Imperial College London

ProfessorPeterLee

Faculty of EngineeringDepartment of Materials

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 6801p.d.lee

 
 
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Location

 

102Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

521 results found

Priyadarshi A, Bin Shahrani S, Choma T, Zrodowski L, Qin L, Leung CLA, Clark SJ, Fezzaa K, Mi J, Lee PD, Eskin D, Tzanakis Iet al., 2024, New insights into the mechanism of ultrasonic atomization for the production of metal powders in additive manufacturing, Additive Manufacturing, Vol: 83

Ultrasonic atomization is one of the promising technologies for producing metal powders for additive manufacturing, where precise control of particle size and morphology is essential. In this study, we coupled an ultrasonic transducer with a carbon fiber plate and atomized liquid droplets and films under different vibration amplitudes. Water, glycerol, and pure aluminum melt were used to study the atomization mechanism and the resulting droplet/powder characteristics, respectively. High-speed optical and ultrafast synchrotron X-ray imaging were used to study in situ the ultrasonic atomization dynamics, including pulsation and clustering of cavities inside the liquid layer/films, development of capillary waves, and formation of liquid droplets. For the first time, we observed and captured the occurrence of cavitation during the atomization of resting drops, films and impact droplets. The inertial cavitation events interfered with the capillary waves across the interphase boundary, puncturing and breaking the boundary to produce atomized mist. The in situ observation revealed the intricate dynamics of ultrasonic atomization and underscored the pivotal role of cavitation events throughout the entire atomization process. We also conducted experiments on ultrasonic atomization of liquid aluminum, producing particles of perfectly spherical shape. The particle size tended to decrease with reduced vibration amplitude Our work has demonstrated the important processing strategies on how to tailor the particle size while ensuring consistent particle shape and morphology, which is the key processing capability for producing high quality powders for additive manufacturing applications.

Journal article

Zhang K, Chen Y, Marussi S, Fan X, Fitzpatrick M, Bhagavath S, Majkut M, Lukic B, Jakata K, Rack A, Jones MA, Shinjo J, Panwisawas C, Leung CLA, Lee PDet al., 2024, Pore evolution mechanisms during directed energy deposition additive manufacturing., Nat Commun, Vol: 15

Porosity in directed energy deposition (DED) deteriorates mechanical performances of components, limiting safety-critical applications. However, how pores arise and evolve in DED remains unclear. Here, we reveal pore evolution mechanisms during DED using in situ X-ray imaging and multi-physics modelling. We quantify five mechanisms contributing to pore formation, migration, pushing, growth, removal and entrapment: (i) bubbles from gas atomised powder enter the melt pool, and then migrate circularly or laterally; (ii) small bubbles can escape from the pool surface, or coalesce into larger bubbles, or be entrapped by solidification fronts; (iii) larger coalesced bubbles can remain in the pool for long periods, pushed by the solid/liquid interface; (iv) Marangoni surface shear flow overcomes buoyancy, keeping larger bubbles from popping out; and (v) once large bubbles reach critical sizes they escape from the pool surface or are trapped in DED tracks. These mechanisms can guide the development of pore minimisation strategies.

Journal article

Li W, Lambert-Garcia R, Getley ACM, Kim K, Bhagavath S, Majkut M, Rack A, Lee PD, Leung CLAet al., 2024, AM-SegNet for additive manufacturing in situ X-ray image segmentation and feature quantification, Virtual and Physical Prototyping, Vol: 19, ISSN: 1745-2759

Synchrotron X-ray imaging has been utilised to detect the dynamic behaviour of molten pools during the metal additive manufacturing (AM) process, where a substantial amount of imaging data is generated. Here, we develop an efficient and robust deep learning model, AM-SegNet, for segmenting and quantifying high-resolution X-ray images and prepare a large-scale database consisting of over 10,000 pixel-labelled images for model training and testing. AM-SegNet incorporates a lightweight convolution block and a customised attention mechanism, capable of performing semantic segmentation with high accuracy (∼96%) and processing speed (< 4 ms per frame). The segmentation results can be used for quantification and multi-modal correlation analysis of critical features (e.g. keyholes and pores). Additionally, the application of AM-SegNet to other advanced manufacturing processes is demonstrated. The proposed method will enable end-users in the manufacturing and imaging domains to accelerate data processing from collection to analytics, and provide insights into the processes’ governing physics.

Journal article

Brunet J, Cook AC, Walsh CL, Cranley J, Tafforeau P, Engel K, Berruyer C, O'Leary EB, Bellier A, Torii R, Werlein C, Jonigk DD, Ackermann M, Dollman K, Lee PDet al., 2023, Multidimensional Analysis of the Adult Human Heart in Health and Disease using Hierarchical Phase-Contrast Tomography (HiP-CT)., bioRxiv

Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP-CT), using new (4th) generation synchrotron sources, potentially overcomes this limitation, allowing micron resolution imaging of intact adult organs with unprecedented detail. In this proof of principle study (n=2), we show the utility of HiP-CT to image whole adult human hearts ex-vivo: one 'control' without known cardiac disease and one with multiple known cardiopulmonary pathologies. The resulting multiscale imaging was able to demonstrate exemplars of anatomy in each cardiac segment along with novel findings in the cardiac conduction system, from gross (20 um/voxel) to cellular scale (2.2 um/voxel), non-destructively, thereby bridging the gap between macroscopic and microscopic investigations. We propose that the technique represents a significant step in virtual autopsy methods for studying structural heart disease, facilitating research into abnormalities across scales and age-groups. It opens up possibilities for understanding and treating disease; and provides a cardiac 'blueprint' with potential for in-silico simulation, device design, virtual surgical training, and bioengineered heart in the future.

Journal article

Fleming TG, Clark SJ, Fan X, Fezzaa K, Leung CLA, Lee PD, Fraser JMet al., 2023, Synchrotron validation of inline coherent imaging for tracking laser keyhole depth, ADDITIVE MANUFACTURING, Vol: 77, ISSN: 2214-8604

Journal article

Bhatt A, Huang Y, Leung CLA, Soundarapandiyan G, Marussi S, Shah S, Atwood RC, Fitzpatrick ME, Tiwari MK, Lee PDet al., 2023, <i>In</i><i> situ</i> characterisation of surface roughness and its amplification during multilayer single-track laser powder bed fusion additive manufacturing, ADDITIVE MANUFACTURING, Vol: 77, ISSN: 2214-8604

Journal article

Fan X, Shevchenko N, Tonry C, Clark SJ, Atwood RC, Eckert S, Pericleous K, Lee PD, Kao Aet al., 2023, Controlling solute channel formation using magnetic fields, ACTA MATERIALIA, Vol: 256, ISSN: 1359-6454

Journal article

Chen Y, Tang YT, Collins DM, Clark SJ, Ludwig W, Rodriguez-Lamas R, Detlefs C, Reed RC, Lee PD, Withers PJ, Yildirim Cet al., 2023, High-resolution 3D strain and orientation mapping within a grain of a directed energy deposition laser additively manufactured superalloy, SCRIPTA MATERIALIA, Vol: 234, ISSN: 1359-6462

Journal article

Iantaffi C, Bele E, Mcarthur D, Lee PD, Leung CLAet al., 2023, Auxetic response of additive manufactured cubic chiral lattices at large plastic strains, MATERIALS & DESIGN, Vol: 233, ISSN: 0264-1275

Journal article

Heyraud A, Tallia F, Sory D, Ting H-K, Tchorzewska A, Liu J, Pilsworth HL, Lee PD, Hanna JV, Rankin SM, Jones JRet al., 2023, 3D printed hybrid scaffolds for bone regeneration using calcium methoxyethoxide as a calcium source, Frontiers in Bioengineering and Biotechnology, Vol: 11, Pages: 1-18, ISSN: 2296-4185

Introduction: Hybrids consist of inorganic and organic co-networks that are indistinguishable above the nanoscale, which can lead to unprecedented combinations of properties, such as high toughness and controlled degradation.Methods: We present 3D printed bioactive hybrid scaffolds for bone regeneration, produced by incorporating calcium into our “Bouncy Bioglass”, using calcium methoxyethoxide (CME) as the calcium precursor. SiO2-CaOCME/PTHF/PCL-diCOOH hybrid “inks” for additive manufacturing (Direct Ink Writing) were optimised for synergy of mechanical properties and open interconnected pore channels.Results and Discussion: Adding calcium improved printability. Changing calcium content (5, 10, 20, 30, and 40 mol.%) of the SiO2-CaOCME/PTHF/PCL-diCOOH hybrids affected printability and mechanical properties of the lattice-like scaffolds. Hybrids containing 30 mol.% calcium in the inorganic network (70S30CCME-CL) printed with 500 µm channels and 100 µm strut size achieved the highest strength (0.90 ± 0.23 MPa) and modulus of toughness (0.22 ± 0.04 MPa). These values were higher than Ca-free SiO2/PTHF/PCL-diCOOH hybrids (0.36 ± 0.14 MPa strength and 0.06 ± 0.01 MPa toughness modulus). Over a period of 90 days of immersion in simulated body fluid (SBF), the 70S30CCME-CL hybrids also kept a stable strain to failure (∼30 %) and formed hydroxycarbonate apatite within three days. The extracts released by the 70S30CCME-CL hybrids in growth medium did not cause cytotoxic effects on human bone marrow stromal cells over 24 h of culture.

Journal article

Soundarapandiyan G, Leung CLA, Johnston C, Chen B, Khan RHU, McNutt P, Bhatt A, Atwood RC, Lee PD, Fitzpatrick MEet al., 2023, <i>In</i><i> situ</i> monitoring the effects of Ti6Al4V powder oxidation during laser powder bed fusion additive manufacturing, INTERNATIONAL JOURNAL OF MACHINE TOOLS & MANUFACTURE, Vol: 190, ISSN: 0890-6955

Journal article

Rees DT, Leung CLA, Elambasseril J, Marussi S, Shah S, Marathe S, Brandt M, Easton M, Lee PDet al., 2023, In situ X-ray imaging of hot cracking and porosity during LPBF of Al-2139 with TiB2 additions and varied process parameters, MATERIALS & DESIGN, Vol: 231, ISSN: 0264-1275

Journal article

Notley S, Chen Y, Thacker NA, Lee PD, Panoutsos Get al., 2023, Synchrotron imaging derived relationship between process parameters and build quality for directed energy deposition additively manufactured IN718, ADDITIVE MANUFACTURING LETTERS, Vol: 6, ISSN: 2772-3690

Journal article

Fleming TG, Rees DT, Marussi S, Connolley T, Atwood RC, Jones MA, Fraser JM, Leung CLA, Lee PDet al., 2023, In situ correlative observation of humping-induced cracking in directed energy deposition of nickel-based superalloys, ADDITIVE MANUFACTURING, Vol: 71, ISSN: 2214-8604

Journal article

Fan X, Fleming TG, Rees DT, Huang Y, Marussi S, Leung CLA, Atwood RC, Kao A, Lee PDet al., 2023, Thermoelectric magnetohydrodynamic control of melt pool flow during laser directed energy deposition additive manufacturing, ADDITIVE MANUFACTURING, Vol: 71, ISSN: 2214-8604

Journal article

Ma S, Shang Z, Shang A, Zhang P, Tang C, Huang Y, Leung CLA, Lee PD, Zhang X, Wang Xet al., 2023, Additive manufacturing enabled synergetic strengthening of bimodal reinforcing particles for aluminum matrix composites, ADDITIVE MANUFACTURING, Vol: 70, ISSN: 2214-8604

Journal article

Brunet J, Walsh CL, Wagner WL, Bellier A, Werlein C, Marussi S, Jonigk DD, Verleden SE, Ackermann M, Lee PD, Tafforeau Pet al., 2023, Preparation of large biological samples for high-resolution, hierarchical, synchrotron phase-contrast tomography with multimodal imaging compatibility, NATURE PROTOCOLS, Vol: 18, Pages: 1441-+, ISSN: 1754-2189

Journal article

Kamp JC, Werlein C, Plucinski EKJ, Neubert L, Welte T, Lee PD, Tafforeau P, Walsh C, Kuehnel MP, Schuppan D, Hoeper MM, Jonigk DD, Ackermann Met al., 2023, Novel insight into pulmonary fibrosis and long COVID, American Journal of Respiratory and Critical Care Medicine, Vol: 207, Pages: 1105-1107, ISSN: 1073-449X

Journal article

Li X, Yang X, Xue C, Wang S, Zhang Y, Wang B, Wang J, Lee PDet al., 2023, Predicting hydrogen microporosity in long solidification range ternary Al-Cu-Li alloys by coupling CALPHAD and cellular automata model, COMPUTATIONAL MATERIALS SCIENCE, Vol: 222, ISSN: 0927-0256

Journal article

Wang A, Wei Q, Luo S, Tang Z, Yang H, Wu Y, Leung CLA, Lee PD, Wang H, Wang Het al., 2023, Blue laser directed energy deposition of aluminum with synchronously enhanced efficiency and quality, ADDITIVE MANUFACTURING LETTERS, Vol: 5, ISSN: 2772-3690

Journal article

Rahmani S, Jafree DJ, Lee PD, Tafforeau P, Jacob J, Bellier A, Ackermann M, Jonigk DD, Shipley RJ, Long DA, Walsh CLet al., 2023, Micro to macro scale analysis of the intact human renal arterial tree with Synchrotron Tomography., bioRxiv

BACKGROUND: The kidney vasculature is exquisitely structured to orchestrate renal function. Structural profiling of the vasculature in intact rodent kidneys, has provided insights into renal haemodynamics and oxygenation, but has never been extended to the human kidney beyond a few vascular generations. We hypothesised that synchrotron-based imaging of a human kidney would enable assessment of vasculature across the whole organ. METHODS: An intact kidney from a 63-year-old male was scanned using hierarchical phase-contrast tomography (HiP-CT), followed by semi-automated vessel segmentation and quantitative analysis. These data were compared to published micro-CT data of whole rat kidney. RESULTS: The intact human kidney vascular network was imaged with HiP-CT at 25 μm voxels, representing a 20-fold increase in resolution compared to clinical CT scanners. Our comparative quantitative analysis revealed the number of vessel generations, vascular asymmetry and a structural organisation optimised for minimal resistance to flow, are conserved between species, whereas the normalised radii are not. We further demonstrate regional heterogeneity in vessel geometry between renal cortex, medulla, and hilum, showing how the distance between vessels provides a structural basis for renal oxygenation and hypoxia. CONCLUSIONS: Through the application of HiP-CT, we have provided the first quantification of the human renal arterial network, with a resolution comparable to that of light microscopy yet at a scale several orders of magnitude larger than that of a renal punch biopsy. Our findings bridge anatomical scales, profiling blood vessels across the intact human kidney, with implications for renal physiology, biophysical modelling, and tissue engineering.

Journal article

Song Z, Boller E, Rack A, Lee PD, Cai Bet al., 2023, Magnetic field-assisted solidification of W319 Al alloy qualified by high-speed synchrotron tomography, Journal of Alloys and Compounds, Vol: 938, Pages: 1-11, ISSN: 0925-8388

Magnetic fields have been widely used to control solidification processes. Here, high-speed synchrotron X-ray tomography was used to study the effect of magnetic fields on solidification. We investigated vertically upward directional solidification of an Al-Si-Cu based W319 alloy without and with a transverse magnetic field of 0.5 T while the sample was rotating. The results revealed the strong effect of a magnetic field on both the primary α-Al phase and secondary β-Al5FeSi intermetallic compounds (IMCs). Without the magnetic field, coarse primary α-Al dendrites were observed with a large macro-segregation zone. When a magnetic field is imposed, much finer dendrites with smaller primary arm spacing were obtained, while macro-segregation was almost eliminated. Segregated solutes were pushed out of the fine dendrites and piled up slightly above the solid/liquid interface, leading to a gradient distribution of the secondary β-IMCs. This work demonstrates that rotating the sample under a transversal magnetic field is a simple yet effective method to homogenise the temperature and composition distributions, which can be used to control the primary phase and the distribution of iron-rich intermetallics during solidification.

Journal article

Xian RP, Brunet J, Huang Y, Wagner WL, Lee PD, Tafforeau P, Walsh CLet al., 2023, A closer look at high-energy X-ray-induced bubble formation during soft tissue imaging

<jats:title>Abstract</jats:title><jats:p>Improving the scalability of tissue imaging throughput with bright, coherent X-rays requires identifying and mitigating artifacts resulting from the interactions between X-rays and matter. At synchrotron sources, long-term imaging of soft tissues in solution can result in gas bubble formation or cavitation, which dramatically compromises image quality and integrity of the samples. By combining in-line phase-contrast cineradiography with<jats:italic>operando</jats:italic>gas chromatography, we were able to track the onset and evolution of high-energy X-ray-induced gas bubbles in ethanol-embedded soft tissue samples for tens of minutes (2 to 3 times the typical scan times). We demonstrate quantitatively that vacuum degassing of the sample during preparation can significantly delay bubble formation, offering up to a twofold improvement in dose tolerance, depending on the tissue type. However, once nucleated, bubble growth is faster in degassed than undegassed samples, indicating their distinct metastable states at bubble onset. Gas chromatography analysis shows increased solvent vaporization concurrent with bubble formation, yet the quantities of dissolved gases remain unchanged. Coupling features extracted from the radiographs with computational analysis of bubble characteristics, we uncover dose-controlled kinetics and nucleation site-specific growth. These hallmark signatures provide quantitative constraints on the driving mechanisms of bubble formation and growth. Overall, the observations highlight bubble formation as a critical, yet often overlooked hurdle in upscaling X-ray imaging for biological tissues and soft materials and we offer an empirical foundation for their understanding and imaging protocol optimization. More importantly, our approaches establish a top-down scheme to decipher the complex, multiscale radiation-matter interactions in these applications.</jats:p><jats:sec&g

Journal article

Ackermann M, Tafforeau P, Brunet J, Kamp JC, Werlein C, Kuehnel MP, Jacob J, Walsh CL, Lee PD, Welte T, Jonigk DDet al., 2023, Comment on: Intrapulmonary shunt and alveolar dead space in a cohort of patients with acute COVID-19 pneumonitis and early recovery, EUROPEAN RESPIRATORY JOURNAL, Vol: 61, ISSN: 0903-1936

Journal article

Disney CM, Vo NT, Bodey AJ, Bay BK, Lee PDet al., 2023, Image quality and scan time optimisation for <i>in situ</i> phase contrast x-ray tomography of the intervertebral disc, JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, Vol: 138, ISSN: 1751-6161

Journal article

Torres-Orozco R, Cronin SJ, Pardo N, Kosik S, Ukstins I, Heinrich M, Lee PDet al., 2023, Complex decompression and fragmentation of mingled andesite magmas driving multi-phase Plinian eruptions at Mt. Taranaki, New Zealand, Journal of Volcanology and Geothermal Research, Vol: 433, Pages: 1-28, ISSN: 0377-0273

Estimating the kinetics of andesite magma vesiculation and crystallization inside volcanic plumbing systems is key for unraveling andesite Plinian eruption dynamics. The conduit kinetics provide the necessary input data for estimating the magma flow rates driving magma ascent and the fragmentation mechanisms controlling shifts in eruption explosivity and style. This information is crucial for increasing knowledge on expected hazards and for developing realistic eruption scenarios. In this work, we estimate conduit magma vesiculation and crystallization kinetics during the 3300 cal BP Upper Inglewood Plinian eruptive episode of Mount Taranaki, New Zealand. This episode comprised (i) low-intensity, conduit-opening phases of dome-collapse PDCs; (ii) pre-climactic, highly explosive phases of diverse PDCs, of up to violent 18-km-runout lateral blasts; (iii) climactic phases of steady 22-km-high Plinian eruption columns; and (iv) waning phases of column-collapse PDCs. By employing synchrotron microtomography, combined with mineral/glass chemistry and electron-microscopy, we quantified 3D vesicle and crystal size and shape distributions in juvenile pyroclasts over time, and corresponding number densities ranging from 1.1 × 105 to 2.5 × 106 mm−3 for vesicles, and from 8.0 × 104 to 5.1 × 106 mm−3 for crystals. Our results indicate that tapping of chemically alike yet rheologically contrasting magmas over a multi-phase andesite eruptive episode is linked to: (a) mafic magma recharge and differentiation in multiple storage reservoirs at distinct crustal levels, (b) stepwise to rapid magma decompression while mingling, producing variable pre- and syn-eruptive degassing and crystallization, and (c) syn-eruptive changes in melt viscosity, strain rate, localized shear deformation, and conduit geometry. The earliest and least explosive eruptive phases (≈ 2 × 106 kg s−1) were produced at the slowest rates of magma decompression (

Journal article

Hughes AE, Winkler DA, Carr J, Lee PD, Yang YS, Laleh M, Tan MYet al., 2022, Corrosion Inhibition, Inhibitor Environments, and the Role of Machine Learning, Corrosion and Materials Degradation, Vol: 3, Pages: 672-693

Machine learning (ML) is providing a new design paradigm for many areas of technology, including corrosion inhibition. However, ML models require relatively large and diverse training sets to be most effective. This paper provides an overview of developments in corrosion inhibitor research, focussing on how corrosion performance data can be incorporated into machine learning and how large sets of inhibitor performance data that are suitable for training robust ML models can be developed through various corrosion inhibition testing approaches, especially high-throughput performance testing. It examines different types of environments where corrosion by-products and electrolytes operate, with a view to understanding how conventional inhibitor testing methods may be better designed, chosen, and applied to obtain the most useful performance data for inhibitors. The authors explore the role of modern characterisation techniques in defining corrosion chemistry in occluded structures (e.g., lap joints) and examine how corrosion inhibition databases generated by these techniques can be exemplified by recent developments. Finally, the authors briefly discuss how the effects of specific structures, alloy microstructures, leaching structures, and kinetics in paint films may be incorporated into machine learning strategies.

Journal article

Leung CLA, Luczyniec D, Guo E, Marussi S, Atwood RC, Meisnar M, Saunders B, Lee PDet al., 2022, Quantification of Interdependent Dynamics during Laser Additive Manufacturing Using X-Ray Imaging Informed Multi-Physics and Multiphase Simulation, ADVANCED SCIENCE, Vol: 9

Journal article

Guastamacchia MGR, Xue R, Madi K, Pitkeathly WTE, Lee PD, Webb SED, Cartmell SH, Dalgarno PAet al., 2022, Instantaneous 4D micro-particle image velocimetry (mu PIV) via multifocal microscopy (MUM), Scientific Reports, Vol: 12, ISSN: 2045-2322

Multifocal microscopy (MUM), a technique to capture multiple fields of view (FOVs) from distinct axial planes simultaneously and on one camera, was used to perform micro-particle image velocimetry (µPIV) to reconstruct velocity and shear stress fields imposed by a liquid flowing around a cell. A diffraction based multifocal relay was used to capture images from three different planes with 630 nm axial spacing from which the axial positions of the flow-tracing particles were calculated using the image sharpness metric. It was shown that MUM can achieve an accuracy on the calculated velocity of around (0.52 ± 0.19) µm/s. Using fixed cells, MUM imaged the flow perturbations at sub-cellular level, which showed characteristics similar to those observed in the literature. Using live cells as an exemplar, MUM observed the effect of changing cell morphology on the local flow during perfusion. Compared to standard confocal laser scanning microscope, MUM offers a clear advantage in acquisition speed for µPIV (over 300 times faster). This is an important characteristic for rapidly evolving biological systems where there is the necessity to monitor in real time entire volumes to correlate the sample responses to the external forces.

Journal article

Ackermann M, Kamp JC, Werlein C, Walsh CL, Stark H, Prade V, Surabattula R, Wagner WL, Disney C, Bodey AJ, Illig T, Leeming DJ, Karsdal MA, Tzankov A, Boor P, Kühnel MP, Länger FP, Verleden SE, Kvasnicka HM, Kreipe HH, Haverich A, Black SM, Walch A, Tafforeau P, Lee PD, Hoeper MM, Welte T, Seeliger B, David S, Schuppan D, Mentzer SJ, Jonigk DDet al., 2022, The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling, EBioMedicine, Vol: 85, ISSN: 2352-3964

BACKGROUND: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response. METHODS: We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients' hospitalization time. FINDINGS: The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19. INTERPRETATION: Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID. FUNDING: This project

Journal article

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