High-resolution volumetric computed tomography (CT) is essential for accurate diagnosis and treatment planning in thoracic diseases; however, it is limited by radiation dose and hardware costs. We present the Transformer Volumetric Super-Resolution Network (\textbf{TVSRN-V2}), a transformer-based super-resolution (SR) framework designed for practical deployment in clinical lung CT analysis. Built from scalable components, including Through-Plane Attention Blocks (TAB) and Swin Transformer V2 -- our model effectively reconstructs fine anatomical details in low-dose CT volumes and integrates seamlessly with downstream analysis pipelines. We evaluate its effectiveness on three critical lung cancer tasks -- lobe segmentation, radiomics, and prognosis -- across multiple clinical cohorts. To enhance robustness across variable acquisition protocols, we introduce pseudo-low-resolution augmentation, simulating scanner diversity without requiring private data. TVSRN-V2 demonstrates a significant improvement in segmentation accuracy (+4\% Dice), higher radiomic feature reproducibility, and enhanced predictive performance (+0.06 C-index and AUC). These results indicate that SR-driven recovery of structural detail significantly enhances clinical decision support, positioning TVSRN-V2 as a well-engineered, clinically viable system for dose-efficient imaging and quantitative analysis in real-world CT workflows.

Accurate segmentation of pheochromocytoma (PCC) in abdominal CT scans is essential for tumor burden estimation, prognosis, and treatment planning. It may also help infer genetic clusters, reducing reliance on expensive testing. This study systematically evaluates anatomical priors to identify configurations that improve deep learning-based PCC segmentation. We employed the nnU-Net framework to evaluate eleven annotation strategies for accurate 3D segmentation of pheochromocytoma, introducing a set of novel multi-class schemes based on organ-specific anatomical priors. These priors were derived from adjacent organs commonly surrounding adrenal tumors (e.g., liver, spleen, kidney, aorta, adrenal gland, and pancreas), and were compared against a broad body-region prior used in previous work. The framework was trained and tested on 105 contrast-enhanced CT scans from 91 patients at the NIH Clinical Center. Performance was measured using Dice Similarity Coefficient (DSC), Normalized Surface Distance (NSD), and instance-wise F1 score. Among all strategies, the Tumor + Kidney + Aorta (TKA) annotation achieved the highest segmentation accuracy, significantly outperforming the previously used Tumor + Body (TB) annotation across DSC (p = 0.0097), NSD (p = 0.0110), and F1 score (25.84% improvement at an IoU threshold of 0.5), measured on a 70-30 train-test split. The TKA model also showed superior tumor burden quantification (R^2 = 0.968) and strong segmentation across all genetic subtypes. In five-fold cross-validation, TKA consistently outperformed TB across IoU thresholds (0.1 to 0.5), reinforcing its robustness and generalizability. These findings highlight the value of incorporating relevant anatomical context in deep learning models to achieve precise PCC segmentation, supporting clinical assessment and longitudinal monitoring.

Medical image segmentation suffers from data scarcity, particularly in polyp detection where annotation requires specialized expertise. We present SynDiff, a framework combining text-guided synthetic data generation with efficient diffusion-based segmentation. Our approach employs latent diffusion models to generate clinically realistic synthetic polyps through text-conditioned inpainting, augmenting limited training data with semantically diverse samples. Unlike traditional diffusion methods requiring iterative denoising, we introduce direct latent estimation enabling single-step inference with T x computational speedup. On CVC-ClinicDB, SynDiff achieves 96.0% Dice and 92.9% IoU while maintaining real-time capability suitable for clinical deployment. The framework demonstrates that controlled synthetic augmentation improves segmentation robustness without distribution shift. SynDiff bridges the gap between data-hungry deep learning models and clinical constraints, offering an efficient solution for deployment in resourcelimited medical settings.

Interpretability is critical in high-stakes domains such as medical imaging, where understanding model decisions is essential for clinical adoption. In this work, we introduce Sparse Autoencoder (SAE)-based interpretability to breast imaging by analyzing {Mammo-CLIP}, a vision--language foundation model pretrained on large-scale mammogram image--report pairs. We train a patch-level \texttt{Mammo-SAE} on Mammo-CLIP to identify and probe latent features associated with clinically relevant breast concepts such as \textit{mass} and \textit{suspicious calcification}. Our findings reveal that top activated class level latent neurons in the SAE latent space often tend to align with ground truth regions, and also uncover several confounding factors influencing the model's decision-making process. Additionally, we analyze which latent neurons the model relies on during downstream finetuning for improving the breast concept prediction. This study highlights the promise of interpretable SAE latent representations in providing deeper insight into the internal workings of foundation models at every layer for breast imaging.

Classification between first episode psychosis (FEP) patients and healthy controls is of particular interest to the study of schizophrenia. However, predicting psychosis with cognitive assessments alone is prone to human errors and often lacks biological evidence to back up the findings. In this work, we combined a multimodal dataset of structural MRI and cognitive data to disentangle the detection of first-episode psychosis with a machine learning approach. For this purpose, we proposed a robust detection pipeline that explores the variables in high-order feature space. We applied the pipeline to Human Connectome Project for Early Psychosis (HCP-EP) dataset with 108 participants in EP and 47 controls. The pipeline demonstrated strong performance with 74.67% balanced accuracy on this task. Further feature analysis shows that the model is capable of identifying verified causative biological factors for the occurrence of psychosis based on volumetric MRI measurements, which suggests the potential of data-driven approaches for the search for neuroimaging biomarkers in future studies.

Dementia is a complex condition whose multifaceted nature poses significant challenges in the diagnosis, prognosis, and treatment of patients. Despite the availability of large open-source data fueling a wealth of promising research, effective translation of preclinical findings to clinical practice remains difficult. This barrier is largely due to the complexity of unstructured and disparate preclinical and clinical data, which traditional analytical methods struggle to handle. Novel analytical techniques involving Deep Learning (DL), however, are gaining significant traction in this regard. Here, we have investigated the potential of a cascaded multimodal DL-based system (TelDem), assessing the ability to integrate and analyze a large, heterogeneous dataset (n=7,159 patients), applied to three clinically relevant use cases. Using a Cascaded Multi-Modal Mixing Transformer (CMT), we assessed TelDems validity and (using a Cross-Modal Fusion Norm - CMFN) model explainability in (i) differential diagnosis between healthy individuals, AD, and three sub-types of frontotemporal lobar degeneration (ii) disease staging from healthy cognition to mild cognitive impairment (MCI) and AD, and (iii) predicting progression from MCI to AD. Our findings show that the CMT enhances diagnostic and prognostic accuracy when incorporating multimodal data compared to unimodal modeling and that cerebrospinal fluid (CSF) biomarkers play a key role in accurate model decision making. These results reinforce the power of DL technology in tapping deeper into already existing data, thereby accelerating preclinical dementia research by utilizing clinically relevant information to disentangle complex dementia pathophysiology.

The OncotypeDX 21-gene assay is a widely adopted tool for estimating recurrence risk and informing chemotherapy decisions in early-stage, hormone receptor-positive, HER2-negative breast cancer. Although informative, its high cost and long turnaround time limit accessibility and delay treatment in low- and middle-income countries, creating a need for alternative solutions. This study presents a deep learning-based approach for predicting OncotypeDX recurrence scores directly from hematoxylin and eosin-stained whole slide images. Our approach leverages a deep learning foundation model pre-trained on 171,189 slides via self-supervised learning, which is fine-tuned for our task. The model was developed and validated using five independent cohorts, out of which three are external. On the two external cohorts that include OncotypeDX scores, the model achieved an AUC of 0.825 and 0.817, and identified 21.9% and 25.1% of the patients as low-risk with sensitivity of 0.97 and 0.95 and negative predictive value of 0.97 and 0.96, showing strong generalizability despite variations in staining protocols and imaging devices. Kaplan-Meier analysis demonstrated that patients classified as low-risk by the model had a significantly better prognosis than those classified as high-risk, with a hazard ratio of 4.1 (P<0.001) and 2.0 (P<0.01) on the two external cohorts that include patient outcomes. This artificial intelligence-driven solution offers a rapid, cost-effective, and scalable alternative to genomic testing, with the potential to enhance personalized treatment planning, especially in resource-constrained settings.

Recent advances in Artificial Intelligence (AI) have started disrupting the healthcare industry, especially medical imaging, and AI devices are increasingly being deployed into clinical practice. Such classifiers have previously demonstrated the ability to discern a range of protected demographic attributes (like race, age, sex) from medical images with unexpectedly high performance, a sensitive task which is difficult even for trained physicians. In this study, we motivate and introduce a general explainable AI (XAI) framework called DREAM (DiscoveRing and Explaining AI Mechanisms) for interpreting how AI models trained on medical images predict protected attributes. Focusing on two modalities, radiology and dermatology, we are successfully able to train high-performing classifiers for predicting race from chest x-rays (ROC-AUC score of [~]0.96) and sex from dermoscopic lesions (ROC-AUC score of [~]0.78). We highlight how incorrect use of these demographic shortcuts can have a detrimental effect on the performance of a clinically relevant downstream task like disease diagnosis under a domain shift. Further, we employ various XAI techniques to identify specific signals which can be leveraged to predict sex. Finally, we propose a technique, which we callremoval via balancing, to quantify how much a signal contributes to the classification performance. Using this technique and the signals identified, we are able to explain [~]15% of the total performance for radiology and [~]42% of the total performance for dermatology. We envision DREAM to be broadly applicable to other modalities and demographic attributes. This analysis not only underscores the importance of cautious AI application in healthcare but also opens avenues for improving the transparency and reliability of AI-driven diagnostic tools.

Accurate segmentation of pheochromocytoma (PCC) in abdominal CT scans is essential for tumor burden estimation, prognosis, and treatment planning. It may also help infer genetic clusters, reducing reliance on expensive testing. This study systematically evaluates anatomical priors to identify configurations that improve deep learning-based PCC segmentation. We employed the nnU-Net framework to evaluate eleven annotation strategies for accurate 3D segmentation of pheochromocytoma, introducing a set of novel multi-class schemes based on organ-specific anatomical priors. These priors were derived from adjacent organs commonly surrounding adrenal tumors (e.g., liver, spleen, kidney, aorta, adrenal gland, and pancreas), and were compared against a broad body-region prior used in previous work. The framework was trained and tested on 105 contrast-enhanced CT scans from 91 patients at the NIH Clinical Center. Performance was measured using Dice Similarity Coefficient (DSC), Normalized Surface Distance (NSD), and instance-wise F1 score. Among all strategies, the Tumor + Kidney + Aorta (TKA) annotation achieved the highest segmentation accuracy, significantly outperforming the previously used Tumor + Body (TB) annotation across DSC (p = 0.0097), NSD (p = 0.0110), and F1 score (25.84% improvement at an IoU threshold of 0.5), measured on a 70-30 train-test split. The TKA model also showed superior tumor burden quantification (R^2 = 0.968) and strong segmentation across all genetic subtypes. In five-fold cross-validation, TKA consistently outperformed TB across IoU thresholds (0.1 to 0.5), reinforcing its robustness and generalizability. These findings highlight the value of incorporating relevant anatomical context into deep learning models to achieve precise PCC segmentation, offering a valuable tool to support clinical assessment and longitudinal disease monitoring in PCC patients.

Diffusion models have shown great promise in medical image denoising and reconstruction, but their application to Positron Emission Tomography (PET) imaging remains limited by tracer-specific contrast variability and high computational demands. In this work, we proposed an anatomical prior-guided PET image reconstruction method based on diffusion models, inspired by the deep diffusion image prior (DDIP) framework. The proposed method alternated between diffusion sampling and model fine-tuning guided by the PET sinogram, enabling the reconstruction of high-quality images from various PET tracers using a score function pretrained on a dataset of another tracer. To improve computational efficiency, the half-quadratic splitting (HQS) algorithm was adopted to decouple network optimization from iterative PET reconstruction. The proposed method was evaluated using one simulation and two clinical datasets. For the simulation study, a model pretrained on [$^{18}$F]FDG data was tested on amyloid-negative PET data to assess out-of-distribution (OOD) performance. For the clinical-data validation, ten low-dose [$^{18}$F]FDG datasets and one [$^{18}$F]Florbetapir dataset were tested on a model pretrained on data from another tracer. Experiment results show that the proposed PET reconstruction method can generalize robustly across tracer distributions and scanner types, providing an efficient and versatile reconstruction framework for low-dose PET imaging.