Visualizing liver anatomy, physiology and pharmacology using multiphoton microscopy

Abstract

Multiphoton microscopy (MPM) has become increasingly popular and widely used in both basic and clinical liver studies over the past few years. This technology provides insights into deep live tissues with less photobleaching and phototoxicity, which helps us to better understand the cellular morphology, microenvironment, immune responses and spatiotemporal dynamics of drugs and therapeutic cells in the healthy and diseased liver. This review summarizes the principles, opportunities, applications and limitations of MPM in hepatology. A key emphasis is on the use of fluorescence lifetime imaging (FLIM) to add additional quantification and specificity to the detection of endogenous fluorescent species in the liver as well as exogenous molecules and nanoparticles that are applied to the liver in vivo. We anticipate that in the near future MPM‐FLIM will advance our understanding of the cellular and molecular mechanisms of liver diseases, and will be evaluated from bench to bedside, leading to real‐time histology of human liver diseases.

Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology

“…The possibility of simultaneously detecting different EFs ensures that AF optical biopsy can provide a comprehensive picture of liver state and functionality . However, the procedure requires direct contact via optical fibres in order to probe the liver or to collect liver tissue or bile specimens.…”

“…59 The possibility of simultaneously detecting different EFs ensures that AF optical biopsy can provide a comprehensive picture of liver state and functionality. 59,76,92,93,132 However, the procedure requires direct contact via optical fibres in order to probe the liver or to collect liver tissue or bile specimens. The consequent invasiveness can be acceptable during surgery or transplantation, but hinders routine follow-up of liver disorder, because of drawbacks which are comparable to those affecting conventional liver biopsy.…”

Metabolic imaging and secondary ion mass spectrometry to define the structure and function of liver with acute and chronic pathology

“…These parameters display specific changes in liver hepatocytes suffering common pathological diseases. 20,21 As a continuation of our previous works, 22,23 here we analyze acute and chronic liver pathology during the progression of pathological changes in hepatocytes at the cellular and molecular level, using multiphoton microscopy and mass spectrometry to obtain new data. The data can be used to develop new criteria for the identification of hepatic pathology, aimed at providing rapid analysis of liver quality in order to plan surgery and to avoid postoperative liver failure.…”

Automated classification of hepatocellular carcinoma differentiation using multiphoton microscopy and deep learning

“…Multiphoton microscopy (MPM) has emerged as a promising, rapid, label‐free and high‐resolution microscopic imaging technique, suitable for examining unprocessed tissue samples. It is predicted to be developing into an irreplaceable imaging technology in cancer detection and research . While the technique enables tomographic deep‐imaging of substances in biological tissues using longer‐wavelength infrared lasers, samples can also be observed for longer durations with these lasers because of reduced photodamage.…”