Andrew Zhang

Muhammad Shaban, Yuzhou Chang, Huaying Qiu et al.

Foundation models have begun to transform image analysis by acting as pretrained generalist backbones that can be adapted to many tasks even when post-training data are limited, yet their impact on spatial proteomics, imaging that maps proteins at single-cell resolution, remains limited. Here, we introduce KRONOS, a foundation model built for spatial proteomics. KRONOS was trained in a self-supervised manner on over 47 million image patches covering 175 protein markers, 16 tissue types, and 8 fluorescence-based imaging platforms. We introduce key architectural adaptations to address the high-dimensional, multi-channel, and heterogeneous nature of multiplex imaging. We demonstrate that KRONOS learns biologically meaningful representations across multiple scales, ranging from cellular and microenvironment to tissue levels, enabling it to address diverse downstream tasks, including cell phenotyping, region classification, and patient stratification. Evaluated across 11 independent cohorts, KRONOS achieves state-of-the-art performance across cell phenotyping, treatment response prediction, and retrieval tasks, and is highly data-efficient. KRONOS also introduces the paradigm of segmentation-free patch-level processing for efficient and scalable spatial proteomics analysis, allowing cross-institutional comparisons, and as an image reverse search engine for spatial patterns. Together, these results position KRONOS as a flexible and scalable tool for spatial proteomics. The model is publicly accessible at https://github.com/mahmoodlab/KRONOS.

Md. Atabuzzaman, Andrew Zhang, Chris Thomas

Large Vision-Language Models (LVLMs) have demonstrated impressive performance on vision-language reasoning tasks. However, their potential for zero-shot fine-grained image classification, a challenging task requiring precise differentiation between visually similar categories, remains underexplored. We present a novel method that transforms zero-shot fine-grained image classification into a visual question-answering framework, leveraging LVLMs' comprehensive understanding capabilities rather than relying on direct class name generation. We enhance model performance through a novel attention intervention technique. We also address a key limitation in existing datasets by developing more comprehensive and precise class description benchmarks. We validate the effectiveness of our method through extensive experimentation across multiple fine-grained image classification benchmarks. Our proposed method consistently outperforms the current state-of-the-art (SOTA) approach, demonstrating both the effectiveness of our method and the broader potential of LVLMs for zero-shot fine-grained classification tasks. Code and Datasets: https://github.com/Atabuzzaman/Fine-grained-classification

Tong Ding, Sophia J. Wagner, Andrew H. Song et al.

The field of computational pathology has been transformed with recent advances in foundation models that encode histopathology region-of-interests (ROIs) into versatile and transferable feature representations via self-supervised learning (SSL). However, translating these advancements to address complex clinical challenges at the patient and slide level remains constrained by limited clinical data in disease-specific cohorts, especially for rare clinical conditions. We propose TITAN, a multimodal whole slide foundation model pretrained using 335,645 WSIs via visual self-supervised learning and vision-language alignment with corresponding pathology reports and 423,122 synthetic captions generated from a multimodal generative AI copilot for pathology. Without any finetuning or requiring clinical labels, TITAN can extract general-purpose slide representations and generate pathology reports that generalize to resource-limited clinical scenarios such as rare disease retrieval and cancer prognosis. We evaluate TITAN on diverse clinical tasks and find that TITAN outperforms both ROI and slide foundation models across machine learning settings such as linear probing, few-shot and zero-shot classification, rare cancer retrieval and cross-modal retrieval, and pathology report generation.

Anurag Vaidya, Andrew Zhang, Guillaume Jaume et al.

Foundation models are reshaping computational pathology by enabling transfer learning, where models pre-trained on vast datasets can be adapted for downstream diagnostic, prognostic, and therapeutic response tasks. Despite these advances, foundation models are still limited in their ability to encode the entire gigapixel whole-slide images without additional training and often lack complementary multimodal data. Here, we introduce Threads, a slide-level foundation model capable of generating universal representations of whole-slide images of any size. Threads was pre-trained using a multimodal learning approach on a diverse cohort of 47,171 hematoxylin and eosin (H&E)-stained tissue sections, paired with corresponding genomic and transcriptomic profiles - the largest such paired dataset to be used for foundation model development to date. This unique training paradigm enables Threads to capture the tissue's underlying molecular composition, yielding powerful representations applicable to a wide array of downstream tasks. In extensive benchmarking across 54 oncology tasks, including clinical subtyping, grading, mutation prediction, immunohistochemistry status determination, treatment response prediction, and survival prediction, Threads outperformed all baselines while demonstrating remarkable generalizability and label efficiency. It is particularly well suited for predicting rare events, further emphasizing its clinical utility. We intend to make the model publicly available for the broader community.

Andrew Zhang, Anushka Sivakumar, Chiawei Tang et al.

Discrete diffusion models are a new class of text generators that offer advantages such as bidirectional context use, parallelizable generation, and flexible prompting compared to autoregressive models. However, a critical limitation of discrete diffusion models is their inability to perform flexible-length or flexible-position text infilling without access to ground-truth positional data. We introduce \textbf{DDOT} (\textbf{D}iscrete \textbf{D}iffusion with \textbf{O}ptimal \textbf{T}ransport Position Coupling), the first discrete diffusion model to overcome this challenge. DDOT jointly denoises token values and token positions, employing a novel sample-level Optimal Transport (OT) coupling. This coupling preserves relative token ordering while dynamically adjusting the positions and length of infilled segments, a capability previously missing in text diffusion. Our method is orthogonal to existing discrete text diffusion methods and is compatible with various pretrained text denoisers. Extensive experiments on text infilling benchmarks such as One-Billion-Word and Yelp demonstrate that DDOT outperforms naive diffusion baselines. Furthermore, DDOT achieves performance on par with state-of-the-art non-autoregressive models and enables significant improvements in training efficiency and flexibility.

Hani Alomari, Anushka Sivakumar, Andrew Zhang et al.

Cross-modal image-text retrieval is challenging because of the diverse possible associations between content from different modalities. Traditional methods learn a single-vector embedding to represent semantics of each sample, but struggle to capture nuanced and diverse relationships that can exist across modalities. Set-based approaches, which represent each sample with multiple embeddings, offer a promising alternative, as they can capture richer and more diverse relationships. In this paper, we show that, despite their promise, these set-based representations continue to face issues including sparse supervision and set collapse, which limits their effectiveness. To address these challenges, we propose Maximal Pair Assignment Similarity to optimize one-to-one matching between embedding sets which preserve semantic diversity within the set. We also introduce two loss functions to further enhance the representations: Global Discriminative Loss to enhance distinction among embeddings, and Intra-Set Divergence Loss to prevent collapse within each set. Our method achieves state-of-the-art performance on MS-COCO and Flickr30k without relying on external data.

Andrew Zhang, Hao Wang, Shuchang Ye et al.

Patient motion during medical image acquisition causes blurring, ghosting, and distorts organs, which makes image interpretation challenging. Current state-of-the-art algorithms using Generative Adversarial Network (GAN)-based methods with their ability to learn the mappings between corrupted images and their ground truth via Structural Similarity Index Measure (SSIM) loss effectively generate motion-free images. However, we identified the following limitations: (i) they mainly focus on global structural characteristics and therefore overlook localized features that often carry critical pathological information, and (ii) the SSIM loss function struggles to handle images with varying pixel intensities, luminance factors, and variance. In this study, we propose Motion-Aware Image SYnthesis (MAISY) which initially characterize motion and then uses it for correction by: (a) leveraging the foundation model Segment Anything Model (SAM), to dynamically learn spatial patterns along anatomical boundaries where motion artifacts are most pronounced and, (b) introducing the Variance-Selective SSIM (VS-SSIM) loss which adaptively emphasizes spatial regions with high pixel variance to preserve essential anatomical details during artifact correction. Experiments on chest and head CT datasets demonstrate that our model outperformed the state-of-the-art counterparts, with Peak Signal-to-Noise Ratio (PSNR) increasing by 40%, SSIM by 10%, and Dice by 16%.