Hien V. Nguyen

Hung Q. Vo, Huy Q. Vo, Son T. Ly et al.

Conventional tissue image analysis software provides foundational capabilities for cellular analysis, including segmentation, basic morphological feature extraction, and spatial organization analysis. However, these tools often require manual intervention and are not well integrated with code-driven automation, limiting efficiency and scalability for complex spatial tissue studies. In addition, they offer limited flexibility for custom analyses, as they typically support only a fixed set of pre-implemented spatial cellular features. To address these limitations, we propose CodeCytos, a coding-based reasoning agent framework that enables dynamic, programmable interaction with spatial molecular imaging data to improve automation and customization. CodeCytos is designed to streamline the exploration of custom spatial cellular features and adapt to diverse research needs. We demonstrate its utility through case studies on four expert-curated datasets from distinct tissue types: frontal cortex, non-small-cell lung cancer, pancreas, and tonsil. We evaluate CodeCytos under a realistic minimal prompt setting, where bioscientists pose simple questions without task-specific instructions or contextual information about spatial cellular analysis, and benchmark multiple LLM backbones with strong coding capabilities. We further show that incorporating tailored, domain-agnostic few-shot in-context coding-reasoning examples (randomly sampled demonstrations outside the spatial analysis domain) can substantially improve performance without requiring costly, expert-crafted in-domain demonstrations. Overall, CodeCytos outperforms baseline approaches, highlighting the potential of code-action agents to assist with custom feature exploration in spatial molecular imaging and to accelerate biomarker discovery.

Huy Q. Vo, Pietro A. Cicalese, Surya Seshan et al.

The thrombotic microangiopathies (TMAs) manifest in renal biopsy histology with a broad spectrum of acute and chronic findings. Precise diagnostic criteria for a renal biopsy diagnosis of TMA are missing. As a first step towards a machine learning- and computer vision-based analysis of wholes slide images from renal biopsies, we trained a segmentation model for the decisive diagnostic kidney tissue compartments artery, arteriole, glomerulus on a set of whole slide images from renal biopsies with TMAs and Mimickers (distinct diseases with a similar nephropathological appearance as TMA like severe benign nephrosclerosis, various vasculitides, Bevacizumab-plug glomerulopathy, arteriolar light chain deposition disease). Our segmentation model combines a U-Net-based tissue detection with a Shifted windows-transformer architecture to reach excellent segmentation results for even the most severely altered glomeruli, arterioles and arteries, even on unseen staining domains from a different nephropathology lab. With accurate automatic segmentation of the decisive renal biopsy compartments in human renal vasculopathies, we have laid the foundation for large-scale compartment-specific machine learning and computer vision analysis of renal biopsy repositories with TMAs.

Son T. Ly, Bai Lin, Hung Q. Vo et al.

Reliable large-scale cell detection and segmentation is the fundamental first step to understanding biological processes in the brain. The ability to phenotype cells at scale can accelerate preclinical drug evaluation and system-level brain histology studies. The impressive advances in deep learning offer a practical solution to cell image detection and segmentation. Unfortunately, categorizing cells and delineating their boundaries for training deep networks is an expensive process that requires skilled biologists. This paper presents a novel self-supervised Dual-Loss Adaptive Masked Autoencoder (DAMA) for learning rich features from multiplexed immunofluorescence brain images. DAMA's objective function minimizes the conditional entropy in pixel-level reconstruction and feature-level regression. Unlike existing self-supervised learning methods based on a random image masking strategy, DAMA employs a novel adaptive mask sampling strategy to maximize mutual information and effectively learn brain cell data. To the best of our knowledge, this is the first effort to develop a self-supervised learning method for multiplexed immunofluorescence brain images. Our extensive experiments demonstrate that DAMA features enable superior cell detection, segmentation, and classification performance without requiring many annotations.

Son Thai Ly, Hien V. Nguyen

Adapting foundation models to new clinical sites remains challenging in practice. Domain shift and scarce annotations must be handled by experts, yet many clinical groups do not have ready access to skilled AI engineers to tune adapter designs and training recipes. As a result, adaptation cycles can stretch from weeks to months, particularly in few-shot settings. Existing PEFT methods either require manual adapter configuration or automated searches that are computationally infeasible in few-shot 3D settings. We propose SEA-PEFT (SElf-Auditing Parameter-Efficient Fine-Tuning) to automate this process. SEA-PEFT treats adapter configuration as an online allocation problem solved during fine-tuning rather than through manual, fixed-topology choices. SEA-PEFT uses a search-audit-allocate loop that trains active adapters, estimates each adapter's Dice utility by momentarily toggling it off, and then reselects the active set under a parameter budget using a greedy knapsack allocator. Exponential Moving Average and Interquartile Range smoothing, together with a Finite-State Ranking controller, stabilize the loop and improve reliability in high-noise few-shot regimes. On TotalSegmentator and FLARE'22, SEA-PEFT improves mean Dice by 2.4--2.8 points over the strongest fixed-topology PEFT baselines across 1/5/10-shot settings while training <1% of parameters. For reproducibility purposes, we made our code publicly available at https://github.com/tsly123/SEA_PEFT

Son Thai Ly, Hien V. Nguyen

Adapting vision transformer foundation models through parameter-efficient fine-tuning (PEFT) methods has become increasingly popular. These methods optimize a limited subset of parameters, enabling efficient adaptation without the need to fine-tune the entire model while still achieving competitive performance. However, traditional PEFT methods may limit the model's capacity to capture complex patterns, especially those associated with high-frequency spectra. This limitation becomes particularly problematic as existing research indicates that high-frequency features are crucial for distinguishing subtle image structures. To address this issue, we introduce FreqFit, a novel Frequency Fine-tuning module between ViT blocks to enhance model adaptability. FreqFit is simple yet surprisingly effective, and can be integrated with all existing PEFT methods to boost their performance. By manipulating features in the frequency domain, our approach allows models to capture subtle patterns more effectively. Extensive experiments on 24 datasets, using both supervised and self-supervised foundational models with various state-of-the-art PEFT methods, reveal that FreqFit consistently improves performance over the original PEFT methods with performance gains ranging from 1% to 16%. For instance, FreqFit-LoRA surpasses the performances of state-of-the-art baselines on CIFAR100 by more than 10% even without applying regularization or strong augmentation. For reproducibility purposes, the source code is available at https://github.com/tsly123/FreqFiT.

Hung Q. Vo, Pengyu Yuan, Zheng Yin et al.

Self-supervised learning (SSL) has garnered substantial interest within the machine learning and computer vision communities. Two prominent approaches in SSL include contrastive-based learning and self-distillation utilizing cropping augmentation. Lately, masked image modeling (MIM) has emerged as a more potent SSL technique, employing image inpainting as a pretext task. MIM creates a strong inductive bias toward meaningful spatial and semantic understanding. This has opened up new opportunities for SSL to contribute not only to classification tasks but also to more complex applications like object detection and image segmentation. Building upon this progress, our research paper introduces a scalable and practical SSL approach centered around more challenging pretext tasks that facilitate the acquisition of robust features. Specifically, we leverage multi-scale image reconstruction from randomly masked input images as the foundation for feature learning. Our hypothesis posits that reconstructing high-resolution images enables the model to attend to finer spatial details, particularly beneficial for discerning subtle intricacies within medical images. The proposed SSL features help improve classification performance on the Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM) dataset. In pathology classification, our method demonstrates a 3\% increase in average precision (AP) and a 1\% increase in the area under the receiver operating characteristic curve (AUC) when compared to state-of-the-art (SOTA) algorithms. Moreover, in mass margins classification, our approach achieves a 4\% increase in AP and a 2\% increase in AUC.

Hung Q. Vo, Samira Zare, Son T. Ly et al.

Despite significant progress in robust deep learning techniques for mammogram breast cancer classification, their reliability in real-world clinical development settings remains uncertain. The translation of these models to clinical practice faces challenges due to variations in medical centers, imaging protocols, and patient populations. To enhance their robustness, invariant learning methods have been proposed, prioritizing causal factors over misleading features. However, their effectiveness in clinical development and impact on mammogram classification require investigation. This paper reassesses the application of invariant learning for breast cancer risk estimation based on mammograms. Utilizing diverse multi-site public datasets, it represents the first study in this area. The objective is to evaluate invariant learning's benefits in developing robust models. Invariant learning methods, including Invariant Risk Minimization and Variance Risk Extrapolation, are compared quantitatively against Empirical Risk Minimization. Evaluation metrics include accuracy, average precision, and area under the curve. Additionally, interpretability is examined through class activation maps and visualization of learned representations. This research examines the advantages, limitations, and challenges of invariant learning for mammogram classification, guiding future studies to develop generalized methods for breast cancer prediction on whole mammograms in out-of-domain scenarios.

Hung Q. Vo, Pengyu Yuan, Tiancheng He et al.

Accurate breast lesion risk estimation can significantly reduce unnecessary biopsies and help doctors decide optimal treatment plans. Most existing computer-aided systems rely solely on mammogram features to classify breast lesions. While this approach is convenient, it does not fully exploit useful information in clinical reports to achieve the optimal performance. Would clinical features significantly improve breast lesion classification compared to using mammograms alone? How to handle missing clinical information caused by variation in medical practice? What is the best way to combine mammograms and clinical features? There is a compelling need for a systematic study to address these fundamental questions. This paper investigates several multimodal deep networks based on feature concatenation, cross-attention, and co-attention to combine mammograms and categorical clinical variables. We show that the proposed architectures significantly increase the lesion classification performance (average area under ROC curves from 0.89 to 0.94). We also evaluate the model when clinical variables are missing.

S. Kevin Zhou, Hoang Ngan Le, Khoa Luu et al.

Deep reinforcement learning (DRL) augments the reinforcement learning framework, which learns a sequence of actions that maximizes the expected reward, with the representative power of deep neural networks. Recent works have demonstrated the great potential of DRL in medicine and healthcare. This paper presents a literature review of DRL in medical imaging. We start with a comprehensive tutorial of DRL, including the latest model-free and model-based algorithms. We then cover existing DRL applications for medical imaging, which are roughly divided into three main categories: (I) parametric medical image analysis tasks including landmark detection, object/lesion detection, registration, and view plane localization; (ii) solving optimization tasks including hyperparameter tuning, selecting augmentation strategies, and neural architecture search; and (iii) miscellaneous applications including surgical gesture segmentation, personalized mobile health intervention, and computational model personalization. The paper concludes with discussions of future perspectives.

Aryan Mobiny, Hien V. Nguyen, Supratik Moulik et al.

Deep neural networks (DNNs) have achieved state-of-the-art performances in many important domains, including medical diagnosis, security, and autonomous driving. In these domains where safety is highly critical, an erroneous decision can result in serious consequences. While a perfect prediction accuracy is not always achievable, recent work on Bayesian deep networks shows that it is possible to know when DNNs are more likely to make mistakes. Knowing what DNNs do not know is desirable to increase the safety of deep learning technology in sensitive applications. Bayesian neural networks attempt to address this challenge. However, traditional approaches are computationally intractable and do not scale well to large, complex neural network architectures. In this paper, we develop a theoretical framework to approximate Bayesian inference for DNNs by imposing a Bernoulli distribution on the model weights. This method, called MC-DropConnect, gives us a tool to represent the model uncertainty with little change in the overall model structure or computational cost. We extensively validate the proposed algorithm on multiple network architectures and datasets for classification and semantic segmentation tasks. We also propose new metrics to quantify the uncertainty estimates. This enables an objective comparison between MC-DropConnect and prior approaches. Our empirical results demonstrate that the proposed framework yields significant improvement in both prediction accuracy and uncertainty estimation quality compared to the state of the art.