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.

Accurate and efficient simulation of wave equations is crucial in computational wave imaging applications, such as ultrasound computed tomography (USCT), which reconstructs tissue material properties from observed scattered waves. Traditional numerical solvers for wave equations are computationally intensive and often unstable, limiting their practical applications for quasi-real-time image reconstruction. Neural operators offer an innovative approach by accelerating PDE solving using neural networks; however, their effectiveness in realistic imaging is limited because existing datasets oversimplify real-world complexity. In this paper, we present OpenBreastUS, a large-scale wave equation dataset designed to bridge the gap between theoretical equations and practical imaging applications. OpenBreastUS includes 8,000 anatomically realistic human breast phantoms and over 16 million frequency-domain wave simulations using real USCT configurations. It enables a comprehensive benchmarking of popular neural operators for both forward simulation and inverse imaging tasks, allowing analysis of their performance, scalability, and generalization capabilities. By offering a realistic and extensive dataset, OpenBreastUS not only serves as a platform for developing innovative neural PDE solvers but also facilitates their deployment in real-world medical imaging problems. For the first time, we demonstrate efficient in vivo imaging of the human breast using neural operator solvers.

In convolutional neural networks (CNNs), downsampling operations are crucial to model performance. Although traditional downsampling methods (such as maximum pooling and cross-row convolution) perform well in feature aggregation, receptive field expansion, and computational reduction, they may lead to the loss of key spatial information in semantic segmentation tasks, thereby affecting the pixel-by-pixel prediction accuracy.To this end, this study proposes a downsampling method based on information complementarity - Hybrid Pooling Downsampling (HPD). The core is to replace the traditional method with MinMaxPooling, and effectively retain the light and dark contrast and detail features of the image by extracting the maximum value information of the local area.Experiment on various CNN architectures on the ACDC and Synapse datasets show that HPD outperforms traditional methods in segmentation performance, and increases the DSC coefficient by 0.5% on average. The results show that the HPD module provides an efficient solution for semantic segmentation tasks.

Recent advances in medical image segmentation have been driven by deep learning; however, most existing methods remain limited by modality-specific designs and exhibit poor adaptability to dynamic medical imaging scenarios. The Segment Anything Model 2 (SAM2) and its related variants, which introduce a streaming memory mechanism for real-time video segmentation, present new opportunities for prompt-based, generalizable solutions. Nevertheless, adapting these models to medical video scenarios typically requires large-scale datasets for retraining or transfer learning, leading to high computational costs and the risk of catastrophic forgetting. To address these challenges, we propose DD-SAM2, an efficient adaptation framework for SAM2 that incorporates a Depthwise-Dilated Adapter (DD-Adapter) to enhance multi-scale feature extraction with minimal parameter overhead. This design enables effective fine-tuning of SAM2 on medical videos with limited training data. Unlike existing adapter-based methods focused solely on static images, DD-SAM2 fully exploits SAM2's streaming memory for medical video object tracking and segmentation. Comprehensive evaluations on TrackRad2025 (tumor segmentation) and EchoNet-Dynamic (left ventricle tracking) datasets demonstrate superior performance, achieving Dice scores of 0.93 and 0.97, respectively. To the best of our knowledge, this work provides an initial attempt at systematically exploring adapter-based SAM2 fine-tuning for medical video segmentation and tracking. Code, datasets, and models will be publicly available at https://github.com/apple1986/DD-SAM2.

In intensive care units (ICUs), patients with complex clinical conditions require vigilant monitoring and prompt interventions. Chest X-rays (CXRs) are a vital diagnostic tool, providing insights into clinical trajectories, but their irregular acquisition limits their utility. Existing tools for CXR interpretation are constrained by cross-sectional analysis, failing to capture temporal dynamics. To address this, we introduce CXR-TFT, a novel multi-modal framework that integrates temporally sparse CXR imaging and radiology reports with high-frequency clinical data, such as vital signs, laboratory values, and respiratory flow sheets, to predict the trajectory of CXR findings in critically ill patients. CXR-TFT leverages latent embeddings from a vision encoder that are temporally aligned with hourly clinical data through interpolation. A transformer model is then trained to predict CXR embeddings at each hour, conditioned on previous embeddings and clinical measurements. In a retrospective study of 20,000 ICU patients, CXR-TFT demonstrated high accuracy in forecasting abnormal CXR findings up to 12 hours before they became radiographically evident. This predictive capability in clinical data holds significant potential for enhancing the management of time-sensitive conditions like acute respiratory distress syndrome, where early intervention is crucial and diagnoses are often delayed. By providing distinctive temporal resolution in prognostic CXR analysis, CXR-TFT offers actionable 'whole patient' insights that can directly improve clinical outcomes.

Deep learning models often hallucinate, producing realistic artifacts that are not truly present in the sample. This can have dire consequences for scientific and medical inverse problems, such as MRI and microscopy denoising, where accuracy is more important than perceptual quality. Uncertainty quantification techniques, such as conformal prediction, can pinpoint outliers and provide guarantees for image regression tasks, improving reliability. However, existing methods utilize a linear constant scaling factor to calibrate uncertainty bounds, resulting in larger, less informative bounds. We propose QUTCC, a quantile uncertainty training and calibration technique that enables nonlinear, non-uniform scaling of quantile predictions to enable tighter uncertainty estimates. Using a U-Net architecture with a quantile embedding, QUTCC enables the prediction of the full conditional distribution of quantiles for the imaging task. During calibration, QUTCC generates uncertainty bounds by iteratively querying the network for upper and lower quantiles, progressively refining the bounds to obtain a tighter interval that captures the desired coverage. We evaluate our method on several denoising tasks as well as compressive MRI reconstruction. Our method successfully pinpoints hallucinations in image estimates and consistently achieves tighter uncertainty intervals than prior methods while maintaining the same statistical coverage.