Reasoning is a hallmark of human intelligence, enabling adaptive decision-making in complex and unfamiliar scenarios. In contrast, machine intelligence remains bound to training data, lacking the ability to dynamically refine solutions at inference time. While some recent advances have explored reasoning in machines, these efforts are largely limited to verbal domains such as mathematical problem-solving, where explicit rules govern step-by-step reasoning. Other critical real-world tasks - including visual perception, spatial reasoning, and radiological diagnosis - require non-verbal reasoning, which remains an open challenge. Here we present a novel learning paradigm that enables machine reasoning in vision by allowing performance improvement with increasing thinking time (inference-time compute), even under conditions where labelled data is very limited. Inspired by dual-process theories of human cognition in psychology, our approach integrates a fast-thinking System I module for familiar tasks, with a slow-thinking System II module that iteratively refines solutions using self-play reinforcement learning. This paradigm mimics human reasoning by proposing, competing over, and refining solutions in data-scarce scenarios. We demonstrate superior performance through extended thinking time, compared not only to large-scale supervised learning but also foundation models and even human experts, in real-world vision tasks. These tasks include computer-vision benchmarks and cancer localisation on medical images across five organs, showcasing transformative potential for non-verbal machine reasoning.

Fetal cardiovascular magnetic resonance is an emerging tool for prenatal congenital heart disease assessment, but long acquisition times and fetal movements limit its clinical use. This study evaluates the clinical utility of deep learning super-resolution reconstructions for rapidly acquired, low-resolution fetal cardiovascular magnetic resonance. This prospective study included participants with fetal congenital heart disease undergoing fetal cardiovascular magnetic resonance in the third trimester of pregnancy, with axial cine images acquired at normal resolution and low resolution. Low-resolution cine data was subsequently reconstructed using a deep learning super-resolution framework (cine_DL). Acquisition times, apparent signal-to-noise ratio, contrast-to-noise ratio, and edge rise distance were assessed. Volumetry and functional analysis were performed. Qualitative image scores were rated on a 5-point Likert scale. Cardiovascular structures and pathological findings visible in cine_DL images only were assessed. Statistical analysis included the Student paired <i>t</i> test and the Wilcoxon test. A total of 42 participants were included (median gestational age, 35.9 weeks [interquartile range (IQR), 35.1-36.4]). Cine_DL acquisition was faster than cine images acquired at normal resolution (134±9.6 s versus 252±8.8 s; <i>P</i><0.001). Quantitative image quality metrics and image quality scores for cine_DL were higher or comparable with those of cine images acquired at normal-resolution images (eg, fetal motion, 4.0 [IQR, 4.0-5.0] versus 4.0 [IQR, 3.0-4.0]; <i>P</i><0.001). Nonpatient-related artifacts (eg, backfolding) were more pronounced in Cine_DL compared with cine images acquired at normal-resolution images (4.0 [IQR, 4.0-5.0] versus 5.0 [IQR, 3.0-4.0]; <i>P</i><0.001). Volumetry and functional results were comparable. Cine_DL revealed additional structures in 10 of 42 fetuses (24%) and additional pathologies in 5 of 42 fetuses (12%), including partial anomalous pulmonary venous connection. Deep learning super-resolution reconstructions of low-resolution acquisitions shorten acquisition times and achieve diagnostic quality comparable with standard images, while being less sensitive to fetal bulk movements, leading to additional diagnostic findings. Therefore, deep learning super-resolution may improve the clinical utility of fetal cardiovascular magnetic resonance for accurate prenatal assessment of congenital heart disease.

Low-dose computed tomography (LDCT) denoising plays an important role in medical imaging for reducing the radiation dose to patients. Recently, various data-driven and diffusion-based deep learning (DL) methods have been developed and shown promising results in LDCT denoising. However, challenges remain in ensuring generalizability to different datasets and mitigating uncertainty from stochastic sampling. In this paper, we introduce a novel dose-aware diffusion model that effectively reduces CT image noise while maintaining structural fidelity and being generalizable to different dose levels.&#xD;Approach: Our approach employs a physics-based forward process with continuous timesteps, enabling flexible representation of diverse noise levels. We incorporate a computationally efficient noise calibration module in our diffusion framework that resolves misalignment between intermediate results and their corresponding timesteps. Furthermore, we present a simple yet effective method for estimating appropriate timesteps for unseen LDCT images, allowing generalization to an unknown, arbitrary dose levels.&#xD;Main Results: Both qualitative and quantitative evaluation results on Mayo Clinic datasets show that the proposed method outperforms existing denoising methods in preserving the noise texture and restoring anatomical structures. The proposed method also shows consistent results on different dose levels and an unseen dataset.&#xD;Significance: We propose a novel dose-aware diffusion model for LDCT denoising, aiming to address the generalization and uncertainty issues of existing diffusion-based DL methods. Our experimental results demonstrate the effectiveness of the proposed method across different dose levels. We expect that our approach can provide a clinically practical solution for LDCT denoising with its high structural fidelity and computational efficiency.

Fetal MRI is increasingly being employed in the diagnosis of fetal lung anomalies and segmentation-derived total fetal lung volumes are used as one of the parameters for prediction of neonatal outcomes. However, in clinical practice, segmentation is performed manually in 2D motion-corrupted stacks with thick slices which is time consuming and can lead to variations in estimated volumes. Furthermore, there is a known lack of consensus regarding a universal lung parcellation protocol and expected normal total lung volume formulas. The lungs are also segmented as one label without parcellation into lobes. In terms of automation, to the best of our knowledge, there have been no reported works on multi-lobe segmentation for fetal lung MRI. This work introduces the first automated deep learning segmentation pipeline for multi-regional lung segmentation for 3D motion-corrected T2w fetal body images for normal anatomy and congenital diaphragmatic hernia cases. The protocol for parcellation into 5 standard lobes was defined in the population-averaged 3D atlas. It was then used to generate a multi-label training dataset including 104 normal anatomy controls and 45 congenital diaphragmatic hernia cases from 0.55T, 1.5T and 3T acquisition protocols. The performance of 3D Attention UNet network was evaluated on 18 cases and showed good results for normal lung anatomy with expectedly lower Dice values for the ipsilateral lung. In addition, we also produced normal lung volumetry growth charts from 290 0.55T and 3T controls. This is the first step towards automated multi-regional fetal lung analysis for 3D fetal MRI.

Precise aneurysm volume measurement offers a transformative edge for risk assessment and treatment planning in clinical settings. Currently, clinical assessments rely heavily on manual review of medical imaging, a process that is time-consuming and prone to inter-observer variability. The widely accepted standard-of-care primarily focuses on measuring aneurysm diameter at its widest point, providing a limited perspective on aneurysm morphology and lacking efficient methods to measure aneurysm volumes. Yet, volume measurement can offer deeper insight into aneurysm progression and severity. In this study, we propose an automated approach that leverages the strengths of pre-trained neural networks and expert systems to delineate aneurysm boundaries and compute volumes on an unannotated dataset from 60 patients. The dataset includes slice-level start/end annotations for aneurysm but no pixel-wise aorta segmentations. Our method utilizes a pre-trained UNet to automatically locate the aorta, employs SAM2 to track the aorta through vascular irregularities such as aneurysms down to the iliac bifurcation, and finally uses a Long Short-Term Memory (LSTM) network or expert system to identify the beginning and end points of the aneurysm within the aorta. Despite no manual aorta segmentation, our approach achieves promising accuracy, predicting the aneurysm start point with an R2 score of 71%, the end point with an R2 score of 76%, and the volume with an R2 score of 92%. This technique has the potential to facilitate large-scale aneurysm analysis and improve clinical decision-making by reducing dependence on annotated datasets.

Recent innovations in vector flow imaging promise to bring the modality closer to clinical application and allow for more comprehensive high-frame-rate vascular assessments. One such innovation is plane-wave multi-angle vector Doppler, where pulsed Doppler principles from multiple steering angles are used to realize vector flow imaging at frame rates upward of 1,000 frames per second (fps). Currently, vector Doppler is limited by the presence of aliasing artifacts that have prevented its reliable realization at the bedside. In this work, we present a new aliasing-resistant vector Doppler imaging system that can be deployed at the bedside using a programmable ultrasound core, graphics processing unit (GPU) processing, and deep learning principles. The framework supports two operational modes: 1) live imaging at 17 fps where vector flow imaging serves to guide image view navigation in blood vessels with complex dynamics; 2) on-demand replay mode where flow data acquired at high frame rates of over 1,000 fps is depicted as a slow-motion playback at 60 fps using an aliasing-resistant vector projectile visualization. Using our new system, aliasing-free vector flow cineloops were successfully obtained in a stenosis phantom experiment and in human bifurcation imaging scans. This system represents a major engineering advance towards the clinical adoption of vector flow imaging.

Long axial field-of-view PET scanners offer increased field-of-view and sensitivity compared to traditional PET scanners. However, a significant cost is associated with the densely packed photodetectors required for the extended-coverage systems, limiting clinical utilisation. To mitigate the cost limitations, alternative sparse system configurations have been proposed, allowing an extended field-of-view PET design with detector costs similar to a standard PET system, albeit at the expense of image quality. In this work, we propose a deep sinogram restoration network to fill in the missing sinogram data. Our method utilises a modified Residual U-Net, trained on clinical PET scans from a GE Signa PET/MR, simulating the removal of 50% of the detectors in a chessboard pattern (retaining only 25% of all lines of response). The model successfully recovers missing counts, with a mean absolute error below two events per pixel, outperforming 2D interpolation in both sinogram and reconstructed image domain. Notably, the predicted sinograms exhibit a smoothing effect, leading to reconstructed images lacking sharpness in finer details. Despite these limitations, the model demonstrates a substantial capacity for compensating for the undersampling caused by the sparse detector configuration. This proof-of-concept study suggests that sparse detector configurations, combined with deep learning techniques, offer a viable alternative to conventional PET scanner designs. This approach supports the development of cost-effective, total body PET scanners, allowing a significant step forward in medical imaging technology.

Magnetic resonance spectroscopic imaging has potential for non-invasive metabolic imaging of the human brain. Here we report a method that overcomes several long-standing technical barriers associated with clinical magnetic resonance spectroscopic imaging, including long data acquisition times, limited spatial coverage and poor spatial resolution. Our method achieves ultrafast data acquisition using an efficient approach to encode spatial, spectral and J-coupling information of multiple molecules. Physics-informed machine learning is synergistically integrated in data processing to enable reconstruction of high-quality molecular maps. We validated the proposed method through phantom experiments. We obtained high-resolution molecular maps from healthy participants, revealing metabolic heterogeneities in different brain regions. We also obtained high-resolution whole-brain molecular maps in regular clinical settings, revealing metabolic alterations in tumours and multiple sclerosis. This method has the potential to transform clinical metabolic imaging and provide a long-desired capability for non-invasive label-free metabolic imaging of brain function and diseases for both research and clinical applications.

Risk stratification is a key tool in clinical decision-making, yet current approaches often fail to translate sophisticated survival analysis into actionable clinical criteria. We present a novel method for unsupervised machine learning that directly optimizes for survival heterogeneity across patient clusters through a differentiable adaptation of the multivariate logrank statistic. Unlike most existing methods that rely on proxy metrics, our approach represents novel methodology for training any neural network architecture on any data modality to identify prognostically distinct patient groups. We thoroughly evaluate the method in simulation experiments and demonstrate its utility in practice by applying it to two distinct cancer types: analyzing laboratory parameters from multiple myeloma patients and computed tomography images from non-small cell lung cancer patients, identifying prognostically distinct patient subgroups with significantly different survival outcomes in both cases. Post-hoc explainability analyses uncover clinically meaningful features determining the group assignments which align well with established risk factors and thus lend strong weight to the methods utility. This pan-cancer, model-agnostic approach represents a valuable advancement in clinical risk stratification, enabling the discovery of novel prognostic signatures across diverse data types while providing interpretable results that promise to complement treatment personalization and clinical decision-making in oncology and beyond.

IntroductionIntegrated digital diagnostics can support complex surgeries in many anatomic sites, and brain tumour surgery represents one of the most complex cases. Neurosurgeons face several challenges during brain tumour surgeries, such as differentiating critical tissue from brain tumour margins. To overcome these challenges, the STRATUM project will develop a 3D decision support tool for brain surgery guidance and diagnostics based on multimodal data processing, including hyperspectral imaging, integrated as a point-of-care computing tool in neurosurgical workflows. This paper reports the protocol for the development and technical validation of the STRATUM tool. Methods and analysisThis international multicentre, prospective, open, observational cohort study, STRATUM-OS (study: 28 months, pre-recruitment: 2 months, recruitment: 20 months, follow-up: 6 months), with no control group, will collect data from 320 patients undergoing standard neurosurgical procedures to: (1) develop and technically validate the STRATUM tool, and (2) collect the outcome measures for comparing the standard procedure versus the standard procedure plus the use of the STRATUM tool during surgery in a subsequent historically controlled non-randomized clinical trial. Ethics and disseminationThe protocol was approved by the participant Ethics Committees. Results will be disseminated in scientific conferences and peer-reviewed journals. Trial registration number[Pending Number] ARTICLE SUMMARYO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LISTRATUM-OS will be the first multicentre prospective observational study to develop and technically validate a 3D decision support tool for brain surgery guidance and diagnostics in real-time based on artificial intelligence and multimodal data processing, including the emerging hyperspectral imaging modality. C_LIO_LIThis study encompasses a prospective collection of multimodal pre, intra and postoperative medical data, including innovative imaging modalities, from patients with intra-axial brain tumours. C_LIO_LIThis large observational study will act as historical control in a subsequent clinical trial to evaluate a fully-working prototype. C_LIO_LIAlthough the estimated sample size is deemed adequate for the purpose of the study, the complexity of the clinical context and the type of surgery could potentially lead to under-recruitment and under-representation of less prevalent tumour types. C_LI