Finding a contrast agent that a surgeon could use to help delineate cancer cells from healthy ones
Jonathan Liu wants to see inside people’s brains. Specifically, he is working on a way he hopes will eventually give neurosurgeons a clearer look at the difference between malignant cells they want to remove in a specific type of tumor and healthy cells they’d rather not touch.
Taking out too many cells can damage the health of a patient, while not removing enough can give the tumor a chance to grow.
An assistant professor in biomedical engineering at Stony Brook University, Liu has tapped into his background in engineering to create microscopes that, in connection with a chemical called a contrast agent that lights up cancer cells, surgeons may one day use to see the edges of a tumor.
A doctor would “spray the contrast agent on at the final stages of surgery,” he explained. “It’s a way to check if there are any residual tumor cells.”
At this point, Liu and his graduate students, Danni Wang, Steven Leigh and Ye Chen, in conjunction with Stanford University, where Liu started this work as a postdoctoral student, have developed a system in animal models of medulloblastoma, a type of brain cancer, that makes the tumor glow.
In those animal models, medulloblastoma cells have a higher than normal amount of protein on their surface called Vascular Endothelial Growth Factor Receptor 1 (or VEGFR-1). Liu and his colleagues looked for a contrast agent that would stick to this protein and make it easy to find for surgeons.
“This is a specific contrast agent that we believe is labeling the tumor cells very accurately,” Liu said. “Normal cells would not overexpress this particular protein.”
The transition from these animal models of medulloblastoma to human forms will likely involve considerable study. Cancers can be highly variable and Liu explained that he wouldn’t expect all medulloblastomas to express VEGFR-1.
While the contrast agent and microscope could be years away from use in an operating room, the choice of a topical chemical, rather than a dye injected into a patient, may expedite the review process through the Food and Drug Administration.
Using a dye means the overall dosage could be lower, which would limit the introduction of the dye into the patient’s circulation.
Surgery has not yet reached the point where doctors can choose single cells to remove, Liu offered. Many brain tumor margins are diffuse and the cells can infiltrate and migrate through the brain, he explained. The goal, however, is to give the surgeon better guidelines.
A patient typically goes through chemotherapy to handle the remaining tumor. When surgeons remove more of the tumor, the postoperative therapies are generally also more effective, he asserted.
While the contrast agent the Stony Brook scientist used is innovative, the strengths of the design come from building the three-dimensional microscopes.
Liu designed a tabletop system for the recent results that were published in Translational Oncology. He is also creating a miniature handheld version that would be considerably more compact, in the form of a pen-like device.
As either a tabletop version or a handheld type, the microscope is “highly customized,” he related. “There’s nothing there that you can buy and get off the shelf.”
At Stanford, Liu built a similar microscope for the gastrointestinal tract. At Stony Brook, he has a new grant to develop a microscope to help with the early detection of oral cancers.
Receiving approval from regulators to use the newest microscope designs in the brain will require careful steps to ensure the instrument remains sterilized.
“You have to be very stringent,” Liu assured. He may surround the microscope in a plastic sheath, as medical researchers have done with similar devices.
Liu lives in Port Jefferson with his wife, Evie, a violin teacher who works at the Stony Brook School and gives lessons from home. They are both of Chinese descent and grew up in Hawaii.
Liu is an amateur surfer and enjoys going to the South Shore when a storm along the coast kicks up larger waves.
If he weren’t a scientist, Liu said he might consider a career as a doctor. He appreciates a physician’s opportunity to have a positive impact on their patients’ lives.
Still, he recognizes that his translational research may one day help those same patients.