BackgroundCarotid plaque presence is associated with cardiovascular risk, even among asymptomatic individuals. While deep learning has shown promise for carotid plaque phenotyping in patients with advanced atherosclerosis, its application in population-based settings of asymptomatic individuals remains unexplored. MethodsWe developed a YOLOv8-based model for plaque detection using carotid ultrasound images from 19,499 participants of the population-based UK Biobank (UKB) and fine-tuned it for external validation in the BiDirect study (N = 2,105). Cox regression was used to estimate the impact of plaque presence and count on major cardiovascular events. To explore the genetic architecture of carotid atherosclerosis, we conducted a genome-wide association study (GWAS) meta-analysis of the UKB and CHARGE cohorts. Mendelian randomization (MR) assessed the effect of genetic predisposition to vascular risk factors on carotid atherosclerosis. ResultsOur model demonstrated high performance with accuracy, sensitivity, and specificity exceeding 85%, enabling identification of carotid plaques in 45% of the UKB population (aged 47-83 years). In the external BiDirect cohort, a fine-tuned model achieved 86% accuracy, 78% sensitivity, and 90% specificity. Plaque presence and count were associated with risk of major adverse cardiovascular events (MACE) over a follow-up of up to seven years, improving risk reclassification beyond the Pooled Cohort Equations. A GWAS meta-analysis of carotid plaques uncovered two novel genomic loci, with downstream analyses implicating targets of investigational drugs in advanced clinical development. Observational and MR analyses showed associations between smoking, LDL cholesterol, hypertension, and odds of carotid atherosclerosis. ConclusionsOur model offers a scalable solution for early carotid plaque detection, potentially enabling automated screening in asymptomatic individuals and improving plaque phenotyping in population-based cohorts. This approach could advance large-scale atherosclerosis research. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/24315675v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): [email protected]@27a04corg.highwire.dtl.DTLVardef@18cef18org.highwire.dtl.DTLVardef@1a53d8f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHICAL ABSTRACT.C_FLOATNO ASCVD - Atherosclerotic Cardiovascular Disease, CVD - Cardiovascular disease, PCE - Pooled Cohort Equations, TP- true positive, FN - False Negative, FP - False Positive, TN - True Negative, GWAS - Genome-Wide Association Study. C_FIG CLINICAL PERSPECTIVECarotid ultrasound is a well-established method for assessing subclinical atherosclerosis with potential to improve cardiovascular risk assessment in asymptomatic individuals. Deep learning could automate plaque screening and enable processing of large imaging datasets, reducing the need for manual annotation. Integrating such large-scale carotid ultrasound datasets with clinical, genetic, and other relevant data can advance cardiovascular research. Prior studies applying deep learning to carotid ultrasound have focused on technical tasks-plaque classification, segmentation, and characterization-in small sample sizes of patients with advanced atherosclerosis. However, they did not assess the potential of deep learning in detecting plaques in asymptomatic individuals at the population level. We developed an efficient deep learning model for the automated detection and quantification of early carotid plaques in ultrasound imaging, primarily in asymptomatic individuals. The model demonstrated high accuracy and external validity across population-based cohort studies. Predicted plaque prevalence aligned with known cardiovascular risk factors. Importantly, predicted plaque presence and count were associated with future cardiovascular events and improved reclassification of asymptomatic individuals into clinically meaningful risk categories. Integrating our model predictions with genetic data identified two novel loci associated with carotid plaque presence--both previously linked to cardiovascular disease--highlighting the models potential for population-scale atherosclerosis research. Our model provides a scalable solution for automated carotid plaque phenotyping in ultrasound images at the population level. These findings support its use for automated screening in asymptomatic individuals and for streamlining plaque phenotyping in large cohorts, thereby advancing research on subclinical atherosclerosis in the general population.

Resting-state functional MRI (rs-fMRI), a promising method for interrogating different brain functional networks from a single MRI acquisition, is increasingly used in clinical presurgical and other pretherapeutic brain mapping. However, challenges in standardization of acquisition, preprocessing, and analysis methods across centers and variability in results interpretation complicate its clinical use. Additionally, inherent problems regarding reliability of language lateralization, interpatient variability of cognitive network representation, dynamic aspects of intranetwork and internetwork connectivity, and effects of neurovascular uncoupling on network detection still must be overcome. Although deep learning solutions and further methodologic standardization will help address these issues, rs-fMRI remains generally considered an adjunct to task-based fMRI (tb-fMRI) for clinical presurgical mapping. Nonetheless, in many clinical instances, rs-fMRI may offer valuable additional information that supplements tb-fMRI, especially if tb-fMRI is inadequate due to patient performance or other limitations. Future growth in clinical applications of rs-fMRI is anticipated as challenges are increasingly addressed. This <i>AJR</i> Expert Panel Narrative Review summarizes the current state and emerging clinical utility of rs-fMRI, focusing on its role in presurgical mapping. Ongoing controversies and limitations in clinical applicability are presented and future directions are discussed, including the developing role of rs-fMRI in neuromodulation treatment of various neurologic disorders.

Low-field portable magnetic resonance imaging (pMRI) devices address a crucial requirement in the realm of healthcare by offering the capability for on-demand and timely access to MRI, especially in the context of routine stroke emergency. Nevertheless, images acquired by these devices often exhibit poor clarity and low resolution, resulting in their reduced potential to support precise diagnostic evaluations and lesion quantification. In this paper, we propose a 3D deep learning based model, named Stroke-Aware CycleGAN (SA-CycleGAN), to enhance the quality of low-field images for further improving diagnosis of routine stroke. Firstly, based on traditional CycleGAN, SA-CycleGAN incorporates a prior of stroke lesions by applying a novel spatial feature transform mechanism. Secondly, gradient difference losses are combined to deal with the problem that the synthesized images tend to be overly smooth. We present a dataset comprising 101 paired high-field and low-field diffusion-weighted imaging (DWI), which were acquired through dual scans of the same patient in close temporal proximity. Our experiments demonstrate that SA-CycleGAN is capable of generating images with higher quality and greater clarity compared to the original low-field DWI. Additionally, in terms of quantifying stroke lesions, SA-CycleGAN outperforms existing methods. The lesion volume exhibits a strong correlation between the generated images and the high-field images, with R=0.852. In contrast, the lesion volume correlation between the low-field images and the high-field images is notably lower, with R=0.462. Furthermore, the mean absolute difference in lesion volumes between the generated images and high-field images (1.73±2.03 mL) was significantly smaller than the difference between the low-field images and high-field images (2.53±4.24 mL). It shows that the synthesized images not only exhibit superior visual clarity compared to the low-field acquired images, but also possess a high degree of consistency with high-field images. In routine clinical practice, the proposed SA-CycleGAN offers an accessible and cost-effective means of rapidly obtaining higher-quality images, holding the potential to enhance the efficiency and accuracy of stroke diagnosis in routine clinical settings. The code and trained models will be released on GitHub: SA-CycleGAN.

Major depressive disorder (MDD) has been increasingly understood as a disorder of network-level functional dysconnectivity. However, previous brain connectome studies have primarily relied on node-centric approaches, neglecting critical edge-edge interactions that may capture essential features of network dysfunction. This study included resting-state functional MRI data from 838 MDD patients and 881 healthy controls (HC) across 23 sites. We applied a novel edge-centric connectome model to estimate edge functional connectivity and identify overlapping network communities. Regional functional diversity was quantified via normalized entropy based on community overlap patterns. Neurobiological decoding was performed to map brain-wide relationships between functional diversity alterations and patterns of gene expression and neurotransmitter distribution. Comparative machine learning analyses further evaluated the diagnostic utility of edge-centric versus node-centric connectome representations. Compared with HC, MDD patients exhibited significantly increased functional diversity within the prefrontal-striatal-thalamic reward circuit. Neurobiological decoding analysis revealed that functional diversity alterations in MDD were spatially associated with transcriptional patterns enriched for inflammatory processes, as well as distribution of 5-HT1B receptors. Machine learning analyses demonstrated superior classification performance of edge-centric models over traditional node-centric approaches in distinguishing MDD patients from HC at the individual level. Our findings highlighted that abnormal functional diversity within the reward processing system might underlie multi-level neurobiological mechanisms of MDD. The edge-centric connectome approach offers a valuable tool for identifying disease biomarkers, characterizing individual variation and advancing current understanding of complex network configuration in psychiatric disorders.

Artificial intelligence (AI) and combinatorial optimization drive applications across science and industry, but their increasing energy demands challenge the sustainability of digital computing. Most unconventional computing systems^1-7 target either AI or optimization workloads and rely on frequent, energy-intensive digital conversions, limiting efficiency. These systems also face application-hardware mismatches, whether handling memory-bottlenecked neural models, mapping real-world optimization problems or contending with inherent analog noise. Here we introduce an analog optical computer (AOC) that combines analog electronics and three-dimensional optics to accelerate AI inference and combinatorial optimization in a single platform. This dual-domain capability is enabled by a rapid fixed-point search, which avoids digital conversions and enhances noise robustness. With this fixed-point abstraction, the AOC implements emerging compute-bound neural models with recursive reasoning potential and realizes an advanced gradient-descent approach for expressive optimization. We demonstrate the benefits of co-designing the hardware and abstraction, echoing the co-evolution of digital accelerators and deep learning models, through four case studies: image classification, nonlinear regression, medical image reconstruction and financial transaction settlement. Built with scalable, consumer-grade technologies, the AOC paves a promising path for faster and sustainable computing. Its native support for iterative, compute-intensive models offers a scalable analog platform for fostering future innovation in AI and optimization.

Generating realistic MRIs to accurately predict future changes in the structure of brain is an invaluable tool for clinicians in assessing clinical outcomes and analysing the disease progression at the patient level. However, current existing methods present some limitations: (i) some approaches fail to explicitly capture the relationship between structural changes and time intervals, especially when trained on age-imbalanced datasets; (ii) others rely only on scan interpolation, which lack clinical utility, as they generate intermediate images between timepoints rather than future pathological progression; and (iii) most approaches rely on 2D slice-based architectures, thereby disregarding full 3D anatomical context, which is essential for accurate longitudinal predictions. We propose a 3D Temporally-Aware Diffusion Model (TADM-3D), which accurately predicts brain progression on MRI volumes. To better model the relationship between time interval and brain changes, TADM-3D uses a pre-trained Brain-Age Estimator (BAE) that guides the diffusion model in the generation of MRIs that accurately reflect the expected age difference between baseline and generated follow-up scans. Additionally, to further improve the temporal awareness of TADM-3D, we propose the Back-In-Time Regularisation (BITR), by training TADM-3D to predict bidirectionally from the baseline to follow-up (forward), as well as from the follow-up to baseline (backward). Although predicting past scans has limited clinical applications, this regularisation helps the model generate temporally more accurate scans. We train and evaluate TADM-3D on the OASIS-3 dataset, and we validate the generalisation performance on an external test set from the NACC dataset. The code will be available upon acceptance.

Synthetic tumors in medical images offer controllable characteristics that facilitate the training of machine learning models, leading to an improved segmentation performance. However, the existing methods of tumor synthesis yield suboptimal performances when tumor occupies a large spatial volume, such as breast tumor segmentation in MRI with a large field-of-view (FOV), while commonly used tumor generation methods are based on small patches. In this paper, we propose a 3D medical diffusion model, called SynBT, to generate high-quality breast tumor (BT) in contrast-enhanced MRI images. The proposed model consists of a patch-to-volume autoencoder, which is able to compress the high-resolution MRIs into compact latent space, while preserving the resolution of volumes with large FOV. Using the obtained latent space feature vector, a mask-conditioned diffusion model is used to synthesize breast tumors within selected regions of breast tissue, resulting in realistic tumor appearances. We evaluated the proposed method for a tumor segmentation task, which demonstrated the proposed high-quality tumor synthesis method can facilitate the common segmentation models with performance improvement of 2-3% Dice Score on a large public dataset, and therefore provides benefits for tumor segmentation in MRI images.

To develop and validate a non-invasive deep learning model that integrates voxel-level radiomics with multi-sequence MRI to predict microsatellite instability (MSI) status in patients with endometrial carcinoma (EC). This two-center retrospective study included 375 patients with pathologically confirmed EC from two medical centers. Patients underwent preoperative multiparametric MRI (T2WI, DWI, CE-T1WI), and MSI status was determined by immunohistochemistry. Tumor regions were manually segmented, and voxel-level radiomics features were extracted following IBSI guidelines. A dual-channel 3D deep neural network based on the Vision-Mamba architecture was constructed to jointly process voxel-wise radiomics feature maps and MR images. The model was trained and internally validated on cohorts from Center I and tested on an external cohort from Center II. Performance was compared with Vision Transformer, 3D-ResNet, and traditional radiomics models. Interpretability was assessed with feature importance ranking and SHAP value visualization. The Vision-Mamba model achieved strong predictive performance across all datasets. In the external test cohort, it yielded an AUC of 0.866, accuracy of 0.875, sensitivity of 0.833, and specificity of 0.900, outperforming other models. Integrating voxel-level radiomics features with MRI enabled the model to better capture both local and global tumor heterogeneity compared to traditional approaches. Interpretability analysis identified glszm_SizeZoneNonUniformityNormalized, ngtdm_Busyness, and glcm_Correlation as top features, with SHAP analysis revealing that tumor parenchyma, regions of enhancement, and diffusion restriction were pivotal for MSI prediction. The proposed voxel-level radiomics and deep learning model provides a robust, non-invasive tool for predicting MSI status in endometrial carcinoma, potentially supporting personalized treatment decision-making.

Computed tomography (CT) remains the primary modality for assessing renal tumors; however, tumor identification and segmentation rely heavily on manual interpretation by clinicians, which is time-consuming and subject to inter-observer variability. The heterogeneity of tumor appearance and indistinct margins further complicate accurate delineation, impacting histopathological classification, treatment planning, and prognostic assessment. There is a pressing clinical need for an automated segmentation tool to enhance diagnostic workflows and support clinical decision-making with results that are reliable, accurate, and reproducible. This study developed a fully automated pipeline based on the DeepMedic 3D convolutional neural network for the segmentation of kidneys and renal tumors through multi-scale feature extraction. The model was trained and evaluated using 5-fold cross-validation on a dataset of 382 contrast-enhanced CT scans manually annotated by experienced physicians. Image preprocessing included Hounsfield unit conversion, windowing, 3D reconstruction, and voxel resampling. Post-processing was also employed to refine output masks and improve model generalizability. The proposed model achieved high performance in kidney segmentation, with an average Dice coefficient of 93.82 ± 1.38%, precision of 94.86 ± 1.59%, and recall of 93.66 ± 1.77%. In renal tumor segmentation, the model attained a Dice coefficient of 88.19 ± 1.24%, precision of 90.36 ± 1.90%, and recall of 88.23 ± 2.02%. Visual comparisons with ground truth annotations confirmed the clinical relevance and accuracy of the predictions. The proposed DeepMedic-based framework demonstrates robust, accurate segmentation of kidneys and renal tumors on CT images. With its potential for real-time application, this model could enhance diagnostic efficiency and treatment planning in renal oncology.

This study aimed to evaluate the diagnostic performance of an artificial intelligence (AI)-enhanced model for detecting lung cancer on computed tomography (CT) images of the chest. It assessed diagnostic accuracy, sensitivity, specificity, and interpretative consistency across normal, benign, and malignant cases. An exploratory analysis was performed using the publicly available IQ-OTH/NCCD dataset, comprising 110 CT cases (55 normal, 15 benign, 40 malignant). A pre-trained convolutional neural network in Google AI Studio was fine-tuned using 25 training images and tested on a separate image from each case. Quantitative evaluation of diagnostic accuracy and qualitative content analysis of AI-generated reports was conducted to assess diagnostic patterns and interpretative behavior. The AI model achieved an overall accuracy of 75.5 %, with a sensitivity of 74.5 % and specificity of 76.4 %. The area under the ROC curve (AUC) for all cases was 0.824 (95 % CI: 0.745-0.897), indicating strong discriminative power. Malignant cases had the highest classification performance (AUC = 0.902), while benign cases were more challenging to classify (AUC = 0.615). Qualitative analysis showed the AI used consistent radiological terminology, but demonstrated oversensitivity to ground-glass opacities, contributing to false positives in non-malignant cases. The AI model showed promising diagnostic potential, particularly in identifying malignancies. However, specificity limitations and interpretative errors in benign and normal cases underscore the need for human oversight and continued model refinement. AI-enhanced CT interpretation can improve efficiency in high-volume settings but should serve as a decision-support tool rather than a replacement for expert image review.