Dual-Reference Source-Free Active Domain Adaptation for Nasopharyngeal Carcinoma Tumor Segmentation across Multiple Hospitals.

Nasopharyngeal carcinoma (NPC) is a prevalent and clinically significant malignancy that predominantly impacts the head and neck area. Precise delineation of the Gross Tumor Volume (GTV) plays a pivotal role in ensuring effective radiotherapy for NPC. Despite recent methods that have achieved promising results on GTV segmentation, they are still limited by lacking carefully-annotated data and hard-to-access data from multiple hospitals in clinical practice. Although some unsupervised domain adaptation (UDA) has been proposed to alleviate this problem, unconditionally mapping the distribution distorts the underlying structural information, leading to inferior performance. To address this challenge, we devise a novel Sourece-Free Active Domain Adaptation framework to facilitate domain adaptation for the GTV segmentation task. Specifically, we design a dual reference strategy to select domain-invariant and domain-specific representative samples from a specific target domain for annotation and model fine-tuning without relying on source-domain data. Our approach not only ensures data privacy but also reduces the workload for oncologists as it just requires annotating a few representative samples from the target domain and does not need to access the source data. We collect a large-scale clinical dataset comprising 1057 NPC patients from five hospitals to validate our approach. Experimental results show that our method outperforms the previous active learning (e.g., AADA and MHPL) and UDA (e.g., Tent and CPR) methods, and achieves comparable results to the fully supervised upper bound, even with few annotations, highlighting the significant medical utility of our approach. In addition, there is no public dataset about multi-center NPC segmentation, we will release code and dataset for future research (Git).

PA-Seg: Learning From Point Annotations for 3D Medical Image Segmentation Using Contextual Regularization and Cross Knowledge Distillation.

The success of Convolutional Neural Networks (CNNs) in 3D medical image segmentation relies on massive fully annotated 3D volumes for training that are time-consuming and labor-intensive to acquire. In this paper, we propose to annotate a segmentation target with only seven points in 3D medical images, and design a two-stage weakly supervised learning framework PA-Seg. In the first stage, we employ geodesic distance transform to expand the seed points to provide more supervision signal. To further deal with unannotated image regions during training, we propose two contextual regularization strategies, i.e., multi-view Conditional Random Field (mCRF) loss and Variance Minimization (VM) loss, where the first one encourages pixels with similar features to have consistent labels, and the second one minimizes the intensity variance for the segmented foreground and background, respectively. In the second stage, we use predictions obtained by the model pre-trained in the first stage as pseudo labels. To overcome noises in the pseudo labels, we introduce a Self and Cross Monitoring (SCM) strategy, which combines self-training with Cross Knowledge Distillation (CKD) between a primary model and an auxiliary model that learn from soft labels generated by each other. Experiments on public datasets for Vestibular Schwannoma (VS) segmentation and Brain Tumor Segmentation (BraTS) demonstrated that our model trained in the first stage outperformed existing state-of-the-art weakly supervised approaches by a large margin, and after using SCM for additional training, the model's performance was close to its fully supervised counterpart on the BraTS dataset.

Ambiguity-selective consistency regularization for mean-teacher semi-supervised medical image segmentation.

Semi-supervised learning has greatly advanced medical image segmentation since it effectively alleviates the need of acquiring abundant annotations from experts, wherein the mean-teacher model, known as a milestone of perturbed consistency learning, commonly serves as a standard and simple baseline. Inherently, learning from consistency can be regarded as learning from stability under perturbations. Recent improvement leans toward more complex consistency learning frameworks, yet, little attention is paid to the consistency target selection. Considering that the ambiguous regions from unlabeled data contain more informative complementary clues, in this paper, we improve the mean-teacher model to a novel ambiguity-consensus mean-teacher (AC-MT) model. Particularly, we comprehensively introduce and benchmark a family of plug-and-play strategies for ambiguous target selection from the perspectives of entropy, model uncertainty and label noise self-identification, respectively. Then, the estimated ambiguity map is incorporated into the consistency loss to encourage consensus between the two models' predictions in these informative regions. In essence, our AC-MT aims to find out the most worthwhile voxel-wise targets from the unlabeled data, and the model especially learns from the perturbed stability of these informative regions. The proposed methods are extensively evaluated on left atrium segmentation and brain tumor segmentation. Encouragingly, our strategies bring substantial improvement over recent state-of-the-art methods. The ablation study further demonstrates our hypothesis and shows impressive results under various extreme annotation conditions.

PyMIC: A deep learning toolkit for annotation-efficient medical image segmentation.

BACKGROUND AND OBJECTIVE: Open-source deep learning toolkits are one of the driving forces for developing medical image segmentation models that are essential for computer-assisted diagnosis and treatment procedures. Existing toolkits mainly focus on fully supervised segmentation that assumes full and accurate pixel-level annotations are available. Such annotations are time-consuming and difficult to acquire for segmentation tasks, which makes learning from imperfect labels highly desired for reducing the annotation cost. We aim to develop a new deep learning toolkit to support annotation-efficient learning for medical image segmentation, which can accelerate and simplify the development of deep learning models with limited annotation budget, e.g., learning from partial, sparse or noisy annotations. METHODS: Our proposed toolkit named PyMIC is a modular deep learning library for medical image segmentation tasks. In addition to basic components that support development of high-performance models for fully supervised segmentation, it contains several advanced components that are tailored for learning from imperfect annotations, such as loading annotated and unannounced images, loss functions for unannotated, partially or inaccurately annotated images, and training procedures for co-learning between multiple networks, etc. PyMIC is built on the PyTorch framework and supports development of semi-supervised, weakly supervised and noise-robust learning methods for medical image segmentation. RESULTS: We present several illustrative medical image segmentation tasks based on PyMIC: (1) Achieving competitive performance on fully supervised learning; (2) Semi-supervised cardiac structure segmentation with only 10% training images annotated; (3) Weakly supervised segmentation using scribble annotations; and (4) Learning from noisy labels for chest radiograph segmentation. CONCLUSIONS: The PyMIC toolkit is easy to use and facilitates efficient development of medical image segmentation models with imperfect annotations. It is modular and flexible, which enables researchers to develop high-performance models with low annotation cost. The source code is available at:https://github.com/HiLab-git/PyMIC.

Comprehensive Evaluation of a Deep Learning Model for Automatic Organs-at-Risk Segmentation on Heterogeneous Computed Tomography Images for Abdominal Radiation Therapy.

PURPOSE: Our purpose was to develop a deep learning model (AbsegNet) that produces accurate contours of 16 organs at risk (OARs) for abdominal malignancies as an essential part of fully automated radiation treatment planning. METHODS AND MATERIALS: Three data sets with 544 computed tomography scans were retrospectively collected. Data set 1 was split into 300 training cases and 128 test cases (cohort 1) for AbsegNet. Data set 2, including cohort 2 (n = 24) and cohort 3 (n = 20), were used to validate AbsegNet externally. Data set 3, including cohort 4 (n = 40) and cohort 5 (n = 32), were used to clinically assess the accuracy of AbsegNet-generated contours. Each cohort was from a different center. The Dice similarity coefficient and 95th-percentile Hausdorff distance were calculated to evaluate the delineation quality for each OAR. Clinical accuracy evaluation was classified into 4 levels: no revision, minor revisions (0% < volumetric revision degrees [VRD] ≤ 10%), moderate revisions (10% ≤ VRD < 20%), and major revisions (VRD ≥20%). RESULTS: For all OARs, AbsegNet achieved a mean Dice similarity coefficient of 86.73%, 85.65%, and 88.04% in cohorts 1, 2, and 3, respectively, and a mean 95th-percentile Hausdorff distance of 8.92, 10.18, and 12.40 mm, respectively. The performance of AbsegNet outperformed SwinUNETR, DeepLabV3+, Attention-UNet, UNet, and 3D-UNet. When experts evaluated contours from cohorts 4 and 5, 4 OARs (liver, kidney_L, kidney_R, and spleen) of all patients were scored as having no revision, and over 87.5% of patients with contours of the stomach, esophagus, adrenals, or rectum were considered as having no or minor revisions. Only 15.0% of patients with colon and small bowel contours required major revisions. CONCLUSIONS: We propose a novel deep-learning model to delineate OARs on diverse data sets. Most contours produced by AbsegNet are accurate and robust and are, therefore, clinically applicable and helpful to facilitate radiation therapy workflow.

Toward Source-Free Cross Tissues Histopathological Cell Segmentation via Target-Specific Finetuning.

Recognition and quantitative analytics of histopathological cells are the golden standard for diagnosing multiple cancers. Despite recent advances in deep learning techniques that have been widely investigated for the automated segmentation of various types of histopathological cells, the heavy dependency on specific histopathological image types with sufficient supervised annotations, as well as the limited access to clinical data in hospitals, still pose significant challenges in the application of computer-aided diagnosis in pathology. In this paper, we focus on the model generalization of cell segmentation towards cross-tissue histopathological images. Remarkably, a novel target-specific finetuning-based self-supervised domain adaptation framework is proposed to transfer the cell segmentation model to unlabeled target datasets, without access to source datasets and annotations. When performed on the target unlabeled histopathological image set, the proposed method only needs to tune very few parameters of the pre-trained model in a self-supervised manner. Considering the morphological properties of pathological cells, we introduce two constraint terms at both local and global levels into this framework to access more reliable predictions. The proposed cross-domain framework is validated on three different types of histopathological tissues, showing promising performance in self-supervised cell segmentation. Additionally, the whole framework can be further applied to clinical tools in pathology without accessing the original training image data. The code and dataset are released at: https://github.com/NeuronXJTU/SFDA-CellSeg.

Deep learning-based accurate delineation of primary gross tumor volume of nasopharyngeal carcinoma on heterogeneous magnetic resonance imaging: A large-scale and multi-center study.

BACKGROUND AND PURPOSE: The problem of obtaining accurate primary gross tumor volume (GTVp) segmentation for nasopharyngeal carcinoma (NPC) on heterogeneous magnetic resonance imaging (MRI) images with deep learning remains unsolved. Herein, we reported a new deep-learning method than can accurately delineate GTVp for NPC on multi-center MRI scans. MATERIAL AND METHODS: We collected 1057 patients with MRI images from five hospitals and randomly selected 600 patients from three hospitals to constitute a mixed training cohort for model development. The resting patients were used as internal (n = 259) and external (n = 198) testing cohorts for model evaluation. An augmentation-invariant strategy was proposed to delineate GTVp from multi-center MRI images, which encouraged networks to produce similar predictions for inputs with different augmentations to learn invariant anatomical structure features. The Dice similarity coefficient (DSC), 95 % Hausdorff distance (HD95), average surface distance (ASD), and relative absolute volume difference (RAVD) were used to measure segmentation performance. RESULTS: The model-generated predictions had a high overlap ratio with the ground truth. For the internal testing cohorts, the average DSC, HD95, ASD, and RAVD were 0.88, 4.99 mm, 1.03 mm, and 0.13, respectively. For external testing cohorts, the average DSC, HD95, ASD, and RAVD were 0.88, 3.97 mm, 0.97 mm, and 0.10, respectively. No significant differences were found in DSC, HD95, and ASD for patients with different T categories, MRI thickness, or in-plane spacings. Moreover, the proposed augmentation-invariant strategy outperformed the widely-used nnUNet, which uses conventional data augmentation approaches. CONCLUSION: Our proposed method showed a highly accurate GTVp segmentation for NPC on multi-center MRI images, suggesting that it has the potential to act as a generalized delineation solution for heterogeneous MRI images.

Learning COVID-19 Pneumonia Lesion Segmentation From Imperfect Annotations via Divergence-Aware Selective Training.

Automatic segmentation of COVID-19 pneumonia lesions is critical for quantitative measurement for diagnosis and treatment management. For this task, deep learning is the state-of-the-art method while requires a large set of accurately annotated images for training, which is difficult to obtain due to limited access to experts and the time-consuming annotation process. To address this problem, we aim to train the segmentation network from imperfect annotations, where the training set consists of a small clean set of accurately annotated images by experts and a large noisy set of inaccurate annotations by non-experts. To avoid the labels with different qualities corrupting the segmentation model, we propose a new approach to train segmentation networks to deal with noisy labels. We introduce a dual-branch network to separately learn from the accurate and noisy annotations. To fully exploit the imperfect annotations as well as suppressing the noise, we design a Divergence-Aware Selective Training (DAST) strategy, where a divergence-aware noisiness score is used to identify severely noisy annotations and slightly noisy annotations. For severely noisy samples we use an regularization through dual-branch consistency between predictions from the two branches. We also refine slightly noisy samples and use them as supplementary data for the clean branch to avoid overfitting. Experimental results show that our method achieves a higher performance than standard training process for COVID-19 pneumonia lesion segmentation when learning from imperfect labels, and our framework outperforms the state-of-the-art noise-tolerate methods significantly with various clean label percentages.

Semi-supervised medical image segmentation via uncertainty rectified pyramid consistency.

Despite that Convolutional Neural Networks (CNNs) have achieved promising performance in many medical image segmentation tasks, they rely on a large set of labeled images for training, which is expensive and time-consuming to acquire. Semi-supervised learning has shown the potential to alleviate this challenge by learning from a large set of unlabeled images and limited labeled samples. In this work, we present a simple yet efficient consistency regularization approach for semi-supervised medical image segmentation, called Uncertainty Rectified Pyramid Consistency (URPC). Inspired by the pyramid feature network, we chose a pyramid-prediction network that obtains a set of segmentation predictions at different scales. For semi-supervised learning, URPC learns from unlabeled data by minimizing the discrepancy between each of the pyramid predictions and their average. We further present multi-scale uncertainty rectification to boost the pyramid consistency regularization, where the rectification seeks to temper the consistency loss at outlier pixels that may have substantially different predictions than the average, potentially due to upsampling errors or lack of enough labeled data. Experiments on two public datasets and an in-house clinical dataset showed that: 1) URPC can achieve large performance improvement by utilizing unlabeled data and 2) Compared with five existing semi-supervised methods, URPC achieved better or comparable results with a simpler pipeline. Furthermore, we build a semi-supervised medical image segmentation codebase to boost research on this topic: https://github.com/HiLab-git/SSL4MIS.

Automatic Delineation of Gross Tumor Volume Based on Magnetic Resonance Imaging by Performing a Novel Semisupervised Learning Framework in Nasopharyngeal Carcinoma.

PURPOSE: We aimed to validate the accuracy and clinical value of a novel semisupervised learning framework for gross tumor volume (GTV) delineation in nasopharyngeal carcinoma. METHODS AND MATERIALS: Two hundred fifty-eight patients with magnetic resonance imaging data sets were divided into training (n = 180), validation (n = 20), and testing (n = 58) cohorts. Ground truth contours of nasopharynx GTV (GTVnx) and node GTV (GTVnd) were manually delineated by 2 experienced radiation oncologists. Twenty percent (n = 36) labeled and 80% (n = 144) unlabeled images were used to train the model, producing model-generated contours for patients from the testing cohort. Nine experienced experts were invited to revise model-generated GTV in 20 randomly selected patients from the testing cohort. Six junior oncologists were asked to delineate GTV in 12 randomly selected patients from the testing cohort without and with the assistance of the model, and revision degrees were compared under these 2 modes. The Dice similarity coefficient (DSC) was used to quantify the accuracy of the model. RESULTS: The model-generated contours showed a high accuracy compared with ground truth contours, with an average DSC score of 0.83 and 0.80 for GTVnx and GTVnd, respectively. There was no significant difference in DSC score between T1-2 and T3-4 patients (0.81 vs 0.83; P = .223), or between N1-2 and N3 patients (0.80 vs 0.79; P = .807). The mean revision degree was lower than 10% in 19 (95%) patients for GTVnx and in 16 (80%) patients for GTVnd. With assistance of the model, the mean revision degree for GTVnx and GTVnd by junior oncologists was reduced from 25.63% to 7.75% and from 21.38% to 14.44%, respectively. Meanwhile, the delineating efficiency was improved by over 60%. CONCLUSIONS: The proposed semisupervised learning-based model showed a high accuracy for delineating GTV of nasopharyngeal carcinoma. It was clinically applicable and could assist junior oncologists to improve GTV contouring accuracy and save contouring time.

WORD: A large scale dataset, benchmark and clinical applicable study for abdominal organ segmentation from CT image.

Whole abdominal organ segmentation is important in diagnosing abdomen lesions, radiotherapy, and follow-up. However, oncologists' delineating all abdominal organs from 3D volumes is time-consuming and very expensive. Deep learning-based medical image segmentation has shown the potential to reduce manual delineation efforts, but it still requires a large-scale fine annotated dataset for training, and there is a lack of large-scale datasets covering the whole abdomen region with accurate and detailed annotations for the whole abdominal organ segmentation. In this work, we establish a new large-scale Whole abdominal ORgan Dataset (WORD) for algorithm research and clinical application development. This dataset contains 150 abdominal CT volumes (30495 slices). Each volume has 16 organs with fine pixel-level annotations and scribble-based sparse annotations, which may be the largest dataset with whole abdominal organ annotation. Several state-of-the-art segmentation methods are evaluated on this dataset. And we also invited three experienced oncologists to revise the model predictions to measure the gap between the deep learning method and oncologists. Afterwards, we investigate the inference-efficient learning on the WORD, as the high-resolution image requires large GPU memory and a long inference time in the test stage. We further evaluate the scribble-based annotation-efficient learning on this dataset, as the pixel-wise manual annotation is time-consuming and expensive. The work provided a new benchmark for the abdominal multi-organ segmentation task, and these experiments can serve as the baseline for future research and clinical application development.

SCPM-Net: An anchor-free 3D lung nodule detection network using sphere representation and center points matching.

Automatic and accurate lung nodule detection from 3D Computed Tomography (CT) scans plays a vital role in efficient lung cancer screening. Despite the state-of-the-art performance obtained by recent anchor-based detectors using Convolutional Neural Networks (CNNs) for this task, they require predetermined anchor parameters such as the size, number, and aspect ratio of anchors, and have limited robustness when dealing with lung nodules with a massive variety of sizes. To overcome these problems, we propose a 3D sphere representation-based center-points matching detection network (SCPM-Net) that is anchor-free and automatically predicts the position, radius, and offset of nodules without manual design of nodule/anchor parameters. The SCPM-Net consists of two novel components: sphere representation and center points matching. First, to match the nodule annotation in clinical practice, we replace the commonly used bounding box with our proposed bounding sphere to represent nodules with the centroid, radius, and local offset in 3D space. A compatible sphere-based intersection over-union loss function is introduced to train the lung nodule detection network stably and efficiently. Second, we empower the network anchor-free by designing a positive center-points selection and matching (CPM) process, which naturally discards pre-determined anchor boxes. An online hard example mining and re-focal loss subsequently enable the CPM process to be more robust, resulting in more accurate point assignment and mitigation of class imbalance. In addition, to better capture spatial information and 3D context for the detection, we propose to fuse multi-level spatial coordinate maps with the feature extractor and combine them with 3D squeeze-and-excitation attention modules. Experimental results on the LUNA16 dataset showed that our proposed SCPM-Net framework achieves superior performance compared with existing anchor-based and anchor-free methods for lung nodule detection with the average sensitivity at 7 predefined FPs/scan of 89.2%. Moreover, our sphere representation is verified to achieve higher detection accuracy than the traditional bounding box representation of lung nodules. Code is available at: https://github.com/HiLab-git/SCPM-Net.

MIDeepSeg: Minimally interactive segmentation of unseen objects from medical images using deep learning.

Segmentation of organs or lesions from medical images plays an essential role in many clinical applications such as diagnosis and treatment planning. Though Convolutional Neural Networks (CNN) have achieved the state-of-the-art performance for automatic segmentation, they are often limited by the lack of clinically acceptable accuracy and robustness in complex cases. Therefore, interactive segmentation is a practical alternative to these methods. However, traditional interactive segmentation methods require a large number of user interactions, and recently proposed CNN-based interactive segmentation methods are limited by poor performance on previously unseen objects. To solve these problems, we propose a novel deep learning-based interactive segmentation method that not only has high efficiency due to only requiring clicks as user inputs but also generalizes well to a range of previously unseen objects. Specifically, we first encode user-provided interior margin points via our proposed exponentialized geodesic distance that enables a CNN to achieve a good initial segmentation result of both previously seen and unseen objects, then we use a novel information fusion method that combines the initial segmentation with only a few additional user clicks to efficiently obtain a refined segmentation. We validated our proposed framework through extensive experiments on 2D and 3D medical image segmentation tasks with a wide range of previously unseen objects that were not present in the training set. Experimental results showed that our proposed framework 1) achieves accurate results with fewer user interactions and less time compared with state-of-the-art interactive frameworks and 2) generalizes well to previously unseen objects.