Biology subjects

Urban, T.

Publications and source records attributed to Urban, T..

14 recordsLinked to original sources

bioRxiv2026

Cross-species structure-mechanics prediction in the intervertebral disc

Despite long-standing uncertainty regarding the suitability of animal intervertebral disc (IVD) models for the study of human IVD pathophysiology, few cross-species studies have integrated hierarchical structure with mechanical function. In this study, we present a multiscale structure-mechanics framework combining synchrotron computed tomography (sCT), fibre tracing, digital volume correlation (DVC) with structure-based mechanical inference and finite-element modelling. Rat, mini-pig and human IVDs (n = 3/species) were imaged by sCT, with rat and mini-pig discs additionally subjected to in situ uniaxial compression and DVC. A Structure Index (SI), integrating local structural anisotropy and fibre orientation, was developed to regionally pinpoint the location of mechanically vulnerable regions. Cross-species comparison showed scale-dependent structural conservation: gross disc and lamellar organisation retained common regional features, whereas fibre-bundle architecture exhibited greater species- and regional divergence. Despite these differences, lower SI was consistently associated with elevated deformation in rat and mini-pig discs across multiple strain measures. Structure-strain inverse correlations became tighter within progressively higher-strain domains, reaching Spearman p values of approximately -0.5 to -0.7 for several strain components. Synthetic fibre phantoms confirmed that SI reflects a coupling of fibre orientation and organisation, with additional sensitivity to fibre number in poorly organised configurations. In human discs with varying degrees of degeneration, SI revealed spatial heterogeneity and redistribution of structurally vulnerable regions. Fibril-informed homogenisation provided anisotropic material properties for organ-scale finite-element modelling that independently supported SI-based predictions. Overall, these findings establish a cross-species framework linking hierarchical collagen architecture to mechanical vulnerability and provide a basis for non-invasive, structure-driven biomechanical assessment of human IVD degeneration and mechanical risk.

bioengineering↗

bioRxiv2026

Revealing multiscale architecture of the intact human spine using hierarchical phase contrast tomography

Background: Computed tomography (CT) and magnetic resonance imaging (MRI) provide detailed clinical assessment of the human spine; however, their millimeter-scale spatial resolution limits direct visualization of tissue microarchitecture and interfaces. Hierarchical phase-contrast tomography (HiP-CT) enables ex vivo non-destructive, micron-resolution imaging of intact human organs without exogenous contrast agents, extending anatomical assessment to spatial scales inaccessible to conventional clinical imaging. Purpose: To evaluate the capability of HiP-CT to visualize macro- to microanatomy of an intact adult human spine ex vivo. Methods: An intact spine (C1-L5) from a 62-year-old male donor without known skeletal disease was formalin-fixed and imaged by HiP-CT at the European Synchrotron. Whole-spine imaging was performed at 16.26 m isotropic voxels, with selected regions of interest imaged using 2.2 m voxels. Ex vivo MRI using clinical sequences was performed for anatomical comparison. Three-dimensional segmentation and quantitative analyses included intervertebral disc (IVD) grading, annulus fibrosus fiber tracing, and vertebral trabecular micro-morphometry. Results: HiP-CT enabled high spatial-resolution, multiscale imaging of the intact human spine, simultaneously visualizing vertebral bone and endplate, IVDs, spinal cord and meninges, nerve roots and ganglia, vasculature, ligaments, and musculature. Three-dimensional segmentation and virtual sectioning mapped neurovascular anatomy and vertebral vascular supply, without exogenous contrast enhancement, while preserving their relationships with surrounding tissues. Whole-spine images enabled quantitative analysis of annulus fibrosus fiber organization and vertebral trabecular microarchitecture, permitting the detection of focal posterolateral fiber disruption at the L4-L5 IVD and regional differences in trabecular architecture between cervical and lumbar vertebral bodies. Local tomography resolved annulus fibrosus lamellae, vertebral endplate Haversian systems, and facet joint hyaline cartilage at micron resolution. Conclusions: HiP-CT enables non-destructive, multiscale three-dimensional imaging of the intact human spine while preserving tissue relationships across spatial scales and hard-soft tissue boundaries. HiP-CT could provide an ex vivo microanatomical reference for future correlation with clinical imaging investigations of spinal disease and in the development and validation of imaging biomarkers.

bioengineering↗

bioRxiv2026

Multiscale mapping of venous remodelling in idiopathic pulmonary fibrosis

The integrity of the pulmonary vasculature is a key determinant of lung health, yet challenges in visualisation and quantification have hindered interrogation of its pathophysiological role in chronic lung disease. Here, we align recent advances in microscale image acquisition with novel computer vision-based vessel segmentation models to demonstrate expansion of the bronchial and pulmonary veins across varying severities of tissue remodelling in idiopathic pulmonary fibrosis (IPF). Relating these imaging findings to molecular data in control, mild, and severe fibrosis, we show that bronchial venous endothelial cells expand beyond their physiological peribronchial niche even in mild disease, acquiring persistent angiogenic, inflammatory, and matrix-remodelling programmes that define a specialised fibrovascular-immune interface. Finally, we relate these microscale and molecular observations to clinical CT imaging, demonstrating that intrapulmonary vein enlargement independently associates with worsened survival across three IPF cohorts. Collectively, our multimodal, multiscale approach connects previously unresolved three-dimensional venous architecture to its molecular endothelial correlate, establishing venous enlargement as a prognostically significant and clinically relevant feature of IPF. Our analytical approach also demonstrates how biological discoveries made in intact ex vivo human organs can translate into measurable phenotypes in living patients, providing a template for other organs and diseases.

pathology↗

bioRxiv2026

BigHeart: Mapping connectivity in the adult human heart at the micron scale

The human heart depends on coordinated muscular, electrical, vascular, lymphatic, and neural systems, but their three-dimensional relationships remain unresolved at microscopic resolution across an intact adult organ. Using hierarchical phase-contrast tomography, we generated a continuous three-dimensional structural reference of a whole adult human heart at 8.01 micrometer isotropic voxel size, without sectioning or staining. Organ-wide imaging revealed hierarchical myocardial architecture, and quantitative orientation analysis identified regional differences in myocardial cell aggregate organization. The atrioventricular conduction axis was traced into a distinct subendocardial Purkinje network interfacing with working myocardium. Integrated segmentation showed that coronary vessels, lymphatic collectors, and autonomic nerves occupy shared epicardial corridors. This publicly accessible dataset integrates cardiac systems within a common spatial framework for anatomy, computational modeling, and future molecular atlases.

physiology↗

bioRxiv2026

Revisiting the Structure of the Ventricular Myocardium in Tetralogy of Fallot Using Hierarchical Phase Contrast Tomography and Structure Tensor Analysis

BACKGROUNDIn tetralogy of Fallot (ToF), changes in right ventricular function (as assessed by strain or TAPSE) reflect altered myocardial structure. Direct three-dimensional anatomical evidence supporting these changes remains limited. The objective of this study was to non-destructively characterize myocardial architecture in pediatric ToF hearts using Hierarchical Phase-Contrast Tomography (HiP-CT) and structure tensor analysis. METHODSTwenty ToF and control pediatric hearts were imaged at the European Synchrotron, ESRF. Myocyte orientation was assessed through structure tensor analysis and distributed high-performance computing. A region-specific framework was developed for analysis of the right ventricle. The predominant direction of myocardial aggregates (their helical angle) was compared across ventricular regions. RESULTSSignificant differences in orientation were found in all ToF segments vs controls (left ventricle, right ventricular inlet, right ventricular outflow tract, septum; p < 0.001). Myocytes in the ToF right ventricular inlet were more circumferential overall, with regional heterogeneity. Contrary to traditional models, no discrete middle layer was found in the ToF right ventricle; instead, a shift towards more circumferentially orientated myocytes and disrupted septal and outflow components was observed. Right ventricular contribution to the septum was greater in ToF (47.3% vs 34.0%; p = 0.0026), with extension of ventricular insertion points disrupting septal architecture. There were more longitudinally oriented myocytes in the ToF right ventricular outflow tract, consistent with hypertrophied septoparietal trabeculations. Left ventricular structure in ToF demonstrated a greater proportion of circumferentially oriented myocytes compared to controls. CONCLUSIONSWe reveal profound alterations in ToF myocardial organization which broadly align with clinical observations and provide the first open-access HiP-CT congenital heart disease data as a basis for future computational modelling. Clinical PerspectiveWhole-heart HiP-CT demonstrates a loss of normal LV-RV distinction in the ToF myocardium, alongside extensive septal disarray. These findings provide a structural substrate for RV dysfunction, ventricular-ventricular interaction, and arrhythmogenesis in ToF, challenging traditional layer-based models of ventricular myocardium. Understanding myocardial organization as a continuous, developmentally patterned three-dimensional structure is essential for accurate interpretation of ventricular mechanics and disease progression. Although HiP-CT imaging is not applicable in vivo, the structural phenotypes identified in this study generate testable hypotheses for clinical imaging. Future work should focus on correlating ex-vivo measures with in-vivo imaging markers derived from cardiac magnetic resonance, including strain, TAPSE, and assessment of ventricular interactions. Investigating myocardial phenotype across the life-course, from fetal life to adulthood, paired with multi-omics mapped to these three-dimensional datasets, may help elucidate mechanisms underlying myocardial remodeling in ToF and support the development of novel therapeutic approaches.

physiology↗

bioRxiv2026

Hierarchical X-ray microscopy and mesoscopic diffusion MRI in the same brain reveal the human connectome across scales

We present a multimodal pipeline for 3D imaging of cerebral white-matter archi-tecture across scales, from whole-brain axonal projections down to individual myelinated axons. After diffusion MRI, an adult ex vivo human hemisphere undergoes label-free imaging with Hierarchical Phase-Contrast Tomography (HiP-CT) from 20 {micro}m/voxel in the whole hemisphere to 2 {micro}m/voxel in areas of interest, with intrinsic cross-scale alignment. A 4 cm tissue block extracted from the hemisphere is reimaged with HiP-CT at 0.857 {micro}m/voxel, enabling direct visualisation of single myelinated axons. After osmium staining, micro-CT at 0.364 {micro}m/voxel and electron microscopy at 4 nm/voxel are acquired in biop-sies from the tissue block to validate the presence of myelinated axons in the label-free HiP-CT contrast. Spanning three orders of magnitude in resolution, these co-registered multimodal datasets bridge microscopic wiring and macro-scopic brain organisation, providing a foundation for anatomically grounded whole-brain connectomics.

neuroscience↗

bioRxiv2026

Neuroanatomy of the clitoris

The clitoris is one of the least studied organs of the human body. The detailed anatomy of the clitoris is challenging to address through a gross dissection, as most of its parts are embedded internally, surrounded by pubic bone and several pelvic organs. While clinical imaging methods such as magnetic resonance imaging can capture the gross 3D morphology, they lack the spatial resolution required to resolve the detailed structures. In this study, we generated micron-scale computed tomography images of the female pelvises, leveraging a synchrotron radiation X-ray source. This unique data revealed the complex trajectory of the dorsal nerve of the clitoris, the main sensory nerve of the clitoris. Notably, the nerve trunks within the clitoral glans were revealed, with the maximum diameter ranging from 0.2 to 0.7 mm. They showed a tree-like branching pattern projecting towards the surface of the glans. We also revealed that some branches of the dorsal nerve of the clitoris ramify to innervate the clitoral hood and mons pubis. Finally, the posterior labial nerve, a branch of the perineal nerves, was shown to innervate the surroundings of the clitoris and the labial structures. These findings have an immediate impact on operations performed around the vulva area, such as gender-affirmation surgery and reconstruction surgery after genital mutilation.

neuroscience↗

bioRxiv2026

Hierarchical Phase-Contrast Tomography Imaging: Applicability in biomedical research

ObjectivesHierarchical Phase-Contrast Tomography (HiP-CT) enables non-destructive, multi-scale imaging of whole human organs. We describe how HiP-CT is utilized for biomedical research within the Human Organ Atlas Hub through three case studies: mapping the enteric nervous system (ENS) of the human colon, analysing myocardial and AV conduction architecture in Tetralogy of Fallot (TOF), and characterizing ductal organization in breast carcinoma. The challenges we faced with this novel biomedical data are discussed. MethodsWhole-organ and region-of-interest scans of three types of human organs were acquired at the European Synchrotron Radiation Facility (ESRF) with isotropic voxel sizes ranging from 20 {micro}m to 0.8 {micro}m. For the colon, voxel binning and RootPainter were employed to tackle data size to segment the ENS. For the heart, voxel-wise myocyte orientation mapping was calculated in terabyte-scale datasets with a high-performance computational framework (Cardiotensor). Breast carcinoma samples were correlated with histopathology for structure validation. ResultsHiP-CT revealed the large-scale organization of the ENS in the colon, enabling visualisation of the 3D structures of the ENS across the colon In TOF hearts, analysis uncovered abnormal myocardial structure and heterogeneous conduction system morphology. In breast carcinoma, HiP-CT resolved the full hierarchy of ductal structures and vascular relationships within tumour and peritumoral regions. ConclusionsHiP-CT provides unprecedented, hierarchical insight into intact human organ structure, bridging the gap between histology and radiology. Advances in knowledgeHiP-CT establishes a new ex vivo radiological modality capable of linking microscale pathology to whole-organ context, advancing translational research in neurogastroenterology, cardiology, and oncology

biophysics↗

bioRxiv2026

Evolution of Hierarchical Phase-Contrast Tomography on the European Synchrotron beamlines BM05 and BM18: a whole adult human brain imaging case study

Hierarchical Phase-Contrast Tomography (HiP-CT) was recently developed to enable the ex-vivo imaging of human organs at multiple scales from whole organ down to cellular level. Using whole adult human brain imaging as a case study, this manuscript shows the evolution of this technique from its initial development at the BM05 beamline to its transition and current status at BM18. Thanks to the higher coherence, larger beam size, higher energies and larger propagation distances available at BM18 and due to the European Synchrotrons Extremely Brilliant Source upgrade (ESRF-EBS), this transition resulted in significantly improved data quality, resolution, sensitivity and speed. More recently, the implementation of a new generation of larger sCMOS cameras, helical scanning (including dedicated reconstruction algorithm developments), binning at the chip and projections levels, and the design of high-efficiency optics allowed to progressively improve the trade-off between dose and image quality, while simultaneously reducing scanning times. All these acquisition schemes present the current status of full organ imaging using HiP-CT and represent the constant efforts for the improvement of the technique towards the investigation of human organs in health, disease and aging. SynopsisThis manuscript shows the evolution of Hierarchical Phase-Contrast Tomography (HiP-CT) from its origins at the BM05 beamline to its transition to BM18 (ESRF-EBS). The novel hardware and scanning approach developments resulted in significantly improved data quality, resolution, sensitivity and speed. The case of whole adult brain imaging is presented to demonstrate the current possibilities of full organ imaging with local micron resolution using HiP-CT.

neuroscience↗

bioRxiv2025

Resolving near-micron scale features within a whole sheep head using Hierarchical Phase-Contrast Tomography

BackgroundHierarchical Phase-Contrast Tomography (HiP-CT) was developed to image ex vivo intact human soft-tissue organs with local near-micron scale resolution. PurposeWe demonstrate the application of HiP-CT in combination with the recently developed Eikonal Phase Retrieval (EPR) for resolving anatomical features in large hard and soft tissue structures on a sheep head, and show the applicability for zooming to resolve anatomical features with near-micron scale resolution. Materials and MethodsWe imaged an entire skinned sheep head prepared in 70 % ethanol with HiP-CT at an isotropic voxel size of 16.5 {micro}m using the recently developed Eikonal Phase Retrieval (EPR) to reduce artefacts from bones. Local tomography zooms were taken in regions of interest: the eye (4.23 {micro}m voxels) and the coronal suture (2.20 {micro}m voxels). To compare to clinical imaging, we acquired T2-weighted MRI and CT of the sheep head and evaluated the contrast-to-noise ratio for differentiation of white and grey matter in the brain for all modalities. Further evaluations on HiP-CT images include structure tensor analysis for structural orientation in the brain as well as fibre tracking in the coronal suture. ResultsHiP-CT combined with EPR achieved high contrast for both hard and soft tissue. Comparison to MRI showed similar soft-tissue contrast, but much higher spatial resolution. Structure tensor analysis in the brain revealed the orientation of the major white matter bundles. In the eye, near-micron scale features such as retinal layers and the bundles in the optic nerve were visualized. Fiber tracking allowed analysis of the orientation of collagen fiber bundles in the coronal suture. ConclusionThis work highlights the potential of HiP-CT to image a complete sheep head, ex vivo, and hierarchically zoom without sectioning to resolve few-microns features locally, enabling comprehensive three-dimensional visualization of intricate cranial structures and their spatial interrelations. Summary statementTechnical developments in HiP-CT enable ex vivo X-ray imaging of an intact sheep head with local resolution to near-micron scale, demonstrating future viability on a human head. Key resultsO_LIA whole sheep head was imaged with synchrotron-based hierarchical phase-contrast tomography coupled with Eikonal Phase-retrieval with 16.5 {micro}m isotropic voxels. C_LIO_LIThe high contrast for both hard and soft tissue enabled differentiation of brain white and grey matter, the optic nerve and bone features within the skull. C_LIO_LILocal tomography zoom scans in an eye (4.23 {micro}m voxels) and coronal suture (2.20 {micro}m voxels) allowed visualization and analysis of near-micron sized features. C_LI

bioengineering↗

bioRxiv2025

The Heterogeneous Nature of Atrioventricular Conduction Tissues in Tetralogy of Fallot demonstrated by Hierarchical Phase-contrast Tomography - redefining the anatomic substrate

ObjectivesPostoperative arrhythmias are frequent after Tetralogy of Fallot (ToF) repair, yet anatomic substrate and preventive strategies remain poorly defined. Using hierarchical phase-contrast tomography (HiP-CT) the atrioventricular conduction system in pediatric ToF specimens was investigated non-destructively and in 3D. MethodsEighteen whole-heart specimens (11 ToF, 7 controls) were imaged at the European Synchrotron, ESRF. Segmentation and 3D renderings demonstrated gross morphology. Morphology, size, depth and course of the non-branching bundle and right bundle branch (RBB) were quantified using custom computational pipelines. Segmentations were visualized in VheaRts, a Unity3D-based XR platform. ResultsThe ToF conduction system was more draped than in controls, bilaterally spanning the septum, resembling early embryonic architecture. The RBB was variable in origin, course and morphologic structure with significantly smaller indexed cross-sectional area in native ToF versus controls (0.05 {+/-} 0.20 vs 0.50 {+/-} 0.20 mm{superscript 2}, p = 0.005). One anomalous fasciculo-ventricular connection and six dead-end tracts were found. Regions at surgical risk included the posterior-inferior margin of the ventricular septal defect (VSD) and the septal crest along its nadir. The superior margin of the VSD at its intersection with the aortic root was free of conduction tissue. The HiP-CT to VR pipeline enabled interactive 3D visualization of conduction pathways relative to key structures. ConclusionsThis first pediatric cardiac HiP-CT series reveals a broader anomalous conduction complex in ToF, including variable RBB origin and hypoplasia, providing insight into preoperative vulnerability, arrhythmia, and surgical risk. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/692356v1_fig7.gif" ALT="Figure 7"> View larger version (50K): org.highwire.dtl.DTLVardef@1b39e89org.highwire.dtl.DTLVardef@16d49c2org.highwire.dtl.DTLVardef@5884borg.highwire.dtl.DTLVardef@136fc24_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 7:C_FLOATNO Graphical Abstract C_FIG

developmental biology↗

bioRxiv2025

The Human Organ Atlas

We present the Human Organ Atlas (HOA), an open data repository making accessible multiscale 3D imaging of human organs. The repository also provides software tools and training resources enabling worldwide access, sharing, and analysis of these datasets, facilitating further research and the continued expansion of the HOA. The images are generated using a synchrotron imaging technique - Hierarchical Phase-Contrast Tomography (HiP-CT) that uses the ESRFs Extremely Brilliant Source, spanning whole organ imaging at around 20 m/voxel with local volumes of interest within the intact organs imaged down to [~] 1 m/voxel. This offers a comprehensive exploration of human anatomy, providing unparalleled insights into intricate structures and spatial relationships. The Human Organ Atlas offers researchers, clinicians, and educators a valuable resource for anatomical study, image analysis, medical education, and large-scale data mining.

bioinformatics↗

bioRxiv2019

Kinetic characteristics of propofol-induced inhibition of electron-transfer chain and fatty acid oxidation in human and rodent skeletal and cardiac muscles

IntroductionPropofol causes a profound inhibition of fatty acid oxidation (FAO) and reduces spare electron transfer chain (ETC) capacity in a range of human and rodent cells and tissues - a feature that might be related to the pathogenesis of Propofol Infusion Syndrome. We aimed to explore the mechanism of propofol-induced alteration of bioenergetic pathways by describing its kinetic characteristics.\n\nMethodsWe obtained samples of skeletal and cardiac muscle from Wistar rat (n=3) and human subjects: vastus lateralis from hip surgery patients (n=11) and myocardium from brain-dead organ donors (n=10). We assessed mitochondrial functional indices using standard SUIT protocol and high resolution respirometry in fresh tissue homogenates with or without short-term exposure to a range of propofol concentration (2.5-100 g/ml). After finding concentrations of propofol causing partial inhibition of a particular pathways, we used that concentration to construct kinetic curves by plotting oxygen flux against substrate concentration during its stepwise titration in the presence or absence of propofol. By spectrophotometry we also measured the influence of the same propofol concentrations on the activity of isolated respiratory complexes.\n\nResultsWe found that human muscle and cardiac tissues are more sensitive to propofol-mediated inhibition of bioenergetic pathways than rats tissue. In human homogenates, palmitoyl carnitine-driven respiration was inhibited at much lower concentrations of propofol than that required for a reduction of ETC capacity, suggesting FAO inhibition mechanism different from downstream limitation or carnitine-palmitoyl transferase-1 inhibition. Inhibition of Complex I was characterised by more marked reduction of Vmax, in keeping with non-competitive nature of the inhibition and the pattern was similar to the inhibition of Complex II or ETC capacity. There was no inhibition of Complex IV nor increased leak through inner mitochondrial membrane with up to 100 g/ml of propofol. If measured in isolation by spectrophotometry, propofol 10 g/ml did not affect the activity of any respiratory complexes.\n\nConclusionIn human skeletal and heart muscle homogenates, propofol in concentrations that are achieved in propofol-anaesthetized patients, causes a direct inhibition of fatty acid oxidation, in addition to inhibiting flux of electrons through inner mitochondrial membrane. The inhibition is more marked in human as compared to rodent tissues.

pharmacology and toxicology↗

bioRxiv2018

Alcoholism Gender Differences in Brain Responsivity to Emotional Stimuli

Men and women may use alcohol to regulate their emotions differently, with corresponding differences in neural responses. We examined how photographs of emotional stimuli impacted brain activity obtained through functional magnetic resonance imaging (fMRI) from 42 alcoholic (25 women) and 46 nonalcoholic (24 women) participants. Brain responsivity was blunted in alcoholic compared to nonalcoholic groups. Further analyses indicated significant gender differences in the impact of alcoholism. Brain activation of the alcoholic men (ALCM) was significantly lower than that of the alcoholic women (ALCW) and nonalcoholic men (NCM) in regions including the inferior parietal gyrus, anterior cingulate gyrus, and postcentral gyrus, whereas activation was higher in the ALCW than in the nonalcoholic women (NCW) in superior frontal and supramarginal cortical regions. The reduced brain reactivity of ALCM and increases for ALCW highlighted divergent brain regions and gender effects, suggesting possible differences in the underlying basis for development of alcohol use disorders.

neuroscience↗