Human lung virtual histology by multi-scale x-ray phase-contrast computed tomography

2023-05-11 | journal article. A publication with affiliation to the University of Göttingen.

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​Human lung virtual histology by multi-scale x-ray phase-contrast computed tomography​
Reichmann, J. ; Verleden, S. E; Kühnel, M.; Kamp, J. C; Werlein, C.; Neubert, L. & Müller, J.-H. et al.​ (2023) 
Physics in Medicine and Biology,.​ DOI: 

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Reichmann, Jakob ; Verleden, Stijn E; Kühnel, Mark; Kamp, Jan C; Werlein, Christopher; Neubert, Lavinia; Müller, Jan-Hendrik; Bui, Thanh Quynh; Ackermann, Maximilian; Jonigk, Danny; Salditt, Tim
As the central organ of the respiratory system, the human lung is responsible for supplying oxygen to the blood, which reaches the erythrocytes by diffusion through the alveolar walls and is then distributed throughout the body. By exploiting the difference in electron density detected by a phase shift in soft tissue, high-resolution X-ray phase-contrast computed tomography (XPCT) can resolve biological structures in a sub-μm range, shedding new light on the three-dimensional structure of the lungs, physiological functions and pathological mechanisms. This work presents both synchrotron and laboratory XPCT results of postmortem tissue from autopsies and biopsies embedded with various preparation protocols such as precision-cut lung slices, cryogenically fixed lung tissue, as well as paraffin and alcohol fixed tissue. The selection of pathological abnormalities includes channel of Lambert, bronchus-associated lymphoid tissue, alveolar capillary dysplasia with misalignment of pulmonary veins. Subsequently, quantification and visualization approaches are presented. The overall high image quality even of in-house XPCT scans for the case of FFPE biopsies can be exploited for a wide range of pulmonary pathologies and translated to dedicated and optimized instrumentation which could be operated in clinical setting. By using synchrotron radiation, contrast can be further increased to resolve sub-μm sized features down to the sub-cellular level. The results demonstrate that a wide range of preparation protocols including sample mounting in liquids can be used. With XPCT, poorly understood 3D structures can be identified in larger volume overview and subsequently studied in more detail at higher resolution. With the full 3D structure, the respective physiological functions of airways or vascular networks, and the different pathophysiologic mechanisms can be elucidated or at least underpinned with structural data. Moreover, synchrotron data can be used to validate laboratory protocols and provide ground truth for standardizing the method. .
Issue Date
Physics in Medicine and Biology 
SFB 1456: Mathematik des Experiments: Die Herausforderung indirekter Messungen in den Naturwissenschaften 
EXC 2067: Multiscale Bioimaging 
SFB 1456 | Cluster A | A03: Dimensionality reduction and regression in Wasserstein space for quantitative 3D histology 
Institut für Röntgenphysik 
Working Group
RG Salditt (Structure of Biomolecular Assemblies and X-Ray Physics) 



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