Zonated quantification of steatosis in an entire mouse liver.
Many physiological processes and pathological conditions in livers are spatially heterogeneous, forming patterns at the lobular length scale or varying across the organ. Steatosis, a common liver disease characterized by lipids accumulating in hepatocytes, exhibits heterogeneity at both these spatial scales. The main goal of the present study was to provide a method for zonated quantification of the steatosis patterns found in an entire mouse liver. As an example application, the results were employed in a pharmacokinetics simulation. For the analysis, an automatic detection of the lipid vacuoles was used in multiple slides of histological serial sections covering an entire mouse liver. Lobuli were determined semi-automatically and zones were defined within the lobuli. Subsequently, the lipid content of each zone was computed. The steatosis patterns were found to be predominantly periportal, with a notable organ-scale heterogeneity. The analysis provides a quantitative description of the extent of steatosis in unprecedented detail. The resulting steatosis patterns were successfully used as a perturbation to the liver as part of an exemplary whole-body pharmacokinetics simulation for the antitussive drug dextromethorphan. The zonated quantification is also applicable to other pathological conditions that can be detected in histological images. Besides being a descriptive research tool, this quantification could perspectively complement diagnosis based on visual assessment of histological images.
Fraunhofer MEVIS, Universitätsallee 29, 28359 Bremen, Germany. Electronic address: ole.schwen@mevis.fraunhofer.de.
Lars Ole
LO
Schwen
Fraunhofer MEVIS, Universitätsallee 29, 28359 Bremen, Germany. Electronic address: andre.homeyer@mevis.fraunhofer.de.
André
A
Homeyer
Fraunhofer MEVIS, Universitätsallee 29, 28359 Bremen, Germany; Jacobs University, Campus Ring 1, 28759 Bremen, Germany. Electronic address: michael.schwier@mevis.fraunhofer.de.
Michael
M
Schwier
Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, University Hospital Jena, Drackendorfer Str. 1, 07747 Jena, Germany. Electronic address: uta.dahmen@med.uni-jena.de.
Uta
U
Dahmen
Institute of Pathology, Klinikum Chemitz, Flemmingstraße 2, 09116 Chemnitz, Germany. Electronic address: olaf.dirsch@googlemail.com.
Olaf
O
Dirsch
Computational Systems Biology, Bayer Technology Services, Kaiser-Wilhelm-Allee 1, 51368 Leverkusen, Germany; Aachen Institute for Advanced Study in Computational Engineering Sciences, RWTH Aachen University, Schinkelstr. 2, 52062 Aachen, Germany. Electronic address: arne.schenk.ext@bayer.com.
Arne
A
Schenk
Computational Systems Biology, Bayer Technology Services, Kaiser-Wilhelm-Allee 1, 51368 Leverkusen, Germany; Institute of Applied Microbiology, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany. Electronic address: lars.kuepfer@bayer.com.
Lars
L
Kuepfer
Fraunhofer MEVIS, Universitätsallee 29, 28359 Bremen, Germany; Jacobs University, Campus Ring 1, 28759 Bremen, Germany. Electronic address: tobias.preusser@mevis.fraunhofer.de.
Tobias
T
Preusser
Fraunhofer MEVIS, Universitätsallee 29, 28359 Bremen, Germany. Electronic address: andrea.schenk@mevis.fraunhofer.de.
Andrea
A
Schenk
D000818:Animals; D003198:Computer Simulation; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008954:Models, Biological; D014617:Vacuoles / Q000378:metabolism / Q000473:pathology
Dextromethorphan; Histological serial sections; Pharmacokinetics simulations; Quantitative image analysis; Steatosis; Virtual Liver; Whole-slide scans; Zonation