Jianxu Chen

Jianning Li, Zongwei Zhou, Jiancheng Yang et al.

Prior to the deep learning era, shape was commonly used to describe the objects. Nowadays, state-of-the-art (SOTA) algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from numerous shape-related publications in premier vision conferences as well as the growing popularity of ShapeNet (about 51,300 models) and Princeton ModelNet (127,915 models). For the medical domain, we present a large collection of anatomical shapes (e.g., bones, organs, vessels) and 3D models of surgical instrument, called MedShapeNet, created to facilitate the translation of data-driven vision algorithms to medical applications and to adapt SOTA vision algorithms to medical problems. As a unique feature, we directly model the majority of shapes on the imaging data of real patients. As of today, MedShapeNet includes 23 dataset with more than 100,000 shapes that are paired with annotations (ground truth). Our data is freely accessible via a web interface and a Python application programming interface (API) and can be used for discriminative, reconstructive, and variational benchmarks as well as various applications in virtual, augmented, or mixed reality, and 3D printing. Exemplary, we present use cases in the fields of classification of brain tumors, facial and skull reconstructions, multi-class anatomy completion, education, and 3D printing. In future, we will extend the data and improve the interfaces. The project pages are: https://medshapenet.ikim.nrw/ and https://github.com/Jianningli/medshapenet-feedback

Annika Reinke, Minu D. Tizabi, Michael Baumgartner et al.

Validation metrics are key for the reliable tracking of scientific progress and for bridging the current chasm between artificial intelligence (AI) research and its translation into practice. However, increasing evidence shows that particularly in image analysis, metrics are often chosen inadequately in relation to the underlying research problem. This could be attributed to a lack of accessibility of metric-related knowledge: While taking into account the individual strengths, weaknesses, and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multi-stage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides the first reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Focusing on biomedical image analysis but with the potential of transfer to other fields, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. To facilitate comprehension, illustrations and specific examples accompany each pitfall. As a structured body of information accessible to researchers of all levels of expertise, this work enhances global comprehension of a key topic in image analysis validation.

Lukas Johanns, Marilin Moor, Davide Panzeri et al.

Biological image analysis increasingly demands integration across heterogeneous tools, programming environments, and domain knowledge that few researchers can command simultaneously. We present Agentic-J, a containerised, multi-agent AI assistant, primarily for ImageJ/Fiji that enables biologists to specify analysis tasks in natural language, from nuclei segmentation and cell tracking to multi-condition quantification. The agent generates executable scripts organised into a documented project structure, so every analysis decision is traceable and the workflow can be reproduced or shared. The specialised sub-agents handle plugin management, code generation, debugging, quality assurance, and statistical reporting. In this paper we introduce the system's design, demonstrate real biological microscopy image analysis workflows, and detailed the technical implementation.

Justin Sonneck, Jianxu Chen

Over the past decade, deep learning (DL) research in computer vision has been growing rapidly, with many advances in DL-based image analysis methods for biomedical problems. In this work, we introduce MMV_Im2Im, a new open-source python package for image-to-image transformation in bioimaging applications. MMV_Im2Im is designed with a generic image-to-image transformation framework that can be used for a wide range of tasks, including semantic segmentation, instance segmentation, image restoration, and image generation, etc.. Our implementation takes advantage of state-of-the-art machine learning engineering techniques, allowing researchers to focus on their research without worrying about engineering details. We demonstrate the effectiveness of MMV_Im2Im on more than ten different biomedical problems, showcasing its general potentials and applicabilities. For computational biomedical researchers, MMV_Im2Im provides a starting point for developing new biomedical image analysis or machine learning algorithms, where they can either reuse the code in this package or fork and extend this package to facilitate the development of new methods. Experimental biomedical researchers can benefit from this work by gaining a comprehensive view of the image-to-image transformation concept through diversified examples and use cases. We hope this work can give the community inspirations on how DL-based image-to-image transformation can be integrated into the assay development process, enabling new biomedical studies that cannot be done only with traditional experimental assays. To help researchers get started, we have provided source code, documentation, and tutorials for MMV_Im2Im at https://github.com/MMV-Lab/mmv_im2im under MIT license.

Peixian Liang, Yizhe Zhang, Yifan Ding et al.

Deep learning (DL) based semantic segmentation methods have achieved excellent performance in biomedical image segmentation, producing high quality probability maps to allow extraction of rich instance information to facilitate good instance segmentation. While numerous efforts were put into developing new DL semantic segmentation models, less attention was paid to a key issue of how to effectively explore their probability maps to attain the best possible instance segmentation. We observe that probability maps by DL semantic segmentation models can be used to generate many possible instance candidates, and accurate instance segmentation can be achieved by selecting from them a set of "optimized" candidates as output instances. Further, the generated instance candidates form a well-behaved hierarchical structure (a forest), which allows selecting instances in an optimized manner. Hence, we propose a novel framework, called hierarchical earth mover's distance (H-EMD), for instance segmentation in biomedical 2D+time videos and 3D images, which judiciously incorporates consistent instance selection with semantic-segmentation-generated probability maps. H-EMD contains two main stages. (1) Instance candidate generation: capturing instance-structured information in probability maps by generating many instance candidates in a forest structure. (2) Instance candidate selection: selecting instances from the candidate set for final instance segmentation. We formulate a key instance selection problem on the instance candidate forest as an optimization problem based on the earth mover's distance (EMD), and solve it by integer linear programming. Extensive experiments on eight biomedical video or 3D datasets demonstrate that H-EMD consistently boosts DL semantic segmentation models and is highly competitive with state-of-the-art methods.

Shanghang Zhang, Gaole Dai, Tiejun Huang et al.

Rapid advancements in imaging techniques and analytical methods over the past decade have revolutionized our ability to comprehensively probe the biological world at multiple scales, pinpointing the type, quantity, location, and even temporal dynamics of biomolecules. The surge in data complexity and volume presents significant challenges in translating this wealth of information into knowledge. The recently emerged Multimodal Large Language Models (MLLMs) exhibit strong emergent capacities, such as understanding, analyzing, reasoning, and generalization. With these capabilities, MLLMs hold promise to extract intricate information from biological images and data obtained through various modalities, thereby expediting our biological understanding and aiding in the development of novel computational frameworks. Previously, such capabilities were mostly attributed to humans for interpreting and summarizing meaningful conclusions from comprehensive observations and analysis of biological images. However, the current development of MLLMs shows increasing promise in serving as intelligent assistants or agents for augmenting human researchers in biology research

Zixuan Pan, Jianxu Chen, Yiyu Shi

Denoising diffusion probabilistic models have recently demonstrated state-of-the-art generative performance and have been used as strong pixel-level representation learners. This paper decomposes the interrelation between the generative capability and representation learning ability inherent in diffusion models. We present the masked diffusion model (MDM), a scalable self-supervised representation learner for semantic segmentation, substituting the conventional additive Gaussian noise of traditional diffusion with a masking mechanism. Our proposed approach convincingly surpasses prior benchmarks, demonstrating remarkable advancements in both medical and natural image semantic segmentation tasks, particularly in few-shot scenarios.

Shuo Zhao, Yu Zhou, Jianxu Chen

Biomedical image segmentation is critical for precise structure delineation and downstream analysis. Traditional methods often struggle with noisy data, while deep learning models such as U-Net have set new benchmarks in segmentation performance. nnU-Net further automates model configuration, making it adaptable across datasets without extensive tuning. However, it requires a substantial amount of annotated data for cross-validation, posing a challenge when only raw images but no labels are available. Large foundation models offer zero-shot generalizability, but may underperform on specific datasets with unique characteristics, limiting their direct use for analysis. This work addresses these bottlenecks by proposing a data-centric AI workflow that leverages active learning and pseudo-labeling to combine the strengths of traditional neural networks and large foundation models while minimizing human intervention. The pipeline starts by generating pseudo-labels from a foundation model, which are then used for nnU-Net's self-configuration. Subsequently, a representative core-set is selected for minimal manual annotation, enabling effective fine-tuning of the nnU-Net model. This approach significantly reduces the need for manual annotations while maintaining competitive performance, providing an accessible solution for biomedical researchers to apply state-of-the-art AI techniques in their segmentation tasks. The code is available at https://github.com/MMV-Lab/AL_BioMed_img_seg.

Yu Zhou, Justin Sonneck, Sweta Banerjee et al.

Artificial intelligence (AI) has been widely used in bioimage image analysis nowadays, but the efficiency of AI models, like the energy consumption and latency is not ignorable due to the growing model size and complexity, as well as the fast-growing analysis needs in modern biomedical studies. Like we can compress large images for efficient storage and sharing, we can also compress the AI models for efficient applications and deployment. In this work, we present EfficientBioAI, a plug-and-play toolbox that can compress given bioimaging AI models for them to run with significantly reduced energy cost and inference time on both CPU and GPU, without compromise on accuracy. In some cases, the prediction accuracy could even increase after compression, since the compression procedure could remove redundant information in the model representation and therefore reduce over-fitting. From four different bioimage analysis applications, we observed around 2-5 times speed-up during inference and 30-80$\%$ saving in energy. Cutting the runtime of large scale bioimage analysis from days to hours or getting a two-minutes bioimaging AI model inference done in near real-time will open new doors for method development and biomedical discoveries. We hope our toolbox will facilitate resource-constrained bioimaging AI and accelerate large-scale AI-based quantitative biological studies in an eco-friendly way, as well as stimulate further research on the efficiency of bioimaging AI.

Shuo Zhao, Jianxu Chen

Generalist biomedical image segmentation models such as Cellpose are increasingly applied across diverse imaging modalities and cell types. However, two critical challenges remain underexplored: (1) the extent of training data redundancy and (2) the impact of cross domain transfer on model retention. In this study, we conduct a systematic empirical analysis of these challenges using Cellpose as a case study. First, to assess data redundancy, we propose a simple dataset quantization (DQ) strategy for constructing compact yet diverse training subsets. Experiments on the Cyto dataset show that image segmentation performance saturates with only 10% of the data, revealing substantial redundancy and potential for training with minimal annotations. Latent space analysis using MAE embeddings and t-SNE confirms that DQ selected patches capture greater feature diversity than random sampling. Second, to examine catastrophic forgetting, we perform cross domain finetuning experiments and observe significant degradation in source domain performance, particularly when adapting from generalist to specialist domains. We demonstrate that selective DQ based replay reintroducing just 5-10% of the source data effectively restores source performance, while full replay can hinder target adaptation. Additionally, we find that training domain sequencing improves generalization and reduces forgetting in multi stage transfer. Our findings highlight the importance of data centric design in biomedical image segmentation and suggest that efficient training requires not only compact subsets but also retention aware learning strategies and informed domain ordering. The code is available at https://github.com/MMV-Lab/biomedseg-efficiency.

Zixuan Pan, Jun Xia, Zheyu Yan et al.

Reconstruction-based methods, particularly those leveraging autoencoders, have been widely adopted for anomaly detection task in brain MRI. Unlike most existing works try to improve the task accuracy through architectural or algorithmic innovations, we tackle this task from image quality assessment (IQA) perspective, an under-explored direction in the field. Due to the limitations of conventional metrics such as l1 in capturing the nuanced differences in reconstructed images for medical anomaly detection, we propose fusion quality, a novel metric that wisely integrates the structure-level sensitivity of Structural Similarity Index Measure (SSIM) with the pixel-level precision of l1. The metric offers a more comprehensive assessment of reconstruction quality, considering intensity (subtractive property of l1 and divisive property of SSIM), contrast, and structural similarity. Furthermore, the proposed metric makes subtle regional variations more impactful in the final assessment. Thus, considering the inherent divisive properties of SSIM, we design an average intensity ratio (AIR)-based data transformation that amplifies the divisive discrepancies between normal and abnormal regions, thereby enhancing anomaly detection. By fusing the aforementioned two components, we devise the IQA approach. Experimental results on two distinct brain MRI datasets show that our IQA approach significantly enhances medical anomaly detection performance when integrated with state-of-the-art baselines.

Rongyu Zhang, Hongyu Dong, Gaole Dai et al.

The rapid adoption of data-driven methods in biomedicine has intensified concerns over privacy, governance, and regulation, limiting raw data sharing and hindering the assembly of representative cohorts for clinically relevant AI. This landscape necessitates practical, efficient privacy solutions, as cryptographic defenses often impose heavy overhead and differential privacy can degrade performance, leading to sub-optimal outcomes in real-world settings. Here, we present a lightweight federated learning method, INFL, based on Implicit Neural Representations that addresses these challenges. Our approach integrates plug-and-play, coordinate-conditioned modules into client models, embeds a secret key directly into the architecture, and supports seamless aggregation across heterogeneous sites. Across diverse biomedical omics tasks, including cohort-scale classification in bulk proteomics, regression for perturbation prediction in single-cell transcriptomics, and clustering in spatial transcriptomics and multi-omics with both public and private data, we demonstrate that INFL achieves strong, controllable privacy while maintaining utility, preserving the performance necessary for downstream scientific and clinical applications.

Yu Zhou, Jan Sollmann, Jianxu Chen

With the fast development of modern microscopes and bioimaging techniques, an unprecedentedly large amount of imaging data are being generated, stored, analyzed, and even shared through networks. The size of the data poses great challenges for current data infrastructure. One common way to reduce the data size is by image compression. This present study analyzes classic and deep learning based image compression methods, and their impact on deep learning based image processing models. Deep learning based label-free prediction models (i.e., predicting fluorescent images from bright field images) are used as an example application for comparison and analysis. Effective image compression methods could help reduce the data size significantly without losing necessary information, and therefore reduce the burden on data management infrastructure and permit fast transmission through the network for data sharing or cloud computing. To compress images in such a wanted way, multiple classical lossy image compression techniques are compared to several AI-based compression models provided by and trained with the CompressAI toolbox using python. These different compression techniques are compared in compression ratio, multiple image similarity measures and, most importantly, the prediction accuracy from label-free models on compressed images. We found that AI-based compression techniques largely outperform the classic ones and will minimally affect the downstream label-free task in 2D cases. In the end, we hope the present study could shed light on the potential of deep learning based image compression and the impact of image compression on downstream deep learning based image analysis models.

Ye Zhang, Yu Zhou, Yifeng Wang et al.

Cell instance segmentation is critical to analyzing biomedical images, yet accurately distinguishing tightly touching cells remains a persistent challenge. Existing instance segmentation frameworks, including detection-based, contour-based, and distance mapping-based approaches, have made significant progress, but balancing model performance with computational efficiency remains an open problem. In this paper, we propose a novel cell instance segmentation method inspired by the four-color theorem. By conceptualizing cells as countries and tissues as oceans, we introduce a four-color encoding scheme that ensures adjacent instances receive distinct labels. This reformulation transforms instance segmentation into a constrained semantic segmentation problem with only four predicted classes, substantially simplifying the instance differentiation process. To solve the training instability caused by the non-uniqueness of four-color encoding, we design an asymptotic training strategy and encoding transformation method. Extensive experiments on various modes demonstrate our approach achieves state-of-the-art performance. The code is available at https://github.com/zhangye-zoe/FCIS.

Zixuan Pan, Kaiyuan Tang, Jun Xia et al.

2D Gaussian Splatting has emerged as a novel image representation technique that can support efficient rendering on low-end devices. However, scaling to high-resolution images requires optimizing and storing millions of unstructured Gaussian primitives independently, leading to slow convergence and redundant parameters. To address this, we propose Structured Gaussian Image (SGI), a compact and efficient framework for representing high-resolution images. SGI decomposes a complex image into multi-scale local spaces defined by a set of seeds. Each seed corresponds to a spatially coherent region and, together with lightweight multi-layer perceptrons (MLPs), generates structured implicit 2D neural Gaussians. This seed-based formulation imposes structural regularity on otherwise unstructured Gaussian primitives, which facilitates entropy-based compression at the seed level to reduce the total storage. However, optimizing seed parameters directly on high-resolution images is a challenging and non-trivial task. Therefore, we designed a multi-scale fitting strategy that refines the seed representation in a coarse-to-fine manner, substantially accelerating convergence. Quantitative and qualitative evaluations demonstrate that SGI achieves up to 7.5x compression over prior non-quantized 2D Gaussian methods and 1.6x over quantized ones, while also delivering 1.6x and 6.5x faster optimization, respectively, without degrading, and often improving, image fidelity. Code is available at https://github.com/zx-pan/SGI.

Simon Püttmann, Jonathan Jair Sànchez Contreras, Lennart Kowitz et al.

Accurate 3D microscopy image segmentation is critical for quantitative bioimage analysis but even state-of-the-art foundation models yield error-prone results. Therefore, manual curation is still widely used for either preparing high-quality training data or fixing errors before analysis. We present VessQC, an open-source tool for uncertainty-guided curation of large 3D microscopy segmentations. By integrating uncertainty maps, VessQC directs user attention to regions most likely containing biologically meaningful errors. In a preliminary user study uncertainty-guided correction significantly improved error detection recall from 67% to 94.0% (p=0.007) without a significant increase in total curation time. VessQC thus enables efficient, human-in-the-loop refinement of volumetric segmentations and bridges a key gap in real-world applications between uncertainty estimation and practical human-computer interaction. The software is freely available at github.com/MMV-Lab/VessQC.

Ye Zhang, Yu Zhou, Jingwen Qi et al.

Deep learning based automated pathological diagnosis has markedly improved diagnostic efficiency and reduced variability between observers, yet its clinical adoption remains limited by opaque model decisions and a lack of traceable rationale. To address this, recent multimodal visual reasoning architectures provide a unified framework that generates segmentation masks at the pixel level alongside semantically aligned textual explanations. By localizing lesion regions and producing expert style diagnostic narratives, these models deliver the transparent and interpretable insights necessary for dependable AI assisted pathology. Building on these advancements, we propose PathMR, a cell-level Multimodal visual Reasoning framework for Pathological image analysis. Given a pathological image and a textual query, PathMR generates expert-level diagnostic explanations while simultaneously predicting cell distribution patterns. To benchmark its performance, we evaluated our approach on the publicly available PathGen dataset as well as on our newly developed GADVR dataset. Extensive experiments on these two datasets demonstrate that PathMR consistently outperforms state-of-the-art visual reasoning methods in text generation quality, segmentation accuracy, and cross-modal alignment. These results highlight the potential of PathMR for improving interpretability in AI-driven pathological diagnosis. The code will be publicly available in https://github.com/zhangye-zoe/PathMR.

Yulong Li, Jianxu Chen, Xiwei Liu et al.

Medical foundation models generate narrative explanations but cannot quantify intervention effects, detect evidence conflicts, or validate literature claims, limiting clinical auditability. We propose causal compilation, a paradigm that transforms medical evidence from narrative text into executable code. The paradigm standardizes heterogeneous research evidence into structured estimand objects, each explicitly specifying intervention contrast, effect scale, time horizon, and target population, supporting six executable causal queries: do-calculus, counterfactual reasoning, temporal trajectories, heterogeneous effects, mechanistic decomposition, and joint interventions. We instantiate this paradigm in DoAtlas-1, compiling 1,445 effect kernels from 754 studies through effect standardization, conflict-aware graph construction, and real-world validation (Human Phenotype Project, 10,000 participants). The system achieves 98.5% canonicalization accuracy and 80.5% query executability. This paradigm shifts medical AI from text generation to executable, auditable, and verifiable causal reasoning.

Kewen Cao, Jianxu Chen, Yongbing Zhang et al.

Automated pathology image analysis is central to clinical diagnosis, but clinicians still ask which slide features drive a model's decision and why. Vision-language models can produce natural language explanations, but these are often correlational and lack verifiable evidence. In this paper, we introduce an SQL-centered agentic framework that enables both feature measurement and reasoning to be auditable. Specifically, after extracting human-interpretable cellular features, Feature Reasoning Agents compose and execute SQL queries over feature tables to aggregate visual evidence into quantitative findings. A Knowledge Comparison Agent then evaluates these findings against established pathological knowledge, mirroring how pathologists justify diagnoses from measurable observations. Extensive experiments evaluated on two pathology visual question answering datasets demonstrate our method improves interpretability and decision traceability while producing executable SQL traces that link cellular measurements to diagnostic conclusions.

Xiwei Liu, Yulong Li, Xinlin Zhuang et al.

Medical Vision-Language Models have shown promising potential in clinical decision support, yet they remain prone to factual hallucinations due to insufficient grounding in localized pathological evidence. Existing medical alignment methods primarily operate at the response level through preference optimization, improving output correctness but leaving intermediate reasoning weakly connected to visual regions. Although chain-of-thought (CoT) enhances multimodal reasoning, it remains largely text-centric, limiting effective integration of clinical visual cues. To address this gap, we propose ClinCoT, a clinical-aware visual chain-of-thought framework that transforms preference optimization from response-level correction to visual-driven reasoning. We introduce an automatic data generation pipeline that constructs clinically grounded preference pairs through reasoning with hypotheses-driven region proposals. Multiple Med-LLMs evaluators rank and assign scores to each response, and these rankings serve as supervision to train the target model. We further introduce a scoring-based margin-aware optimization strategy that incorporates both preference ranking and score difference to refine region-level reasoning trajectories. To maintain alignment as the model's policy evolves during training, we adopt an iterative learning scheme that dynamically regenerates preference data. Extensive experiments on three medical VQA and report generation benchmarks demonstrate that ClinCoT consistently improves factual grounding and achieves superior performance compared with existing preference-based alignment methods.

Xiaowei Xu, Justin Sonneck, Hongxiao Wang et al.

Autonomous migration is essential for the function of immune cells such as neutrophils and plays a pivotal role in diverse diseases. Recently, we introduced ComplexEye, a multi-lens array microscope comprising 16 independent aberration-corrected glass lenses arranged at the pitch of a 96-well plate, capable of capturing high-resolution movies of migrating cells. This architecture enables high-throughput live-cell video microscopy for migration analysis, supporting routine quantification of autonomous motility with strong potential for clinical translation. However, ComplexEye and similar high-throughput imaging platforms generate data at an exponential rate, imposing substantial burdens on storage and transmission. To address this challenge, we present FlowRoI, a fast optical-flow-based region of interest (RoI) extraction framework designed for high-throughput image compression in immune cell migration studies. FlowRoI estimates optical flow between consecutive frames and derives RoI masks that reliably cover nearly all migrating cells. The raw image and its corresponding RoI mask are then jointly encoded using JPEG2000 to enable RoI-aware compression. FlowRoI operates with high computational efficiency, achieving runtimes comparable to standard JPEG2000 and reaching an average throughput of about 30 frames per second on a modern laptop equipped with an Intel i7-1255U CPU. In terms of image quality, FlowRoI yields higher peak signal-to-noise ratio (PSNR) in cellular regions and achieves 2.0-2.2x higher compression rates at matched PSNR compared to standard JPEG2000.

Peixian Liang, Yifan Ding, Yizhe Zhang et al.

State-of-the-art (SOTA) methods for cell instance segmentation are based on deep learning (DL) semantic segmentation approaches, focusing on distinguishing foreground pixels from background pixels. In order to identify cell instances from foreground pixels (e.g., pixel clustering), most methods decompose instance information into pixel-wise objectives, such as distances to foreground-background boundaries (distance maps), heat gradients with the center point as heat source (heat diffusion maps), and distances from the center point to foreground-background boundaries with fixed angles (star-shaped polygons). However, pixel-wise objectives may lose significant geometric properties of the cell instances, such as shape, curvature, and convexity, which require a collection of pixels to represent. To address this challenge, we present a novel pixel clustering method, called Ceb (for Cell boundaries), to leverage cell boundary features and labels to divide foreground pixels into cell instances. Starting with probability maps generated from semantic segmentation, Ceb first extracts potential foreground-foreground boundaries with a revised Watershed algorithm. For each boundary candidate, a boundary feature representation (called boundary signature) is constructed by sampling pixels from the current foreground-foreground boundary as well as the neighboring background-foreground boundaries. Next, a boundary classifier is used to predict its binary boundary label based on the corresponding boundary signature. Finally, cell instances are obtained by dividing or merging neighboring regions based on the predicted boundary labels. Extensive experiments on six datasets demonstrate that Ceb outperforms existing pixel clustering methods on semantic segmentation probability maps. Moreover, Ceb achieves highly competitive performance compared to SOTA cell instance segmentation methods.

Annika Reinke, Minu D. Tizabi, Carole H. Sudre et al.

While the importance of automatic image analysis is continuously increasing, recent meta-research revealed major flaws with respect to algorithm validation. Performance metrics are particularly key for meaningful, objective, and transparent performance assessment and validation of the used automatic algorithms, but relatively little attention has been given to the practical pitfalls when using specific metrics for a given image analysis task. These are typically related to (1) the disregard of inherent metric properties, such as the behaviour in the presence of class imbalance or small target structures, (2) the disregard of inherent data set properties, such as the non-independence of the test cases, and (3) the disregard of the actual biomedical domain interest that the metrics should reflect. This living dynamically document has the purpose to illustrate important limitations of performance metrics commonly applied in the field of image analysis. In this context, it focuses on biomedical image analysis problems that can be phrased as image-level classification, semantic segmentation, instance segmentation, or object detection task. The current version is based on a Delphi process on metrics conducted by an international consortium of image analysis experts from more than 60 institutions worldwide.

Hongxiao Wang, Hao Zheng, Jianxu Chen et al.

Automatic histopathology image segmentation is crucial to disease analysis. Limited available labeled data hinders the generalizability of trained models under the fully supervised setting. Semi-supervised learning (SSL) based on generative methods has been proven to be effective in utilizing diverse image characteristics. However, it has not been well explored what kinds of generated images would be more useful for model training and how to use such images. In this paper, we propose a new data guided generative method for histopathology image segmentation by leveraging the unlabeled data distributions. First, we design an image generation module. Image content and style are disentangled and embedded in a clustering-friendly space to utilize their distributions. New images are synthesized by sampling and cross-combining contents and styles. Second, we devise an effective data selection policy for judiciously sampling the generated images: (1) to make the generated training set better cover the dataset, the clusters that are underrepresented in the original training set are covered more; (2) to make the training process more effective, we identify and oversample the images of "hard cases" in the data for which annotated training data may be scarce. Our method is evaluated on glands and nuclei datasets. We show that under both the inductive and transductive settings, our SSL method consistently boosts the performance of common segmentation models and attains state-of-the-art results.

Peixian Liang, Jianxu Chen, Hao Zheng et al.

The Encoder-Decoder architecture is a main stream deep learning model for biomedical image segmentation. The encoder fully compresses the input and generates encoded features, and the decoder then produces dense predictions using encoded features. However, decoders are still under-explored in such architectures. In this paper, we comprehensively study the state-of-the-art Encoder-Decoder architectures, and propose a new universal decoder, called cascade decoder, to improve semantic segmentation accuracy. Our cascade decoder can be embedded into existing networks and trained altogether in an end-to-end fashion. The cascade decoder structure aims to conduct more effective decoding of hierarchically encoded features and is more compatible with common encoders than the known decoders. We replace the decoders of state-of-the-art models with our cascade decoder for several challenging biomedical image segmentation tasks, and the considerable improvements achieved demonstrate the efficacy of our new decoding method.

Peixian Liang, Jianxu Chen, Pavel A. Brodskiy et al.

Wing disc pouches of fruit flies are a powerful genetic model for studying physiological intercellular calcium ($Ca^{2+}$) signals for dynamic analysis of cell signaling in organ development and disease studies. A key to analyzing spatial-temporal patterns of $Ca^{2+}$ signal waves is to accurately align the pouches across image sequences. However, pouches in different image frames may exhibit extensive intensity oscillations due to $Ca^{2+}$ signaling dynamics, and commonly used multimodal non-rigid registration methods may fail to achieve satisfactory results. In this paper, we develop a new two-phase non-rigid registration approach to register pouches in image sequences. First, we conduct segmentation of the region of interest. (i.e., pouches) using a deep neural network model. Second, we obtain an optimal transformation and align pouches across the image sequences. Evaluated using both synthetic data and real pouch data, our method considerably outperforms the state-of-the-art non-rigid registration methods.

Lin Yang, Yizhe Zhang, Jianxu Chen et al.

Image segmentation is a fundamental problem in biomedical image analysis. Recent advances in deep learning have achieved promising results on many biomedical image segmentation benchmarks. However, due to large variations in biomedical images (different modalities, image settings, objects, noise, etc), to utilize deep learning on a new application, it usually needs a new set of training data. This can incur a great deal of annotation effort and cost, because only biomedical experts can annotate effectively, and often there are too many instances in images (e.g., cells) to annotate. In this paper, we aim to address the following question: With limited effort (e.g., time) for annotation, what instances should be annotated in order to attain the best performance? We present a deep active learning framework that combines fully convolutional network (FCN) and active learning to significantly reduce annotation effort by making judicious suggestions on the most effective annotation areas. We utilize uncertainty and similarity information provided by FCN and formulate a generalized version of the maximum set cover problem to determine the most representative and uncertain areas for annotation. Extensive experiments using the 2015 MICCAI Gland Challenge dataset and a lymph node ultrasound image segmentation dataset show that, using annotation suggestions by our method, state-of-the-art segmentation performance can be achieved by using only 50% of training data.

Jianxu Chen, Sreya Banerjee, Abhinav Grama et al.

In this paper, we consider the problem of automatically segmenting neuronal cells in dual-color confocal microscopy images. This problem is a key task in various quantitative analysis applications in neuroscience, such as tracing cell genesis in Danio rerio (zebrafish) brains. Deep learning, especially using fully convolutional networks (FCN), has profoundly changed segmentation research in biomedical imaging. We face two major challenges in this problem. First, neuronal cells may form dense clusters, making it difficult to correctly identify all individual cells (even to human experts). Consequently, segmentation results of the known FCN-type models are not accurate enough. Second, pixel-wise ground truth is difficult to obtain. Only a limited amount of approximate instance-wise annotation can be collected, which makes the training of FCN models quite cumbersome. We propose a new FCN-type deep learning model, called deep complete bipartite networks (CB-Net), and a new scheme for leveraging approximate instance-wise annotation to train our pixel-wise prediction model. Evaluated using seven real datasets, our proposed new CB-Net model outperforms the state-of-the-art FCN models and produces neuron segmentation results of remarkable quality

Xiaoming Chen, Jianxu Chen, Danny Z. Chen et al.

Convolution is a fundamental operation in many applications, such as computer vision, natural language processing, image processing, etc. Recent successes of convolutional neural networks in various deep learning applications put even higher demand on fast convolution. The high computation throughput and memory bandwidth of graphics processing units (GPUs) make GPUs a natural choice for accelerating convolution operations. However, maximally exploiting the available memory bandwidth of GPUs for convolution is a challenging task. This paper introduces a general model to address the mismatch between the memory bank width of GPUs and computation data width of threads. Based on this model, we develop two convolution kernels, one for the general case and the other for a special case with one input channel. By carefully optimizing memory access patterns and computation patterns, we design a communication-optimized kernel for the special case and a communication-reduced kernel for the general case. Experimental data based on implementations on Kepler GPUs show that our kernels achieve 5.16X and 35.5% average performance improvement over the latest cuDNN library, for the special case and the general case, respectively.

Jianxu Chen, Chukka Srinivas

Automatic detection of lymphocyte in H&E images is a necessary first step in lots of tissue image analysis algorithms. An accurate and robust automated lymphocyte detection approach is of great importance in both computer science and clinical studies. Most of the existing approaches for lymphocyte detection are based on traditional image processing algorithms and/or classic machine learning methods. In the recent years, deep learning techniques have fundamentally transformed the way that a computer interprets images and have become a matchless solution in various pattern recognition problems. In this work, we design a new deep neural network model which extends the fully convolutional network by combining the ideas in several recent techniques, such as shortcut links. Also, we design a new training scheme taking the prior knowledge about lymphocytes into consideration. The training scheme not only efficiently exploits the limited amount of free-form annotations from pathologists, but also naturally supports efficient fine-tuning. As a consequence, our model has the potential of self-improvement by leveraging the errors collected during real applications. Our experiments show that our deep neural network model achieves good performance in the images of different staining conditions or different types of tissues.

Jianxu Chen, Lin Yang, Yizhe Zhang et al.

Segmentation of 3D images is a fundamental problem in biomedical image analysis. Deep learning (DL) approaches have achieved state-of-the-art segmentation perfor- mance. To exploit the 3D contexts using neural networks, known DL segmentation methods, including 3D convolution, 2D convolution on planes orthogonal to 2D image slices, and LSTM in multiple directions, all suffer incompatibility with the highly anisotropic dimensions in common 3D biomedical images. In this paper, we propose a new DL framework for 3D image segmentation, based on a com- bination of a fully convolutional network (FCN) and a recurrent neural network (RNN), which are responsible for exploiting the intra-slice and inter-slice contexts, respectively. To our best knowledge, this is the first DL framework for 3D image segmentation that explicitly leverages 3D image anisotropism. Evaluating using a dataset from the ISBI Neuronal Structure Segmentation Challenge and in-house image stacks for 3D fungus segmentation, our approach achieves promising results comparing to the known DL-based 3D segmentation approaches.