Nicha C. Dvornek

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.

Leya Barrientos, Yuexi Du, Nicha C. Dvornek

Ultrasound is widely used in obstetric care due to its safety, accessibility, and real-time imaging. However, interpretation remains operator-dependent and susceptible to noise and artifacts. Deep learning models have shown strong performance to solve these problem, but they typically require large annotated datasets that are difficult to obtain in clinical ultrasound. Foundation models (FMs) offer an alternative, using a large number of ultrasound images to learn transferable representations that can generalize with limited labeled data. This work presents a comprehensive benchmark of ultrasound-specific FMs for fetal plane classification. We evaluated four ultrasound FMs (USFM, MOFO, UltraSAM, FetalCLIP) against two CNN baselines (ResNet50, EfficientNet-V2) and a ViT (DINOv3) pretrained on natural images. We trained all models under two complementary settings: full fine-tuning and linear probing with a frozen encoder. All models were trained using 5-fold patient-level cross-validation on a Spanish fetal ultrasound dataset and tested on both in-domain data and an external African cohort to assess cross-population generalization. We found that FetalCLIP achieved the best results in the linear probing setting (F1 = 0.9261 for in-domain, F1 = 0.9731 for out-of-domain), while USFM performed best in the full fine-tuning setting (F1 = 0.9476 for in-domain, F1 = 0.9515 for out-of-domain). MOFO and UltraSAM degraded most in both settings, underperforming natural image pretrained models in some cases. These findings highlight how the choice of pretrained model strongly affects fetal plane classification performance, since different pretraining objectives lead to different levels of transferability.

Chenyu You, Weicheng Dai, Fenglin Liu et al. · oxford

Recent studies on contrastive learning have achieved remarkable performance solely by leveraging few labels in the context of medical image segmentation. Existing methods mainly focus on instance discrimination and invariant mapping. However, they face three common pitfalls: (1) tailness: medical image data usually follows an implicit long-tail class distribution. Blindly leveraging all pixels in training hence can lead to the data imbalance issues, and cause deteriorated performance; (2) consistency: it remains unclear whether a segmentation model has learned meaningful and yet consistent anatomical features due to the intra-class variations between different anatomical features; and (3) diversity: the intra-slice correlations within the entire dataset have received significantly less attention. This motivates us to seek a principled approach for strategically making use of the dataset itself to discover similar yet distinct samples from different anatomical views. In this paper, we introduce a novel semi-supervised 2D medical image segmentation framework termed Mine yOur owN Anatomy (MONA), and make three contributions. First, prior work argues that every pixel equally matters to the model training; we observe empirically that this alone is unlikely to define meaningful anatomical features, mainly due to lacking the supervision signal. We show two simple solutions towards learning invariances - through the use of stronger data augmentations and nearest neighbors. Second, we construct a set of objectives that encourage the model to be capable of decomposing medical images into a collection of anatomical features in an unsupervised manner. Lastly, we both empirically and theoretically, demonstrate the efficacy of our MONA on three benchmark datasets with different labeled settings, achieving new state-of-the-art under different labeled semi-supervised settings.

Xueqi Guo, Luyao Shi, Xiongchao Chen et al.

The rapid tracer kinetics of rubidium-82 ($^{82}$Rb) and high variation of cross-frame distribution in dynamic cardiac positron emission tomography (PET) raise significant challenges for inter-frame motion correction, particularly for the early frames where conventional intensity-based image registration techniques are not applicable. Alternatively, a promising approach utilizes generative methods to handle the tracer distribution changes to assist existing registration methods. To improve frame-wise registration and parametric quantification, we propose a Temporally and Anatomically Informed Generative Adversarial Network (TAI-GAN) to transform the early frames into the late reference frame using an all-to-one mapping. Specifically, a feature-wise linear modulation layer encodes channel-wise parameters generated from temporal tracer kinetics information, and rough cardiac segmentations with local shifts serve as the anatomical information. We validated our proposed method on a clinical $^{82}$Rb PET dataset and found that our TAI-GAN can produce converted early frames with high image quality, comparable to the real reference frames. After TAI-GAN conversion, motion estimation accuracy and clinical myocardial blood flow (MBF) quantification were improved compared to using the original frames. Our code is published at https://github.com/gxq1998/TAI-GAN.

Yuexi Du, John Onofrey, Nicha C. Dvornek

Contrastive Language-Image Pre-training (CLIP) demonstrates strong potential in medical image analysis but requires substantial data and computational resources. Due to these restrictions, existing CLIP applications in medical imaging focus mainly on modalities like chest X-rays that have abundant image-report data available, leaving many other important modalities underexplored. Here, we propose one of the first adaptations of the full CLIP model to mammography, which presents significant challenges due to labeled data scarcity, high-resolution images with small regions of interest, and class-wise imbalance. We first develop a specialized supervision framework for mammography that leverages its multi-view nature. Furthermore, we design a symmetric local alignment module to better focus on detailed features in high-resolution images. Lastly, we incorporate a parameter-efficient fine-tuning approach for large language models pre-trained with medical knowledge to address data limitations. Our multi-view and multi-scale alignment (MaMA) method outperforms state-of-the-art baselines for three different tasks on two large real-world mammography datasets, EMBED and RSNA-Mammo, with only 52% model size compared with the largest baseline. The code is available at https://github.com/XYPB/MaMA

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.

Yinchi Zhou, Peiyu Duan, Yuexi Du et al.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that encompasses a wide variety of symptoms and degrees of impairment, which makes the diagnosis and treatment challenging. Functional magnetic resonance imaging (fMRI) has been extensively used to study brain activity in ASD, and machine learning methods have been applied to analyze resting state fMRI (rs-fMRI) data. However, fewer studies have explored the recent transformer-based models on rs-fMRI data. Given the superiority of transformer models in capturing long-range dependencies in sequence data, we have developed a transformer-based self-supervised framework that directly analyzes time-series fMRI data without computing functional connectivity. To address over-fitting in small datasets and enhance the model performance, we propose self-supervised pre-training tasks to reconstruct the randomly masked fMRI time-series data, investigating the effects of various masking strategies. We then finetune the model for the ASD classification task and evaluate it using two public datasets and five-fold cross-validation with different amounts of training data. The experiments show that randomly masking entire ROIs gives better model performance than randomly masking time points in the pre-training step, resulting in an average improvement of 10.8% for AUC and 9.3% for subject accuracy compared with the transformer model trained from scratch across different levels of training data availability. Our code is available on GitHub.

Xueqi Guo, Bo Zhou, David Pigg et al.

Subject motion in whole-body dynamic PET introduces inter-frame mismatch and seriously impacts parametric imaging. Traditional non-rigid registration methods are generally computationally intense and time-consuming. Deep learning approaches are promising in achieving high accuracy with fast speed, but have yet been investigated with consideration for tracer distribution changes or in the whole-body scope. In this work, we developed an unsupervised automatic deep learning-based framework to correct inter-frame body motion. The motion estimation network is a convolutional neural network with a combined convolutional long short-term memory layer, fully utilizing dynamic temporal features and spatial information. Our dataset contains 27 subjects each under a 90-min FDG whole-body dynamic PET scan. With 9-fold cross-validation, compared with both traditional and deep learning baselines, we demonstrated that the proposed network obtained superior performance in enhanced qualitative and quantitative spatial alignment between parametric $K_{i}$ and $V_{b}$ images and in significantly reduced parametric fitting error. We also showed the potential of the proposed motion correction method for impacting downstream analysis of the estimated parametric images, improving the ability to distinguish malignant from benign hypermetabolic regions of interest. Once trained, the motion estimation inference time of our proposed network was around 460 times faster than the conventional registration baseline, showing its potential to be easily applied in clinical settings.

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.

Nicha C. Dvornek, Catherine Sullivan, James S. Duncan et al.

The multifactorial etiology of autism spectrum disorder (ASD) suggests that its study would benefit greatly from multimodal approaches that combine data from widely varying platforms, e.g., neuroimaging, genetics, and clinical characterization. Prior neuroimaging-genetic analyses often apply naive feature concatenation approaches in data-driven work or use the findings from one modality to guide posthoc analysis of another, missing the opportunity to analyze the paired multimodal data in a truly unified approach. In this paper, we develop a more integrative model for combining genetic, demographic, and neuroimaging data. Inspired by the influence of genotype on phenotype, we propose using an attention-based approach where the genetic data guides attention to neuroimaging features of importance for model prediction. The genetic data is derived from copy number variation parameters, while the neuroimaging data is from functional magnetic resonance imaging. We evaluate the proposed approach on ASD classification and severity prediction tasks, using a sex-balanced dataset of 228 ASD and typically developing subjects in a 10-fold cross-validation framework. We demonstrate that our attention-based model combining genetic information, demographic data, and functional magnetic resonance imaging results in superior prediction performance compared to other multimodal approaches.

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.

Yuexi Du, Brian Chang, Nicha C. Dvornek

Recent advancements in Contrastive Language-Image Pre-training (CLIP) have demonstrated notable success in self-supervised representation learning across various tasks. However, the existing CLIP-like approaches often demand extensive GPU resources and prolonged training times due to the considerable size of the model and dataset, making them poor for medical applications, in which large datasets are not always common. Meanwhile, the language model prompts are mainly manually derived from labels tied to images, potentially overlooking the richness of information within training samples. We introduce a novel language-image Contrastive Learning method with an Efficient large language model and prompt Fine-Tuning (CLEFT) that harnesses the strengths of the extensive pre-trained language and visual models. Furthermore, we present an efficient strategy for learning context-based prompts that mitigates the gap between informative clinical diagnostic data and simple class labels. Our method demonstrates state-of-the-art performance on multiple chest X-ray and mammography datasets compared with various baselines. The proposed parameter efficient framework can reduce the total trainable model size by 39% and reduce the trainable language model to only 4% compared with the current BERT encoder.

Yuexi Du, Jinglu Wang, Shujie Liu et al.

Large visual language models (VLMs) have shown strong multi-modal medical reasoning ability, but most operate as end-to-end black boxes, diverging from clinicians' evidence-based, staged workflows and hindering clinical accountability. Complementarily, expert visual grounding models can accurately localize regions of interest (ROIs), providing explicit, reliable evidence that improves both reasoning accuracy and trust. In this paper, we introduce CARE, advancing Clinical Accountability in multi-modal medical Reasoning with an Evidence-grounded agentic framework. Unlike existing approaches that couple grounding and reasoning within a single generalist model, CARE decomposes the task into coordinated sub-modules to reduce shortcut learning and hallucination: a compact VLM proposes relevant medical entities; an expert entity-referring segmentation model produces pixel-level ROI evidence; and a grounded VLM reasons over the full image augmented by ROI hints. The VLMs are optimized with reinforcement learning with verifiable rewards to align answers with supporting evidence. Furthermore, a VLM coordinator plans tool invocation and reviews evidence-answer consistency, providing agentic control and final verification. Evaluated on standard medical VQA benchmarks, our CARE-Flow (coordinator-free) improves average accuracy by 10.9% over the same size (10B) state-of-the-art (SOTA). With dynamic planning and answer review, our CARE-Coord yields a further gain, outperforming the heavily pre-trained SOTA by 5.2%. Our experiments demonstrate that an agentic framework that emulates clinical workflows, incorporating decoupled specialized models and explicit evidence, yields more accurate and accountable medical AI.

Fuyao Chen, Yuexi Du, Elèonore V. Lieffrig et al.

Vision Transformers (ViTs) have gained rapid adoption in computational pathology for their ability to model long-range dependencies through self-attention, addressing the limitations of convolutional neural networks that excel at local pattern capture but struggle with global contextual reasoning. Recent pathology-specific foundation models have further advanced performance by leveraging large-scale pretraining. However, standard ViTs remain inherently non-equivariant to transformations such as rotations and reflections, which are ubiquitous variations in histopathology imaging. To address this limitation, we propose Equi-ViT, which integrates an equivariant convolution kernel into the patch embedding stage of a ViT architecture, imparting built-in rotational equivariance to learned representations. Equi-ViT achieves superior rotation-consistent patch embeddings and stable classification performance across image orientations. Our results on a public colorectal cancer dataset demonstrate that incorporating equivariant patch embedding enhances data efficiency and robustness, suggesting that equivariant transformers could potentially serve as more generalizable backbones for the application of ViT in histopathology, such as digital pathology foundation models.

Jiazhen Zhang, Yuexi Du, Nicha C. Dvornek et al.

Automated segmentation plays a pivotal role in medical image analysis and computer-assisted interventions. Despite the promising performance of existing methods based on convolutional neural networks (CNNs), they neglect useful equivariant properties for images, such as rotational and reflection equivariance. This limitation can decrease performance and lead to inconsistent predictions, especially in applications like vessel segmentation where explicit orientation is absent. While existing equivariant learning approaches attempt to mitigate these issues, they substantially increase learning cost, model size, or both. To overcome these challenges, we propose a novel application of an efficient symmetric rotation-equivariant (SRE) convolutional (SRE-Conv) kernel implementation to the U-Net architecture, to learn rotation and reflection-equivariant features, while also reducing the model size dramatically. We validate the effectiveness of our method through improved segmentation performance on retina vessel fundus imaging. Our proposed SRE U-Net not only significantly surpasses standard U-Net in handling rotated images, but also outperforms existing equivariant learning methods and does so with a reduced number of trainable parameters and smaller memory cost. The code is available at https://github.com/OnofreyLab/sre_conv_segm_isbi2025.

Yuexi Du, Jiazhen Zhang, Tal Zeevi et al.

Convolutional neural networks (CNNs) are essential tools for computer vision tasks, but they lack traditionally desired properties of extracted features that could further improve model performance, e.g., rotational equivariance. Such properties are ubiquitous in biomedical images, which often lack explicit orientation. While current work largely relies on data augmentation or explicit modules to capture orientation information, this comes at the expense of increased training costs or ineffective approximations of the desired equivariance. To overcome these challenges, we propose a novel and efficient implementation of the Symmetric Rotation-Equivariant (SRE) Convolution (SRE-Conv) kernel, designed to learn rotation-invariant features while simultaneously compressing the model size. The SRE-Conv kernel can easily be incorporated into any CNN backbone. We validate the ability of a deep SRE-CNN to capture equivariance to rotation using the public MedMNISTv2 dataset (16 total tasks). SRE-Conv-CNN demonstrated improved rotated image classification performance accuracy on all 16 test datasets in both 2D and 3D images, all while increasing efficiency with fewer parameters and reduced memory footprint. The code is available at https://github.com/XYPB/SRE-Conv.

Yuexi Du, Jiazhen Zhang, Nicha C. Dvornek et al.

Symmetry, where certain features remain invariant under geometric transformations, can often serve as a powerful prior in designing convolutional neural networks (CNNs). While conventional CNNs inherently support translational equivariance, extending this property to rotation and reflection has proven challenging, often forcing a compromise between equivariance, efficiency, and information loss. In this work, we introduce Gaussian Mixture Ring Convolution (GMR-Conv), an efficient convolution kernel that smooths radial symmetry using a mixture of Gaussian-weighted rings. This design mitigates discretization errors of circular kernels, thereby preserving robust rotation and reflection equivariance without incurring computational overhead. We further optimize both the space and speed efficiency of GMR-Conv via a novel parameterization and computation strategy, allowing larger kernels at an acceptable cost. Extensive experiments on eight classification and one segmentation datasets demonstrate that GMR-Conv not only matches conventional CNNs' performance but can also surpass it in applications with orientation-less data. GMR-Conv is also proven to be more robust and efficient than the state-of-the-art equivariant learning methods. Our work provides inspiring empirical evidence that carefully applied radial symmetry can alleviate the challenges of information loss, marking a promising advance in equivariant network architectures. The code is available at https://github.com/XYPB/GMR-Conv.

Markus D. Schirmer, Archana Venkataraman, Islem Rekik et al.

Large, open-source consortium datasets have spurred the development of new and increasingly powerful machine learning approaches in brain connectomics. However, one key question remains: are we capturing biologically relevant and generalizable information about the brain, or are we simply overfitting to the data? To answer this, we organized a scientific challenge, the Connectomics in NeuroImaging Transfer Learning Challenge (CNI-TLC), held in conjunction with MICCAI 2019. CNI-TLC included two classification tasks: (1) diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD) within a pre-adolescent cohort; and (2) transference of the ADHD model to a related cohort of Autism Spectrum Disorder (ASD) patients with an ADHD comorbidity. In total, 240 resting-state fMRI time series averaged according to three standard parcellation atlases, along with clinical diagnosis, were released for training and validation (120 neurotypical controls and 120 ADHD). We also provided demographic information of age, sex, IQ, and handedness. A second set of 100 subjects (50 neurotypical controls, 25 ADHD, and 25 ASD with ADHD comorbidity) was used for testing. Models were submitted in a standardized format as Docker images through ChRIS, an open-source image analysis platform. Utilizing an inclusive approach, we ranked the methods based on 16 different metrics. The final rank was calculated using the rank product for each participant across all measures. Furthermore, we assessed the calibration curves of each method. Five participants submitted their model for evaluation, with one outperforming all other methods in both ADHD and ASD classification. However, further improvements are needed to reach the clinical translation of functional connectomics. We are keeping the CNI-TLC open as a publicly available resource for developing and validating new classification methodologies in the field of connectomics.

Juntang Zhuang, Nicha C. Dvornek, Xiaoxiao Li et al.

Deep neural networks are vulnerable to adversarial attacks and hard to interpret because of their black-box nature. The recently proposed invertible network is able to accurately reconstruct the inputs to a layer from its outputs, thus has the potential to unravel the black-box model. An invertible network classifier can be viewed as a two-stage model: (1) invertible transformation from input space to the feature space; (2) a linear classifier in the feature space. We can determine the decision boundary of a linear classifier in the feature space; since the transform is invertible, we can invert the decision boundary from the feature space to the input space. Furthermore, we propose to determine the projection of a data point onto the decision boundary, and define explanation as the difference between data and its projection. Finally, we propose to locally approximate a neural network with its first-order Taylor expansion, and define feature importance using a local linear model. We provide the implementation of our method: \url{https://github.com/juntang-zhuang/explain_invertible}.

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.

Mingquan Lin, Gregory Holste, Song Wang et al.

The CXR-LT series is a community-driven initiative designed to enhance lung disease classification using chest X-rays (CXR). It tackles challenges in open long-tailed lung disease classification and enhances the measurability of state-of-the-art techniques. The first event, CXR-LT 2023, aimed to achieve these goals by providing high-quality benchmark CXR data for model development and conducting comprehensive evaluations to identify ongoing issues impacting lung disease classification performance. Building on the success of CXR-LT 2023, the CXR-LT 2024 expands the dataset to 377,110 chest X-rays (CXRs) and 45 disease labels, including 19 new rare disease findings. It also introduces a new focus on zero-shot learning to address limitations identified in the previous event. Specifically, CXR-LT 2024 features three tasks: (i) long-tailed classification on a large, noisy test set, (ii) long-tailed classification on a manually annotated "gold standard" subset, and (iii) zero-shot generalization to five previously unseen disease findings. This paper provides an overview of CXR-LT 2024, detailing the data curation process and consolidating state-of-the-art solutions, including the use of multimodal models for rare disease detection, advanced generative approaches to handle noisy labels, and zero-shot learning strategies for unseen diseases. Additionally, the expanded dataset enhances disease coverage to better represent real-world clinical settings, offering a valuable resource for future research. By synthesizing the insights and innovations of participating teams, we aim to advance the development of clinically realistic and generalizable diagnostic models for chest radiography.

Fuyao Chen, Yuexi Du, Tal Zeevi et al.

Histopathology evaluation of tissue specimens through microscopic examination is essential for accurate disease diagnosis and prognosis. However, traditional manual analysis by specially trained pathologists is time-consuming, labor-intensive, cost-inefficient, and prone to inter-rater variability, potentially affecting diagnostic consistency and accuracy. As digital pathology images continue to proliferate, there is a pressing need for automated analysis to address these challenges. Recent advancements in artificial intelligence-based tools such as machine learning (ML) models, have significantly enhanced the precision and efficiency of analyzing histopathological slides. However, despite their impressive performance, ML models are invariant only to translation, lacking invariance to rotation and reflection. This limitation restricts their ability to generalize effectively, particularly in histopathology, where images intrinsically lack meaningful orientation. In this study, we develop robust, equivariant histopathological biomarkers through a novel symmetric convolutional kernel via unsupervised segmentation. The approach is validated using prostate tissue micro-array (TMA) images from 50 patients in the Gleason 2019 Challenge public dataset. The biomarkers extracted through this approach demonstrate enhanced robustness and generalizability against rotation compared to models using standard convolution kernels, holding promise for enhancing the accuracy, consistency, and robustness of ML models in digital pathology. Ultimately, this work aims to improve diagnostic and prognostic capabilities of histopathology beyond prostate cancer through equivariant imaging.

Yinchi Zhou, Liang Guo, Huidong Xie et al.

Rb-82 dynamic cardiac PET imaging is widely used for the clinical diagnosis of coronary artery disease (CAD), but its short half-life results in high noise levels that degrade dynamic frame quality and parametric imaging. The lack of paired clean-noisy training data, rapid tracer kinetics, and frame-dependent noise variations further limit the effectiveness of existing deep learning denoising methods. We propose DECADE (A Temporally-Consistent Unsupervised Diffusion model for Enhanced Rb-82 CArdiac PET DEnoising), an unsupervised diffusion framework that generalizes across early- to late-phase dynamic frames. DECADE incorporates temporal consistency during both training and iterative sampling, using noisy frames as guidance to preserve quantitative accuracy. The method was trained and evaluated on datasets acquired from Siemens Vision 450 and Siemens Biograph Vision Quadra scanners. On the Vision 450 dataset, DECADE consistently produced high-quality dynamic and parametric images with reduced noise while preserving myocardial blood flow (MBF) and myocardial flow reserve (MFR). On the Quadra dataset, using 15%-count images as input and full-count images as reference, DECADE outperformed UNet-based and other diffusion models in image quality and K1/MBF quantification. The proposed framework enables effective unsupervised denoising of Rb-82 dynamic cardiac PET without paired training data, supporting clearer visualization while maintaining quantitative integrity.

Rui Wang, Yuexi Du, John Lewin et al.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) plays an important role in breast cancer screening, tumor assessment, and treatment planning and monitoring. The dynamic changes in contrast in different tissues help to highlight the tumor in post-contrast images. However, varying acquisition protocols and individual factors result in large variation in the appearance of tissues, even for images acquired in the same phase (e.g., first post-contrast phase), making automated tumor segmentation challenging. Here, we propose a tumor segmentation method that leverages knowledge of the image acquisition time to modulate model features according to the specific acquisition sequence. We incorporate the acquisition times using feature-wise linear modulation (FiLM) layers, a lightweight method for incorporating temporal information that also allows for capitalizing on the full, variables number of images acquired per imaging study. We trained baseline and different configurations for the time-modulated models with varying backbone architectures on a large public multisite breast DCE-MRI dataset. Evaluation on in-domain images and a public out-of-domain dataset showed that incorporating knowledge of phase acquisition time improved tumor segmentation performance and model generalization.

Yuexi Du, Lihui Chen, Nicha C. Dvornek

Mammography screening is an essential tool for early detection of breast cancer. The speed and accuracy of mammography interpretation have the potential to be improved with deep learning methods. However, the development of a foundation visual language model (VLM) is hindered by limited data and domain differences between natural and medical images. Existing mammography VLMs, adapted from natural images, often ignore domain-specific characteristics, such as multi-view relationships in mammography. Unlike radiologists who analyze both views together to process ipsilateral correspondence, current methods treat them as independent images or do not properly model the multi-view correspondence learning, losing critical geometric context and resulting in suboptimal prediction. We propose GLAM: Global and Local Alignment for Multi-view mammography for VLM pretraining using geometry guidance. By leveraging the prior knowledge about the multi-view imaging process of mammograms, our model learns local cross-view alignments and fine-grained local features through joint global and local, visual-visual, and visual-language contrastive learning. Pretrained on EMBED [14], one of the largest open mammography datasets, our model outperforms baselines across multiple datasets under different settings.

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.

Yinchi Zhou, Tianqi Chen, Jun Hou et al.

Image-to-image translation is a vital component in medical imaging processing, with many uses in a wide range of imaging modalities and clinical scenarios. Previous methods include Generative Adversarial Networks (GANs) and Diffusion Models (DMs), which offer realism but suffer from instability and lack uncertainty estimation. Even though both GAN and DM methods have individually exhibited their capability in medical image translation tasks, the potential of combining a GAN and DM to further improve translation performance and to enable uncertainty estimation remains largely unexplored. In this work, we address these challenges by proposing a Cascade Multi-path Shortcut Diffusion Model (CMDM) for high-quality medical image translation and uncertainty estimation. To reduce the required number of iterations and ensure robust performance, our method first obtains a conditional GAN-generated prior image that will be used for the efficient reverse translation with a DM in the subsequent step. Additionally, a multi-path shortcut diffusion strategy is employed to refine translation results and estimate uncertainty. A cascaded pipeline further enhances translation quality, incorporating residual averaging between cascades. We collected three different medical image datasets with two sub-tasks for each dataset to test the generalizability of our approach. Our experimental results found that CMDM can produce high-quality translations comparable to state-of-the-art methods while providing reasonable uncertainty estimations that correlate well with the translation error.

Yuexi Du, Regina J. Hooley, John Lewin et al.

Digital Breast Tomosynthesis (DBT) is a widely used medical imaging modality for breast cancer screening and diagnosis, offering higher spatial resolution and greater detail through its 3D-like breast volume imaging capability. However, the increased data volume also introduces pronounced data imbalance challenges, where only a small fraction of the volume contains suspicious tissue. This further exacerbates the data imbalance due to the case-level distribution in real-world data and leads to learning a trivial classification model that only predicts the majority class. To address this, we propose a novel method using view-level contrastive Self-supervised Initialization and Fine-Tuning for identifying abnormal DBT images, namely SIFT-DBT. We further introduce a patch-level multi-instance learning method to preserve spatial resolution. The proposed method achieves 92.69% volume-wise AUC on an evaluation of 970 unique studies.

Xueqi Guo, Sule Tinaz, Nicha C. Dvornek

Parkinson's disease (PD) is a common and complex neurodegenerative disorder with 5 stages in the Hoehn and Yahr scaling. Given the heterogeneity of PD, it is challenging to classify early stages 1 and 2 and detect brain function alterations. Functional magnetic resonance imaging (fMRI) is a promising tool in revealing functional connectivity (FC) differences and developing biomarkers in PD. Some machine learning approaches like support vector machine and logistic regression have been successfully applied in the early diagnosis of PD using fMRI data, which outperform classifiers based on manually selected morphological features. However, the early-stage characterization in FC changes has not been fully investigated. Given the complexity and non-linearity of fMRI data, we propose the use of a long short-term memory (LSTM) network to characterize the early stages of PD. The study included 84 subjects (56 in stage 2 and 28 in stage 1) from the Parkinson's Progression Markers Initiative (PPMI), the largest available public PD dataset. Under a repeated 10-fold stratified cross-validation, the LSTM model reached an accuracy of 71.63%, 13.52% higher than the best traditional machine learning method, indicating significantly better robustness and accuracy compared with other machine learning classifiers. We used the learned LSTM model weights to select the top brain regions that contributed to model prediction and performed FC analyses to characterize functional changes with disease stage and motor impairment to gain better insight into the brain mechanisms of PD.

Shiyu Wang, Nicha C. Dvornek

Traditional regression models do not generalize well when learning from small and noisy datasets. Here we propose a novel metamodel structure to improve the regression result. The metamodel is composed of multiple classification base models and a regression model built upon the base models. We test this structure on the prediction of autism spectrum disorder (ASD) severity as measured by the ADOS communication (ADOS COMM) score from resting-state fMRI data, using a variety of base models. The metamodel outperforms traditional regression models as measured by the Pearson correlation coefficient between true and predicted scores and stability. In addition, we found that the metamodel is more flexible and more generalizable.

Nicha C. Dvornek, Pamela Ventola, James S. Duncan

We propose a method for estimating more reproducible functional networks that are more strongly associated with dynamic task activity by using recurrent neural networks with long short term memory (LSTMs). The LSTM model is trained in an unsupervised manner to learn to generate the functional magnetic resonance imaging (fMRI) time-series data in regions of interest. The learned functional networks can then be used for further analysis, e.g., correlation analysis to determine functional networks that are strongly associated with an fMRI task paradigm. We test our approach and compare to other methods for decomposing functional networks from fMRI activity on 2 related but separate datasets that employ a biological motion perception task. We demonstrate that the functional networks learned by the LSTM model are more strongly associated with the task activity and dynamics compared to other approaches. Furthermore, the patterns of network association are more closely replicated across subjects within the same dataset as well as across datasets. More reproducible functional networks are essential for better characterizing the neural correlates of a target task.

Nicha C. Dvornek, Xiaoxiao Li, Juntang Zhuang et al.

Heterogeneous presentation of a neurological disorder suggests potential differences in the underlying pathophysiological changes that occur in the brain. We propose to model heterogeneous patterns of functional network differences using a demographic-guided attention (DGA) mechanism for recurrent neural network models for prediction from functional magnetic resonance imaging (fMRI) time-series data. The context computed from the DGA head is used to help focus on the appropriate functional networks based on individual demographic information. We demonstrate improved classification on 3 subsets of the ABIDE I dataset used in published studies that have previously produced state-of-the-art results, evaluating performance under a leave-one-site-out cross-validation framework for better generalizeability to new data. Finally, we provide examples of interpreting functional network differences based on individual demographic variables.

Juntang Zhuang, Nicha C. Dvornek, Sekhar Tatikonda et al.

Neural ordinary differential equations (Neural ODEs) are a new family of deep-learning models with continuous depth. However, the numerical estimation of the gradient in the continuous case is not well solved: existing implementations of the adjoint method suffer from inaccuracy in reverse-time trajectory, while the naive method and the adaptive checkpoint adjoint method (ACA) have a memory cost that grows with integration time. In this project, based on the asynchronous leapfrog (ALF) solver, we propose the Memory-efficient ALF Integrator (MALI), which has a constant memory cost \textit{w.r.t} number of solver steps in integration similar to the adjoint method, and guarantees accuracy in reverse-time trajectory (hence accuracy in gradient estimation). We validate MALI in various tasks: on image recognition tasks, to our knowledge, MALI is the first to enable feasible training of a Neural ODE on ImageNet and outperform a well-tuned ResNet, while existing methods fail due to either heavy memory burden or inaccuracy; for time series modeling, MALI significantly outperforms the adjoint method; and for continuous generative models, MALI achieves new state-of-the-art performance. We provide a pypi package at \url{https://jzkay12.github.io/TorchDiffEqPack/}

Xiaoxiao Li, Yuan Zhou, Nicha C. Dvornek et al.

Understanding how certain brain regions relate to a specific neurological disorder has been an important area of neuroimaging research. A promising approach to identify the salient regions is using Graph Neural Networks (GNNs), which can be used to analyze graph structured data, e.g. brain networks constructed by functional magnetic resonance imaging (fMRI). We propose an interpretable GNN framework with a novel salient region selection mechanism to determine neurological brain biomarkers associated with disorders. Specifically, we design novel regularized pooling layers that highlight salient regions of interests (ROIs) so that we can infer which ROIs are important to identify a certain disease based on the node pooling scores calculated by the pooling layers. Our proposed framework, Pooling Regularized-GNN (PR-GNN), encourages reasonable ROI-selection and provides flexibility to preserve either individual- or group-level patterns. We apply the PR-GNN framework on a Biopoint Autism Spectral Disorder (ASD) fMRI dataset. We investigate different choices of the hyperparameters and show that PR-GNN outperforms baseline methods in terms of classification accuracy. The salient ROI detection results show high correspondence with the previous neuroimaging-derived biomarkers for ASD.

Junlin Yang, Nicha C. Dvornek, Fan Zhang et al.

This work proposes a pipeline to predict treatment response to intra-arterial therapy of patients with Hepatocellular Carcinoma (HCC) for improved therapeutic decision-making. Our graph neural network model seamlessly combines heterogeneous inputs of baseline MR scans, pre-treatment clinical information, and planned treatment characteristics and has been validated on patients with HCC treated by transarterial chemoembolization (TACE). It achieves Accuracy of $0.713 \pm 0.075$, F1 of $0.702 \pm 0.082$ and AUC of $0.710 \pm 0.108$. In addition, the pipeline incorporates uncertainty estimation to select hard cases and most align with the misclassified cases. The proposed pipeline arrives at more informed intra-arterial therapeutic decisions for patients with HCC via improving model accuracy and incorporating uncertainty estimation.

Nicha C. Dvornek, Xiaoxiao Li, Juntang Zhuang et al.

Recurrent neural networks (RNNs) were designed for dealing with time-series data and have recently been used for creating predictive models from functional magnetic resonance imaging (fMRI) data. However, gathering large fMRI datasets for learning is a difficult task. Furthermore, network interpretability is unclear. To address these issues, we utilize multitask learning and design a novel RNN-based model that learns to discriminate between classes while simultaneously learning to generate the fMRI time-series data. Employing the long short-term memory (LSTM) structure, we develop a discriminative model based on the hidden state and a generative model based on the cell state. The addition of the generative model constrains the network to learn functional communities represented by the LSTM nodes that are both consistent with the data generation as well as useful for the classification task. We apply our approach to the classification of subjects with autism vs. healthy controls using several datasets from the Autism Brain Imaging Data Exchange. Experiments show that our jointly discriminative and generative model improves classification learning while also producing robust and meaningful functional communities for better model understanding.

Junlin Yang, Nicha C. Dvornek, Fan Zhang et al.

Domain Adaptation (DA) has the potential to greatly help the generalization of deep learning models. However, the current literature usually assumes to transfer the knowledge from the source domain to a specific known target domain. Domain Agnostic Learning (DAL) proposes a new task of transferring knowledge from the source domain to data from multiple heterogeneous target domains. In this work, we propose the Domain-Agnostic Learning framework with Anatomy-Consistent Embedding (DALACE) that works on both domain-transfer and task-transfer to learn a disentangled representation, aiming to not only be invariant to different modalities but also preserve anatomical structures for the DA and DAL tasks in cross-modality liver segmentation. We validated and compared our model with state-of-the-art methods, including CycleGAN, Task Driven Generative Adversarial Network (TD-GAN), and Domain Adaptation via Disentangled Representations (DADR). For the DA task, our DALACE model outperformed CycleGAN, TD-GAN ,and DADR with DSC of 0.847 compared to 0.721, 0.793 and 0.806. For the DAL task, our model improved the performance with DSC of 0.794 from 0.522, 0.719 and 0.742 by CycleGAN, TD-GAN, and DADR. Further, we visualized the success of disentanglement, which added human interpretability of the learned meaningful representations. Through ablation analysis, we specifically showed the concrete benefits of disentanglement for downstream tasks and the role of supervision for better disentangled representation with segmentation consistency to be invariant to domains with the proposed Domain-Agnostic Module (DAM) and to preserve anatomical information with the proposed Anatomy-Preserving Module (APM).

Xiaoxiao Li, Nicha C. Dvornek, Juntang Zhuang et al.

Significant progress has been made using fMRI to characterize the brain changes that occur in ASD, a complex neuro-developmental disorder. However, due to the high dimensionality and low signal-to-noise ratio of fMRI, embedding informative and robust brain regional fMRI representations for both graph-level classification and region-level functional difference detection tasks between ASD and healthy control (HC) groups is difficult. Here, we model the whole brain fMRI as a graph, which preserves geometrical and temporal information and use a Graph Neural Network (GNN) to learn from the graph-structured fMRI data. We investigate the potential of including mutual information (MI) loss (Infomax), which is an unsupervised term encouraging large MI of each nodal representation and its corresponding graph-level summarized representation to learn a better graph embedding. Specifically, this work developed a pipeline including a GNN encoder, a classifier and a discriminator, which forces the encoded nodal representations to both benefit classification and reveal the common nodal patterns in a graph. We simultaneously optimize graph-level classification loss and Infomax. We demonstrated that Infomax graph embedding improves classification performance as a regularization term. Furthermore, we found separable nodal representations of ASD and HC groups in prefrontal cortex, cingulate cortex, visual regions, and other social, emotional and execution related brain regions. In contrast with GNN with classification loss only, the proposed pipeline can facilitate training more robust ASD classification models. Moreover, the separable nodal representations can detect the functional differences between the two groups and contribute to revealing new ASD biomarkers.

Junlin Yang, Nicha C. Dvornek, Fan Zhang et al.

A deep learning model trained on some labeled data from a certain source domain generally performs poorly on data from different target domains due to domain shifts. Unsupervised domain adaptation methods address this problem by alleviating the domain shift between the labeled source data and the unlabeled target data. In this work, we achieve cross-modality domain adaptation, i.e. between CT and MRI images, via disentangled representations. Compared to learning a one-to-one mapping as the state-of-art CycleGAN, our model recovers a many-to-many mapping between domains to capture the complex cross-domain relations. It preserves semantic feature-level information by finding a shared content space instead of a direct pixelwise style transfer. Domain adaptation is achieved in two steps. First, images from each domain are embedded into two spaces, a shared domain-invariant content space and a domain-specific style space. Next, the representation in the content space is extracted to perform a task. We validated our method on a cross-modality liver segmentation task, to train a liver segmentation model on CT images that also performs well on MRI. Our method achieved Dice Similarity Coefficient (DSC) of 0.81, outperforming a CycleGAN-based method of 0.72. Moreover, our model achieved good generalization to joint-domain learning, in which unpaired data from different modalities are jointly learned to improve the segmentation performance on each individual modality. Lastly, under a multi-modal target domain with significant diversity, our approach exhibited the potential for diverse image generation and remained effective with DSC of 0.74 on multi-phasic MRI while the CycleGAN-based method performed poorly with a DSC of only 0.52.

Juntang Zhuang, Nicha C. Dvornek, Xiaoxiao Li et al.

Determining biomarkers for autism spectrum disorder (ASD) is crucial to understanding its mechanisms. Recently deep learning methods have achieved success in the classification task of ASD using fMRI data. However, due to the black-box nature of most deep learning models, it's hard to perform biomarker selection and interpret model decisions. The recently proposed invertible networks can accurately reconstruct the input from its output, and have the potential to unravel the black-box representation. Therefore, we propose a novel method to classify ASD and identify biomarkers for ASD using the connectivity matrix calculated from fMRI as the input. Specifically, with invertible networks, we explicitly determine the decision boundary and the projection of data points onto the boundary. Like linear classifiers, the difference between a point and its projection onto the decision boundary can be viewed as the explanation. We then define the importance as the explanation weighted by the gradient of prediction $w.r.t$ the input, and identify biomarkers based on this importance measure. We perform a regression task to further validate our biomarker selection: compared to using all edges in the connectivity matrix, using the top 10\% important edges we generate a lower regression error on 6 different severity scores. Our experiments show that the invertible network is both effective at ASD classification and interpretable, allowing for discovery of reliable biomarkers.

Xiaoxiao Li, Nicha C. Dvornek, Yuan Zhou et al.

Finding the biomarkers associated with ASD is helpful for understanding the underlying roots of the disorder and can lead to earlier diagnosis and more targeted treatment. A promising approach to identify biomarkers is using Graph Neural Networks (GNNs), which can be used to analyze graph structured data, i.e. brain networks constructed by fMRI. One way to interpret important features is through looking at how the classification probability changes if the features are occluded or replaced. The major limitation of this approach is that replacing values may change the distribution of the data and lead to serious errors. Therefore, we develop a 2-stage pipeline to eliminate the need to replace features for reliable biomarker interpretation. Specifically, we propose an inductive GNN to embed the graphs containing different properties of task-fMRI for identifying ASD and then discover the brain regions/sub-graphs used as evidence for the GNN classifier. We first show GNN can achieve high accuracy in identifying ASD. Next, we calculate the feature importance scores using GNN and compare the interpretation ability with Random Forest. Finally, we run with different atlases and parameters, proving the robustness of the proposed method. The detected biomarkers reveal their association with social behaviors. We also show the potential of discovering new informative biomarkers. Our pipeline can be generalized to other graph feature importance interpretation problems.

Xiaoxiao Li, Nicha C. Dvornek, Yuan Zhou et al.

Discovering imaging biomarkers for autism spectrum disorder (ASD) is critical to help explain ASD and predict or monitor treatment outcomes. Toward this end, deep learning classifiers have recently been used for identifying ASD from functional magnetic resonance imaging (fMRI) with higher accuracy than traditional learning strategies. However, a key challenge with deep learning models is understanding just what image features the network is using, which can in turn be used to define the biomarkers. Current methods extract biomarkers, i.e., important features, by looking at how the prediction changes if "ignoring" one feature at a time. In this work, we go beyond looking at only individual features by using Shapley value explanation (SVE) from cooperative game theory. Cooperative game theory is advantageous here because it directly considers the interaction between features and can be applied to any machine learning method, making it a novel, more accurate way of determining instance-wise biomarker importance from deep learning models. A barrier to using SVE is its computational complexity: $2^N$ given $N$ features. We explicitly reduce the complexity of SVE computation by two approaches based on the underlying graph structure of the input data: 1) only consider the centralized coalition of each feature; 2) a hierarchical pipeline which first clusters features into small communities, then applies SVE in each community. Monte Carlo approximation can be used for large permutation sets. We first validate our methods on the MNIST dataset and compare to human perception. Next, to insure plausibility of our biomarker results, we train a Random Forest (RF) to classify ASD/control subjects from fMRI and compare SVE results to standard RF-based feature importance. Finally, we show initial results on ranked fMRI biomarkers using SVE on a deep learning classifier for the ASD/control dataset.

Xiaoxiao Li, Nicha C. Dvornek, Juntang Zhuang et al.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Finding the biomarkers associated with ASD is extremely helpful to understand the underlying roots of the disorder and can lead to earlier diagnosis and more targeted treatment. Although Deep Neural Networks (DNNs) have been applied in functional magnetic resonance imaging (fMRI) to identify ASD, understanding the data-driven computational decision making procedure has not been previously explored. Therefore, in this work, we address the problem of interpreting reliable biomarkers associated with identifying ASD; specifically, we propose a 2-stage method that classifies ASD and control subjects using fMRI images and interprets the saliency features activated by the classifier. First, we trained an accurate DNN classifier. Then, for detecting the biomarkers, different from the DNN visualization works in computer vision, we take advantage of the anatomical structure of brain fMRI and develop a frequency-normalized sampling method to corrupt images. Furthermore, in the ASD vs. control subjects classification scenario, we provide a new approach to detect and characterize important brain features into three categories. The biomarkers we found by the proposed method are robust and consistent with previous findings in the literature. We also validate the detected biomarkers by neurological function decoding and comparing with the DNN activation maps.

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.