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

BACKGROUND AND STUDY AIMS: Confocal endomicroscopy is a unique novel tool for in vivo histology in humans. Due to limitations imposed by the form of the equipment and by sterilization workflows, its use has been limited to the gastrointestinal tract so far. We have developed a rigid miniaturized probe for confocal endomicroscopy of the human liver during laparoscopy. PATIENTS AND METHODS: To assess the feasibility and potential clinical value of this new system (diameter 6.3 mm), 25 patients with liver disease were examined during routine minilaparoscopy under conscious sedation. RESULTS: Subsurface serial images (from surface to 250 microm) were generated in real time after fluorescein injection, permitting visualization of hepatocytes, bile ducts, sinusoids, and collagen fibers in vivo. Typical appearances of liver diseases were identified. Confocal diagnosis of moderate-to-severe steatosis and pericellular fibrosis correlated well with histopathologic analysis of subsequent biopsies (83.3 % and 84.6 %, respectively). In addition, intra-abdominal structures such as gallbladder, omentum, and stomach were analyzed by endomicroscopy. CONCLUSIONS: A miniaturized imaging system for confocal laparoscopy allowed in vivo microscopic analysis of healthy and diseased human liver for the first time during ongoing minilaparoscopy. Although such in vivo imaging does not yet compete with conventional histopathology, this novel confocal laparoscopy system may be of future relevance for immediate morphodynamic analysis in liver disease and the targeting of biopsies in vivo.

In vivo detection of small subsurface melanomas in athymic mice using noninvasive fiber optic confocal imaging.

Fiber optic confocal imaging, following intravenous administration of fluorescently labeled antibodies and Texas Red-dextran, enabled in vivo detection of melanoma and surrounding blood vessels in athymic mice. Human melanoma cells (three cell lines) and cultured normal human skin cells were implanted intradermally into the haunch skin of anesthetized athymic BALB/C mice and allowed to grow to a maximum size of 2 mm diameter. Using three different fluorescein-isothiocyanate-labeled antimelanoma antibodies, single channel confocal images of melanoma cells were obtained in vivo. Using noninvasive techniques, the overall in vivo melanoma detection rate for tumors within 0.2 mm of the skin surface was 84% (27 of 32 tumors). Normal cultured human skin cells were found to have little or no fluorescence after administration of the fluorescein-isothiocyanate-labeled antibodies and tumors were not labeled by an isotype control antibody. Dual channel imaging of the implanted melanoma tumor and surrounding dermal vasculature in vivo showed increased blood vessel density at the melanoma site. Conventional immunoperoxidase histology confirmed that fiber optic confocal imaging was able to detect melanoma tumors up to 0.2 mm below the skin surface, in vivo.