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Biology subjects

Rueckert, D.

Publications and source records attributed to Rueckert, D..

At least 19 recordsLinked to original sources

MedMCP: An Open Agentic Ecosystem for Medical Imaging Workflows

Deep learning has driven rapid progress in medical image analysis, with methods for tasks such as organ segmentation, anomaly detection, and radiology report generation now matching or surpassing expert performance on several benchmarks. While many methods are released as open source, their routine adoption by clinicians and medical researchers remains limited. The bottleneck is not a lack of capable tools, but the absence of infrastructure to make them accessible to non-technical users. To break this barrier, we present MedMCP, an agentic framework that solves this last-mile problem along two axes: (1) a local agentic workspace that lets users apply state-of-the-art image analysis methods through natural language, and (2) a community-driven tool ecosystem that lets developers deploy and distribute capabilities as validated, independently testable servers. MedMCP enforces a strict orchestration-execution boundary in which a local language model translates user intent into workflow plans, while all image analysis is delegated to domain-specific tools. The framework runs entirely on-premise, every side-effecting operation passes through a human-in-the-loop permission gate, and a full provenance trail links each output to the tools, parameters, and inputs that produced it. An inspectable workspace lets users verify intermediate results rather than blindly trusting the agent, and completed sessions distill into deterministic, shareable workflows that re-execute without the agent, turning one-off interactions into reproducible analyses. This paper introduces the project's general idea and describes the design principles that guide its development. Beyond a single toolkit, we envision MedMCP as a community-driven platform where each contributed tool becomes easily accessible, compounding individual efforts into shared capability.

bioinformatics↗

Medical Images as Biomarkers of Ageing - From Global and Local Patterns to Digital Twins

AbstractO_ST_ABSBackgroundC_ST_ABSUnderstanding human ageing across multiple organs is essential for characterising individual health trajectories and identifying abnormal ageing processes. Multiorgan imaging provides an opportunity to quantify biological ageing beyond chronological age. The aim of this study is to assess organ-specific and whole-body ageing patterns and their associations with disease and lifestyle factors. MethodsIn this large-scale study, we evaluate biological ageing patterns using 70,000 MRI scans from the UK Biobank and the German National Cohort. We employ 3D ResNet-18 models to predict chronological age from various body regions (brain, heart, liver, spine, lungs, muscle, and intestine) and the whole body. From these predictions, we derive "age gaps" relative to a strictly healthy reference cohort, which enables the identification of accelerated ageing patterns. We then evaluate associations with chronic diseases and lifestyle factors, and a virtual ageing framework was developed to explore counterfactual scenarios by substituting anatomical regions across subjects, quantifying local impacts on global biological age. ResultsHere we show significant associations between detected accelerated ageing and specific chronic diseases, including multiple sclerosis and chronic obstructive pulmonary disease, as well as lifestyle factors such as smoking and physical activity. Virtual substitution of anatomical regions demonstrates that local substitutions can influence global ageing patterns. ConclusionsThis study demonstrates that multi-organ imaging enables the detection of abnormal ageing patterns at both local and global levels. The presented framework provides a foundation for improved risk stratification and supports the development of personalised approaches to health assessment and disease prevention. Plain Language SummaryAs people age, different organs in the body might not always age at the same pace. Understanding these differences can help to explain a persons health and why they develop diseases earlier than others. In this study, we measure how ageing varies across the body using medical images. We analysed about 70,000 whole-body scans from large population studies in the United Kingdom and Germany. Using AI models, we estimated a persons biological age from images of different organs and compared it with their actual age. We found that faster ageing in specific organs is linked to certain diseases (such as multiple sclerosis) and lifestyle factors (like smoking and physical activity). These findings may help improve early disease detection and support more personalised approaches to health and ageing in the future.

bioinformatics↗

Deep Learning and 3D Imaging Reveal Whole-Body Alterations in Obesity

Many diseases, such as obesity, have systemic effects that impact multiple organ systems throughout the body. However, tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking. Here, we developed a suite of deep learning-based image analysis algorithms (MouseMapper) and integrated it with tissue clearing and light-sheet microscopy to enable a comprehensive analysis of diseases impacting diverse systems across the mouse body. This approach enables the quantitative analysis of cellular and structural changes across the entire mouse body at unprecedented resolution and scale, including tracking nerves over several centimeters in whole animal bodies. To demonstrate its power, we applied MouseMapper to study nervous and immune systems in high-fat diet induced obesity. We uncovered widespread changes in both immune cell distribution and nerve structures, including alterations in the trigeminal nerve characterized by a reduced number of nerve endings in obese mice. These structural abnormalities were associated with functional deficits of whisker sensing and proteomic changes in the trigeminal ganglion, primarily affecting pathways related to axon growth and the complement system. Additionally, we found heterogeneity in obesity-induced whole-body inflammation across different tissues and organs. Our study demonstrates MouseMappers capability to discover and quantify pathological alterations at the whole-body level, offering a powerful approach for investigating the systemic impacts of various diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/608300v1_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@17d2601org.highwire.dtl.DTLVardef@14a2d3dorg.highwire.dtl.DTLVardef@e04114org.highwire.dtl.DTLVardef@d0b8b5_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe developed MouseMapper: AI-driven pipeline for whole-body structural analysis in mice C_LIO_LIMouseMapper revealed obesity-induced changes in nerves and immune cells across multiple organs C_LIO_LIMouseMapper identified facial nerve alterations in obesity linked to impaired whisker sensitivity C_LIO_LIMouseMapper has the potential for holistic 3D analysis of systemic diseases C_LI Supplementary Videos can be seen at: http://discotechnologies.org/MouseMapper/

systems biology↗

The developing Human Connectome Project fetal functional MRI release: Methods and data structures

Recent advances in fetal fMRI present a new opportunity for neuroscience to study functional human brain connectivity at the time of its emergence. Progress in the field however has been hampered by the lack of openly available datasets that can be exploited by researchers across disciplines to develop methods that would address the unique challenges associated with imaging and analysing functional brain in utero, such as unconstrained head motion, dynamically evolving geometric distortions, or inherently low signal-to-noise ratio. Here we describe the developing Human Connectome Projects release of the largest open access fetal fMRI dataset to date, containing 275 scans from 255 fetuses and spanning the period of 20.86 to 38.29 post-menstrual weeks. We present a systematic approach to its pre-processing, implementing multi-band soft SENSE reconstruction, dynamic distortion corrections via phase unwrapping method, slice-to-volume reconstruction and a tailored temporal filtering model, with attention to the prominent sources of structured noise in the in utero fMRI. The dataset is accompanied with an advanced registration infrastructure, enabling group-level data fusion, and contains outputs from the main intermediate processing steps. This allows for various levels of data exploration by the imaging and neuroscientific community, starting from the development of robust pipelines for anatomical and temporal corrections to methods for elucidating the development of functional connectivity in utero. By providing a high-quality template for further method development and benchmarking, the release of the dataset will help to advance fetal fMRI to its deserved and timely place at the forefront of the efforts to build a life-long connectome of the human brain.

neuroscience↗

A spatio-temporaral atlas of the growing brain for fMRI studies

Spatio-temporal atlases of the growing brain can help when building models of brain development, not only for anatomical structure, but also for the changing patterns of activation within the brain. In this paper, we build such an age-dependent atlas using registrations among a large number of anatomical datasets, acquired from neonatal subjects of different ages, and followed by kernel-based regression. fMRI activation data are then registered to this atlas to build a model of the development of brain networks, such as the default and motor networks, at this early age.

neuroscience↗

Maturational networks of fetal brain activity

A key feature of the fetal period is the rapid emergence of organised patterns of spontaneous brain activity. However, characterising this process in utero using functional MRI is inherently challenging and requires analytical methods which can capture the constituent developmental transformations. Here, we introduce a novel analytical framework, termed "maturational networks" (matnets), that achieves this by modelling functional networks as an emerging property of the developing brain. Compared to standard network analysis methods that assume consistent patterns of connectivity across development, our method incorporates age-related changes in connectivity directly into network estimation. We test its performance in a large neonatal sample, finding that the matnets approach characterises adult-like features of functional network architecture with a greater specificity than a standard group-ICA approach; for example, our approach is able to identify a nearly complete default mode network. In the in-utero brain, matnets enables us to reveal the richness of emerging functional connections and the hierarchy of their maturational relationships with remarkable anatomical specificity. We show that the associative areas play a central role within prenatal functional architecture, therefore indicating that functional connections of high-level associative areas start emerging prior to exposure to the extra-utero environment.

neuroscience↗

Development of neonatal brain functional centrality and alterations associated with preterm birth

Formation of the functional connectome in early life underpins future learning and behaviour. However, our understanding of how the functional organisation of brain regions into interconnected hubs (centrality) matures in the early postnatal period is limited, especially in response to factors associated with adverse neurodevelopmental outcomes such as preterm birth. We characterised voxel-wise functional centrality (weighted degree) in 366 neonates from the Developing Human Connectome Project. We tested the hypothesis that functional centrality matures with age at scan in term-born babies and is disrupted by preterm birth. Finally, we asked whether neonatal functional centrality predicts general neurodevelopmental outcomes at 18 months. We report an age-related increase in functional centrality predominantly within visual regions and decrease within motor and auditory regions in term-born infants. Preterm-born infants scanned at term equivalent age had higher functional centrality predominantly within visual regions and lower measures in motor regions. Functional centrality was not related to outcome at 18 months old. Thus, preterm birth appears to affect functional centrality in regions undergoing substantial development during the perinatal period. Our work raises the question of whether these alterations are adaptive or disruptive, and whether they predict neurodevelopmental characteristics that are more subtle or emerge later in life.

neuroscience↗

Benchmarking Geometric Deep Learning for Cortical Segmentation and Neurodevelopmental Phenotype Prediction

The emerging field of geometric deep learning extends the application of convolutional neural networks to irregular domains such as graphs, meshes and surfaces. Several recent studies have explored the potential for using these techniques to analyse and segment the cortical surface. However, there has been no comprehensive comparison of these approaches to one another, nor to existing Euclidean methods, to date. This paper benchmarks a collection of geometric and traditional deep learning models on phenotype prediction and segmentation of sphericalised neonatal cortical surface data, from the publicly available Developing Human Connectome Project (dHCP). Tasks include prediction of postmenstrual age at scan, gestational age at birth and segmentation of the cortical surface into anatomical regions defined by the M-CRIB-S atlas. Performance was assessed not only in terms of model precision, but also in terms of network dependence on image registration, and model interpretation via occlusion. Networks were trained both on sphericalised and anatomical cortical meshes. Findings suggest that the utility of geometric deep learning over traditional deep learning is highly task-specific, which has implications for the design of future deep learning models on the cortical surface. The code, and instructions for data access, are available from https://github.com/Abdulah-Fawaz/Benchmarking-Surface-DL.

neuroscience↗

Structural and functional asymmetry of the neonatal cerebral cortex

Features of brain asymmetry have been implicated in a broad range of cognitive processes; however, their origins are still poorly understood. Using a new left-right symmetric, spatiotemporal cortical surface atlas, we investigated cortical asymmetries in 442 healthy term-born neonates using structural and functional magnetic resonance images from the Developing Human Connectome Project. Cortical asymmetries observed in the term cohort were contextualised in two ways: by comparing them against cortical asymmetries observed in 103 preterm neonates scanned at term-equivalent age, and by comparing structural asymmetries against those observed in 1110 healthy young adults from the Human Connectome Project. Our results demonstrate that the neonatal cortex is markedly asymmetric in both structure and function, and while associations with preterm birth and biological sex were minimal, significant differences exist between birth and adulthood. Although these changes may represent experience-dependent developmental milestones, longitudinal studies across the lifespan are required to fully address these hypotheses.

neuroscience↗

Neonatal multi-modal cortical profiles predict 18-month developmental outcomes

Developmental delays in infanthood often persist, turning into life-long difficulties, and coming at great cost for the individual and community. By examining the developing brain and its relation to developmental outcomes we can start to elucidate how the emergence of brain circuits is manifested in variability of infant motor, cognitive and behavioural capacities. In this study, we examined if cortical structural covariance at birth, indexing coordinated development, is related to later infant behaviour. We included 193 healthy term-born infants from the Developing Human Connectome Project (dHCP). An individual cortical connectivity matrix derived from morphological and microstructural features was computed for each subject (morphometric similarity networks, MSNs) and was used as input for the prediction of behavioural scores at 18 months using Connectome-Based Predictive Modeling (CPM). Neonatal MSNs successfully predicted social-emotional performance. Predictive edges were distributed between and within known functional cortical divisions with a specific important role for primary and posterior cortical regions. These results reveal that multi-modal neonatal cortical profiles showing coordinated maturation are related to developmental outcomes and that network organization at birth provides an early infrastructure for future functional skills.

neuroscience↗

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age

IntroductionThe dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. MethodsWe sought to first map typical cortical micro and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n=270). Then we offer a comprehensive characterisation of the cortical consequences of preterm birth in 78 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. ResultsIn the term-born neonatal brain, we observed regionally specific age-associated changes in cortical morphology and microstructure, including rapid surface expansion, cortical thickness increase, reduction in cortical anisotropy and increase in neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. ConclusionWe showed that preterm birth alters cortical micro and macrostructural maturation near the time of fullterm birth. Deviations from normative development were highly variable between individual preterm infants.

neuroscience↗

Effects of gestational age at birth on perinatal structural brain development in healthy term-born babies

Multiple studies have demonstrated less favourable childhood outcomes in infants born in early term (37-38 weeks gestation) compared to those born at full term (40-41 weeks gestation). While this could be due to higher perinatal morbidity, gestational age at birth may also have a direct effect on the brain and subsequent neurodevelopment in term-born babies. Here we characterise structural brain correlates of gestational age at birth in healthy term-born neonates and their relationship to later neurodevelopmental outcome. We used T2 and diffusion weighted Magnetic Resonance Images acquired in the neonatal period from a cohort (n=454) of healthy babies born at term age (>37 weeks gestation) and scanned between 1 and 41 days after birth. Images were analysed using tensor based morphometry (TBM) and tract based spatial statistics (TBSS). Neurodevelopment was subsequently assessed at age 18 months using the Bayley-III Scales of Infant and Toddler Development, and the effects of gestational age at birth and related neuroimaging findings on outcome were analysed with linear regression. Infants born earlier had areas of higher relative ventricular volume, and lower relative brain volume in the basal ganglia, cerebellum and brainstem. Earlier birth was also associated with lower fractional anisotropy, higher mean, axial and radial diffusivity in major white matter tracts. Gestational age at birth was positively associated with all Bayley-III subscales at age 18 months. Linear regression models predicting outcome from gestational age at birth were significantly improved by adding neuroimaging features associated with gestational age at birth. This work adds to the growing body of evidence of the impact of early term birth and highlights the importance of considering the effect of gestational age at birth in future neuroimaging studies including term-born babies.

neuroscience↗

The developing brain structural and functional connectome fingerprint

In the mature brain, structural and functional connectivity fingerprints can be used to identify the uniqueness of an individual. However, whether the characteristics that make a brain distinguishable from others already exist at birth remains unknown. Here, we used neuroimaging data of preterm born neonates who were scanned twice during the perinatal period to assess the developing brain fingerprint. We found that 62% of the participants could be identified based on the congruence of the later structural connectome to the initial connectivity matrix derived from the earlier timepoint. In contrast, similarity between functional connectomes only allowed to identify 12% of the participants. These suggests that structural connectivity is more stable in early life and can represent a potential connectome fingerprint. Thus, a relatively stable structural connectome appears to support a changing functional connectome at a time when neonates must rapidly acquire new skills to adapt to their new environment.

neuroscience↗

Predicting age and clinical risk from the neonatal connectome

The development of perinatal brain connectivity underpins motor, cognitive and behavioural abilities in later life. Diffusion MRI allows the characterisation of subtle inter-individual differences in structural brain connectivity. Individual brain connectivity maps (connectomes) are by nature high in dimensionality and are complex to interpret. Machine learning methods are a powerful tool to uncover properties of the connectome which are not readily visible, and can give us clues as to how and why individual developmental trajectories differ. In this manuscript we used Deep Neural Networks and Random Forests to predict demographic and neurodevelopmental characteristics from neonatal structural connectomes in a large sample of babies (n = 524) from the developing Human Connectome Project. We achieved an accurate prediction of post menstrual age (PMA) at scan in term-born infants (Mean absolute error (MAE) = 0.72 weeks, r = 0.83 and p<0.001). We also achieved good accuracy when predicting gestational age at birth in a cohort of term and preterm babies scanned at term equivalent age (MAE = 2.21 weeks, r = 0.82, p<0.001). We subsequently used sensitivity analysis to obtain feature relevance from our prediction models, with the most important connections for prediction of PMA and GA found to be predominantly thalamocortical. From our models of PMA at scan for infants born at term, we computed a brain maturation index (predicted age minus actual age) of individual preterm neonates and found a significant correlation between this index and motor outcome at 18 months corrected age. Our results demonstrate the applicability of machine learning techniques in analyses of the neonatal connectome, and suggest that a neural substrate for later developmental outcome is detectable at term equivalent age.

neuroscience↗

Individualized characterization of volumetric development in the preterm brain

The diverse cerebral consequences of preterm birth create significant challenges for understanding pathogenesis or predicting later outcome. Instead of focusing on describing effects common to the group, comparing individual infants against robust normative data offers a powerful alternative to study brain maturation. Here we used Gaussian process regression to create normative curves characterising brain volumetric development in 274 term-born infants, modelling for age at scan and sex. We then compared 89 preterm infants scanned at termequivalent age to these normative charts, relating individual deviations from typical volumetric development to perinatal risk factors and later neurocognitive scores. To test generalisability, we used a second independent dataset comprising of 253 preterm infants scanned using different acquisition parameters and scanner. We describe rapid, non-uniform brain growth during the neonatal period. In both preterm cohorts, cerebral atypicalities were widespread, often multiple, and varied highly between individuals. Deviations from normative development were associated with respiratory support, nutrition, birth weight, and later neurocognition, demonstrating their clinical relevance. Group-level understanding of the preterm brain disguise a large degree of individual differences. We provide a method and normative dataset that offer a more precise characterisation of the cerebral consequences of preterm birth by profiling the individual neonatal brain.

neuroscience↗

Cortical morphology at birth reflects spatio-temporal patterns of gene expression in the fetal brain

Interruption to gestation through preterm birth can significantly impact cortical development and have long-lasting adverse effects on neurodevelopmental outcome. We compared cortical morphology captured by high-resolution, multimodal MRI in n=292 healthy newborn infants (mean age at birth=39.9 weeks) with regional patterns of gene expression in the fetal cortex across gestation (n=156 samples from 16 brains, aged 12 to 37 post-conceptional weeks). We tested the hypothesis that noninvasive measures of cortical structure at birth mirror areal differences in cortical gene expression across gestation, and in a cohort of n=64 preterm infants (mean age at birth = 32.0 weeks), we tested whether cortical alterations observed after preterm birth were associated with altered gene expression in specific developmental cell populations. Neonatal cortical structure was aligned to differential patterns of cell-specific gene expression in the fetal cortex. Principal component analysis of six measures of cortical morphology and microstructure showed that cortical regions were ordered along a principal axis, with primary cortex clearly separated from heteromodal cortex. This axis was correlated to estimated tissue maturity, indexed by differential expression of genes expressed by progenitor cells and neurons; and engaged in stem cell differentiation, neuron migration and forebrain development. Preterm birth was associated with altered regional MRI metrics and patterns of differential gene expression in glial cell populations. The spatial patterning of gene expression in the developing cortex was thus mirrored by regional variation in cortical morphology and microstructure at term, and this was disrupted by preterm birth. This work provides a framework to link molecular mechanisms to noninvasive measures of cortical development in early life and highlights novel pathways to injury in neonatal populations at increased risk of neurodevelopmental disorder.

neuroscience↗

The Developing Human Connectome Project: typical and disrupted functional connectivity across the perinatal period

The Developing Human Connectome Project (dHCP) is an Open Science project which provides the first large sample of neonatal functional MRI (fMRI) data with high temporal and spatial resolution. This data enables mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organisation in humans. Here, we characterise in unprecedented detail the maturation and integrity of resting-state networks (RSNs) at normal term age in 337 infants (including 65 born preterm). First, we applied group independent component analysis (ICA) to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder which occur frequently in preterm children. Overall, we find a robust, modular, symmetrical functional brain organisation at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher-order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.

neuroscience↗

Development of Microstructural and Morphological Cortical Profiles in the Neonatal Brain

In the perinatal brain, regional cortical architecture and connectivity lay the foundations for functional circuits and emerging behaviour. Interruptions or atypical development during or before this period may therefore have long-lasting consequences. However, to be able to investigate these deviations, we need a measure of how this architecture evolves in the typically developing brain. To this end, in a large cohort of 241 term-born infants we used Magnetic Resonance Imaging to estimate cortical profiles based on morphometry and microstructure over the perinatal period (37-44 weeks post-menstrual age, PMA). Using the covariance of these profiles as a measure of inter-areal network similarity (Morphometric Similarity Networks; MSN), we clustered these networks into distinct modules. The resulting modules were consistent and symmetric, and corresponded to known functional distinctions, including sensory-motor, limbic and association regions and were spatially mapped onto known cytoarchitectonic tissue classes. Posterior (parietal, occipital) regions became more morphometrically similar with increasing PMA, while peri-cingulate and medial temporal regions became more dissimilar. Network strength was associated with PMA: Within-network similarity increased over PMA suggesting emerging network distinction. These changes in cortical network architecture over an eight-week period are consistent with, and likely underpin, the highly dynamic behavioural and cognitive development occurring during this critical period. The resulting cortical profiles might provide normative reference to investigate atypical early brain development.

neuroscience↗