With increasing interest in studying biological systems across spatial scales--from centimetres down to nanometres--histology continues to be the gold standard for tissue imaging at cellular resolution, providing an essential bridge between macroscopic and nanoscopic analysis. However, its inherently destructive and two-dimensional nature limits its ability to capture the full three-dimensional complexity of tissue architecture. Here we show that phase-contrast X-ray microscopy can enable three-dimensional virtual histology with subcellular resolution. This technique provides direct quantification of electron density without restrictive assumptions, allowing for direct characterisation of cellular nuclei in a standard laboratory setting. By combining high spatial resolution and soft tissue contrast, with automated segmentation of cell nuclei, we demonstrated virtual H&E staining using machine learning-based style transfer, yielding volumetric datasets compatible with existing histopathological analysis tools. Furthermore, by integrating electron density and the sensitivity to nanometric features of the dark field contrast channel, we achieve stain-free, high-content imaging capable of distinguishing nuclei and extracellular matrix.

Despite continued advances in oncology, cancer remains a leading cause of global mortality, highlighting the need for diagnostic and prognostic tools that are both accurate and interpretable. Unimodal approaches often fail to capture the biological and clinical complexity of tumors. In this study, we present a suite of task-specific AI models that leverage CT imaging, multi-omics profiles, and structured clinical data to address distinct challenges in segmentation, classification, and prognosis. We developed three independent models across large public datasets. Task 1 applied a 3D U-Net to segment pancreatic tumors from CT scans, achieving a Dice Similarity Coefficient (DSC) of 0.7062. Task 2 employed a hierarchical ensemble of omics-based classifiers to distinguish tumor from normal tissue and classify six major cancer types with 98.67% accuracy. Task 3 benchmarked classical machine learning models on clinical data for prognosis prediction across three cancers (LIHC, KIRC, STAD), achieving strong performance (e.g., C-index of 0.820 in KIRC, AUC of 0.978 in LIHC). Across all tasks, explainable AI methods such as SHAP and attention-based visualization enabled transparent interpretation of model outputs. These results demonstrate the value of tailored, modality-aware models and underscore the clinical potential of applying such tailored AI systems for precision oncology. Technical FoundationsO_LISegmentation (Task 1): A custom 3D U-Net was trained using the Task07_Pancreas dataset from the Medical Segmentation Decathlon (MSD). CT images were preprocessed with MONAI-based pipelines, resampled to (64, 96, 96) voxels, and intensity-windowed to HU ranges of -100 to 240. C_LIO_LIClassification (Task 2): Multi-omics data from TCGA--including gene expression, methylation, miRNA, CNV, and mutation profiles--were log-transformed and normalized. Five modality-specific LightGBM classifiers generated meta-features for a late-fusion ensemble. Stratified 5-fold cross-validation was used for evaluation. C_LIO_LIPrognosis (Task 3): Clinical variables from TCGA were curated and imputed (median/mode), with high-missing-rate columns removed. Survival models (e.g., Cox-PH, Random Forest, XGBoost) were trained with early stopping. No omics or imaging data were used in this task. C_LIO_LIInterpretability: SHAP values were computed for all tree-based models, and attention-based overlays were used in imaging tasks to visualize salient regions. C_LI

Robot-assisted radical prostatectomy (RARP) is the standard surgical procedure for the treatment of prostate cancer. RARP requires a trade-off between performing a wider resection in order to reduce the risk of positive surgical margins (PSMs) and performing minimal resection of the nerve bundles that determine functional outcomes, such as incontinence and potency, which affect patients' quality of life. In order to achieve favourable outcomes, a precise understanding of the three-dimensional (3D) anatomy of the prostate, nerve bundles and tumour lesion is needed. This is the protocol for a single-centre feasibility study including a prospective two-arm interventional group (a 3D virtual and a 3D printed prostate model), and a prospective control group. The primary endpoint will be PSM status and the secondary endpoint will be functional outcomes, including incontinence and sexual function. The study will consist of a total of 270 patients: 54 patients will be included in each of the interventional groups (3D virtual, 3D printed models), 54 in the retrospective control group and 108 in the prospective control group. Automated segmentation of prostate gland and lesions will be conducted on multiparametric magnetic resonance imaging (mpMRI) using 'AutoProstate' and 'AutoLesion' deep learning approaches, while manual annotation of the neurovascular bundles, urethra and external sphincter will be conducted on mpMRI by a radiologist. This will result in masks that will be post-processed to generate 3D printed/virtual models. Patients will be allocated to either interventional arm and the surgeon will be given either a 3D printed or a 3D virtual model at the start of the RARP procedure. At the 6-week follow-up, the surgeon will meet with the patient to present PSM status and capture functional outcomes from the patient via questionnaires. We will capture these measures as endpoints for analysis. These questionnaires will be re-administered at 3, 6 and 12 months postoperatively.

Accurate segmentation of lung regions from CT scan images is critical for diagnosing and monitoring respiratory diseases. This study introduces a novel hybrid architecture Adaptive Attention U-NetAA, which combines the strengths of U-Net3 + and Transformer based attention mechanisms models for high-precision lung segmentation. The U-Net3 + module effectively segments the lung region by leveraging its deep convolutional network with nested skip connections, ensuring rich multi-scale feature extraction. A key innovation is introducing an adaptive attention mechanism within the Transformer module, which dynamically adjusts the focus on critical regions in the image based on local and global contextual relationships. This model's adaptive attention mechanism addresses variations in lung morphology, image artifacts, and low-contrast regions, leading to improved segmentation accuracy. The combined convolutional and attention-based architecture enhances robustness and precision. Experimental results on benchmark CT datasets demonstrate that the proposed model achieves an IoU of 0.984, a Dice coefficient of 0.989, a MIoU of 0.972, and an HD95 of 1.22 mm, surpassing state-of-the-art methods. These results establish U-NetAA as a superior tool for clinical lung segmentation, with enhanced accuracy, sensitivity, and generalization capability.

Radiographic images are a cornerstone of medical diagnostics in orthopaedics, with anatomical landmark detection serving as a crucial intermediate step for information extraction. General-purpose foundational segmentation models, such as SAM (Segment Anything Model), do not support landmark segmentation out of the box and require prompts to function. However, in medical imaging, the prompts for landmarks are highly specific. Since SAM has not been trained to recognize such landmarks, it cannot generate accurate landmark segmentations for diagnostic purposes. Even MedSAM, a medically adapted variant of SAM, has been trained to identify larger anatomical structures, such as organs and their parts, and lacks the fine-grained precision required for orthopaedic pelvic landmarks. To address this limitation, we propose leveraging another general-purpose, non-foundational model: YOLO. YOLO excels in object detection and can provide bounding boxes that serve as input prompts for SAM. While YOLO is efficient at detection, it is significantly outperformed by SAM in segmenting complex structures. In combination, these two models form a reliable pipeline capable of segmenting not only a small pilot set of eight anatomical landmarks but also an expanded set of 72 landmarks and 16 regions with complex outlines, such as the femoral cortical bone and the pelvic inlet. By using YOLO-generated bounding boxes to guide SAM, we trained the hybrid model to accurately segment orthopaedic pelvic radiographs. Our results show that the proposed combination of YOLO and SAM yields excellent performance in detecting anatomical landmarks and intricate outlines in orthopaedic pelvic radiographs.

The Segment Anything Model (SAM) has revolutionized image segmentation through its innovative prompt-based approach, yet the critical role of prompt engineering in its success remains underexplored. This paper presents the first comprehensive survey focusing specifically on prompt engineering techniques for SAM and its variants. We systematically organize and analyze the rapidly growing body of work in this emerging field, covering fundamental methodologies, practical applications, and key challenges. Our review reveals how prompt engineering has evolved from simple geometric inputs to sophisticated multimodal approaches, enabling SAM's adaptation across diverse domains including medical imaging and remote sensing. We identify unique challenges in prompt optimization and discuss promising research directions. This survey fills an important gap in the literature by providing a structured framework for understanding and advancing prompt engineering in foundation models for segmentation.

Increased spinal curvature is one of the most recognizable aging traits in the human population. However, despite high prevalence, the etiology of this condition remains poorly understood. To gain better insight into the physiological, biochemical, and genetic risk factors involved, we developed a novel machine learning method to automatically derive thoracic kyphosis and lumbar lordosis angles from dual-energy X-ray absorptiometry (DXA) scans in the UK Biobank Imaging cohort. We carry out genome-wide association and epidemiological association studies to identify genetic and physiological risk factors for both traits. In 41,212 participants, we find that on average males and females gain 2.42° in kyphotic and 1.48° in lordotic angle per decade of life. Increased spinal curvature shows a strong association with decreased muscle mass and bone mineral density. Adiposity demonstrates opposing associations, with decreased kyphosis and increased lordosis. Using Mendelian randomization, we show that genes fundamental to the maintenance of musculoskeletal function (COL11A1, PTHLH, ETFA, TWIST1) and cellular homeostasis such as RNA transcription and DNA repair (RAD9A, MMS22L, HIF1A, RAB28) are likely involved in increased spinal curvature. Our findings reveal a complex interplay between genetics, musculoskeletal health, and age-related changes in spinal curvature, suggesting potential drivers of this universal aging trait.

This study aims to present the Segmentation-based Myocardial Advanced Refinement Tracking (SMART) system, a novel artificial intelligence (AI)-based framework for transthoracic echocardiography (TTE) that incorporates motion tracking and left ventricular (LV) myocardial segmentation for automated LV mass (LVM) and global longitudinal strain (LVGLS) assessment. The SMART system demonstrates LV speckle tracking based on motion vector estimation, refined by structural information using endocardial and epicardial segmentation throughout the cardiac cycle. This approach enables automated measurement of LVM_SMART and LVGLS_SMART. The feasibility of SMART is validated in 111 hypertrophic cardiomyopathy (HCM) patients (median age: 58 years, 69% male) who underwent TTE and cardiac magnetic resonance imaging (CMR). LVGLS_SMART showed a strong correlation with conventional manual LVGLS measurements (Pearson's correlation coefficient [PCC] 0.851; mean difference 0 [-2-0]). When compared to CMR as the reference standard for LVM, the conventional dimension-based TTE method overestimated LVM (PCC 0.652; mean difference: 106 [90-123]), whereas LVM_SMART demonstrated excellent agreement with CMR (PCC 0.843; mean difference: 1 [-11-13]). For predicting extensive myocardial fibrosis, LVGLS_SMART and LVM_SMART exhibited performance comparable to conventional LVGLS and CMR (AUC: 0.72 and 0.66, respectively). Patients identified as high risk for extensive fibrosis by LVGLS_SMART and LVM_SMART had significantly higher rates of adverse outcomes, including heart failure hospitalization, new-onset atrial fibrillation, and defibrillator implantation. The SMART technique provides a comparable LVGLS evaluation and a more accurate LVM assessment than conventional TTE, with predictive values for myocardial fibrosis and adverse outcomes. These findings support its utility in HCM management.

Foundation models like CLIP and SAM have transformed computer vision and medical imaging via low-shot transfer learning. However, deployment of these models hindered by two key challenges: \textit{distribution shift} between training and test data, and \textit{confidence misalignment} that leads to overconfident incorrect predictions. These issues manifest differently in vision-language classification and medical segmentation tasks, yet existing solutions remain domain-specific. We propose \textit{StaRFM}, a unified framework addressing both challenges. It introduces a Fisher information penalty (FIP), extended to 3D medical data via patch-wise regularization, to reduce covariate shift in CLIP and SAM embeddings. Additionally, a confidence misalignment penalty (CMP), reformulated for voxel-level predictions, calibrates uncertainty in segmentation tasks. We theoretically derive PAC-Bayes bounds showing FIP controls generalization via the Fisher-Rao norm, while CMP minimizes calibration error through Brier score optimization. StaRFM shows consistent performance like \texttt{+}3.5\% accuracy and 28\% lower ECE on 19 vision datasets (e.g., ImageNet, Office-Home), 84.7\% DSC and 4.8mm HD95 in medical segmentation (e.g., BraTS, ATLAS), and 40\% lower cross-domain performance gap compared to prior benchmarking methods. The framework is plug-and-play, requiring minimal architectural changes for seamless integration with foundation models. Code and models will be released at https://anonymous.4open.science/r/StaRFM-C0CD/README.md

In medical image segmentation, convolutional neural networks (CNNs) and transformers are dominant. For CNNs, given the local receptive fields of convolutional layers, long-range spatial correlations are captured through consecutive convolutions and pooling. However, as the computational cost and memory footprint can be prohibitively large, 3D models can only afford fewer layers than 2D models with reduced receptive fields and abstract levels. For transformers, although long-range correlations can be captured by multi-head attention, its quadratic complexity with respect to input size is computationally demanding. Therefore, either model may require input size reduction to allow more filters and layers for better segmentation. Nevertheless, given their discrete nature, models trained with patch-wise training or image downsampling may produce suboptimal results when applied on higher resolutions. To address this issue, here we propose the resolution-robust HNOSeg-XS architecture. We model image segmentation by learnable partial differential equations through the Fourier neural operator which has the zero-shot super-resolution property. By replacing the Fourier transform by the Hartley transform and reformulating the problem in the frequency domain, we created the HNOSeg-XS model, which is resolution robust, fast, memory efficient, and extremely parameter efficient. When tested on the BraTS'23, KiTS'23, and MVSeg'23 datasets with a Tesla V100 GPU, HNOSeg-XS showed its superior resolution robustness with fewer than 34.7k model parameters. It also achieved the overall best inference time (< 0.24 s) and memory efficiency (< 1.8 GiB) compared to the tested CNN and transformer models¹.