In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time

Goetz, Martin; Kießlich, Ralf; Dienes, Hans Peter; Drebber, U.; Murr, Elise R.; Hoffman, Arthur; Kanzler, Stephan; Galle, Peter R.; Delaney, Peter; Neurath, MF

doi:10.1055/s-2008-1077296

Cited by 59 publications

(43 citation statements)

References 19 publications

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“…Thus, there is a desperate need for a rapid, accurate and safe histological diagnosis method for the successful diagnosis and management of liver disease. Goetz et al has recently reported the application of confocal laser endomicroscopy for the real-time histological examination of liver disease in both animal models and human [7,8]. This technology allows immediate in vivo subsurface microscopic imaging and has potential to dynamically monitor pathologic events of liver with high resolution.…”

Section: Introductionmentioning

confidence: 99%

Real-time histology in liver disease using multiphoton microscopy with fluorescence lifetime imaging

Wang¹,

Liang²,

Mohammed³

et al. 2015

Biomed. Opt. Express

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Conventional histology with light microscopy is essential in the diagnosis of most liver diseases. Recently, a concept of real-time histology with optical biopsy has been advocated. In this study, live mice livers (normal, with fibrosis, steatosis, hepatocellular carcinoma and ischemiareperfusion injury) were imaged by MPM-FLIM for stain-free real-time histology. The acquired MPM-FLIM images were compared with conventional histological images. MPM-FLIM imaged subsurface cellular and subcellular histopathological hallmarks of live liver in mice models at high resolution. Additional information such as distribution of stellate cell associated autofluorescence and fluorescence lifetime changes was also gathered by MPM-FLIM simultaneously, which cannot be obtained from conventional histology. MPM-FLIM could simultaneously image and quantify the cellular morphology and microenvironment of live livers without conventional biopsy or fluorescent dyes. We anticipate that in the near future MPM-FLIM will be evaluated from bench to bedside, leading to real-time histology and dynamic monitoring of human liver diseases.

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Section: Introductionmentioning

confidence: 99%

Real-time histology in liver disease using multiphoton microscopy with fluorescence lifetime imaging

Wang¹,

Liang²,

Mohammed³

et al. 2015

Biomed. Opt. Express

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“…Noninvasive biomedical imaging techniques such as ultrasonography, computed tomography, and magnetic resonance imaging are widely used to detect liver disease, but they do not have sufficient sensitivity, spatial resolution, or specificity to detect or stage liver disease (Lin et al, 2012). By contrast, virtual biopsies obtained via fluorescence imaging can give an overall view of the liver (Goetz et al, 2008a) as well as provide dynamic information (Goetz et al, 2008b). The latter technique remains useful regardless of sample preparation (e.g., frozen or paraffin-embedded tissue), is easy and fast, has no sampling bias (Gailhouste et al, 2010), and may potentially quantify liver diseases such as fibrosis (He et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Fluorescein has been used to study liver function in humans, permitting visualization of hepatocytes, bile ducts, sinusoids, and collagen fibers in vivo (Goetz et al, 2008a). Fluorescein, which rapidly diffuses throughout the body in seconds, is taken up by the hepatocytes, metabolized to fluorescein monoglucuronide (FG), and excreted into the bile by active transport (Sherman and Fisher, 1986).…”

Section: Introductionmentioning

confidence: 99%

Assessing Steatotic Liver Function after Ischemia-Reperfusion Injury by In Vivo Multiphoton Imaging of Fluorescein Disposition

et al. 2014

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Ischemia-reperfusion injury, a common complication during liver surgery where steatotic livers are more prone to the injury, may become more prevalent in the growing obese population. This study characterizes liver morphology toward understanding changes in subcellular function in steatotic livers exposed to ischemiareperfusion injury through quantitative description of fluorescein distribution obtained by minimally invasive in vivo multiphoton microscopy using a physiologic pharmacokinetic model. Rats were fed a high-fat diet for 7 days to induce liver steatosis. Partial ischemia was induced after reperfusion for 4 hours, when fluorescein (10 mg/kg) was injected intravenously. Liver images, bile, and blood were collected up to 180 minutes after injection. Ischemia-reperfusion injury was associated with an increase in alanine transaminase levels and apoptosis. In addition, steatosis featured lipid droplets and an increase in fluorescein-associated fluorescence observed in hepatocytes via multiphoton imaging. Analysis of the hepatic concentrationtime profiles has suggested that the steatosis-induced increase in fluorescein-associated fluorescence mainly arises by inducing hepatic fluorescein metabolism. The combination of ischemiareperfusion with steatosis exacerbates these effects further. This was confirmed by fluorescence lifetime imaging microscopy showing a decreased average fluorescence lifetime of the liver, which is indicative of an increased production of the metabolite. Our results show the potential of noninvasive dye imaging for improving our understanding of liver disease induced by subcellular changes in vivo, providing further quantitative measures of metabolic and biliary liver function, and hence extending the qualitative liver function tests now available.

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“…35 Finally, a recent case report used pCLE to detect villous structures of intraductal papillary mucinous tumors of the pancreas. 36 …”

Section: Hepatobiliary/pancreasmentioning

confidence: 99%

Confocal Laser Endomicroscopy: A Primer for Pathologists

Paull¹,

Hyatt²,

Wassef³

et al. 2011

Archives of Pathology &Amp; Laboratory Medicine

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N Context.-The advent of new endoscopic optical techniques is likely to change pathologists' role in diagnosis.Objective.-To describe how confocal laser endomicroscopy (CLE) works, show its advantages and limitations compared to cytohistologic biopsy, and explore how it may affect the practice of pathology.Data Sources.-Literature review.Conclusions.-Confocal laser endomicroscopy is proving its ability to provide histology-like images of tissues in vivo to help avoid risks and costs of conventional biopsies. Confocal imaging restricts light to 1 plane, emulating a paraffin section, and topical or systemic optical contrast agents allow subcellular resolution. New contrast agents could theoretically permit molecular characterization. In vivo imaging has begun to demonstrate novel, dynamic types of diagnostic features. Decreased histologic biopsies can be anticipated for a few scenarios. Significant limitations of CLE include the inability to create a tissue archive for broad molecular classification, suboptimal contrast agents, small fields of view and shallow penetration, paucity of clinical validation studies, and problems with reimbursement. Confocal laser endomicroscopy exposes new opportunities for pathologists: CLE technologies can be exploited in pathology, and diagnostic criteria expanded based on endoscopists' discoveries. Potential synergy exists between CLE and cytology, allowing the low-magnification diagnostic architectural changes by CLE and cytomorphology to emulate the full diagnostic information in a histologic biopsy while providing an archive of material for molecular or immunohistochemical studies. Confocal laser endomicroscopy will decrease some types of biopsies, but offers an opportunity for pathologists to find new ways to provide value and improve patient care.

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In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time

Cited by 59 publications

References 19 publications

Real-time histology in liver disease using multiphoton microscopy with fluorescence lifetime imaging

Real-time histology in liver disease using multiphoton microscopy with fluorescence lifetime imaging

Assessing Steatotic Liver Function after Ischemia-Reperfusion Injury by In Vivo Multiphoton Imaging of Fluorescein Disposition

Confocal Laser Endomicroscopy: A Primer for Pathologists

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