From Histopathology Images to Cell Clouds: Learning Slide Representations with Hierarchical Cell Transformer

It is clinically crucial and potentially very beneficial to be able to analyze and model directly the spatial distributions of cells in histopathology whole slide images (WSI). However, most existing WSI datasets lack cell-level annotations, owing to the extremely high cost over giga-pixel images. Thus, it remains an open question whether deep learning models can directly and effectively analyze WSIs from the semantic aspect of cell distributions. In this work, we construct a large-scale WSI dataset with more than 5 billion cell-level annotations, termed WSI-Cell5B, and a novel hierarchical Cell Cloud Transformer (CCFormer) to tackle these challenges. WSI-Cell5B is based on 6,998 WSIs of 11 cancers from The Cancer Genome Atlas Program, and all WSIs are annotated per cell by coordinates and types. To the best of our knowledge, WSI-Cell5B is the first WSI-level large-scale dataset integrating cell-level annotations. On the other hand, CCFormer formulates the collection of cells in each WSI as a cell cloud and models cell spatial distribution. Specifically, Neighboring Information Embedding (NIE) is proposed to characterize the distribution of cells within the neighborhood of each cell, and a novel Hierarchical Spatial Perception (HSP) module is proposed to learn the spatial relationship among cells in a bottom-up manner. The clinical analysis indicates that WSI-Cell5B can be used to design clinical evaluation metrics based on counting cells that effectively assess the survival risk of patients. Extensive experiments on survival prediction and cancer staging show that learning from cell spatial distribution alone can already achieve state-of-the-art (SOTA) performance, i.e., CCFormer strongly outperforms other competing methods.

From Pixels to Gigapixels: Bridging Local Inductive Bias and Long-Range Dependencies with Pixel-Mamba

Histopathology plays a critical role in medical diagnostics, with whole slide images (WSIs) offering valuable insights that directly influence clinical decision-making. However, the large size and complexity of WSIs may pose significant challenges for deep learning models, in both computational efficiency and effective representation learning. In this work, we introduce Pixel-Mamba, a novel deep learning architecture designed to efficiently handle gigapixel WSIs. Pixel-Mamba leverages the Mamba module, a state-space model (SSM) with linear memory complexity, and incorporates local inductive biases through progressively expanding tokens, akin to convolutional neural networks. This enables Pixel-Mamba to hierarchically combine both local and global information while efficiently addressing computational challenges. Remarkably, Pixel-Mamba achieves or even surpasses the quantitative performance of state-of-the-art (SOTA) foundation models that were pretrained on millions of WSIs or WSI-text pairs, in a range of tumor staging and survival analysis tasks, {\bf even without requiring any pathology-specific pretraining}. Extensive experiments demonstrate the efficacy of Pixel-Mamba as a powerful and efficient framework for end-to-end WSI analysis.

Leveraging Semantic Asymmetry for Precise Gross Tumor Volume Segmentation of Nasopharyngeal Carcinoma in Planning CT

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.

Low-Rank Continual Pyramid Vision Transformer: Incrementally Segment Whole-Body Organs in CT with Light-Weighted Adaptation

Deep segmentation networks achieve high performance when trained on specific datasets. However, in clinical practice, it is often desirable that pretrained segmentation models can be dynamically extended to enable segmenting new organs without access to previous training datasets or without training from scratch. This would ensure a much more efficient model development and deployment paradigm accounting for the patient privacy and data storage issues. This clinically preferred process can be viewed as a continual semantic segmentation (CSS) problem. Previous CSS works would either experience catastrophic forgetting or lead to unaffordable memory costs as models expand. In this work, we propose a new continual whole-body organ segmentation model with light-weighted low-rank adaptation (LoRA). We first train and freeze a pyramid vision transformer (PVT) base segmentation model on the initial task, then continually add light-weighted trainable LoRA parameters to the frozen model for each new learning task. Through a holistically exploration of the architecture modification, we identify three most important layers (i.e., patch-embedding, multi-head attention and feed forward layers) that are critical in adapting to the new segmentation tasks, while retaining the majority of the pretrained parameters fixed. Our proposed model continually segments new organs without catastrophic forgetting and meanwhile maintaining a low parameter increasing rate. Continually trained and tested on four datasets covering different body parts of a total of 121 organs, results show that our model achieves high segmentation accuracy, closely reaching the PVT and nnUNet upper bounds, and significantly outperforms other regularization-based CSS methods. When comparing to the leading architecture-based CSS method, our model has a substantial lower parameter increasing rate while achieving comparable performance.

FS-MedSAM2: Exploring the Potential of SAM2 for Few-Shot Medical Image Segmentation without Fine-tuning

The Segment Anything Model 2 (SAM2) has recently demonstrated exceptional performance in zero-shot prompt segmentation for natural images and videos. However, it faces significant challenges when applied to medical images. Since its release, many attempts have been made to adapt SAM2's segmentation capabilities to the medical imaging domain. These efforts typically involve using a substantial amount of labeled data to fine-tune the model's weights. In this paper, we explore SAM2 from a different perspective via making the full use of its trained memory attention module and its ability of processing mask prompts. We introduce FS-MedSAM2, a simple yet effective framework that enables SAM2 to achieve superior medical image segmentation in a few-shot setting, without the need for fine-tuning. Our framework outperforms the current state-of-the-arts on two publicly available medical image datasets. The code is available at https://github.com/DeepMed-Lab-ECNU/FS_MedSAM2.

End-to-end Multi-source Visual Prompt Tuning for Survival Analysis in Whole Slide Images

Survival analysis using pathology images poses a considerable challenge, as it requires the localization of relevant information from the multitude of tiles within whole slide images (WSIs). Current methods typically resort to a two-stage approach, where a pre-trained network extracts features from tiles, which are then used by survival models. This process, however, does not optimize the survival models in an end-to-end manner, and the pre-extracted features may not be ideally suited for survival prediction. To address this limitation, we present a novel end-to-end Visual Prompt Tuning framework for survival analysis, named VPTSurv. VPTSurv refines feature embeddings through an efficient encoder-decoder framework. The encoder remains fixed while the framework introduces tunable visual prompts and adaptors, thus permitting end-to-end training specifically for survival prediction by optimizing only the lightweight adaptors and the decoder. Moreover, the versatile VPTSurv framework accommodates multi-source information as prompts, thereby enriching the survival model. VPTSurv achieves substantial increases of 8.7% and 12.5% in the C-index on two immunohistochemical pathology image datasets. These significant improvements highlight the transformative potential of the end-to-end VPT framework over traditional two-stage methods.

Effective Lymph Nodes Detection in CT Scans Using Location Debiased Query Selection and Contrastive Query Representation in Transformer

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.

Towards a Comprehensive, Efficient and Promptable Anatomic Structure Segmentation Model using 3D Whole-body CT Scans

Segment anything model (SAM) demonstrates strong generalization ability on natural image segmentation. However, its direct adaption in medical image segmentation tasks shows significant performance drops with inferior accuracy and unstable results. It may also requires an excessive number of prompt points to obtain a reasonable accuracy. For segmenting 3D radiological CT or MRI scans, a 2D SAM model has to separately handle hundreds of 2D slices. Although quite a few studies explore adapting SAM into medical image volumes, the efficiency of 2D adaption methods is unsatisfactory and 3D adaptation methods 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. For this purpose, 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 learning 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 and validated using a curated dataset of 1204 CT scans containing 107 whole-body anatomies, reporting significantly better quantitative performance against all previous SAM-derived models by a large margin with much fewer click prompts. Our model can handle segmenting unseen organ as well. Code, data, and our 3D interactive segmentation tool with quasi-real-time responses will be made publicly available.

Modality-Agnostic Structural Image Representation Learning for Deformable Multi-Modality Medical Image Registration

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 multi-modality 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 correspondence across scans with different modalities. In this paper, we propose a modality-agnostic structural representation learning method, which leverages Deep Neighbourhood 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.

Anatomy-Aware Lymph Node Detection in Chest CT using Implicit Station Stratification

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.