To establish a comprehensive reference range for OxNNet-derived first-trimester placental volume (FTPV), based on values observed in healthy pregnancies. Data were obtained from the First Trimester Placental Ultrasound Study, an observational cohort study in which three-dimensional placental ultrasound imaging was performed between 11 + 2 and 14 + 1 weeks' gestation, alongside otherwise routine care. A subgroup of singleton pregnancies resulting in term live birth, without neonatal unit admission or major chromosomal or structural abnormality, were included. Exclusion criteria were fetal growth restriction, maternal diabetes mellitus, hypertensive disorders of pregnancy or other maternal medical conditions (e.g. chronic hypertension, antiphospholipid syndrome, systemic lupus erythematosus). Placental images were processed using the OxNNet toolkit, a software solution based on a fully convolutional neural network, for automated placental segmentation and volume calculation. Quantile regression and the lambda-mu-sigma (LMS) method were applied to model the distribution of FTPV, using both crown-rump length (CRL) and gestational age as predictors. Model fit was assessed using the Akaike information criterion (AIC), and centile curves were constructed for visual inspection. The cohort comprised 2547 cases. The distribution of FTPV across gestational ages was positively skewed, with variation in the distribution at different gestational timepoints. In model comparisons, the LMS method yielded lower AIC values compared with quantile regression models. For predicting FTPV from CRL, the LMS model with the Sinh-Arcsinh distribution achieved the best performance, with the lowest AIC value. For gestational-age-based prediction, the LMS model with the Box-Cox Cole and Green original distribution achieved the lowest AIC value. The LMS models were selected to construct centile charts for FTPV based on both CRL and gestational age. Evaluation of the centile charts revealed strong agreement between predicted and observed centiles, with minimal deviations. Both models demonstrated excellent calibration, and the Z-scores derived using each of the models confirmed normal distribution. This study established reference ranges for FTPV based on both CRL and gestational age in healthy pregnancies. The LMS method provided the best model fit, demonstrating excellent calibration and minimal deviations between predicted and observed centiles. These findings should facilitate the exploration of FTPV as a potential biomarker for adverse pregnancy outcome and provide a foundation for future research into its clinical applications. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The primary goal in neuro-oncology is the maximally safe resection of high-grade glioma (HGG). A more extensive resection improves both overall and disease-free survival, while a complication-free surgery enables better tolerance to adjuvant therapies such as chemotherapy and radiotherapy. Techniques such as 5-aminolevulinic acid (5-ALA) fluorescence and intraoperative ultrasound (ioUS) are valuable for safe resection and cost-effective. However, the benefits of combining these techniques remain undocumented. The aim of this study was to investigate outcomes when combining 5-ALA and ioUS. From January 2019 to January 2024, 72 patients (mean age 62.2 years, 62.5% male) underwent HGG resection at a single hospital. Tumor histology included glioblastoma (90.3%), grade IV astrocytoma (4.1%), grade III astrocytoma (2.8%), and grade III oligodendroglioma (2.8%). Tumor resection was performed under natural light, followed by using 5-ALA and ioUS to detect residual tumor. Biopsies from the surgical bed were analyzed for tumor presence and categorized based on 5-ALA and ioUS results. Results of 5-ALA and ioUS were classified into positive, weak/doubtful, or negative. Histological findings of the biopsies were categorized into solid tumor, infiltration, or no tumor. Sensitivity, specificity, and predictive values for both techniques, separately and combined, were calculated. A machine learning algorithm (HGGPredictor) was developed to predict tumor presence in biopsies. The overall sensitivities of 5-ALA and ioUS were 84.9% and 76%, with specificities of 57.8% and 84.5%, respectively. The combination of both methods in a positive/positive scenario yielded the highest performance, achieving a sensitivity of 91% and specificity of 86%. The positive/doubtful combination followed, with sensitivity of 67.9% and specificity of 95.2%. Area under the curve analysis indicated superior performance when both techniques were combined, in comparison to each method used individually. Additionally, the HGGPredictor tool effectively estimated the quantity of tumor cells in surgical margins. Combining 5-ALA and ioUS enhanced diagnostic accuracy for HGG resection, suggesting a new surgical standard. An intraoperative predictive algorithm could further automate decision-making.

Subvariants of testicular germ cell tumor (TGCT) significantly affect therapeutic strategies and patient prognosis. However, preoperatively distinguishing seminoma (SE) from non-seminoma (n-SE) remains a challenge. This study aimed to evaluate the performance of a deep learning-based super-resolution (SR) US radiomics model for SE/n-SE differentiation. This international multicenter retrospective study recruited patients with confirmed TGCT between 2015 and 2023. A pre-trained SR reconstruction algorithm was applied to enhance native resolution (NR) images. NR and SR radiomics models were constructed, and the superior model was then integrated with clinical features to construct clinical-radiomics models. Diagnostic performance was evaluated by ROC analysis (AUC) and compared with radiologists' assessments using the DeLong test. A total of 486 male patients were enrolled for training (n = 338), domestic (n = 92), and international (n = 59) validation sets. The SR radiomics model achieved AUCs of 0.90, 0.82, and 0.91, respectively, in the training, domestic, and international validation sets, significantly surpassing the NR model (p < 0.001, p = 0.031, and p = 0.001, respectively). The clinical-radiomics model exhibited a significantly higher across both domestic and international validation sets compared to the SR radiomics model alone (0.95 vs 0.82, p = 0.004; 0.97 vs 0.91, p = 0.031). Moreover, the clinical-radiomics model surpassed the performance of experienced radiologists in both domestic (AUC, 0.95 vs 0.85, p = 0.012) and international (AUC, 0.97 vs 0.77, p < 0.001) validation cohorts. The SR-based clinical-radiomics model can effectively differentiate between SE and n-SE. This international multicenter study demonstrated that a radiomics model of deep learning-based SR reconstructed US images enabled effective differentiation between SE and n-SE. Clinical parameters and radiologists' assessments exhibit limited diagnostic accuracy for SE/n-SE differentiation in TGCT. Based on scrotal US images of TGCT, the SR radiomics models performed better than the NR radiomics models. The SR-based clinical-radiomics model outperforms both the radiomics model and radiologists' assessment, enabling accurate, non-invasive preoperative differentiation between SE and n-SE.

Preoperative prediction of lateral lymph node metastasis is clinically crucial for guiding surgical strategy and prognosis assessment, yet precise prediction methods are lacking. We therefore develop Lateral Lymph Node Metastasis Network (LLNM-Net), a bidirectional-attention deep-learning model that fuses multimodal data (preoperative ultrasound images, radiology reports, pathological findings, and demographics) from 29,615 patients and 9836 surgical cases across seven centers. Integrating nodule morphology and position with clinical text, LLNM-Net achieves an Area Under the Curve (AUC) of 0.944 and 84.7% accuracy in multicenter testing, outperforming human experts (64.3% accuracy) and surpassing previous models by 7.4%. Here we show tumors within 0.25 cm of the thyroid capsule carry >72% metastasis risk, with middle and upper lobes as high-risk regions. Leveraging location, shape, echogenicity, margins, demographics, and clinician inputs, LLNM-Net further attains an AUC of 0.983 for identifying high-risk patients. The model is thus a promising for tool for preoperative screening and risk stratification.

Precise assessment of brain aging is crucial for early detection of neurodegenerative disorders and aiding clinical practice. Existing magnetic resonance imaging (MRI)-based methods excel in this task, but they still have room for improvement in capturing local morphological variations across brain regions and preserving the inherent neurobiological topological structures. To develop and validate a deep learning framework incorporating both connectivity and complexity for accurate brain aging estimation, facilitating early identification of neurodegenerative diseases. We used 5889 T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative dataset. We proposed a novel brain vision graph neural network (BVGN), incorporating neurobiologically informed feature extraction modules and global association mechanisms to provide a sensitive deep learning-based imaging biomarker. Model performance was evaluated using mean absolute error (MAE) against benchmark models, while generalization capability was further validated on an external UK Biobank dataset. We calculated the brain age gap across distinct cognitive states and conducted multiple logistic regressions to compare its discriminative capacity against conventional cognitive-related variables in distinguishing cognitively normal (CN) and mild cognitive impairment (MCI) states. Longitudinal track, Cox regression, and Kaplan-Meier plots were used to investigate the longitudinal performance of the brain age gap. The BVGN model achieved an MAE of 2.39 years, surpassing current state-of-the-art approaches while obtaining an interpretable saliency map and graph theory supported by medical evidence. Furthermore, its performance was validated on the UK Biobank cohort (N=34,352) with an MAE of 2.49 years. The brain age gap derived from BVGN exhibited significant difference across cognitive states (CN vs MCI vs Alzheimer disease; P<.001), and demonstrated the highest discriminative capacity between CN and MCI than general cognitive assessments, brain volume features, and apolipoprotein E4 carriage (area under the receiver operating characteristic curve [AUC] of 0.885 vs AUC ranging from 0.646 to 0.815). Brain age gap exhibited clinical feasibility combined with Functional Activities Questionnaire, with improved discriminative capacity in models achieving lower MAEs (AUC of 0.945 vs 0.923 and 0.911; AUC of 0.935 vs 0.900 and 0.881). An increasing brain age gap identified by BVGN may indicate underlying pathological changes in the CN to MCI progression, with each unit increase linked to a 55% (hazard ratio=1.55, 95% CI 1.13-2.13; P=.006) higher risk of cognitive decline in individuals who are CN and a 29% (hazard ratio=1.29, 95% CI 1.09-1.51; P=.002) increase in individuals with MCI. BVGN offers a precise framework for brain aging assessment, demonstrates strong generalization on an external large-scale dataset, and proposes novel interpretability strategies to elucidate multiregional cooperative aging patterns. The brain age gap derived from BVGN is validated as a sensitive biomarker for early identification of MCI and predicting cognitive decline, offering substantial potential for clinical applications.

Clinical decision-making relies heavily on understanding relative positions of anatomical structures and anomalies. Therefore, for Vision-Language Models (VLMs) to be applicable in clinical practice, the ability to accurately determine relative positions on medical images is a fundamental prerequisite. Despite its importance, this capability remains highly underexplored. To address this gap, we evaluate the ability of state-of-the-art VLMs, GPT-4o, Llama3.2, Pixtral, and JanusPro, and find that all models fail at this fundamental task. Inspired by successful approaches in computer vision, we investigate whether visual prompts, such as alphanumeric or colored markers placed on anatomical structures, can enhance performance. While these markers provide moderate improvements, results remain significantly lower on medical images compared to observations made on natural images. Our evaluations suggest that, in medical imaging, VLMs rely more on prior anatomical knowledge than on actual image content for answering relative position questions, often leading to incorrect conclusions. To facilitate further research in this area, we introduce the MIRP , Medical Imaging Relative Positioning, benchmark dataset, designed to systematically evaluate the capability to identify relative positions in medical images.

Intracranial aneurysms (IAs) are abnormal dilations of cerebral blood vessels that, if ruptured, can lead to life-threatening consequences. However, their small size and soft contrast in radiological scans often make it difficult to perform accurate and efficient detection and morphological analyses, which are critical in the clinical care of the disorder. Furthermore, the lack of large public datasets with voxel-wise expert annotations pose challenges for developing deep learning algorithms to address the issues. Therefore, we proposed a novel weakly supervised 3D multi-task UNet that integrates vesselness priors to jointly perform aneurysm detection and segmentation in time-of-flight MR angiography (TOF-MRA). Specifically, to robustly guide IA detection and segmentation, we employ the popular Frangi's vesselness filter to derive soft cerebrovascular priors for both network input and an attention block to conduct segmentation from the decoder and detection from an auxiliary branch. We train our model on the Lausanne dataset with coarse ground truth segmentation, and evaluate it on the test set with refined labels from the same database. To further assess our model's generalizability, we also validate it externally on the ADAM dataset. Our results demonstrate the superior performance of the proposed technique over the SOTA techniques for aneurysm segmentation (Dice = 0.614, 95%HD =1.38mm) and detection (false positive rate = 1.47, sensitivity = 92.9%).

Alzheimer's disease (AD) is accompanied by alterations in retinal vascular density (VD), but the mechanisms remain unclear. This study investigated the relationship among cerebral amyloid-β (Aβ) deposition, VD, and cognitive decline. We enrolled 92 participants, including 47 AD patients and 45 healthy control (HC) participants. VD across retinal subregions was quantified using deep learning-based fundus photography, and cerebral Aβ deposition was measured with ¹⁸F-florbetapir (¹⁸F-AV45) PET/MRI. Using the minimum bounding circle of the optic disc as the diameter (papilla-diameter, PD), VD (total, 0.5-1.0 PD, 1.0-1.5 PD, 1.5-2.0 PD, 2.0-2.5 PD) was calculated. Standardized uptake value ratio (SUVR) for Aβ deposition was computed for global and regional cortical areas, using the cerebellar cortex as the reference region. Cognitive performance was assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation, multiple linear regression, and mediation analyses were used to explore Aβ deposition, VD, and cognition. AD patients exhibited significantly lower VD in all subregions compared to HC (p < 0.05). Reduced VD correlated with higher SUVR in the global cortex and a decline in cognitive abilities (p < 0.05). Mediation analysis indicated that VD influenced MMSE and MoCA through SUVR in the global cortex, with the most pronounced effects observed in the 1.0-1.5 PD range. Retinal VD is associated with cognitive decline, a relationship primarily mediated by cerebral Aβ deposition measured via ¹⁸F-AV45 PET. These findings highlight the potential of retinal VD as a biomarker for early detection in AD.

In clinical practice, medical image analysis often requires efficient execution on resource-constrained mobile devices. However, existing mobile models-primarily optimized for natural images-tend to perform poorly on medical tasks due to the significant information density gap between natural and medical domains. Combining computational efficiency with medical imaging-specific architectural advantages remains a challenge when developing lightweight, universal, and high-performing networks. To address this, we propose a mobile model called Mobile U-shaped Vision Transformer (Mobile U-ViT) tailored for medical image segmentation. Specifically, we employ the newly purposed ConvUtr as a hierarchical patch embedding, featuring a parameter-efficient large-kernel CNN with inverted bottleneck fusion. This design exhibits transformer-like representation learning capacity while being lighter and faster. To enable efficient local-global information exchange, we introduce a novel Large-kernel Local-Global-Local (LGL) block that effectively balances the low information density and high-level semantic discrepancy of medical images. Finally, we incorporate a shallow and lightweight transformer bottleneck for long-range modeling and employ a cascaded decoder with downsample skip connections for dense prediction. Despite its reduced computational demands, our medical-optimized architecture achieves state-of-the-art performance across eight public 2D and 3D datasets covering diverse imaging modalities, including zero-shot testing on four unseen datasets. These results establish it as an efficient yet powerful and generalization solution for mobile medical image analysis. Code is available at https://github.com/FengheTan9/Mobile-U-ViT.

Approximately 70% of adults with chronic obstructive pulmonary disease (COPD) remain undiagnosed. Opportunistic screening using chest computed tomography (CT) scans, commonly acquired in clinical practice, may be used to improve COPD detection through simple, clinically applicable deep-learning models. We developed a lightweight, convolutional neural network (COPDxNet) that utilizes minimally processed chest CT scans to detect COPD. We analyzed 13,043 inspiratory chest CT scans from the COPDGene participants, (9,675 standard-dose and 3,368 low-dose scans), which we randomly split into training (70%) and test (30%) sets at the participant level to no individual contributed to both sets. COPD was defined by postbronchodilator FEV /FVC < 0.70. We constructed a simple, four-block convolutional model that was trained on pooled data and validated on the held-out standard- and low-dose test sets. External validation was performed using standard-dose CT scans from 2,890 SPIROMICS participants and low-dose CT scans from 7,893 participants in the National Lung Screening Trial (NLST). We evaluated performance using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, Brier scores, and calibration curves. On COPDGene standard-dose CT scans, COPDxNet achieved an AUC of 0.92 (95% CI: 0.91 to 0.93), sensitivity of 80.2%, and specificity of 89.4%. On low-dose scans, AUC was 0.88 (95% CI: 0.86 to 0.90). When the COPDxNet model was applied to external validation datasets, it showed an AUC of 0.92 (95% CI: 0.91 to 0.93) in SPIROMICS and 0.82 (95% CI: 0.81 to 0.83) on NLST. The model was well-calibrated, with Brier scores of 0.11 for standard- dose and 0.13 for low-dose CT scans in COPDGene, 0.12 in SPIROMICS, and 0.17 in NLST. COPDxNet demonstrates high discriminative accuracy and generalizability for detecting COPD on standard- and low-dose chest CT scans, supporting its potential for clinical and screening applications across diverse populations.