Three-Dimensional Imaging of Hepatic Sinusoids in Mice Using Synchrotron Radiation Micro-Computed Tomography

Yoon, Yae Jin; Chang, Suho; Kim, Oh Youn; Kang, Bo-Kyeong; Park, Jaesung; Lim, Jae‐Hong; Huang, Jung Yun; Kim, Eui Chong; Byun, Jae Ho; Gho, Yong Song

doi:10.1371/journal.pone.0068600

Cited by 26 publications

(18 citation statements)

References 32 publications

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“…It is generally recognized that hepatic sinusoids play a crucial role in hepatic microcirculation and that abnormalities of hepatic sinusoidal Table 1 Correlation analysis between different characteristics of GST-P positive foci and liver iron content as well as % enhancement of MRI signal morphology and architecture can occur under pathological conditions including carcinogen induction. 22 As the results show in Fig. 4, H&E staining and SEM imaging demonstrate sinusoidal morphology alterations in DEN-3 (red arrow head), compared to control (green arrow head).…”

Section: Resultssupporting

confidence: 53%

MRI contrast enhancement of liver pre-neoplasia using iron–tannic nanoparticles

et al. 2020

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Section: Resultssupporting

confidence: 53%

MRI contrast enhancement of liver pre-neoplasia using iron–tannic nanoparticles

et al. 2020

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“…Third, the terminal zone of the sinusoid/venule is reportedly more “spacious” than the port of exit of the sinusoid from the PV 21,23,24. Such anatomy could support hemodynamic conditions, which facilitate clearance of particles into the CV, and further down into the systemic circulation, thereby contributing to the relative paucity of particles in vicinity of the CV.…”

Section: Discussionmentioning

confidence: 99%

<p>Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure</p>

Gerstenhaber¹,

Marcinkiewicz²,

Barone³

et al. 2019

IJN

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Background We recently reported on long-term comprehensive biocompatibility and biodistribution study of fluorescent nanodiamond particles (NV)-Z-average 800nm (FNDP-(NV)) in rats. FNDP-(NV) primary deposition was found in the liver, yet liver function tests remained normal. Purpose The present study aimed to gain preliminary insights on discrete localization of FNDP-(NV) in liver cells of the hepatic lobule unit and venous micro-vasculature. Kinetics of FDNP-(NV) uptake into liver cells surrogates in culture was conducted along with cell cytokinesis as markers of cells' viability. Methods Preserved liver specimens from a pilot consisting of two animals which were stained for cytoskeletal elements (fluorescein-isothiocyanate-phalloidin) were examined for distribution of FNDP-(NV) by fluorescent microscopy (FM) and Confocal-FM (CFM) using near infra-red fluorescence (NIR). Hepatocellular carcinoma cells (HepG-2) and human umbilical vein endothelial cells (HUVEC) were cultured with FNDP-(NV) and assayed for particle uptake and location using spectrophotometric technology and microscopy. Results HepG-2 and HUVEC displayed rapid (<30 mins) onset and concentration-dependent FNDP-(NV) internalization and formation of peri-nuclear corona. FM/CFM of liver sections revealed FNDP-(NV) presence throughout the hepatic lobules structures marked by spatial distribution, venous microvascular spaces and parenchyma and non-parenchyma cells. Conclusion The robust presence of FNDP-(NV) throughout the hepatic lobules including those internalized within parenchyma cells and agglomerates in the liver venous micro-circulation were not associated with macro or micro histopathological signs nor vascular lesions. Cells cultures indicated normal cytokinesis in cells containing FNDP-(NV) agglomerates. Liver parenchyma cells and the liver microcirculation remain agnostic to presence of FNDP-(NV) in the sinusoids or internalized in the hepatic cells.

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“…Radii of periportal and pericentral sinusoids in mice are r sin,pp = 4.4 μm and r sin,pc = 6.85 μm [ 98 ], respectively. This range is similar to sinusoidal diameters of 7 and 15 μm reported in [ 1 ], so we will use the following formulas for both humans and mice.…”

Section: Methodsmentioning

confidence: 99%

Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations

et al. 2015

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The mammalian liver plays a key role for metabolism and detoxification of xenobiotics in the body. The corresponding biochemical processes are typically subject to spatial variations at different length scales. Zonal enzyme expression along sinusoids leads to zonated metabolization already in the healthy state. Pathological states of the liver may involve liver cells affected in a zonated manner or heterogeneously across the whole organ. This spatial heterogeneity, however, cannot be described by most computational models which usually consider the liver as a homogeneous, well-stirred organ.The goal of this article is to present a methodology to extend whole-body pharmacokinetics models by a detailed liver model, combining different modeling approaches from the literature. This approach results in an integrated four-scale model, from single cells via sinusoids and the organ to the whole organism, capable of mechanistically representing metabolization inhomogeneity in livers at different spatial scales. Moreover, the model shows circulatory mixing effects due to a delayed recirculation through the surrounding organism.To show that this approach is generally applicable for different physiological processes, we show three applications as proofs of concept, covering a range of species, compounds, and diseased states: clearance of midazolam in steatotic human livers, clearance of caffeine in mouse livers regenerating from necrosis, and a parameter study on the impact of different cell entities on insulin uptake in mouse livers.The examples illustrate how variations only discernible at the local scale influence substance distribution in the plasma at the whole-body level. In particular, our results show that simultaneously considering variations at all relevant spatial scales may be necessary to understand their impact on observations at the organism scale.

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Three-Dimensional Imaging of Hepatic Sinusoids in Mice Using Synchrotron Radiation Micro-Computed Tomography

Cited by 26 publications

References 32 publications

MRI contrast enhancement of liver pre-neoplasia using iron–tannic nanoparticles

MRI contrast enhancement of liver pre-neoplasia using iron–tannic nanoparticles

<p>Biocompatibility studies of fluorescent diamond particles-(NV)∼800nm (part V): in vitro kinetics and in vivo localization in rat liver following long-term exposure</p>

Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations

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