Nucleus detection and classification (NDC) in histopathology analysis is a fundamental task that underpins a wide range of high-level pathology applications. However, existing methods heavily rely on labor-intensive nucleus-level annotations and struggle to fully exploit large-scale unlabeled data for learning discriminative nucleus representations. In this work, we propose MUSE (MUlti-scale denSE self-distillation), a novel self-supervised learning method tailored for NDC. At its core is NuLo (Nucleus-based Local self-distillation), a coordinate-guided mechanism that enables flexible local self-distillation based on predicted nucleus positions. By removing the need for strict spatial alignment between augmented views, NuLo allows critical cross-scale alignment, thus unlocking the capacity of models for fine-grained nucleus-level representation. To support MUSE, we design a simple yet effective encoder-decoder architecture and a large field-of-view semi-supervised fine-tuning strategy that together maximize the value of unlabeled pathology images. Extensive experiments on three widely used benchmarks demonstrate that MUSE effectively addresses the core challenges of histopathological NDC. The resulting models not only surpass state-of-the-art supervised baselines but also outperform generic pathology foundation models.

Esophageal cancer is one of the most lethal cancers, with 5-year survival rate of only 20%. Patient outcomes can vary significantly even though they are at the same cancer stage and receive similar treatments. Accurate prognostic prediction for esophageal cancer patients is highly desired to receive personalized precise treatment. Nevertheless, there are very few automated methods yet to fully exploit the preoperative contrast-enhanced computed tomography (CE-CT) imaging for assessing esophageal cancer prognosis. In addition to image patterns, important prognostic factors should encompass tumor size and location, as well as lymph nodes (LNs) involvement, including features such as LN number, size, spatial distribution, and their proximity to tumor. Considering these complexities, we propose a novel Tumor and LN Context-Geometry network for the preoperative prediction of esophageal cancer survival in CE-CT images. Specifically, we 1) focus on learning survival patterns of CT texture via co-attention context modeling at most informative regions, i.e., automatically segmented tumor, LNs and LN-stations; and 2) integrate tumor and LN anatomical and spatial associations into neural geometry modeling for a comprehensive learning of metastatic involvement and tumor invasion to adjacent structures. Empirical studies show our presented framework can improve overall survival prediction performances compared with existing state-of-the-art survival analysis methods, and evidently suggest that incorporating these findings into the existing esophageal cancer staging system would add its clinical values.

F-FDG PET/CT images marks a pivotal breakthrough in oncological diagnostics, substantially improving the accuracy and efficiency of tumor burden assessment. Manual segmentation is often plagued by significant inter-observer variability, underscoring the necessity for automated solutions. The synergistic combination of PET's exceptional sensitivity for detecting metabolic activity with CT's anatomical precision renders accurate segmentation crucial for achieving quantitative and reproducible clinical workflows. However, current methodologies frequently grapple with challenges such as over-segmentation or under-segmentation, inadvertently delineating normal tissues with elevated uptake or neglecting lesions characterized by subtle intensity variations, primarily due to a lack of integrated metabolic and anatomical insights. To address these limitations, we present a novel framework that adeptly integrates clinical expertise regarding anatomical and metabolic cues to refine PET/CT lesion segmentation. Our innovative mixture-of-experts (MoE) based interpretable fusion module skillfully merges complementary modality information while explicitly elucidating the pixel-level contributions of each modality to the final segmentation outcome. Rigorous evaluations across three in-domain benchmarks and two external datasets demonstrate our model's superior segmentation performance and generalizability. Furthermore, our visualizations provide compelling insights into the pivotal role each modality plays in the decision-making process, highlighting our approach's transformative potential in enhancing PET/CT lesion segmentation. Building on this foundation, we further validated the prognostic significance of the features extracted from our proposed framework in the context of PET/CT-based prognosis predictions.

Segment anything model (SAM) demonstrates strong generalization ability on natural image segmentation. However, its direct adaptation in medical image segmentation tasks shows significant performance drops. It also requires an excessive number of prompt points to obtain a reasonable accuracy. Although quite a few studies explore adapting SAM into medical image volumes, the efficiency of 2D adaptation methods is unsatisfactory and 3D adaptation methods are only capable of segmenting specific organs/tumors. In this work, we propose a comprehensive and scalable 3D SAM model for whole-body CT segmentation, named CT-SAM3D. Instead of adapting SAM, we propose a 3D promptable segmentation model using a (nearly) fully labeled CT dataset. To train CT-SAM3D effectively, ensuring the model's accurate responses to higher-dimensional spatial prompts is crucial, and 3D patch-wise training is required due to GPU memory constraints. Therefore, we propose two key technical developments: 1) a progressively and spatially aligned prompt encoding method to effectively encode click prompts in local 3D space; and 2) a cross-patch prompt scheme to capture more 3D spatial context, which is beneficial for reducing the editing workloads when interactively prompting on large organs. CT-SAM3D is trained using a curated dataset of 1204 CT scans containing 107 whole-body anatomies and extensively validated using five datasets, achieving significantly better results against all previous SAM-derived models.

Deep learning has demonstrated exceptional performance in medical image analysis, but its effectiveness degrades significantly when applied to different medical centers due to domain shifts. Lesion detection, a critical task in medical imaging, is particularly impacted by this challenge due to the diversity and complexity of lesions, which can arise from different organs, diseases, imaging devices, and other factors. While collecting data and labels from target domains is a feasible solution, annotating medical images is often tedious, expensive, and requires professionals. To address this problem, we combine active learning with domain-invariant feature learning. We propose a Domain-shift Active Learning (DistAL) framework, which includes a transferable feature learning algorithm and a hybrid sample selection strategy. Feature learning incorporates contrastive-consistency training to learn discriminative and domain-invariant features. The sample selection strategy is called RUDY, which jointly considers Representativeness, Uncertainty, and DiversitY. Its goal is to select samples from the unlabeled target domain for cost-effective annotation. It first selects representative samples to deal with domain shift, as well as uncertain ones to improve class separability, and then leverages K-means++ initialization to remove redundant candidates to achieve diversity. We evaluate our method for the task of lesion detection. By selecting only 1.7% samples from the target domain to annotate, DistAL achieves comparable performance to the method trained with all target labels. It outperforms other AL methods in five experiments on eight datasets collected from different hospitals, using different imaging protocols, annotation conventions, and etiologies.

Automated colorectal cancer (CRC) segmentation in medical imaging is the key to achieving automation of CRC detection, staging, and treatment response monitoring. Compared with magnetic resonance imaging (MRI) and computed tomography colonography (CTC), conventional computed tomography (CT) has enormous potential because of its broad implementation, superiority for the hollow viscera (colon), and convenience without needing bowel preparation. However, the segmentation of CRC in conventional CT is more challenging due to the difficulties presenting with the unprepared bowel, such as distinguishing the colorectum from other structures with similar appearance and distinguishing the CRC from the contents of the colorectum. To tackle these challenges, we introduce DeepCRC-SL, the first automated segmentation algorithm for CRC and colorectum in conventional contrast-enhanced CT scans. We propose a topology-aware deep learning-based approach, which builds a novel 1-D colorectal coordinate system and encodes each voxel of the colorectum with a relative position along the coordinate system. We then induce an auxiliary regression task to predict the colorectal coordinate value of each voxel, aiming to integrate global topology into the segmentation network and thus improve the colorectum's continuity. Self-attention layers are utilized to capture global contexts for the coordinate regression task and enhance the ability to differentiate CRC and colorectum tissues. Moreover, a coordinate-driven self-learning (SL) strategy is introduced to leverage a large amount of unlabeled data to improve segmentation performance. We validate the proposed approach on a dataset including 227 labeled and 585 unlabeled CRC cases by fivefold cross-validation. Experimental results demonstrate that our method outperforms some recent related segmentation methods and achieves the segmentation accuracy in DSC for CRC of 0.669 and colorectum of 0.892, reaching to the performance (at 0.639 and 0.890, respectively) of a medical resident with two years of specialized CRC imaging fellowship.

Establishing dense anatomical correspondence across distinct imaging modalities is a foundational yet challenging procedure for numerous medical image analysis studies and image-guided radiotherapy. Existing multimodality image registration algorithms rely on statistical-based similarity measures or local structural image representations. However, the former is sensitive to locally varying noise, while the latter is not discriminative enough to cope with complex anatomical structures in multimodal scans, causing ambiguity in determining the anatomical correspon-dence across scans with different modalities. In this paper, we propose a modality-agnostic structural representation learning method, which leverages Deep Neighbour-hood Self-similarity (DNS) and anatomy-aware contrastive learning to learn discriminative and contrast-invariance deep structural image representations (DSIR) without the need for anatomical delineations or pre-aligned training images. We evaluate our method on multiphase CT, abdomen MR-CT, and brain MR T1w-T2w registration. Comprehensive results demonstrate that our method is superior to the conventional local structural representation and statistical-based similarity measures in terms of discriminability and accuracy.

Deep learning has been widely used in medical image segmentation and other aspects. However, the performance of existing medical image segmentation models has been limited by the challenge of obtaining sufficient high-quality labeled data due to the prohibitive data annotation cost. To alleviate this limitation, we propose a new text-augmented medical image segmentation model LViT (Language meets Vision Transformer). In our LViT model, medical text annotation is incorporated to compensate for the quality deficiency in image data. In addition, the text information can guide to generate pseudo labels of improved quality in the semi-supervised learning. We also propose an Exponential Pseudo label Iteration mechanism (EPI) to help the Pixel-Level Attention Module (PLAM) preserve local image features in semi-supervised LViT setting. In our model, LV (Language-Vision) loss is designed to supervise the training of unlabeled images using text information directly. For evaluation, we construct three multimodal medical segmentation datasets (image + text) containing X-rays and CT images. Experimental results show that our proposed LViT has superior segmentation performance in both fully-supervised and semi-supervised setting. The code and datasets are available at https://github.com/HUANGLIZI/LViT.

Intrathoracic airway segmentation in computed tomography is a prerequisite for various respiratory disease analyses such as chronic obstructive pulmonary disease, asthma and lung cancer. Due to the low imaging contrast and noises execrated at peripheral branches, the topological-complexity and the intra-class imbalance of airway tree, it remains challenging for deep learning-based methods to segment the complete airway tree (on extracting deeper branches). 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 per 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 iterative self-learning scheme to segment toward the complete airway tree. For generating pseudo-labels to achieve higher sensitivity (while retaining similar specificity), 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 achieves the top performance 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) 6.1% more detected tree length and 5.2% more tree branches, while maintaining comparable precision.

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 segmentation classes are incrementally added. In the 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 sufficiently representative image features for new classes to be subsequently and validly segmented, while avoiding the catastrophic forgetting in CSS. To maintain a single network model complexity, each decoder is progressively pruned using neural architecture search and teacher-student based knowledge distillation. Finally, we propose a body-part and anomaly-aware output merging module to combine organ predictions originating from different decoders and incorporate both healthy and pathological organs appearing in different datasets. Trained and validated on 3D CT scans of 2500+ patients from four datasets, our single network can segment a total of 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).

3D delineation of anatomical structures is a cardinal goal in medical imaging analysis. Prior to deep learning, statistical shape models (SSMs) that imposed anatomical constraints and produced high quality surfaces were a core technology. Today’s fully-convolutional networks (FCNs), while dominant, do not offer these capabilities. We present deep implicit statistical shape models (DISSMs), a new approach that marries the representation power of deep networks with the benefits of SSMs. DISSMs use an implicit representation to produce compact and descriptive deep surface embeddings that permit statistical models of anatomical variance. To reliably fit anatomically plausible shapes to an image, we introduce a novel rigid and non-rigid pose estimation pipeline that is modelled as a Markov decision process (MDP). Intra-dataset experiments on the task of pathological liver segmentation demonstrate that DISSMs can perform more robustly than four leading FCN models, including nnU-Net + an adversarial prior: reducing the mean Hausdorff distance (HD) by 7.5-14.3 mm and improving the worst case Dice-Sørensen coefficient (DSC) by 1.2-2.3%. More critically, cross-dataset experiments on an external and highly challenging clinical dataset demonstrate that DISSMs improve the mean DSC and HD by 2.1-5.9% and 9.9-24.5 mm, respectively, and the worst-case DSC by 5.4-7.3%. Supplemental validation on a highly challenging and low-contrast larynx dataset further demonstrate DISSM’s improvements. These improvements are over and above any benefits from representing delineations with high-quality surfaces.

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

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 online.11https://github.com/viggin/DeepLesion_manual_test_set

OAR segmentation is a critical step in radiotherapy of head and neck (H&N) cancer, where inconsistencies across radiation oncologists and prohibitive labor costs motivate automated approaches. However, leading methods using standard fully convolutional network workflows that are challenged when the number of OARs becomes large, e.g. > 40. For such scenarios, insights can be gained from the stratification approaches seen in manual clinical OAR delineation. This is the goal of our work, where we introduce stratified organ at risk segmentation (SOARS), an approach that stratifies OARs into anchor, mid-level, and small & hard (S&H) categories. SOARS stratifies across two dimensions. The first dimension is that distinct processing pipelines are used for each OAR category. In particular, inspired by clinical practices, anchor OARs are used to guide the mid-level and S&H categories. The second dimension is that distinct network architectures are used to manage the significant contrast, size, and anatomy variations between different OARs. We use differentiable neural architecture search (NAS), allowing the network to choose among 2D, 3D or Pseudo-3D convolutions. Extensive 4-fold cross-validation on 142 H&N cancer patients with 42 manually labeled OARs, the most comprehensive OAR dataset to date, demonstrates that both pipeline- and NAS-stratification significantly improves quantitative performance over the state-of-the-art (from 69.52% to 73.68% in absolute Dice scores). Thus, SOARS provides a powerful and principled means to manage the highly complex segmentation space of OARs.

Quantification of cerebral white matter hyperintensities (WMH) of presumed vascular origin is of key importance in many neurological research studies. Currently, measurements are often still obtained from manual segmentations on brain MR images, which is a laborious procedure. The automatic WMH segmentation methods exist, but a standardized comparison of the performance of such methods is lacking. We organized a scientific challenge, in which developers could evaluate their methods on a standardized multi-center/-scanner image dataset, giving an objective comparison: the WMH Segmentation Challenge. Sixty T1 + FLAIR images from three MR scanners were released with the manual WMH segmentations for training. A test set of 110 images from five MR scanners was used for evaluation. The segmentation methods had to be containerized and submitted to the challenge organizers. Five evaluation metrics were used to rank the methods: 1) Dice similarity coefficient; 2) modified Hausdorff distance (95th percentile); 3) absolute log-transformed volume difference; 4) sensitivity for detecting individual lesions; and 5) F1-score for individual lesions. In addition, the methods were ranked on their inter-scanner robustness; 20 participants submitted their methods for evaluation. This paper provides a detailed analysis of the results. In brief, there is a cluster of four methods that rank significantly better than the other methods, with one clear winner. The inter-scanner robustness ranking shows that not all the methods generalize to unseen scanners. The challenge remains open for future submissions and provides a public platform for method evaluation.

Skeletonization offers a compact representation of an object while preserving important topological and geometrical features. Literature on skeletonization of binary objects is quite mature. However, challenges involved with skeletonization of fuzzy objects are mostly unanswered. This paper presents a new theory and algorithm of skeletonization for fuzzy objects, evaluates its performance, and demonstrates its applications. A formulation of fuzzy grassfire propagation is introduced; its relationships with fuzzy distance functions, level sets, and geodesics are discussed; and several new theoretical results are presented in the continuous space. A notion of collision-impact of fire-fronts at skeletal points is introduced, and its role in filtering noisy skeletal points is demonstrated. A fuzzy object skeletonization algorithm is developed using new notions of surface- and curve-skeletal voxels, digital collision-impact, filtering of noisy skeletal voxels, and continuity of skeletal surfaces. A skeletal noise pruning algorithm is presented using branch-level significance. Accuracy and robustness of the new algorithm are examined on computer-generated phantoms and micro- and conventional CT imaging of trabecular bone specimens. An application of fuzzy object skeletonization to compute structure-width at a low image resolution is demonstrated, and its ability to predict bone strength is examined. Finally, the performance of the new fuzzy object skeletonization algorithm is compared with two binary object skeletonization methods.

Traditional arc skeletonization algorithms using the principle of Blum's transform, often, produce unwanted spurious branches due to boundary irregularities and digital effects on objects and other artifacts. This paper presents a new robust approach of extracting arc skeletons for three-dimensional (3-D) elongated fuzzy objects, which avoids spurious branches without requiring post-pruning. Starting from a root voxel, the method iteratively expands the skeleton by adding a new branch in each iteration that connects the farthest voxel to the current skeleton using a minimum-cost geodesic path. The path-cost function is formulated using a novel measure of local significance factor defined by fuzzy distance transform field, which forces the path to stick to the centerline of the object. The algorithm terminates when dilated skeletal branches fill the entire object volume or the current farthest voxel fails to generate a meaningful branch. Accuracy of the algorithm has been evaluated using computer-generated blurred and noisy phantoms with known skeletons. Performance of the method in terms of false and missing skeletal branches, as defined by human expert, has been examined using in vivo CT imaging of human intrathoracic airways. Experimental results from both experiments have established the superiority of the new method as compared to a widely used conventional method in terms of accuracy of medialness as well as robustness of true and false skeletal branches.