Confocal Laser Endomicroscopy Uncovers Previously Unknown Organ

Using imaging technology called probe-based confocal laser endomicroscopy, researchers have identified a previously unknown feature of human anatomy that could have implications for the function of organs, tissues and diseases.

The technology combines an endoscope — the slender camera-toting probe traditionally snaked down the throat to view the insides of organs — with a laser that lights up tissues and sensors that analyze the reflected fluorescent patterns. It offers a microscopic view of living tissues instead of fixed ones.

The study, led by researchers at New York University (NYU) School of Medicine, reveals that layers of the body long thought to be dense, connective tissues are instead interconnected, fluid-filled compartments supported by a meshwork of connective tissue proteins. This layer of moving fluid, which drains into the lymphatic system, could explain why cancer that invades it becomes much more likely to spread.

The interstitium, a recently discovered organ, is seen here beneath the top layer of skin, but it is also in tissue layers lining the gut, lungs, blood vessels and muscles. The organ was found through microendoscopy. Courtesy of Jill Gregory and Mount Sinai Health System.

The researchers say that no one saw these compartments before because the process of making tissue fixed, which includes dyeing the sample to highlight key features, also drains away fluid from the sample. According to researchers, the removal of fluid causes the connective protein meshwork surrounding once fluid-filled compartments to collapse.

Using endomicroscopy, in 2015 researchers at Beth Israel Medical Center discovered a series of interconnected cavities in the submucosal tissue layer that did not match any known anatomy. When professor Neil Theise, M.D., made biopsy slides of the same tissue, the reticular pattern found by the endomicroscopy disappeared. The team would later confirm that very thin spaces seen in biopsy slides, traditionally thought to be tears in the tissue, were instead the remnants of collapsed, previously fluid-filled compartments.

For the current study, the team collected tissue specimens of bile ducts during 12 cancer surgeries where the pancreas and bile duct were removed. Minutes before clamping off blood flow to the target tissue, patients underwent confocal microscopy for live-tissue imaging. Once the team recognized this new space in images of bile ducts, they further recognized it throughout the body, wherever tissues moved or were compressed by force. The study defines the interstitium (i.e., interstitial fluid) as an organ in its own right and as one of the largest organs in the body.

“This finding has potential to drive dramatic advances in medicine, including the possibility that the direct sampling of interstitial fluid may become a powerful diagnostic tool,” said Theise.

The research was published in Scientific Reports (doi:10.1038/s41598-018-23062-6).