Estimation and Analysis of Slice Propagation Uncertainty in 3D Anatomy Segmentation

Supervised methods for 3D anatomy segmentation demonstrate superior performance but are often limited by the availability of annotated data. This limitation has led to a growing interest in self-supervised approaches in tandem with the abundance of available un-annotated data. Slice propagation has emerged as an self-supervised approach that leverages slice registration as a self-supervised task to achieve full anatomy segmentation with minimal supervision. This approach significantly reduces the need for domain expertise, time, and the cost associated with building fully annotated datasets required for training segmentation networks. However, this shift toward reduced supervision via deterministic networks raises concerns about the trustworthiness and reliability of predictions, especially when compared with more accurate supervised approaches. To address this concern, we propose the integration of calibrated uncertainty quantification (UQ) into slice propagation methods, providing insights into the model's predictive reliability and confidence levels. Incorporating uncertainty measures enhances user confidence in self-supervised approaches, thereby improving their practical applicability. We conducted experiments on three datasets for 3D abdominal segmentation using five UQ methods. The results illustrate that incorporating UQ improves not only model trustworthiness, but also segmentation accuracy. Furthermore, our analysis reveals various failure modes of slice propagation methods that might not be immediately apparent to end-users. This study opens up new research avenues to improve the accuracy and trustworthiness of slice propagation methods.

StainDiffuser: MultiTask Dual Diffusion Model for Virtual Staining

Hematoxylin and Eosin (H&E) staining is the most commonly used for disease diagnosis and tumor recurrence tracking. Hematoxylin excels at highlighting nuclei, whereas eosin stains the cytoplasm. However, H&E stain lacks details for differentiating different types of cells relevant to identifying the grade of the disease or response to specific treatment variations. Pathologists require special immunohistochemical (IHC) stains that highlight different cell types. These stains help in accurately identifying different regions of disease growth and their interactions with the cell's microenvironment. The advent of deep learning models has made Image-to-Image (I2I) translation a key research area, reducing the need for expensive physical staining processes. Pix2Pix and CycleGAN are still the most commonly used methods for virtual staining applications. However, both suffer from hallucinations or staining irregularities when H&E stain has less discriminate information about the underlying cells IHC needs to highlight (e.g.,CD3 lymphocytes). Diffusion models are currently the state-of-the-art models for image generation and conditional generation tasks. However, they require extensive and diverse datasets (millions of samples) to converge, which is less feasible for virtual staining applications.Inspired by the success of multitask deep learning models for limited dataset size, we propose StainDiffuser, a novel multitask dual diffusion architecture for virtual staining that converges under a limited training budget. StainDiffuser trains two diffusion processes simultaneously: (a) generation of cell-specific IHC stain from H&E and (b) H&E-based cell segmentation using coarse segmentation only during training. Our results show that StainDiffuser produces high-quality results for easier (CK8/18,epithelial marker) and difficult stains(CD3, Lymphocytes).

EfficientMorph: Parameter-Efficient Transformer-Based Architecture for 3D Image Registration

Transformers have emerged as the state-of-the-art architecture in medical image registration, outperforming convolutional neural networks (CNNs) by addressing their limited receptive fields and overcoming gradient instability in deeper models. Despite their success, transformer-based models require substantial resources for training, including data, memory, and computational power, which may restrict their applicability for end users with limited resources. In particular, existing transformer-based 3D image registration architectures face three critical gaps that challenge their efficiency and effectiveness. Firstly, while mitigating the quadratic complexity of full attention by focusing on local regions, window-based attention mechanisms often fail to adequately integrate local and global information. Secondly, feature similarities across attention heads that were recently found in multi-head attention architectures indicate a significant computational redundancy, suggesting that the capacity of the network could be better utilized to enhance performance. Lastly, the granularity of tokenization, a key factor in registration accuracy, presents a trade-off; smaller tokens improve detail capture at the cost of higher computational complexity, increased memory demands, and a risk of overfitting. Here, we propose EfficientMorph, a transformer-based architecture for unsupervised 3D image registration. It optimizes the balance between local and global attention through a plane-based attention mechanism, reduces computational redundancy via cascaded group attention, and captures fine details without compromising computational efficiency, thanks to a Hi-Res tokenization strategy complemented by merging operations. Notably, EfficientMorph sets a new benchmark for performance on the OASIS dataset with 16-27x fewer parameters.

MASSM: An End-to-End Deep Learning Framework for Multi-Anatomy Statistical Shape Modeling Directly From Images

Statistical Shape Modeling (SSM) is an effective method for quantitatively analyzing anatomical variations within populations. However, its utility is limited by the need for manual segmentations of anatomies, a task that relies on the scarce expertise of medical professionals. Recent advances in deep learning have provided a promising approach that automatically generates statistical representations from unsegmented images. Once trained, these deep learning-based models eliminate the need for manual segmentation for new subjects. Nonetheless, most current methods still require manual pre-alignment of image volumes and specifying a bounding box around the target anatomy prior for inference, resulting in a partially manual inference process. Recent approaches facilitate anatomy localization but only estimate statistical representations at the population level. However, they cannot delineate anatomy directly in images and are limited to modeling a single anatomy. Here, we introduce MASSM, a novel end-to-end deep learning framework that simultaneously localizes multiple anatomies in an image, estimates population-level statistical representations, and delineates each anatomy. Our findings emphasize the crucial role of local correspondences, showcasing their indispensability in providing superior shape information for medical imaging tasks.

Multi-Set Inoculation: Assessing Model Robustness Across Multiple Challenge Sets

Language models, given their black-box nature, often exhibit sensitivity to input perturbations, leading to trust issues due to hallucinations. To bolster trust, it's essential to understand these models' failure modes and devise strategies to enhance their performance. In this study, we propose a framework to study the effect of input perturbations on language models of different scales, from pre-trained models to large language models (LLMs). We use fine-tuning to train a robust model to perturbations, and we investigate whether exposure to one perturbation improves or degrades the model's performance on other perturbations. To address multi-perturbation robustness, we suggest three distinct training strategies. We also extend the framework to LLMs via a chain of thought(COT) prompting with exemplars. We instantiate our framework for the Tabular-NLI task and show that the proposed strategies train the model robust to different perturbations without losing accuracy on a given dataset.

Structural Cycle GAN for Virtual Immunohistochemistry Staining of Gland Markers in the Colon

With the advent of digital scanners and deep learning, diagnostic operations may move from a microscope to a desktop. Hematoxylin and Eosin (H&E) staining is one of the most frequently used stains for disease analysis, diagnosis, and grading, but pathologists do need different immunohistochemical (IHC) stains to analyze specific structures or cells. Obtaining all of these stains (H&E and different IHCs) on a single specimen is a tedious and time-consuming task. Consequently, virtual staining has emerged as an essential research direction. Here, we propose a novel generative model, Structural Cycle-GAN (SC-GAN), for synthesizing IHC stains from H&E images, and vice versa. Our method expressly incorporates structural information in the form of edges (in addition to color data) and employs attention modules exclusively in the decoder of the proposed generator model. This integration enhances feature localization and preserves contextual information during the generation process. In addition, a structural loss is incorporated to ensure accurate structure alignment between the generated and input markers. To demonstrate the efficacy of the proposed model, experiments are conducted with two IHC markers emphasizing distinct structures of glands in the colon: the nucleus of epithelial cells (CDX2) and the cytoplasm (CK818). Quantitative metrics such as FID and SSIM are frequently used for the analysis of generative models, but they do not correlate explicitly with higher-quality virtual staining results. Therefore, we propose two new quantitative metrics that correlate directly with the virtual staining specificity of IHC markers.

ADASSM: Adversarial Data Augmentation in Statistical Shape Models From Images

Statistical shape models (SSM) have been well-established as an excellent tool for identifying variations in the morphology of anatomy across the underlying population. Shape models use consistent shape representation across all the samples in a given cohort, which helps to compare shapes and identify the variations that can detect pathologies and help in formulating treatment plans. In medical imaging, computing these shape representations from CT/MRI scans requires time-intensive preprocessing operations, including but not limited to anatomy segmentation annotations, registration, and texture denoising. Deep learning models have demonstrated exceptional capabilities in learning shape representations directly from volumetric images, giving rise to highly effective and efficient Image-to-SSM. Nevertheless, these models are data-hungry and due to the limited availability of medical data, deep learning models tend to overfit. Offline data augmentation techniques, that use kernel density estimation based (KDE) methods for generating shape-augmented samples, have successfully aided Image-to-SSM networks in achieving comparable accuracy to traditional SSM methods. However, these augmentation methods focus on shape augmentation, whereas deep learning models exhibit image-based texture bias results in sub-optimal models. This paper introduces a novel strategy for on-the-fly data augmentation for the Image-to-SSM framework by leveraging data-dependent noise generation or texture augmentation. The proposed framework is trained as an adversary to the Image-to-SSM network, augmenting diverse and challenging noisy samples. Our approach achieves improved accuracy by encouraging the model to focus on the underlying geometry rather than relying solely on pixel values.

InfoSync: Information Synchronization across Multilingual Semi-structured Tables

Information Synchronization of semi-structured data across languages is challenging. For instance, Wikipedia tables in one language should be synchronized across languages. To address this problem, we introduce a new dataset InfoSyncC and a two-step method for tabular synchronization. InfoSync contains 100K entity-centric tables (Wikipedia Infoboxes) across 14 languages, of which a subset (3.5K pairs) are manually annotated. The proposed method includes 1) Information Alignment to map rows and 2) Information Update for updating missing/outdated information for aligned tables across multilingual tables. When evaluated on InfoSync, information alignment achieves an F1 score of 87.91 (en <-> non-en). To evaluate information updation, we perform human-assisted Wikipedia edits on Infoboxes for 603 table pairs. Our approach obtains an acceptance rate of 77.28% on Wikipedia, showing the effectiveness of the proposed method.

To pretrain or not to pretrain? A case study of domain-specific pretraining for semantic segmentation in histopathology

Annotating medical imaging datasets is costly, so fine-tuning (or transfer learning) is the most effective method for digital pathology vision applications such as disease classification and semantic segmentation. However, due to texture bias in models trained on real-world images, transfer learning for histopathology applications might result in underperforming models, which necessitates the need for using unlabeled histopathology data and self-supervised methods to discover domain-specific characteristics. Here, we tested the premise that histopathology-specific pretrained models provide better initializations for pathology vision tasks, i.e., gland and cell segmentation. In this study, we compare the performance of gland and cell segmentation tasks with domain-specific and non-domain-specific pretrained weights. Moreover, we investigate the data size at which domain-specific pretraining produces a statistically significant difference in performance. In addition, we investigated whether domain-specific initialization improves the effectiveness of out-of-domain testing on distinct datasets but the same task. The results indicate that performance gain using domain-specific pretraining depends on both the task and the size of the training dataset. In instances with limited dataset sizes, a significant improvement in gland segmentation performance was also observed, whereas models trained on cell segmentation datasets exhibit no improvement.

Unsupervised Domain Adaptation for Semantic Segmentation via Feature-space Density Matching

Semantic segmentation is a critical step in automated image interpretation and analysis where pixels are classified into one or more predefined semantically meaningful classes. Deep learning approaches for semantic segmentation rely on harnessing the power of annotated images to learn features indicative of these semantic classes. Nonetheless, they often fail to generalize when there is a significant domain (i.e., distributional) shift between the training (i.e., source) data and the dataset(s) encountered when deployed (i.e., target), necessitating manual annotations for the target data to achieve acceptable performance. This is especially important in medical imaging because different image modalities have significant intra- and inter-site variations due to protocol and vendor variability. Current techniques are sensitive to hyperparameter tuning and target dataset size. This paper presents an unsupervised domain adaptation approach for semantic segmentation that alleviates the need for annotating target data. Using kernel density estimation, we match the target data distribution to the source data in the feature space. We demonstrate that our results are comparable or superior on multiple-site prostate MRI and histopathology images, which mitigates the need for annotating target data.