If you can see nerves better, you would avoid injuring them
For generations, surgeons operating near the delicate nerves of the head and neck have worked at the edge of what the human eye can perceive, knowing that a moment's misjudgment could silence a voice or numb a face forever. Now, a fluorescent compound called bevonescein — the first nerve-specific imaging agent to pass human safety trials — offers a way to make the invisible visible, illuminating fragile nerve tissue in real time under the surgeon's light. Developed through a collaboration between Stanford, Vanderbilt, and Alume Biosciences, this milestone extends fluorescence imaging from the detection of cancer to the preservation of the healthy structures surrounding it, marking a quiet but profound expansion of what surgical precision can mean.
- Nerve damage during head and neck surgery remains one of medicine's most consequential and underacknowledged risks, capable of robbing patients of speech, sensation, or swallowing function even when an operation is otherwise successful.
- Every previous attempt to create a nerve-specific fluorescent agent that works in humans has failed — bevonescein's passage through human safety trials is the first crack in that wall.
- Injected into the bloodstream before surgery, bevonescein binds to nerve tissue and causes it to glow under specialized operating-room lighting, giving surgeons a real-time visual map of what must not be cut.
- Phase 3 clinical trials are now underway across multiple centers, with Vanderbilt enrolling the largest cohort, and an FDA approval application is expected in the near future.
- If approved, the technology could move beyond oncology to become a standard safeguard in any surgery where nerves are at risk, fundamentally shifting the calculus of surgical harm prevention.
Surgeons operating on tumors in the head and neck have always contended with a cruel paradox: the nerves most at risk of damage are among the hardest to see. Thin, fragile, and woven through dense tissue, they can be severed or bruised in an instant, leaving patients with permanent numbness, weakness, or a lost voice. A new fluorescent compound called bevonescein may finally change that equation.
Published this week in Nature Communications and led by Eben Rosenthal, chair of otolaryngology and head and neck surgery at Vanderbilt University Medical Center, the research confirms that bevonescein — a synthetic peptide bonded to a fluorescent dye — is safe for use in humans. When infused into a patient's bloodstream before surgery, it seeks out nerve tissue and binds to it. Under specialized lighting in the operating room, those nerves glow, rendered as visible as if traced in highlighter.
The principle behind the technology is not new. Rosenthal has spent years pioneering fluorescence imaging to help surgeons identify and remove tumors with greater precision. What is new is applying that same logic in reverse — not to find what must be cut, but to protect what must be spared. "If you can see nerves better, you would avoid injuring them," said Sarah Rohde, division chief of head and neck surgery and lead investigator for the Phase 3 trials.
The significance of the moment lies in what came before it: every prior attempt to develop a nerve-specific fluorescent agent that works in living humans has failed. Bevonescein, developed by Alume Biosciences and tested across multiple centers with Vanderbilt enrolling the most participants, is the first to succeed. The work was conducted in partnership with Yu-Jin Lee of Stanford University and supported in part by the National Institutes of Health.
With Phase 3 trials now underway, Rosenthal anticipates an FDA approval application in the near future. Approval would position bevonescein as a standard surgical tool — one that could reduce life-altering complications not only in cancer operations but across the broader landscape of head and neck surgery, wherever a nerve stands between a patient and permanent harm.
Surgeons have long faced a problem that no amount of skill can entirely solve: the nerves that run through the neck and head are thin, fragile, and easy to damage when cutting away tumors or repairing tissue. A single slip of the scalpel can leave a patient with permanent numbness, weakness, or loss of voice. Now, for the first time, a fluorescent dye called bevonescein has passed human safety trials, offering surgeons a way to see those nerves light up in real time during an operation.
The breakthrough comes from work led by Eben Rosenthal, chair of otolaryngology and head and neck surgery at Vanderbilt University Medical Center, and published this week in Nature Communications. Bevonescein is a synthetic peptide—a short chain of amino acids—bonded to a fluorescent dye. When injected into a patient's bloodstream before surgery, it binds to nerve tissue. Under special lighting in the operating room, the nerves glow, making them visible to the surgeon as clearly as if they were marked with a highlighter.
The concept is not new in principle. Surgeons have been using fluorescence imaging for years to spot cancer during operations—Rosenthal himself has pioneered that work at Vanderbilt. A tumor lit up by fluorescent dye is easier to remove completely and with greater precision. The leap here is applying the same principle to healthy tissue that needs to be preserved. "Nerve injury is a major problem related to surgical intervention," said Sarah Rohde, division chief of head and neck surgery and the lead investigator for the Phase 3 trials. "The idea is that if you can see nerves better, you would avoid injuring them."
What makes this moment significant is that previous attempts to create nerve-specific fluorescent imaging agents succeeded only in animals. Bevonescein is the first to clear human safety testing. The research was conducted across multiple centers nationwide, with Vanderbilt enrolling the largest number of study participants. The work was led by Yu-Jin Lee of Stanford University in partnership with Alume Biosciences, the company that developed the compound.
Rosenthal frames the achievement as part of a larger shift in how surgeons think about their work. "Cancer is a surgical disease," he said. "Most cancers get surgery." With fluorescence imaging, surgeons can see the cancer light up, making treatment more precise. Now that same precision is becoming available for protecting the structures around tumors—the nerves that control speech, swallowing, and sensation. The technology bridges oncology and general surgery, offering a tool that could reduce complications across many types of head and neck procedures.
The research was funded in part by the National Institutes of Health and by Alume Biosciences. With Phase 3 trials now underway, Rosenthal said he expects the company to seek FDA approval in the near future. If approved, bevonescein could become a standard part of the surgical toolkit, changing how surgeons approach any operation where nerves are at risk. For patients, it could mean the difference between walking out of surgery with full function and living with permanent damage from an operation that otherwise went well.
Notable Quotes
Nerve injury is a major problem related to surgical intervention. The idea is that if you can see nerves better, you would avoid injuring them.— Sarah Rohde, division chief of head and neck surgery
Cancer is a surgical disease. Most cancers get surgery. With fluorescence imaging, you can see the cancer light up, which makes it easier to treat.— Eben Rosenthal, chair of otolaryngology
The Hearth Conversation Another angle on the story
Why does seeing a nerve during surgery matter so much? Surgeons have been operating on necks for decades.
They have, but they've been doing it partly blind. Nerves are thin and they blend into surrounding tissue. A surgeon can know anatomically where a nerve should be, but once you're inside the body, everything looks similar. You can damage a nerve without realizing it until the patient wakes up with a paralyzed vocal cord or numb face.
And this dye solves that by making the nerve visible?
Exactly. You inject it before surgery, it travels through the bloodstream and attaches to nerve tissue, and then under special light in the operating room, the nerve glows. It's like turning on a light in a dark room.
Has fluorescence imaging been used in surgery before?
Yes, but for cancer. Surgeons have been using it for years to see tumors light up and make sure they remove all of them. This is the first time it's worked for protecting healthy nerves.
What took so long to get from animal studies to human trials?
Safety. You can't just assume something that works in a rat will work safely in a person. You have to test it carefully, watch for side effects, make sure the dye doesn't accumulate in organs or cause problems. This is the first agent to pass that scrutiny.
What happens next?
Phase 3 trials are underway now. If those go well, the company will ask the FDA for approval. If approved, it becomes part of standard surgical practice—any surgeon doing head and neck work could use it.