Weakly SSM : On the Viability of Weakly Supervised Segmentations for Statistical Shape Modeling

Statistical Shape Models (SSMs) excel at identifying population level anatomical variations, which is at the core of various clinical and biomedical applications, including morphology-based diagnostics and surgical planning. However, the effectiveness of SSM is often constrained by the necessity for expert-driven manual segmentation, a process that is both time-intensive and expensive, thereby restricting their broader application and utility. Recent deep learning approaches enable the direct estimation of Statistical Shape Models (SSMs) from unsegmented images. While these models can predict SSMs without segmentation during deployment, they do not address the challenge of acquiring the manual annotations needed for training, particularly in resource-limited settings. Semi-supervised and foundation models for anatomy segmentation can mitigate the annotation burden. Yet, despite the abundance of available approaches, there are no established guidelines to inform end-users on their effectiveness for the downstream task of constructing SSMs. In this study, we systematically evaluate the potential of weakly supervised methods as viable alternatives to manual segmentation's for building SSMs. We establish a new performance benchmark by employing various semi-supervised and foundational model methods for anatomy segmentation under low annotation settings, utilizing the predicted segmentation's for the task of SSM. We compare the modes of shape variation and use quantitative metrics to compare against a shape model derived from a manually annotated dataset. Our results indicate that some methods produce noisy segmentation, which is very unfavorable for SSM tasks, while others can capture the correct modes of variations in the population cohort with 60-80\% reduction in required manual annotation.

NTSEBENCH: Cognitive Reasoning Benchmark for Vision Language Models

Cognitive textual and visual reasoning tasks, such as puzzles, series, and analogies, demand the ability to quickly reason, decipher, and evaluate patterns both textually and spatially. While LLMs and VLMs, through extensive training on large amounts of human-curated data, have attained a high level of pseudo-human intelligence in some common sense reasoning tasks, they still struggle with more complex reasoning tasks that require cognitive understanding. In this work, we introduce a new dataset, NTSEBench, designed to evaluate the cognitive multi-modal reasoning and problem-solving skills of large models. The dataset comprises 2,728 multiple-choice questions comprising of a total of 4,642 images across 26 categories sampled from the NTSE examination conducted nationwide in India, featuring both visual and textual general aptitude questions that do not rely on rote learning. We establish baselines on the dataset using state-of-the-art LLMs and VLMs. To facilitate a comparison between open source and propriety models, we propose four distinct modeling strategies to handle different modalities (text and images) in the dataset instances.

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.

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.