UniReg: Foundation Model for Controllable Medical Image Registration

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.

A Continual Learning-driven Model for Accurate and Generalizable Segmentation of Clinically Comprehensive and Fine-grained Whole-body Anatomies in CT

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.

From Slices to Sequences: Autoregressive Tracking Transformer for Cohesive and Consistent 3D Lymph Node Detection in CT Scans

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. Datasets will be released upon acceptance.

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.

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.

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.