Lawrence H. Staib

Jiyao Wang, Peiyu Duan, Nicha C. Dvornek et al.

Functional magnetic resonance imaging (fMRI) is a powerful tool for investigating human brain function. However, the high cost of data acquisition and the inherent subjectivity of psychiatric rating scales often lead to datasets with small sample sizes and variable label quality, especially when targeting a specific neurological condition. Combined with the inherently high dimensionality of fMRI data, these limitations substantially increase the risk of model overfitting. Recent years have seen growing interest in developing fMRI foundation models by combining multiple datasets; however, the computational resources needed for pretraining and fine-tuning are often prohibitive. We show that a lightweight self-supervised framework yields representations that generalize across diverse downstream tasks, outperforming fully supervised baselines and approaching the performance of large-scale models. We introduce BrainSimSiam, a data-efficient self-supervised representation learning framework that leverages positive-only data pairs to learn robust and generalizable features. We demonstrate that the learned representations achieve strong performance across multiple downstream classification and regression tasks, highlighting the potential of BrainSimSiam for data-limited neuroimaging applications.

Junlin Yang, Tian Yu, Nicha C. Dvornek et al.

Hepatocellular carcinoma (HCC) is biologically heterogeneous, shaped by the interplay between hepatic functional reserve and tumor-related oncologic factors; thus, similar survival outcomes may reflect fundamentally different underlying biological processes. Prognostic modeling in HCC is informed by rich multimodal information from multiparametric MRI and radiology reports from routine clinical practice. Existing prognostic vision-language models (VLMs) learn a single entangled latent representation that blends hepatic and tumor-related factors, limiting both accuracy and biological interpretability. We present BioFact-MoE, a biologically factorized Mixture of Experts (MoE) framework that explicitly decomposes liver and tumor factors via biologically supervised experts within a residual MoE survival architecture. On a HCC cohort of N=588 patients (pretrained on 4,582 3D MRI image-report pairs), BioFact-MoE consistently improves survival prediction over all baselines across time horizons, achieving 12-, 18-, and 24-month AUCs of 75.33%, 75.85%, and 73.96%. Beyond scalar risk prediction, gated expert weights enable phenotype-aware risk stratification. Pathway-informed gating uncovers clinically meaningful treatment-associated survival heterogeneity. In held-out validation, hepatic and tumor embeddings show selective associations with liver function and tumor burden markers, respectively (p<0.05), without supervision. The code is available at https://github.com/jy-639/BioFact-MoE.

Jiyao Wang, Nicha C. Dvornek, Lawrence H. Staib et al.

Insufficiency of training data is a persistent issue in medical image analysis, especially for task-based functional magnetic resonance images (fMRI) with spatio-temporal imaging data acquired using specific cognitive tasks. In this paper, we propose an approach for generating synthetic fMRI sequences that can then be used to create augmented training datasets in downstream learning tasks. To synthesize high-resolution task-specific fMRI, we adapt the $α$-GAN structure, leveraging advantages of both GAN and variational autoencoder models, and propose different alternatives in aggregating temporal information. The synthetic images are evaluated from multiple perspectives including visualizations and an autism spectrum disorder (ASD) classification task. The results show that the synthetic task-based fMRI can provide effective data augmentation in learning the ASD classification task.

Peiyu Duan, Jiyao Wang, Nicha C. Dvornek et al.

Task-based fMRI provides a direct readout of task-evoked neural dynamics, but it is expensive and difficult to acquire at scale, motivating rest-to-task synthesis from widely available resting-state fMRI (rsfMRI). We propose FM-fMRI, an event-conditioned flow-matching model that learns a continuous-time conditional vector field to generate task ROI time series from a subject's rsfMRI and the task event information. The formulation enables fast ODE-based sampling and flexible conditioning over heterogeneous event schedules. Rather than optimizing for pointwise reconstruction, we evaluated generated signals using complementary criteria that probe temporal and spectral structure, subject and group-level connectome consistency, and distributional alignment. On the public Human Connectome Project and internal BioPoint autism cohort, FM-fMRI achieves the strongest spectral and connectivity agreement and improved distribution-level matching over conditional diffusion, generative adversarial networks (GANs), and variational autoencoders (VAEs) baselines. Furthermore, we augment the BioPoint cohort by synthesizing task-fMRI ROI time series with our method, improving downstream autism classification and demonstrating practical utility in data-limited clinical settings. The code will be available on GitHub.

Tal Zeevi, Eléonore V. Lieffrig, Lawrence H. Staib et al.

Uncertainty maps highlight unreliable regions in segmentation predictions. However, most uncertainty evaluation metrics treat voxels independently, ignoring spatial context and anatomical structure. As a result, they may assign identical scores to qualitatively distinct patterns (e.g., scattered vs. boundary-aligned uncertainty). We propose three spatially aware metrics that incorporate structural and boundary information and conduct a thorough validation on medical imaging data from the prostate zonal segmentation challenge within the Medical Segmentation Decathlon. Our results demonstrate improved alignment with clinically important factors and better discrimination between meaningful and spurious uncertainty patterns.

Tal Zeevi, Lawrence H. Staib, John A. Onofrey

Monte-Carlo (MC) Dropout provides a practical solution for estimating predictive distributions in deterministic neural networks. Traditional dropout, applied within the signal space, may fail to account for frequency-related noise common in medical imaging, leading to biased predictive estimates. A novel approach extends Dropout to the frequency domain, allowing stochastic attenuation of signal frequencies during inference. This creates diverse global textural variations in feature maps while preserving structural integrity -- a factor we hypothesize and empirically show is contributing to accurately estimating uncertainties in semantic segmentation. We evaluated traditional MC-Dropout and the MC-frequency Dropout in three segmentation tasks involving different imaging modalities: (i) prostate zones in biparametric MRI, (ii) liver tumors in contrast-enhanced CT, and (iii) lungs in chest X-ray scans. Our results show that MC-Frequency Dropout improves calibration, convergence, and semantic uncertainty, thereby improving prediction scrutiny, boundary delineation, and has the potential to enhance medical decision-making.

Xueqi Guo, Luyao Shi, Xiongchao Chen et al.

Inter-frame motion in dynamic cardiac positron emission tomography (PET) using rubidium-82 (82-Rb) myocardial perfusion imaging impacts myocardial blood flow (MBF) quantification and the diagnosis accuracy of coronary artery diseases. However, the high cross-frame distribution variation due to rapid tracer kinetics poses a considerable challenge for inter-frame motion correction, especially for early frames where intensity-based image registration techniques often fail. To address this issue, we propose a novel method called Temporally and Anatomically Informed Generative Adversarial Network (TAI-GAN) that utilizes an all-to-one mapping to convert early frames into those with tracer distribution similar to the last reference frame. The TAI-GAN consists of a feature-wise linear modulation layer that encodes channel-wise parameters generated from temporal information and rough cardiac segmentation masks with local shifts that serve as anatomical information. Our proposed method was evaluated on a clinical 82-Rb PET dataset, and the results show that our TAI-GAN can produce converted early frames with high image quality, comparable to the real reference frames. After TAI-GAN conversion, the motion estimation accuracy and subsequent myocardial blood flow (MBF) quantification with both conventional and deep learning-based motion correction methods were improved compared to using the original frames.

Xiaoran Zhang, Byung-Woo Hong, Hyoungseob Park et al.

We propose a model-agnostic, progressive test-time energy adaptation approach for medical image segmentation. Maintaining model performance across diverse medical datasets is challenging, as distribution shifts arise from inconsistent imaging protocols and patient variations. Unlike domain adaptation methods that require multiple passes through target data - impractical in clinical settings - our approach adapts pretrained models progressively as they process test data. Our method leverages a shape energy model trained on source data, which assigns an energy score at the patch level to segmentation maps: low energy represents in-distribution (accurate) shapes, while high energy signals out-of-distribution (erroneous) predictions. By minimizing this energy score at test time, we refine the segmentation model to align with the target distribution. To validate the effectiveness and adaptability, we evaluated our framework on eight public MRI (bSSFP, T1- and T2-weighted) and X-ray datasets spanning cardiac, spinal cord, and lung segmentation. We consistently outperform baselines both quantitatively and qualitatively.

Tal Zeevi, Ravid Shwartz-Ziv, Yann LeCun et al.

Accurate uncertainty estimation is crucial for deploying neural networks in risk-sensitive applications such as medical diagnosis. Monte Carlo Dropout is a widely used technique for approximating predictive uncertainty by performing stochastic forward passes with dropout during inference. However, using static dropout rates across all layers and inputs can lead to suboptimal uncertainty estimates, as it fails to adapt to the varying characteristics of individual inputs and network layers. Existing approaches optimize dropout rates during training using labeled data, resulting in fixed inference-time parameters that cannot adjust to new data distributions, compromising uncertainty estimates in Monte Carlo simulations. In this paper, we propose Rate-In, an algorithm that dynamically adjusts dropout rates during inference by quantifying the information loss induced by dropout in each layer's feature maps. By treating dropout as controlled noise injection and leveraging information-theoretic principles, Rate-In adapts dropout rates per layer and per input instance without requiring ground truth labels. By quantifying the functional information loss in feature maps, we adaptively tune dropout rates to maintain perceptual quality across diverse medical imaging tasks and architectural configurations. Our extensive empirical study on synthetic data and real-world medical imaging tasks demonstrates that Rate-In improves calibration and sharpens uncertainty estimates compared to fixed or heuristic dropout rates without compromising predictive performance. Rate-In offers a practical, unsupervised, inference-time approach to optimizing dropout for more reliable predictive uncertainty estimation in critical applications.

Jiyao Wang, Nicha C. Dvornek, Peiyu Duan et al.

Functional MRI measuring BOLD signal is an increasingly important imaging modality in studying brain functions and neurological disorders. It can be acquired in either a resting-state or a task-based paradigm. Compared to resting-state fMRI, task-based fMRI is acquired while the subject is performing a specific task designed to enhance study-related brain activities. Consequently, it generally has more informative task-dependent signals. However, due to the variety of task designs, it is much more difficult than in resting state to aggregate task-based fMRI acquired in different tasks to train a generalizable model. To resolve this complication, we propose a supervised task-aware network TA-GAT that jointly learns a general-purpose encoder and task-specific contextual information. The encoder-generated embedding and the learned contextual information are then combined as input to multiple modules for performing downstream tasks. We believe that the proposed task-aware architecture can plug-and-play in any neural network architecture to incorporate the prior knowledge of fMRI tasks into capturing functional brain patterns.

Jiyao Wang, Nicha C. Dvornek, Peiyu Duan et al.

In recent years, graph neural networks (GNNs) have been widely applied in the analysis of brain fMRI, yet defining the connectivity between ROIs remains a challenge in noisy fMRI data. Among all approaches, Functional Connectome (FC) is the most popular method. Computed by the correlation coefficients between ROI time series, FC is a powerful and computationally efficient way to estimate ROI connectivity. However, it is well known for neglecting structural connections and causality in ROI interactions. Also, FC becomes much more noisy in the short spatio-temporal sliding-window subsequences of fMRI. Effective Connectome (EC) is proposed as a directional alternative, but is difficult to accurately estimate. Furthermore, for optimal GNN performance, usually only a small percentage of the strongest connections are selected as sparse edges, resulting in oversimplification of complex brain connections. To tackle these challenges, we propose the Spatio-Temporal Node Attention Graph Neural Network (STNAGNN) as a data-driven alternative that combines sparse predefined FC with dense data-driven spatio-temporal connections, allowing for flexible and spatio-temporal learning of ROI interaction patterns.

Allen Lu, Nripesh Parajuli, Maria Zontak et al.

Reliable motion estimation and strain analysis using 3D+time echocardiography (4DE) for localization and characterization of myocardial injury is valuable for early detection and targeted interventions. However, motion estimation is difficult due to the low-SNR that stems from the inherent image properties of 4DE, and intelligent regularization is critical for producing reliable motion estimates. In this work, we incorporated the notion of domain adaptation into a supervised neural network regularization framework. We first propose an unsupervised autoencoder network with biomechanical constraints for learning a latent representation that is shown to have more physiologically plausible displacements. We extended this framework to include a supervised loss term on synthetic data and showed the effects of biomechanical constraints on the network's ability for domain adaptation. We validated both the autoencoder and semi-supervised regularization method on in vivo data with implanted sonomicrometers. Finally, we showed the ability of our semi-supervised learning regularization approach to identify infarcted regions using estimated regional strain maps with good agreement to manually traced infarct regions from postmortem excised hearts.

Nicha C. Dvornek, Daniel Yang, Archana Venkataraman et al.

Treating children with autism spectrum disorders (ASD) with behavioral interventions, such as Pivotal Response Treatment (PRT), has shown promise in recent studies. However, deciding which therapy is best for a given patient is largely by trial and error, and choosing an ineffective intervention results in loss of valuable treatment time. We propose predicting patient response to PRT from baseline task-based fMRI by the novel application of a random forest and tree bagging strategy. Our proposed learning pipeline uses random forest regression to determine candidate brain voxels that may be informative in predicting treatment response. The candidate voxels are then tested stepwise for inclusion in a bagged tree ensemble. After the predictive model is constructed, bias correction is performed to further increase prediction accuracy. Using data from 19 ASD children who underwent a 16 week trial of PRT and a leave-one-out cross-validation framework, the presented learning pipeline was tested against several standard methods and variations of the pipeline and resulted in the highest prediction accuracy.