Recent Advances and the Potential for Clinical Use of Autofluorescence Detection of Extra-Ophthalmic Tissues

Wizenty, Jonas; Schumann, Teresa; Theil, Donna; Stockmann, Martin; Pratschke, Johann; Tacke, Frank; Aigner, Felix; Wuensch, Tilo

doi:10.3390/molecules25092095

Cited by 13 publications

(6 citation statements)

References 183 publications

(214 reference statements)

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“…In this section attention is paid prevalently to the biomolecules acting as endogenous fluorophores and to their possible pathophysiological meaning, rather than on the almost countless clinical optically based diagnostic applications described in dedicated papers and reviews [264][265][266][267][268][269][270][271][272][273].…”

Section: Normal and Altered Cell And Tissuesmentioning

confidence: 99%

Light and Autofluorescence, Multitasking Features in Living Organisms

Croce

2021

Photochem

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Organisms belonging to all life kingdoms may have the natural capacity to fluoresce. Autofluorescence events depend on the presence of natural biomolecules, namely endogenous fluorophores, with suitable chemical properties in terms of conjugated double bonds, aromatic or more complex structures with oxidized and crosslinked bonds, ensuring an energy status able to permit electronic transitions matching with the energy of light in the UV-visible-near-IR spectral range. Emission of light from biological substrates has been reported since a long time, inspiring unceasing and countless studies. Early notes on autofluorescence of vegetables have been soon followed by attention to animals. Investigations on full living organisms from the wild environment have been driven prevalently by ecological and taxonomical purposes, while studies on cells, tissues and organs have been mainly promoted by diagnostic aims. Interest in autofluorescence is also growing as a sensing biomarker in food production and in more various industrial processes. The associated technological advances have supported investigations ranging from the pure photochemical characterization of specific endogenous fluorophores to their possible functional meanings and biological relevance, making fluorescence a valuable intrinsic biomarker for industrial and diagnostic applications, in a sort of real time, in situ biochemical analysis. This review aims to provide a wide-ranging report on the most investigated natural fluorescing biomolecules, from microorganisms to plants and animals of different taxonomic degrees, with their biological, environmental or biomedical issues relevant for the human health. Hence, some notes in the different sections dealing with different biological subject are also interlaced with human related issues. Light based events in biological subjects have inspired an almost countless literature, making it almost impossible to recall here all associated published works, forcing to apologize for the overlooked reports. This Review is thus proposed as an inspiring source for Readers, addressing them to additional literature for an expanded information on specific topics of more interest.

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Section: Normal and Altered Cell And Tissuesmentioning

confidence: 99%

Light and Autofluorescence, Multitasking Features in Living Organisms

Croce

2021

Photochem

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“…Trimodal imaging combining white-light endoscopy, AF imaging and narrow-brand imaging has already been described [17,18], but this technique has never been applied for inflammation detection in stomach. This device uses excitation light between 390 and 470 nm at the limit of the visible while the re-emission was arbitrarily and globally captured between 500 and 630 nm.…”

Section: Discussionmentioning

confidence: 99%

Multimodal imaging as optical biopsy system for gastritis diagnosis in humans, and input of the mouse model

et al. 2021

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Background: Gastric inflammation is a major risk factor for gastric cancer. Current endoscopic methods are not able to efficiently detect and characterize gastric inflammation, leading to a sub-optimal patients' care. New non-invasive methods are needed. Reflectance mucosal light analysis is of particular interest in this context. The aim of our study was to analyze reflectance light and specific autofluorescence signals, both in humans and in a mouse model of gastritis. Methods: We recruited patients undergoing gastroendoscopic procedure during which reflectance was analysed with a multispectral camera. In parallel, the gastritis mouse model of Helicobacter pylori infection was used to investigate reflectance from ex vivo gastric samples using a spectrometer. In both cases, autofluorescence signals were measured using a confocal microscope. Findings: In gastritis patients, reflectance modifications were significant in near-infrared spectrum, with a decrease between 610 and 725 nm and an increase between 750 and 840 nm. Autofluorescence was also modified, showing variations around 550 nm of emission. In H. pylori infected mice developing gastric inflammatory lesions, we observed significant reflectance modifications 18 months after infection, with increased intensity between 617 and 672 nm. Autofluorescence was significantly modified after 1, 3 and 6 months around 550 and 630 nm. Both in human and in mouse, these reflectance data can be considered as biomarkers and accurately predicted inflammatory state. Interpretation: In this pilot study, using a practical measuring device, we identified in humans, modification of reflectance spectra in the visible spectrum and for the first time in near-infrared, associated with inflammatory gastric states. Furthermore, both in the mouse model and humans, we also observed modifications of autofluorescence associated with gastric inflammation. These innovative data pave the way to deeper validation studies on larger cohorts, for further development of an optical biopsy system to detect gastritis and finally to better surveil this important gastric cancer risk factor. Funding: The project was funded by the ANR EMMIE (ANR-15-CE17-0015) and the French Gastroenterology Society (SNFGE).

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“…By using Ilastik, for instance, it is feasible not only to segment a cell population based on a single marker-expression, but on the co-expression of several markers, including DAPI, that would consequently eliminate irrelevant signal. This is particularly relevant when performing immunohistochemistry on FFPE samples or when dealing with intrinsic tissue components known to be autofluorescent [ 21 , 22 ]. A systematic approach using multiplex immunostaining could very well be used for screening and preliminary characterization of poorly described patient conditions or experimental models.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Immune Microenvironment on A Single Archival Formalin-Fixed Paraffin-Embedded Tissue Section by An Immediately Implementable Multiplex Fluorescence Immunostaining Protocol

Guillot

Kohlhepp

Bruneau

et al. 2020

Cancers

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Technological breakthroughs have fundamentally changed our understanding on the complexity of the tumor microenvironment at the single-cell level. Characterizing the immune cell composition in relation to spatial distribution and histological changes may provide important diagnostic and therapeutic information. Immunostaining on formalin-fixed paraffin-embedded (FFPE) tissue samples represents a widespread and simple procedure, allowing the visualization of cellular distribution and processes, on preserved tissue structure. Recent advances in microscopy and molecular biology have made multiplexing accessible, yet technically challenging. We herein describe a novel, simple and cost-effective method for a reproducible and highly flexible multiplex immunostaining on archived FFPE tissue samples, which we optimized for solid organs (e.g., liver, intestine, lung, kidney) from mice and humans. Our protocol requires limited specific equipment and reagents, making multiplexing (>12 antibodies) immediately implementable to any histology laboratory routinely performing immunostaining. Using this method on single sections and combining it with automated whole-slide image analysis, we characterize the hepatic immune microenvironment in preclinical mouse models of liver fibrosis, steatohepatitis and hepatocellular carcinoma (HCC) and on human-patient samples with chronic liver diseases. The data provide useful insights into tissue organization and immune–parenchymal cell-to-cell interactions. It also highlights the profound macrophage heterogeneity in liver across premalignant conditions and HCC.

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Recent Advances and the Potential for Clinical Use of Autofluorescence Detection of Extra-Ophthalmic Tissues

Cited by 13 publications

References 183 publications

Light and Autofluorescence, Multitasking Features in Living Organisms

Light and Autofluorescence, Multitasking Features in Living Organisms

Multimodal imaging as optical biopsy system for gastritis diagnosis in humans, and input of the mouse model

Deciphering the Immune Microenvironment on A Single Archival Formalin-Fixed Paraffin-Embedded Tissue Section by An Immediately Implementable Multiplex Fluorescence Immunostaining Protocol

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