar appearance but different semantic meanings (\textit{e.g.}, two adjacent structures without clear borders); (2) matching voxels with similar semantics but markedly different appearance (\textit{e.g.}, the same vessel before and after contrast injection); and (3) cross-modality matching (\textit{e.g.}, CT-MRI landmark-based registration). To overcome these challenges, we propose universal anatomical embedding (UAE), which is a unified framework designed to learn appearance, semantic, and cross-modality anatomical embeddings. Specifically, UAE incorporates three key innovations: (1) semantic embedding learning with prototypical contrastive loss; (2) a fixed-point-based matching strategy; and (3) an iterative approach for cross-modality embedding learning. We thoroughly evaluated UAE across intra- and inter-modality tasks, including one-shot landmark detection, lesion tracking on longitudinal CT scans, and CT-MRI affine/rigid registration with varying field of view. Our results suggest that UAE outperforms state-of-the-art methods, offering a robust and versatile approach for landmark based medical image analysis tasks. Code and trained models are available at: \href{https://shorturl.at/bgsB3}

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.

Xianghua Ye, Dazhou Guo, Chen-kan Tseng et al.

Background: The current clinical workflow for esophageal gross tumor volume (GTV) contouring relies on manual delineation of high labor-costs and interuser variability. Purpose: To validate the clinical applicability of a deep learning (DL) multi-modality esophageal GTV contouring model, developed at 1 institution whereas tested at multiple ones. Methods and Materials: We collected 606 esophageal cancer patients from four institutions. 252 institution-1 patients had a treatment planning-CT (pCT) and a pair of diagnostic FDG-PETCT; 354 patients from other 3 institutions had only pCT. A two-streamed DL model for GTV segmentation was developed using pCT and PETCT scans of a 148 patient institution-1 subset. This built model had the flexibility of segmenting GTVs via only pCT or pCT+PETCT combined. For independent evaluation, the rest 104 institution-1 patients behaved as unseen internal testing, and 354 institutions 2-4 patients were used for external testing. We evaluated manual revision degrees by human experts to assess the contour-editing effort. The performance of the deep model was compared against 4 radiation oncologists in a multiuser study with 20 random external patients. Contouring accuracy and time were recorded for the pre-and post-DL assisted delineation process. Results: Our model achieved high segmentation accuracy in internal testing (mean Dice score: 0.81 using pCT and 0.83 using pCT+PET) and generalized well to external evaluation (mean DSC: 0.80). Expert assessment showed that the predicted contours of 88% patients need only minor or no revision. In multi-user evaluation, with the assistance of a deep model, inter-observer variation and required contouring time were reduced by 37.6% and 48.0%, respectively. Conclusions: Deep learning predicted GTV contours were in close agreement with the ground truth and could be adopted clinically with mostly minor or no changes.

Fengze Liu, Ke Yan, Adam Harrison et al.

In this work, we introduce a fast and accurate method for unsupervised 3D medical image registration. This work is built on top of a recent algorithm SAM, which is capable of computing dense anatomical/semantic correspondences between two images at the pixel level. Our method is named SAME, which breaks down image registration into three steps: affine transformation, coarse deformation, and deep deformable registration. Using SAM embeddings, we enhance these steps by finding more coherent correspondences, and providing features and a loss function with better semantic guidance. We collect a multi-phase chest computed tomography dataset with 35 annotated organs for each patient and conduct inter-subject registration for quantitative evaluation. Results show that SAME outperforms widely-used traditional registration techniques (Elastix FFD, ANTs SyN) and learning based VoxelMorph method by at least 4.7% and 2.7% in Dice scores for two separate tasks of within-contrast-phase and across-contrast-phase registration, respectively. SAME achieves the comparable performance to the best traditional registration method, DEEDS (from our evaluation), while being orders of magnitude faster (from 45 seconds to 1.2 seconds).

Dazhou Guo, Xianghua Ye, Jia Ge et al.

Lymph node station (LNS) delineation from computed tomography (CT) scans is an indispensable step in radiation oncology workflow. High inter-user variabilities across oncologists and prohibitive laboring costs motivated the automated approach. Previous works exploit anatomical priors to infer LNS based on predefined ad-hoc margins. However, without voxel-level supervision, the performance is severely limited. LNS is highly context-dependent - LNS boundaries are constrained by anatomical organs - we formulate it as a deep spatial and contextual parsing problem via encoded anatomical organs. This permits the deep network to better learn from both CT appearance and organ context. We develop a stratified referencing organ segmentation protocol that divides the organs into anchor and non-anchor categories and uses the former's predictions to guide the later segmentation. We further develop an auto-search module to identify the key organs that opt for the optimal LNS parsing performance. Extensive four-fold cross-validation experiments on a dataset of 98 esophageal cancer patients (with the most comprehensive set of 12 LNSs + 22 organs in thoracic region to date) are conducted. Our LNS parsing model produces significant performance improvements, with an average Dice score of 81.1% +/- 6.1%, which is 5.0% and 19.2% higher over the pure CT-based deep model and the previous representative approach, respectively.

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).

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.