Needle-based Confocal Laser Endomicroscopy to Assess Liver Histology in Vivo

Background: Confocal endomicroscopy enables histopathology of the GI lumen to be observed in vivo. Recent prototypes of a confocal miniprobe are thin enough to be introduced through a needle.

Objective: To evaluate the ability of needle-based confocal laser endomicroscopy to distinguish between normal and cirrhotic liver tissue in vivo in a rat model.

Design: Feasibility study, nonsurvival animal experiments.

Setting: Academic research facility.

Intervention: Three normal control and 4 cirrhotic rats were examined under general anesthesia. The liver was exposed by laparotomy and imaged by using 3 different prototypes of confocal miniprobes, with 0, 50, and 100 μm working distances. Images were acquired on the surface of the liver capsule and through a 19-gauge needle inserted into the liver parenchyma. Real-time sequences were recorded after intravenous injection of fluorescein. Biopsy specimens were taken for standard histopathology.

Main Outcome Measurements: Confocal microscopic images of the surface and interior of livers in normal and cirrhotic rats.

Results: Miniprobes with 50 or 100 μm working distances identified cords of hepatocytes radiating toward central venules in normal livers and distorted hepatic architecture in cirrhotic livers when the miniprobes were either placed on the liver capsule or inserted into the parenchyma. The miniprobe with a 0 μm working distance identified a novel reticular pattern on the liver surface that was detected only in cirrhosis. Like the 2 longer-working-distance probes, this probe also identified cords of hepatocytes radiating toward central venules in normal livers and distorted hepatic architecture in cirrhotic livers, but this occurred only when the probe was inserted into the parenchyma.

Limitations: Data were assessed in an experimental animal setting, confocal imaging was performed invasively during laparotomy, only 1 model of cirrhosis was used, and no noncirrhotic liver diseases were examined.

Conclusion: Needle-based confocal laser endomicroscopy provides sufficient detail to distinguish normal from cirrhotic livers in a rat model. This innovative, minimally invasive technique has the potential to provide real-time identification of liver histology during EUS or natural-orifice transluminal endoscopic surgery procedures.