In the future, a tiny scanning fiber endoscope combined with a surgical robot and a tumor-lighting fluorescent dye, may help improve outcomes for patients with less aggressive forms of brain cancer.

A tiny scanning fiber endoscope developed by a team led by Eric Seibel, a professor with appointments in bioengineering and electrical engineering at the University of Washington, may help assist fluorescence-guided brain tumor resections.

After debulking a tumor within the brain, it’s important to find and remove any remaining tumor cells. This extremely daunting task is made even more challenging because it’s critical not to remove any excess healthy brain tissues—they won’t regrow.

Seibel’s scanning fiber endoscope is remarkably tiny—1 to 2 millimeters in diameter, or smaller than a grain of rice. “The scope has a little rigid tip and a long flexible shaft that could be used on the tip of surgical tools or a surgical robot,” said Seibel.

The work now being carried out by Seibel’s group is funded by National Institutes of Health and brings the tiny endoscope together with other key pieces: a fluorescence indicator, a small cancer-binding fluorescent dye, and a surgical robot for this delicate and often tedious surgical procedure.

: This green “Tumor Painted” brain tumor in a mouse brain has cancer cells that aren’t visible during surgery without the green color contrast on the blue brain surface background. Red lines show a sampling of the laser beam scan pattern that generates the video imaging.

Copyright: University of Washington.

Being able to view fluorescence is critical for locating brain tumor cells while using a fluorescence indicator like the one developed by Jim Olson, a pediatric neuro-oncologist at the Fred Hutchinson Cancer Research Center and Seattle Children’s Hospital. Olson's product, which is produced by Blaze Bioscience, is called Tumor Paint. The concept is, intriguingly, based on scorpion venom. Synthetic molecules that mimic the venom (but do not actually contain it) are combined with a fluorescent dye and then injected into a patient’s bloodstream, where they travel to the brain, pass by healthy tissue, adhere to cancer cells and light them up.

“Currently, one of the problems with research being done using fluorescence indicators is that few are being done within the infrared,” said Seibel. “It’s typically done at the visible light, which doesn’t penetrate as deeply into the body. Ideally, we’d like to see deeper—a millimeter or more down—to determine whether there’s a tumor there that can help guide a resection.”

Blaze Bioscience is using fluorescent near-infrared light, according to Seibel, which provides stronger signals from deeper within tissue and allows researchers to see more. “Even though the procedure is like excavating a tumor, you want to see a little deeper to know how deep to cut,” he explained. “The little extra depth of the near-infrared signal tells you how deep to cut.”

An important feature of the endoscope is that “it uses extremely low power, which means that the little molecules that are attached to the tumors and fluorescing don’t photobleach or fade,” Seibel added, “because if they fade you’ve lost your signal forever. ”

Having tools and technology that improve resection and reduce the invasiveness for dealing with these vexing tumors is win-win for the patients

The final piece of the puzzle, surgical robots like Raven, developed by professor Blake Hannaford’s BioRobotics Laboratory at the University of Washington, feature a lack of vibration and unimaginably accurate positioning, which are highly desirable for this type of surgery. “Robots are highly dexterous, move at many degrees of freedom, and can be very small, so are ideal for ‘hunt and peck’ tumor cell removal to get the cleanest margins possible,” said Seibel. “So we think it’s a good application for our research.”

The group’s goal is to one day help improve the outcomes for patients with less aggressive forms of brain tumors. “This could really tip the scales in favor of the percentage of patients who thrive after surgery—for the ones that we just need to have a bit better vision and procedural fine-tuning from the fluorescence eye on the tip of the robotic tool,” Seibel added.

“Many of the tumors within the brain are highly malignant and invasive. There is always a tension between being maximally aggressive to take out more, while being as conservative as possible to minimize the damage caused by the surgery,” said Eric C. Leuthardt, MD, and a professor of neurological surgery and biomedical engineering at Washington University School of Medicine in St. Louis, who was not involved with the research. “Having tools and technology that improve resection and reduce the invasiveness for dealing with these vexing tumors is win-win for the patients. The work that Seibel’s group is doing is promising and I hope it continues to move toward clinical application.”

The group’s work is currently in the prototype stage. “We only recently started working with the fluorescent indicator on mice brains because it took time to put our systems together and to verify that they work on synthetic phantoms, which are sort of replicas of what the brain surgery would look like,” Seibel noted.