William Speier

Ricky K. Taira, Anders O. Garlid, William Speier

Medical natural language processing (NLP) systems are a key enabling technology for transforming Big Data from clinical report repositories to information used to support disease models and validate intervention methods. However, current medical NLP systems fall considerably short when faced with the task of logically interpreting clinical text. In this paper, we describe a framework inspired by mechanisms of human cognition in an attempt to jump the NLP performance curve. The design centers about a hierarchical semantic compositional model (HSCM) which provides an internal substrate for guiding the interpretation process. The paper describes insights from four key cognitive aspects including semantic memory, semantic composition, semantic activation, and hierarchical predictive coding. We discuss the design of a generative semantic model and an associated semantic parser used to transform a free-text sentence into a logical representation of its meaning. The paper discusses supportive and antagonistic arguments for the key features of the architecture as a long-term foundational framework.

Saarang Panchavati, Uddhav Panchavati, Corey Arnold et al.

Electroencephalography (EEG) is a widely used tool for studying brain function, with applications in clinical neuroscience, diagnosis, and brain-computer interfaces (BCIs). Recent EEG foundation models trained on large unlabeled corpora aim to learn transferable representations, but their effectiveness remains unclear; reported improvements over smaller task-specific models are often modest, sensitive to downstream adaptation and fine-tuning strategies, and limited under linear probing. We hypothesize that one contributing factor is the reliance on signal reconstruction as the primary self-supervised learning (SSL) objective, which biases representations toward high-variance artifacts rather than task-relevant neural structure. To address this limitation, we explore an SSL paradigm based on Joint Embedding Predictive Architectures (JEPA), which learn by predicting latent representations instead of reconstructing raw signals. While earlier JEPA-style methods often rely on additional heuristics to ensure training stability, recent advances such as LeJEPA provide a more principled and stable formulation. We introduce Laya, the first EEG foundation model based on LeJEPA. Across a range of EEG benchmarks, Laya demonstrates improved performance under linear probing compared to reconstruction-based baselines, suggesting that latent predictive objectives offer a promising direction for learning transferable, high-level EEG representations.

Ashwath Radhachandran, Vedrana Ivezić, Shreeram Athreya et al.

Ultrasound (US) imaging poses unique challenges for representation learning due to its inherently noisy acquisition process. The low signal-to-noise ratio and stochastic speckle patterns hinder standard self-supervised learning methods relying on a pixel-level reconstruction objective. Joint-Embedding Predictive Architectures (JEPAs) address this drawback by predicting masked latent representations rather than raw pixels. However, standard approaches depend on hyperparameter-brittle and computationally expensive online teachers updated via exponential moving average. We propose US-JEPA, a self-supervised framework that adopts the Static-teacher Asymmetric Latent Training (SALT) objective. By using a frozen, domain-specific teacher to provide stable latent targets, US-JEPA decouples student-teacher optimization and pushes the student to expand upon the semantic priors of the teacher. In addition, we provide the first rigorous comparison of all publicly available state-of-the-art ultrasound foundation models on UltraBench, a public dataset benchmark spanning multiple organs and pathological conditions. Under linear probing for diverse classification tasks, US-JEPA achieves performance competitive with or superior to domain-specific and universal vision foundation model baselines. Our results demonstrate that masked latent prediction provides a stable and efficient path toward robust ultrasound representations.

Vedrana Ivezić, Mara Pleasure, Ashwath Radhachandran et al.

Though self-supervised learning (SSL) has demonstrated incredible ability to learn robust representations from unlabeled data, the choice of optimal SSL strategy can lead to vastly different performance outcomes in specialized domains. Joint embedding architectures (JEAs) and joint embedding predictive architectures (JEPAs) have shown robustness to noise and strong semantic feature learning compared to pixel reconstruction-based SSL methods, leading to widespread adoption in medical imaging. However, no prior work has systematically investigated which SSL objective is better aligned with the spatial organization of clinically relevant signal. In this work, we empirically investigate how the choice of SSL method impacts the learned representations in medical imaging. We select two representative imaging modalities characterized by unique noise profiles: ultrasound and histopathology. When informative signal is spatially localized, as in histopathology, JEAs are more effective due to their view-invariance objective. In contrast, when diagnostically relevant information is globally structured, such as the macroscopic anatomy present in liver ultrasounds, JEPAs are optimal. These differences are especially evident in the clinical relevance of the learned features, as independently validated by board-certified radiologists and pathologists. Together, our results provide a framework for matching SSL objectives to the structural and noise properties of medical imaging modalities.

Haoyue Zhang, Jennifer S. Polson, Eric J. Yang et al.

For acute ischemic stroke (AIS) patients with large vessel occlusions, clinicians must decide if the benefit of mechanical thrombectomy (MTB) outweighs the risks and potential complications following an invasive procedure. Pre-treatment computed tomography (CT) and angiography (CTA) are widely used to characterize occlusions in the brain vasculature. If a patient is deemed eligible, a modified treatment in cerebral ischemia (mTICI) score will be used to grade how well blood flow is reestablished throughout and following the MTB procedure. An estimation of the likelihood of successful recanalization can support treatment decision-making. In this study, we proposed a fully automated prediction of a patient's recanalization score using pre-treatment CT and CTA imaging. We designed a spatial cross attention network (SCANet) that utilizes vision transformers to localize to pertinent slices and brain regions. Our top model achieved an average cross-validated ROC-AUC of 77.33 $\pm$ 3.9\%. This is a promising result that supports future applications of deep learning on CT and CTA for the identification of eligible AIS patients for MTB.

Shreeram Athreya, Andrew Melehy, Sujit Silas Armstrong Suthahar et al.

Objective: Molecular testing (MT) classifies cytologically indeterminate thyroid nodules as benign or malignant with high sensitivity but low positive predictive value (PPV), only using molecular profiles, ignoring ultrasound (US) imaging and biopsy. We address this limitation by applying attention multiple instance learning (AMIL) to US images. Methods: We retrospectively reviewed 333 patients with indeterminate thyroid nodules at UCLA medical center (259 benign, 74 malignant). A multi-modal deep learning AMIL model was developed, combining US images and MT to classify the nodules as benign or malignant and enhance the malignancy risk stratification of MT. Results: The final AMIL model matched MT sensitivity (0.946) while significantly improving PPV (0.477 vs 0.448 for MT alone), indicating fewer false positives while maintaining high sensitivity. Conclusion: Our approach reduces false positives compared to MT while maintaining the same ability to identify positive cases, potentially reducing unnecessary benign thyroid resections in patients with indeterminate nodules.

Ekaterina Redekop, Mara Pleasure, Zichen Wang et al.

Prostate cancer (PCa) was the most frequently diagnosed cancer among American men in 2023. The histological grading of biopsies is essential for diagnosis, and various deep learning-based solutions have been developed to assist with this task. Existing deep learning frameworks are typically applied to individual 2D cross-sections sliced from 3D biopsy tissue specimens. This process impedes the analysis of complex tissue structures such as glands, which can vary depending on the tissue slice examined. We propose a novel digital pathology data source called a "volumetric core," obtained via the extraction and co-alignment of serially sectioned tissue sections using a novel morphology-preserving alignment framework. We trained an attention-based multiple-instance learning (ABMIL) framework on deep features extracted from volumetric patches to automatically classify the Gleason Grade Group (GGG). To handle volumetric patches, we used a modified video transformer with a deep feature extractor pretrained using self-supervised learning. We ran our morphology-preserving alignment framework to construct 10,210 volumetric cores, leaving out 30% for pretraining. The rest of the dataset was used to train ABMIL, which resulted in a 0.958 macro-average AUC, 0.671 F1 score, 0.661 precision, and 0.695 recall averaged across all five GGG significantly outperforming the 2D baselines.

Ekaterina Redekop, Mara Pleasure, Zichen Wang et al.

The rapid growth of digital pathology and advances in self-supervised deep learning have enabled the development of foundational models for various pathology tasks across diverse diseases. While multimodal approaches integrating diverse data sources have emerged, a critical gap remains in the comprehensive integration of whole-slide images (WSIs) with spatial transcriptomics (ST), which is crucial for capturing critical molecular heterogeneity beyond standard hematoxylin & eosin (H&E) staining. We introduce SPADE, a foundation model that integrates histopathology with ST data to guide image representation learning within a unified framework, in effect creating an ST-informed latent space. SPADE leverages a mixture-of-data experts technique, where experts are created via two-stage imaging feature-space clustering using contrastive learning to learn representations of co-registered WSI patches and gene expression profiles. Pre-trained on the comprehensive HEST-1k dataset, SPADE is evaluated on 20 downstream tasks, demonstrating significantly superior few-shot performance compared to baseline models, highlighting the benefits of integrating morphological and molecular information into one latent space. Code and pretrained weights are available at https://github.com/uclabair/SPADE.

Chao Chen, Zhihong Chen, Xinyu Jin et al.

Bone age assessment (BAA) is clinically important as it can be used to diagnose endocrine and metabolic disorders during child development. Existing deep learning based methods for classifying bone age use the global image as input, or exploit local information by annotating extra bounding boxes or key points. However, training with the global image underutilizes discriminative local information, while providing extra annotations is expensive and subjective. In this paper, we propose an attention-guided approach to automatically localize the discriminative regions for BAA without any extra annotations. Specifically, we first train a classification model to learn the attention maps of the discriminative regions, finding the hand region, the most discriminative region (the carpal bones), and the next most discriminative region (the metacarpal bones). Guided by those attention maps, we then crop the informative local regions from the original image and aggregate different regions for BAA. Instead of taking BAA as a general regression task, which is suboptimal due to the label ambiguity problem in the age label space, we propose using joint age distribution learning and expectation regression, which makes use of the ordinal relationship among hand images with different individual ages and leads to more robust age estimation. Extensive experiments are conducted on the RSNA pediatric bone age data set. Using no training annotations, our method achieves competitive results compared with existing state-of-the-art semi-automatic deep learning-based methods that require manual annotation. Code is available at https: //github.com/chenchao666/Bone-Age-Assessment.

Saarang Panchavati, Corey Arnold, William Speier

This work explores the potential of foundation models, specifically a Mamba-based selective state space model, for enhancing EEG analysis in neurological disorder diagnosis. EEG, crucial for diagnosing conditions like epilepsy, presents significant challenges due to its noisy, high-dimensional, and nonlinear nature. Traditional machine learning methods have made advances in automating EEG analysis but often fail to capture its complex spatio-temporal dynamics. Recent advances in deep learning, particularly in sequence modeling, offer new avenues for creating more generalized and expressive models capable of handling such complexities. By training a Mamba-based model on a large dataset containing seizure and non-seizure EEG recordings through a self-supervised reconstruction task followed by a seizure detection task, we demonstrate the model's effectiveness, achieving an AUROC of 0.72 on a held-out test set. This approach marks a significant step toward developing large-scale, clinically applicable foundation models for EEG data analysis.

Shreeram Athreya, Ashwath Radhachandran, Vedrana Ivezić et al.

Purpose: The objective of this work is to introduce an advanced framework designed to enhance ultrasound images, especially those captured by portable hand-held devices, which often produce lower quality images due to hardware constraints. Additionally, this framework is uniquely capable of effectively handling non-registered input ultrasound image pairs, addressing a common challenge in medical imaging. Materials and Methods: In this retrospective study, we utilized an enhanced generative adversarial network (CycleGAN) model for ultrasound image enhancement across five organ systems. Perceptual loss, derived from deep features of pretrained neural networks, is applied to ensure the human-perceptual quality of the enhanced images. These images are compared with paired images acquired from high resolution devices to demonstrate the model's ability to generate realistic high-quality images across organ systems. Results: Preliminary validation of the framework reveals promising performance metrics. The model generates images that result in a Structural Similarity Index (SSI) score of 0.722, Locally Normalized Cross-Correlation (LNCC) score of 0.902 and 28.802 for the Peak Signal-to-Noise Ratio (PSNR) metric. Conclusion: This work presents a significant advancement in medical imaging through the development of a CycleGAN model enhanced with Perceptual Loss (PL), effectively bridging the quality gap between ultrasound images from varied devices. By training on paired images, the model not only improves image quality but also ensures the preservation of vital anatomic structural content. This approach may improve equity in access to healthcare by enhancing portable device capabilities, although further validation and optimizations are necessary for broader clinical application.

Nithin Parthasarathy, James Soetedjo, Saarang Panchavati et al.

Amyotrophic lateral sclerosis (ALS) severely impairs patients' ability to communicate, often leading to a decline in their quality of life within a few years of diagnosis. The P300 speller brain-computer interface (BCI) offers an alternative communication method by interpreting a subject's EEG response to characters presented on a grid interface. This paper addresses the common speed limitations encountered in training efficient P300-based multi-subject classifiers by introducing innovative "across-subject" classifiers. We leverage a combination of the second-generation Generative Pre-Trained Transformer (GPT2) and Dijkstra's algorithm to optimize stimuli and suggest word completion choices based on typing history. Additionally, we employ a multi-layered smoothing technique to accommodate out-of-vocabulary (OOV) words. Through extensive simulations involving random sampling of EEG data from subjects, we demonstrate significant speed enhancements in typing passages containing rare and OOV words. These optimizations result in approximately 10% improvement in character-level typing speed and up to 40% improvement in multi-word prediction. We demonstrate that augmenting standard row/column highlighting techniques with layered word prediction yields close-to-optimal performance. Furthermore, we explore both "within-subject" and "across-subject" training techniques, showing that speed improvements are consistent across both approaches.

Ekaterina Redekop, Mara Pleasure, Vedrana Ivezic et al.

Foundation models in digital pathology use massive datasets to learn useful compact feature representations of complex histology images. However, there is limited transparency into what drives the correlation between dataset size and performance, raising the question of whether simply adding more data to increase performance is always necessary. In this study, we propose a prototype-guided diffusion model to generate high-fidelity synthetic pathology data at scale, enabling large-scale self-supervised learning and reducing reliance on real patient samples while preserving downstream performance. Using guidance from histological prototypes during sampling, our approach ensures biologically and diagnostically meaningful variations in the generated data. We demonstrate that self-supervised features trained on our synthetic dataset achieve competitive performance despite using ~60x-760x less data than models trained on large real-world datasets. Notably, models trained using our synthetic data showed statistically comparable or better performance across multiple evaluation metrics and tasks, even when compared to models trained on orders of magnitude larger datasets. Our hybrid approach, combining synthetic and real data, further enhanced performance, achieving top results in several evaluations. These findings underscore the potential of generative AI to create compelling training data for digital pathology, significantly reducing the reliance on extensive clinical datasets and highlighting the efficiency of our approach.

Irsyad Adam, Steven Swee, Erika Yilin et al.

In this work, we study the problem pertaining to personalized classification of subclinical atherosclerosis by developing a hierarchical graph neural network framework to leverage two characteristic modalities of a patient: clinical features within the context of the cohort, and molecular data unique to individual patients. Current graph-based methods for disease classification detect patient-specific molecular fingerprints, but lack consistency and comprehension regarding cohort-wide features, which are an essential requirement for understanding pathogenic phenotypes across diverse atherosclerotic trajectories. Furthermore, understanding patient subtypes often considers clinical feature similarity in isolation, without integration of shared pathogenic interdependencies among patients. To address these challenges, we introduce ATHENA: Atherosclerosis Through Hierarchical Explainable Neural Network Analysis, which constructs a novel hierarchical network representation through integrated modality learning; subsequently, it optimizes learned patient-specific molecular fingerprints that reflect individual omics data, enforcing consistency with cohort-wide patterns. With a primary clinical dataset of 391 patients, we demonstrate that this heterogeneous alignment of clinical features with molecular interaction patterns has significantly boosted subclinical atherosclerosis classification performance across various baselines by up to 13% in area under the receiver operating curve (AUC) and 20% in F1 score. Taken together, ATHENA enables mechanistically-informed patient subtype discovery through explainable AI (XAI)-driven subnetwork clustering; this novel integration framework strengthens personalized intervention strategies, thereby improving the prediction of atherosclerotic disease progression and management of their clinical actionable outcomes.

Nithin Parthasarathy, James Soetedjo, Saarang Panchavati et al.

Amyotrophic lateral sclerosis (ALS), a progressive neuromuscular degenerative disease, severely restricts patient communication capacity within a few years of onset, resulting in a significant deterioration of quality of life. The P300 speller brain computer interface (BCI) offers an alternative communication medium by leveraging a subject's EEG response to characters traditionally highlighted on a character grid on a graphical user interface (GUI). A recurring theme in P300-based research is enhancing performance to enable faster subject interaction. This study builds on that theme by addressing key limitations, particularly in the training of multi-subject classifiers, and by integrating advanced language models to optimize stimuli presentation and word prediction, thereby improving communication efficiency. Furthermore, various advanced large language models such as Generative Pre-Trained Transformer (GPT2), BERT, and BART, alongside Dijkstra's algorithm, are utilized to optimize stimuli and provide word completion choices based on the spelling history. In addition, a multi-layered smoothing approach is applied to allow for out-of-vocabulary (OOV) words. By conducting extensive simulations based on randomly sampled EEG data from subjects, we show substantial speed improvements in typing passages that include rare and out-of-vocabulary (OOV) words, with the extent of improvement varying depending on the language model utilized. The gains through such character-level interface optimizations are approximately 10%, and GPT2 for multi-word prediction provides gains of around 40%. In particular, some large language models achieve performance levels within 10% of the theoretical performance limits established in this study. In addition, both within and across subjects, training techniques are explored, and speed improvements are shown to hold in both cases.

Haoyue Zhang, Jennifer S Polson, Kambiz Nael et al.

Treatment of acute ischemic strokes (AIS) is largely contingent upon the time since stroke onset (TSS). However, TSS may not be readily available in up to 25% of patients with unwitnessed AIS. Current clinical guidelines for patients with unknown TSS recommend the use of MRI to determine eligibility for thrombolysis, but radiology assessments have high inter-reader variability. In this work, we present deep learning models that leverage MRI diffusion series to classify TSS based on clinically validated thresholds. We propose an intra-domain task-adaptive transfer learning method, which involves training a model on an easier clinical task (stroke detection) and then refining the model with different binary thresholds of TSS. We apply this approach to both 2D and 3D CNN architectures with our top model achieving an ROC-AUC value of 0.74, with a sensitivity of 0.70 and a specificity of 0.81 for classifying TSS < 4.5 hours. Our pretrained models achieve better classification metrics than the models trained from scratch, and these metrics exceed those of previously published models applied to our dataset. Furthermore, our pipeline accommodates a more inclusive patient cohort than previous work, as we did not exclude imaging studies based on clinical, demographic, or image processing criteria. When applied to this broad spectrum of patients, our deep learning model achieves an overall accuracy of 75.78% when classifying TSS < 4.5 hours, carrying potential therapeutic implications for patients with unknown TSS.

Jiayun Li, Wenyuan Li, Anthony Sisk et al.

Histopathological images provide rich information for disease diagnosis. Large numbers of histopathological images have been digitized into high resolution whole slide images, opening opportunities in developing computational image analysis tools to reduce pathologists' workload and potentially improve inter- and intra- observer agreement. Most previous work on whole slide image analysis has focused on classification or segmentation of small pre-selected regions-of-interest, which requires fine-grained annotation and is non-trivial to extend for large-scale whole slide analysis. In this paper, we proposed a multi-resolution multiple instance learning model that leverages saliency maps to detect suspicious regions for fine-grained grade prediction. Instead of relying on expensive region- or pixel-level annotations, our model can be trained end-to-end with only slide-level labels. The model is developed on a large-scale prostate biopsy dataset containing 20,229 slides from 830 patients. The model achieved 92.7% accuracy, 81.8% Cohen's Kappa for benign, low grade (i.e. Grade group 1) and high grade (i.e. Grade group >= 2) prediction, an area under the receiver operating characteristic curve (AUROC) of 98.2% and an average precision (AP) of 97.4% for differentiating malignant and benign slides. The model obtained an AUROC of 99.4% and an AP of 99.8% for cancer detection on an external dataset.

Wenyuan Li, Zichen Wang, Yuguang Yue et al.

In this work, we investigate semi-supervised learning (SSL) for image classification using adversarial training. Previous results have illustrated that generative adversarial networks (GANs) can be used for multiple purposes. Triple-GAN, which aims to jointly optimize model components by incorporating three players, generates suitable image-label pairs to compensate for the lack of labeled data in SSL with improved benchmark performance. Conversely, Bad (or complementary) GAN, optimizes generation to produce complementary data-label pairs and force a classifier's decision boundary to lie between data manifolds. Although it generally outperforms Triple-GAN, Bad GAN is highly sensitive to the amount of labeled data used for training. Unifying these two approaches, we present unified-GAN (UGAN), a novel framework that enables a classifier to simultaneously learn from both good and bad samples through adversarial training. We perform extensive experiments on various datasets and demonstrate that UGAN: 1) achieves state-of-the-art performance among other deep generative models, and 2) is robust to variations in the amount of labeled data used for training.

Janaki Sheth, Ariel Tankus, Michelle Tran et al.

Brain-Computer Interfaces (BCI) help patients with faltering communication abilities due to neurodegenerative diseases produce text or speech output by direct neural processing. However, practical implementation of such a system has proven difficult due to limitations in speed, accuracy, and generalizability of the existing interfaces. To this end, we aim to create a BCI system that decodes text directly from neural signals. We implement a framework that initially isolates frequency bands in the input signal encapsulating differential information regarding production of various phonemic classes. These bands then form a feature set that feeds into an LSTM which discerns at each time point probability distributions across all phonemes uttered by a subject. Finally, these probabilities are fed into a particle filtering algorithm which incorporates prior knowledge of the English language to output text corresponding to the decoded word. Performance of this model on data obtained from six patients shows encouragingly high levels of accuracy at speeds and bit rates significantly higher than existing BCI communication systems. Further, in producing an output, our network abstains from constraining the reconstructed word to be from a given bag-of-words, unlike previous studies. The success of our proposed approach, offers promise for the employment of a BCI interface by patients in unfettered, naturalistic environments.

Jiayun Li, Wenyuan Li, Arkadiusz Gertych et al.

Histology review is often used as the `gold standard' for disease diagnosis. Computer aided diagnosis tools can potentially help improve current pathology workflows by reducing examination time and interobserver variability. Previous work in cancer grading has focused mainly on classifying pre-defined regions of interest (ROIs), or relied on large amounts of fine-grained labels. In this paper, we propose a two-stage attention-based multiple instance learning model for slide-level cancer grading and weakly-supervised ROI detection and demonstrate its use in prostate cancer. Compared with existing Gleason classification models, our model goes a step further by utilizing visualized saliency maps to select informative tiles for fine-grained grade classification. The model was primarily developed on a large-scale whole slide dataset consisting of 3,521 prostate biopsy slides with only slide-level labels from 718 patients. The model achieved state-of-the-art performance for prostate cancer grading with an accuracy of 85.11\% for classifying benign, low-grade (Gleason grade 3+3 or 3+4), and high-grade (Gleason grade 4+3 or higher) slides on an independent test set.

Wenyuan Li, Zichen Wang, Jiayun Li et al.

Recently, semi-supervised learning methods based on generative adversarial networks (GANs) have received much attention. Among them, two distinct approaches have achieved competitive results on a variety of benchmark datasets. Bad GAN learns a classifier with unrealistic samples distributed on the complement of the support of the input data. Conversely, Triple GAN consists of a three-player game that tries to leverage good generated samples to boost classification results. In this paper, we perform a comprehensive comparison of these two approaches on different benchmark datasets. We demonstrate their different properties on image generation, and sensitivity to the amount of labeled data provided. By comprehensively comparing these two methods, we hope to shed light on the future of GAN-based semi-supervised learning.