Imperial College London

ProfessorPeterWeinberg

Faculty of EngineeringDepartment of Bioengineering

Professor in Cardiovascular Mechanics
 
 
 
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Contact

 

+44 (0)20 7594 1517p.weinberg Website

 
 
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Location

 

4.10Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

185 results found

Yan J, Wang B, Riemer K, Hansen-Shearer J, Lerendegui M, Toulemonde M, Rowlands CJ, Weinberg PD, Tang Met al., 2023, Fast 3D super-resolution ultrasound with adaptive weight-based beamforming, IEEE Transactions on Biomedical Engineering, Vol: 70, Pages: 2752-2761, ISSN: 0018-9294

Objective: Super-resolution ultrasound (SRUS) imaging through localising and tracking sparse microbubbles has been shown to reveal microvascular structure and flow beyond the wave diffraction limit. Most SRUS studies use standard delay and sum (DAS) beamforming, where high side lobes and broad main lobes make isolation and localisation of densely distributed bubbles challenging, particularly in 3D due to the typically small aperture of matrix array probes. Method: This study aimed to improve 3D SRUS by implementing a new fast 3D coherence beamformer based on channel signal variance. Two additional fast coherence beamformers, that have been implemented in 2D were implemented in 3D for the first time as comparison: a nonlinear beamformer with p-th root compression and a coherence factor beamformer. The 3D coherence beamformers, together with DAS, were compared in computer simulation, on a microflow phantom and in vivo. Results: Simulation results demonstrated that all three adaptive weight-based beamformers can narrow the main lobe suppress the side lobes, while maintaining the weaker scatter signals. Improved 3D SRUS images of microflow phantom and a rabbit kidney within a 3-second acquisition were obtained using the adaptive weight-based beamformers, when compared with DAS. Conclusion: The adaptive weight-based 3D beamformers can improve the SRUS and the proposed variance-based beamformer performs best in simulations and experiments. Significance: Fast 3D SRUS would significantly enhance the potential utility of this emerging imaging modality in a broad range of biomedical applications.

Journal article

Gray SG, Weinberg PD, 2023, Biomechanical determinants of endothelial permeability assessed in standard and modified hollow-fibre bioreactors, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 20, ISSN: 1742-5689

Journal article

Weinberg PD, 2023, Receptor-mediated vs fluid-phase transcytosis of LDL, ATHEROSCLEROSIS, Vol: 378, ISSN: 0021-9150

Journal article

Arshad M, Cheng S, van Reeuwijk M, Sherwin SJ, Weinberg PDet al., 2023, Modification of the swirling well cell culture model to alter shear stress metrics, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 120, Pages: 1254-1268, ISSN: 0006-3592

Journal article

Riemer K, Toulemonde M, Yan J, Lerendegui M, Stride E, Weinberg PD, Dunsby C, Tang M-Xet al., 2023, Fast and selective super-resolution ultrasound in vivo with acoustically activated nanodroplets, IEEE Transactions on Medical Imaging, Vol: 42, Pages: 1056-1067, ISSN: 0278-0062

Perfusion by the microcirculation is key to the development, maintenance and pathology of tissue. Its measurement with high spatiotemporal resolution is consequently valuable but remains a challenge in deep tissue. Ultrasound Localization Microscopy (ULM) provides very high spatiotemporal resolution but the use of microbubbles requires low contrast agent concentrations, a long acquisition time, and gives little control over the spatial and temporal distribution of the microbubbles. The present study is the first to demonstrate Acoustic Wave Sparsely-Activated Localization Microscopy (AWSALM) and fast-AWSALM for in vivo super-resolution ultrasound imaging, offering contrast on demand and vascular selectivity. Three different formulations of acoustically activatable contrast agents were used. We demonstrate their use with ultrasound mechanical indices well within recommended safety limits to enable fast on-demand sparse activation and destruction at very high agent concentrations. We produce super-localization maps of the rabbit renal vasculature with acquisition times between 5.5 s and 0.25 s, and a 4-fold improvement in spatial resolution. We present the unique selectivity of AWSALM in visualizing specific vascular branches and downstream microvasculature, and we show super-localized kidney structures in systole (0.25 s) and diastole (0.25 s) with fast-AWSALM outdoing microbubble based ULM. In conclusion, we demonstrate the feasibility of fast and selective measurement of microvascular dynamics in vivo with subwavelength resolution using ultrasound and acoustically activatable nanodroplet contrast agents.

Journal article

Rickman M, Ghim M, Pang K, Rocha ACVH, Drudi EM, Sureda-Vives M, Ayoub N, Tajadura-Ortega V, George SJ, Weinberg PD, Warboys CMet al., 2023, Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-D-catenin-dependent pathway, JOURNAL OF CELL SCIENCE, Vol: 136, ISSN: 0021-9533

Journal article

Rowland EM, Riemer KA, Lichtenstein KEVIN, Tang M-X, Weinberg PDet al., 2023, NON-INVASIVE ASSESSMENT BY B-MODE ULTRASOUND OF ARTERIAL PULSE WAVE INTENSITY AND ITS REDUCTION DURING VENTRICULAR DYSFUNCTION, ULTRASOUND IN MEDICINE AND BIOLOGY, Vol: 49, Pages: 473-488, ISSN: 0301-5629

Journal article

Pang KT, Ghim M, Sarathchandra P, Warboys CM, Yacoub MH, Chester AH, Weinberg PDet al., 2023, Shear-mediated ALK5 expression regulates endothelial activation, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 642, Pages: 90-96, ISSN: 0006-291X

Journal article

Shih K-CJ, Peiffer V, Rowland EM, Sowinski P, Weinberg PDet al., 2023, Non-linear shrinkage of Batson's #17 resin during vascular corrosion casting, JOURNAL OF ANATOMY, Vol: 242, Pages: 76-80, ISSN: 0021-8782

Journal article

Sahni J, Arshad M, Schake MA, Brooks JR, Yang R, Weinberg PD, Pedrigi RMet al., 2023, Characterizing nuclear morphology and expression of eNOS in vascular endothelial cells subjected to a continuous range of wall shear stress magnitudes and directionality, JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, Vol: 137, ISSN: 1751-6161

Journal article

Weinberg PDD, Schroter RCC, Parker KHH, Bull AMJ, Miller TEE, Moore Jr JEEet al., 2022, In Memoriam: Colin Caro 1925-2022, JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME, Vol: 144, ISSN: 0148-0731

Journal article

Weinberg P, Ghim M, Warboys C, Yang S-W, David K, Eustaquio Jet al., 2022, NO synthesis but not apoptosis, mitosis or inflammation can explain correlations between flow directionality and paracellular permeability of cultured endothelium, International Journal of Molecular Sciences, Vol: 23, ISSN: 1422-0067

Haemodynamic wall shear stress varies from site to site within the arterial system and is thought to cause local variation in endothelial permeability to macromolecules. Our aim was to investigate mechanisms underlying the changes in paracellular permeability caused by different patterns of shear stress in long-term culture. We used the swirling well system and a substrate-binding tracer that permits visualisation of transport at the cellular level. Permeability increased in the centre of swirled wells, where flow is highly multidirectional, and decreased towards the edge, where flow is more uniaxial, compared to static controls. Overall, there was a reduction in permeability. There were also decreases in early- and late-stage apoptosis, proliferation and mitosis, and there were significant correlations between the first three and permeability when considering variation from the centre to the edge under flow. However, data from static controls did not fit the same relation and a cell-by-cell analysis showed that <5% of uptake under shear was associated with each of these events. Nuclear translocation of NF-κB p65 increased and then decreased with the duration of applied shear, as did permeability, but the spatial correlation between them was not significant. Application of an NO synthase inhibitor abolished the overall decrease in permeability caused by chronic shear and the difference in permeability between the centre and edge of the well. Hence shear and paracellular permeability appear to be linked by NO synthesis and not by apoptosis, mitosis or inflammation. The effect was mediated by an increase in transport through tricellular junctions.

Journal article

Weinberg P, 2022, Haemodynamic wall shear stress, endothelial permeability and atherosclerosis – a triad of controversy, Frontiers in Bioengineering and Biotechnology, Vol: 10, Pages: 1-29, ISSN: 2296-4185

A striking feature of atherosclerosis is its patchy distribution with the vascular system; certain arteries and certain locations within each artery are preferentially affected. Identifying the local risk factors underlying this phenomenon may lead to new therapeutic strategies. The large variation in lesion prevalence in areas of curvature and branching has motivated a search for haemodynamic triggers, particular those related to wall shear stress (WSS). The fact that lesions are rich in blood-derived lipids has motivated studies of local endothelial permeability. However, the location of lesions, the underlying haemodynamic triggers, the role of permeability, the routes by which lipids cross the endothelium, and the mechanisms by which WSS affects permeability have all been areas of controversy. This review presents evidence for and against the current consensus that lesions are triggered by low and/or oscillatory WSS and that this type of shear profile leads to elevated entry of low density lipoprotein (LDL) into the wall via widened intercellular junctions; it also evaluates more recent evidence that lesion location changes with age, that multidirectional shear stress plays a key role, that LDL dominantly crosses the endothelium by transcytosis, and that the link between flow and permeability results from hitherto unrecognised shear-sensitive mediators.

Journal article

Weinberg P, Riemer K, Rowland E, Broughton-Venner J, Leow CH, Tang Met al., 2022, Contrast agent free assessment of blood flow and wall shear stress in the rabbit aorta using ultrasound image velocimetry, Ultrasound in Medicine and Biology, Vol: 48, Pages: 437-449, ISSN: 0301-5629

Blood flow velocity and wall shear stress (WSS) influence and are influencedby vascular disease. Their measurement is consequently useful in the laboratory and clinic. Contrast enhanced ultrasound image velocimetry (UIV) canestimate them accurately but the need to inject contrast agents limits utility. Singular value decomposition and high frame rate imaging may rendercontrast agents dispensable. Here we determined whether contrast agent freeUIV can measure flow and WSS. In simulation, accurate measurements wereachieved with a signal-to-noise ratio of 13.5 dB or higher. Signal intensity inthe rabbit aorta increased monotonically with mechanical index and was lowest during stagnant flow and uneven across the vessel. In vivo measurementswith contrast free and contrast enhanced UIV differed by 4.4 % and 1.9 % forvelocity magnitude and angle and by 9.47 % for WSS. Bland–Altman analysis of waveforms showed good agreement between contrast free and contrast enhanced UIV. In five rabbits the root-mean-square error was as low as 0.022m/s (0.81 %) and 0.11 Pa (1.7 %). This study demonstrates that with anoptimised protocol, UIV can assess flow and WSS without contrast agents.Unlike contrast enhanced UIV, it could be routinely employed.

Journal article

Reavette RM, Sherwin SJ, Tang M-X, Weinberg PDet al., 2021, Wave intensity analysis combined with machine learning can detect impaired stroke volume in simulations of heart failure, Frontiers in Bioengineering and Biotechnology, Vol: 9, Pages: 1-13, ISSN: 2296-4185

Heart failure is treatable, but in the United Kingdom, the 1-, 5- and 10-year mortality rates are 24.1, 54.5 and 75.5%, respectively. The poor prognosis reflects, in part, the lack of specific, simple and affordable diagnostic techniques; the disease is often advanced by the time a diagnosis is made. Previous studies have demonstrated that certain metrics derived from pressure-velocity-based wave intensity analysis are significantly altered in the presence of impaired heart performance when averaged over groups, but to date, no study has examined the diagnostic potential of wave intensity on an individual basis, and, additionally, the pressure waveform can only be obtained accurately using invasive methods, which has inhibited clinical adoption. Here, we investigate whether a new form of wave intensity based on noninvasive measurements of arterial diameter and velocity can detect impaired heart performance in an individual. To do so, we have generated a virtual population of two-thousand elderly subjects, modelling half as healthy controls and half with an impaired stroke volume. All metrics derived from the diameter-velocity-based wave intensity waveforms in the carotid, brachial and radial arteries showed significant crossover between groups-no one metric in any artery could reliably indicate whether a subject's stroke volume was normal or impaired. However, after applying machine learning to the metrics, we found that a support vector classifier could simultaneously achieve up to 99% recall and 95% precision. We conclude that noninvasive wave intensity analysis has significant potential to improve heart failure screening and diagnosis.

Journal article

Arshad M, Rowland EM, Riemer K, Sherwin SJ, Weinberg PDet al., 2021, Improvement and validation of a computational model of flow in the swirling well cell culture model, Biotechnology and Bioengineering, ISSN: 0006-3592

Effects of fluid dynamics on cells are often studied by growing the cells on the base of cylindrical wells or dishes that are swirled on the horizontal platform of an orbital shaker. The swirling culture medium applies a shear stress to the cells that varies in magnitude and directionality from the centre to the edge of the vessel. Computational fluid dynamics methods are used to simulate the flow and hence calculate shear stresses at the base of the well. The shear characteristics at each radial location are then compared with cell behaviour at the same position. Previous simulations have generally ignored effects of surface tension and wetting, and results have only occasionally been experimentally validated. We investigated whether such idealized simulations are sufficiently accurate, examining a commonly-used swirling well configuration. The breaking wave predicted by earlier simulations was not seen, and the edge-to-centre difference in shear magnitude (but not directionality) almost disappeared, when surface tension and wetting were included. Optical measurements of fluid height and velocity agreed well only with the computational model that incorporated surface tension and wetting. These results demonstrate the importance of including accurate fluid properties in computational models of the swirling well method.

Journal article

Weinberg P, Warboys CM, 2021, S1P in the development of atherosclerosis: roles of haemodynamic wall shear stress and endothelial permeability, Tissue Barriers, Vol: 9, Pages: 1-18, ISSN: 2168-8362

Atherosclerosis is characterised by focal accumulations of lipid within the arterial wall, thought to arise from effects of haemodynamic wall shear stress (WSS) on endothelial permeability. Identifying pathways that mediate effects of shear on permeability could therefore provide new therapeutic opportunities. Here we consider whether the sphingosine-1-phosphate (S1P) pathway could constitute such a route. We review effects of S1P in endothelial barrier function, the influence of WSS on S1P production and signalling, the results of trials investigating S1P in experimental atherosclerosis in mice, and associations between S1P levels and cardiovascular disease in humans. Although it seems clear that S1P reduces endothelial permeability and responds to WSS, the evidence that it influences atherosclerosis is equivocal. The effects of specifically pro- and anti-atherosclerotic WSS profiles on the S1P pathway require investigation, as do influences of S1P on the vesicular pathways likely to dominate low density lipoprotein transport across endothelium.

Journal article

Ghim M, Pang KT, Burnap SA, Baig F, Yin X, Arshad M, Mayr M, Weinberg PDet al., 2021, Endothelial cells exposed to atheroprotective flow secrete follistatin-like 1 protein which reduces transcytosis and inflammation, Atherosclerosis, Vol: 333, Pages: 56-66, ISSN: 0021-9150

Background and aimsWhen endothelium is cultured in wells swirled on an orbital shaker, cells at the well centre experience putatively pro-atherogenic flow whereas those near the edge experience putatively atheroprotective flow. Transcellular transport is decreased equally in both regions, consistent with it being reduced by a mediator released from cells in one part of the well and mixed in the swirling medium. Similar effects have been reported for pro-inflammatory changes. Here we identify the mediator and the flow characteristics that stimulate its release.Methods and resultsMedium conditioned by cells swirled at the edge, but not by cells swirled at the centre or cultured under static conditions, significantly reduced transendothelial transport of a low density lipoprotein (LDL)-sized tracer and tumor necrosis factor α (TNF-α)-induced vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression, activation of nuclear factor κB (NF-κB), and monocyte adhesion. An inhibitor of transcytosis similarly decreased tracer transport. Mass spectrometry identified follistatin-like 1 (FSTL1) as a candidate mediator. Cells from the swirled edge produced significantly more FSTL1 than cells from the swirled centre or from static wells. Exogenous FSTL1 reduced transendothelial transport of the LDL-sized tracer and of LDL itself, as well as TNF-α-induced VCAM-1 and ICAM-1 expression. Bone morphogenetic protein (4BMP4) increased transendothelial transport of the LDL-sized tracer and expression of VCAM-1 and ICAM-1; these effects were abolished by FSTL1.ConclusionsPutatively atheroprotective flow stimulates production of FSTL1 from cultured endothelial cells. FSTL1 reduces transcellular transport of LDL-sized particles and of LDL itself, and inhibits endothelial activation. If this also occurs in vivo, it may account for the atheroprotective nature of such flow.

Journal article

Pang KT, Ghim M, Liu C, Tay HM, Fhu CW, Chia RN, Qiu B, Sarathchandra P, Chester AH, Yacoub MH, Wilkinson FL, Weston R, Warboys CM, Hou HW, Weinberg PD, Wang Xet al., 2021, Leucine-Rich α-2-Glycoprotein 1 Suppresses Endothelial Cell Activation Through ADAM10-Mediated Shedding of TNF-α Receptor, FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, Vol: 9, ISSN: 2296-634X

Journal article

Weinberg P, Pang K, Ghim M, Arshad M, Wang Xet al., 2021, Segmenting growth of endothelial cells in 6-well plates on an orbital shaker for mechanobiological studies, Journal of Visualized Experiments, Vol: 2021, ISSN: 1940-087X

Shear stress induced on the arterial wall by the flow of blood affects endothelial cell morphology and function. Low magnitude, oscillatory and multidirectional shear stresses have all been postulated to stimulate a pro-atherosclerotic phenotype in endothelial cells, whereas high magnitude and unidirectional or uniaxial shear are thought to promote endothelial homeostasis. These hypotheses require further investigation, but traditional in vitro techniques have limitations, and are particularly poor at imposing multidirectional shear stresses on cells. One method that is gaining increasing use is to culture endothelial cells in standard multi-well plates on the platform of an orbital shaker; in this simple, low-cost, high-throughput and chronic method, the swirling medium produces different patterns and magnitudes of shear, including multidirectional shear, in different parts of the well. However, it has a significant limitation: cells in one region, exposed to one type of flow, may release mediators into the medium that affect cells in other parts of the well, exposed to different flows, hence distorting the apparent relation between flow and phenotype. Here we present an easy and affordable modification of the method that allows cells to be exposed only to specific shear stress characteristics. Cells seeding is restricted to a defined region of the well by coating the region of interest with fibronectin, followed by passivation using passivating solution. Subsequently, the plates can be swirled on the shaker, resulting in exposure of cells to well-defined shear profiles such as low magnitude multidirectional shear or high magnitude uniaxial shear, depending on their location. As before, the use of standard cell-culture plasticware allows straightforward further analysis of the cells. The modification has already allowed the demonstration of soluble mediators, released from endothelium under defined shear stress characteristics, that affect cells located elsewhere i

Journal article

Weinberg P, Arshad M, Ghim M, Mohamied Y, Sherwin Set al., 2021, Endothelial cells do not align with the mean wall shear stress vector, Journal of the Royal Society Interface, Vol: 18, Pages: 1-10, ISSN: 1742-5662

Alignment of arterial endothelial cells with the mean wall shear stress (WSS) vector is the prototypical example of their responsiveness to flow. However, evidence for this behaviour rests on experiments where many WSS metrics had the same orientation or where they were incompletely characterised. In the present study, we tested the phenomenon more rigorously. Aortic endothelial cells were cultured in cylindrical wells on the platform of an orbital shaker. In this system, orientation would differ depending on the WSS metric to which the cells aligned. Variation in flow features and hence in possible orientations was further enhanced by altering the viscosity of the medium. Orientation of endothelial nuclei was compared to WSS characteristics obtained by computational fluid dynamics. At low mean WSS magnitudes, endothelial cells aligned with the modal WSS vector whilst at high mean WSS magnitudes they aligned so as to minimise the shear acting across their long axis (“transverse WSS”). Their failure to align with the mean WSS vector implies that other aspects of endothelial behaviour attributed to this metric require re-examination. The evolution of a mechanism for minimising transverse WSS is consistent with it having detrimental effects on the cells and with its putative role in atherogenesis.

Journal article

Rowland EM, Bailey EL, Weinberg PD, 2021, Estimating Arterial Cyclic Strain from the Spacing of Endothelial Nuclei, EXPERIMENTAL MECHANICS, Vol: 61, Pages: 171-190, ISSN: 0014-4851

Journal article

Dumas R, Riemer K, Toulemonde M, Lerendegui M, Weinberg PD, Tang M-X, Varray Fet al., 2021, 4D ultrafast blood flow imaging comparison: vector Doppler, transverse oscillation and speckle tracking, IEEE International Ultrasonics Symposium (IEEE IUS), Publisher: IEEE, ISSN: 1948-5719

Conference paper

Reavette RM, Sherwin SJ, Tang M, Weinberg PDet al., 2020, Comparison of arterial wave intensity analysis by pressure-velocity and diameter-velocity methods in a virtual population of adult subjects., Proceedings of the Institution of Mechanical Engineers Part H: Journal of Engineering in Medicine, Vol: 234, Pages: 1260-1276, ISSN: 0954-4119

Pressure-velocity-based analysis of arterial wave intensity gives clinically relevant information about the performance of the heart and vessels, but its utility is limited because accurate pressure measurements can only be obtained invasively. Diameter-velocity-based wave intensity can be obtained noninvasively using ultrasound; however, due to the nonlinear relationship between blood pressure and arterial diameter, the two wave intensities might give disparate clinical indications. To test the magnitude of the disagreement, we have generated an age-stratified virtual population to investigate how the two dominant nonlinearities 'viscoelasticity and strain-stiffening' cause the two formulations to differ. We found strong agreement between the pressure-velocity and diameter-velocity methods, particularly for the systolic wave energy, the ratio between systolic and diastolic wave heights, and older subjects. The results are promising regarding the introduction of noninvasive wave intensities in the clinic.

Journal article

Weinberg P, Dazzi M, Rowland E, Mohri Zet al., 2020, 3D confocal microscope imaging of macromolecule uptake in the intact brachiocephalic artery, Atherosclerosis, Vol: 310, Pages: 93-101, ISSN: 0021-9150

Background and aimsElevated uptake of plasma macromolecules by the arterial wall is an early event in atherogenesis. Existing optical techniques for detecting macromolecular tracers in the wall have poor depth penetration and hence require en face imaging of flattened arterial segments. Imaging uptake in undistorted curved and branched vessels would be useful in understanding disease development.MethodsDepth penetration was increased by applying optical clearing techniques. The rat aorto-brachiocephalic junction was imaged intact by confocal microscopy after it had been exposed to circulating rhodamine-labelled albumin in vivo, fixed in situ, excised and then cleared with benzyl alcohol/benzyl benzoate. Tracer uptake was mapped onto a 3D surface mesh of the arterial geometry.ResultsTracer fluorescence was detectable throughout the wall closest to the objective lens and, despite a vessel diameter of c. 1 mm, in the wall on the other side of the artery, across the lumen. By tile scanning, tracer concentrations were mapped in the aorta, the brachiocephalic artery and their junction without opening or flattening either vessel. Optical clearing was also shown to be compatible with immunofluorescent staining and imaging of experimental atherosclerosis.ConclusionsThe technique obviates the need for labour-intensive sample preparation associated with standard en face imaging. More importantly, it preserves arterial geometry, facilitating co-localisation of uptake maps with maps of biomechanical factors, which typically exist on 3D surface meshes. It will permit the correlation of haemodynamic wall shear stress with macromolecule permeability more accurately in regions of high curvature or branching, such as in the coronary arteries.

Journal article

Ghim M, Mohamied Y, Weinberg PD, 2020, The role of tricellular junctions in the transport of macromolecules across endothelium, Cardiovascular Engineering and Technology, Vol: 12, Pages: 101-113, ISSN: 1869-408X

PurposeTransport of water and solutes across vascular endothelium is important in normal physiology and critical in the development of various diseases, including atherosclerosis. However, there is debate about the routes for such transport. We recently showed that an albumin-sized tracer crossed endothelium at bicellular and tricellular junctions, a tracer having the size of high density lipoprotein crossed only through tricellular junctions, and a tracer with the size of low density lipoprotein was unable to cross by either route and instead traversed the cells themselves. Here we review previous work on the structure and function of tricellular junctions. We then describe a study in which we assessed the role of such junctions in the transport of an albumin-sized tracer.MethodsWe examined normal endothelial monolayers, the effect of agonists that modify their permeability, and the influence of different patterns of shear stress.ResultsUnder normal conditions, approximately 85% of transendothelial transport occurred through tricellular junctions. This fraction was unchanged when permeability was reduced by sphingosine-1-phosphate or increased by thrombin, and also did not differ between endothelium exposed to multidirectional as opposed to uniaxial shear stress despite a > 50% difference in permeability.ConclusionThese data show that tricellular junctions dominate normal transport of this tracer and largely determine influences of agonists and shear. The effects were attributable to changes in both the number and conductivity of the junctions. Further investigation of these structures will lead to increased understanding of endothelial barrier function and may suggest new therapeutic strategies in disease.

Journal article

Riemer K, Rowland EM, Leow CH, Tang MX, Weinberg PDet al., 2020, Determining haemodynamic wall shear stress in the rabbit aorta in vivo using contrast-enhanced ultrasound image velocimetry, Annals of Biomedical Engineering, Vol: 48, Pages: 1728-1739, ISSN: 0090-6964

Abnormal blood flow and wall shear stress (WSS) can cause and be caused by cardiovascular disease. To date, however, no standard method has been established for mapping WSS in vivo. Here we demonstrate wide-field assessment of WSS in the rabbit abdominal aorta using contrast-enhanced ultrasound image velocimetry (UIV). Flow and WSS measurements were made independent of beam angle, curvature or branching. Measurements were validated in an in silico model of the rabbit thoracic aorta with moving walls and pulsatile flow. Mean errors over a cardiac cycle for velocity and WSS were 0.34 and 1.69%, respectively. In vivo time average WSS in a straight segment of the suprarenal aorta correlated highly with simulations (PC = 0.99) with a mean deviation of 0.29 Pa or 5.16%. To assess fundamental plausibility of the measurement, UIV WSS was compared to an analytic approximation derived from the Poiseuille equation; the discrepancy was 17%. Mapping of WSS was also demonstrated in regions of arterial branching. High time average WSS (TAWSSxz = 3.4 Pa) and oscillatory flow (OSIxz = 0.3) were observed near the origin of conduit arteries. In conclusion, we have demonstrated that contrast-enhanced UIV is capable of measuring spatiotemporal variation in flow velocity, arterial wall location and hence WSS in vivo with high accuracy over a large field of view.

Journal article

Ghim M, Weinberg PD, Warboys CM, 2020, β-CATENIN TRANSCRIPTIONAL ACTIVITY REGULATES THE PERMEABILITY OF ENDOTHELIAL CELLS EXPOSED TO DISTURBED FLOW, Publisher: SPRINGER, Pages: 284-284, ISSN: 0920-3206

Conference paper

Riemer K, Toulemonde M, Rowland EM, Leow CH, Tang M-X, Weinberg PDet al., 2020, 4D Blood Flow and Wall Shear Stress measured using Volumetric Ultrasound Image Velocimetry, IEEE International Ultrasonics Symposium (IEEE IUS), Publisher: IEEE, ISSN: 1948-5719

Conference paper

Zhang G, Toulemonde M, Riemer K, Zhu J, Harput S, Christensen-Jeffries K, Zhu Z, Wang B, Leow CH, Weinberg P, Dunsby C, Tang M-Xet al., 2020, Effects of Mechanical Index on Repeated Sparse Activation of Nanodroplets In Vivo, IEEE International Ultrasonics Symposium (IEEE IUS), Publisher: IEEE, ISSN: 1948-5719

Conference paper

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