Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies

Kong C, Bobe S, Pilger C, Lachetta M, Øie CI, Kirschnick N, Mönkemöller V, Hübner W, Förster C, Schüttpelz M, Kiefer F, et al. (2021)
Frontiers in Physiology 12: 637136.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Kong, CihangUniBi; Bobe, Stefanie; Pilger, ChristianUniBi; Lachetta, MarioUniBi; Øie, Cristina Ionica; Kirschnick, Nils; Mönkemöller, ViolaUniBi; Hübner, WolfgangUniBi ; Förster, Christine; Schüttpelz, MarkUniBi ; Kiefer, Friedemann; Huser, ThomasUniBi
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Abstract / Bemerkung
The liver as the largest organ in the human body is composed of a complex macroscopic and microscopic architecture that supports its indispensable function to maintain physiological homeostasis. Optical imaging of the human liver is particularly challenging because of the need to cover length scales across 7 orders of magnitude (from the centimeter scale to the nanometer scale) in order to fully assess the ultrastructure of the entire organ down to the subcellular scale and probe its physiological function. This task becomes even more challenging the deeper within the organ one hopes to image, because of the strong absorption and scattering of visible light by the liver. Here, we demonstrate how optical imaging methods utilizing highly specific fluorescent labels, as well as label-free optical methods can seamlessly cover this entire size range in excised, fixed human liver tissue and we exemplify this by reconstructing the biliary tree in three-dimensional space. Imaging of tissue beyond approximately 0.5 mm length requires optical clearing of the human liver. We present the successful use of optical projection tomography and light-sheet fluorescence microscopy to derive information about the liver architecture on the millimeter scale. The intermediate size range is covered using label-free structural and chemically sensitive methods, such as second harmonic generation and coherent anti-Stokes Raman scattering microscopy. Laser-scanning confocal microscopy extends the resolution to the nanoscale, allowing us to ultimately image individual liver sinusoidal endothelial cells and their fenestrations by super-resolution structured illumination microscopy. This allowed us to visualize the human hepatobiliary system in 3D down to the cellular level, which indicates that reticular biliary networks communicate with portal bile ducts via single or a few ductuli. Non-linear optical microscopy enabled us to identify fibrotic regions extending from the portal field to the parenchyma, along with microvesicular steatosis in liver biopsies from an older patient. Lastly, super-resolution microscopy allowed us to visualize and determine the size distribution of fenestrations in human liver sinusoidal endothelial cells for the first time under aqueous conditions. Thus, this proof-of-concept study allows us to demonstrate, how, in combination, these techniques open up a new chapter in liver biopsy analysis.
Erscheinungsjahr
2021
Zeitschriftentitel
Frontiers in Physiology
Band
12
Art.-Nr.
637136
eISSN
1664-042X
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld gefördert.
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https://pub.uni-bielefeld.de/record/2952160

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Kong C, Bobe S, Pilger C, et al. Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies. Frontiers in Physiology. 2021;12: 637136.
Kong, C., Bobe, S., Pilger, C., Lachetta, M., Øie, C. I., Kirschnick, N., Mönkemöller, V., et al. (2021). Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies. Frontiers in Physiology, 12, 637136. https://doi.org/10.3389/fphys.2021.637136
Kong, C., Bobe, S., Pilger, C., Lachetta, M., Øie, C. I., Kirschnick, N., Mönkemöller, V., Hübner, W., Förster, C., Schüttpelz, M., et al. (2021). Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies. Frontiers in Physiology 12:637136.
Kong, C., et al., 2021. Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies. Frontiers in Physiology, 12: 637136.
C. Kong, et al., “Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies”, Frontiers in Physiology, vol. 12, 2021, : 637136.
Kong, C., Bobe, S., Pilger, C., Lachetta, M., Øie, C.I., Kirschnick, N., Mönkemöller, V., Hübner, W., Förster, C., Schüttpelz, M., Kiefer, F., Huser, T., Schulte am Esch, J.: Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies. Frontiers in Physiology. 12, : 637136 (2021).
Kong, Cihang, Bobe, Stefanie, Pilger, Christian, Lachetta, Mario, Øie, Cristina Ionica, Kirschnick, Nils, Mönkemöller, Viola, Hübner, Wolfgang, Förster, Christine, Schüttpelz, Mark, Kiefer, Friedemann, Huser, Thomas, and Schulte am Esch, Jan. “Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies”. Frontiers in Physiology 12 (2021): 637136.
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