Seeing What’s Invisible: How 5-ALA is Changing Brain Tumor Surgery

“At the margins of gliomas, the distinction between tumor and adjacent healthy brain tissue is not always,” said Dr. Francesco Pucci, Assistant Professor and Neurosurgeon at the University of Illinois Chicago (UIC). “This makes it sometimes difficult to be confident in the operating room that the entire malignant tumor was removed.”

This is especially true for high-grade and infiltrative gliomas, aggressive tumors that may not grow in neat, encapsulated masses — instead, they spread in diffuse patterns deep into surrounding tissue.

So, how do you remove something you cannot clearly see? And how do you ensure removal of the entire, without taking healthy brain tissue that a patient needs for motor, language, or cognitive function? That’s the question neurosurgeons have long grappled with—and the answer may come in the form of a fluorescent label.

Before the procedure, the process begins with something surprisingly simple: a drink.

5-ALA (5-aminolevulinic acid) is an oral compound administered to patients as a liquid solution in the hours before surgery. Once inside the body, it accumulates preferentially in malignant glioma cells, causing them to glow a vivid pink under blue and ultraviolet light.

Malignant gliomas are some of the deadliest types of brain cancer, formed from glial cells, which provide physical support for neurons. While most cancers have clearly distinguishable borders, gliomas infiltrate brain tissues in such a way that at the borders it may be visually indistinguishable from more normal surrounding tissue, thus creating a difficult task in surgically removing them. Safe removal of the entire MRI-enhancing component of the tumor, or “gross total resection,” is critical to improving overall survival in patients with glioblastoma.

In response, UIC has been participating in a clinical trial for HIVEN®, a device developed by Marginum Ltd, specializing in the detection of fluorescence-based tissue monitoring.

After 5-ALA administration, the malignant tumor tissue glows under blue light, but the healthy brain tissue does not. This provides real-time definition of tumor margins without disrupting the standard surgical workflow. Operating under blue light can be difficult to see normal brain anatomy and critical blood vessels. HIVEN provides an additional method to detect fluorescence. As small amounts of the brain tumor are removed from the brain, the tissue passes through a device that detects fluorescence from 5-ALA and provides audible feedback to the surgeon. There is therefore real-time continuous feedback to the surgeon about whether the tissue is a malignant tumor or more normal brain tissue.

UIC is the first institution in the United States to use this technology to detect fluorescent malignant cells during brain tumor surgery, a milestone that reflects the institution’s long-standing commitment to advancing neurosurgical innovation.

“We are excited to be the first to use this technology to treat brain tumors,” said Dr. Pucci. “This device allows us an additional modality to detect 5-ALA fluorescence with the goal of maximizing the extent of tumor resection, which is often the first and most important step in improving a patient’s outcome after diagnosis of glioblastoma.”

For the surgical team at UIC, the goal is that greater precision in the operating room translates directly into better patient outcomes, including fewer residual tumor cells left behind.

Seeing what was previously invisible, Dr. Pucci and his team are able to identify and remove not only the central tumor mass, but also infiltrating cancer cells lurking just beyond the tumor’s visible margins—the very cells most likely to fuel a recurrence.

The team operates using a modified surgical microscope that switches between two modes: standard white light, which shows the brain as it normally appears, and blue light, which activates fluorescence. Under blue light, the malignant tissue glows pink while healthy brain tissue remains dark, creating a visual distinction that would otherwise be impossible to make with the naked eye.

“In some cases where a tumor may infiltrate important brain regions and networks, like those that are responsible for movement and language function, we perform intraoperative brain mapping

to ensure that the patient’s functional and neurological condition is preserved.” Dr. Pucci shared.

Complete tumor removal is achieved in roughly 70% of cases when 5-ALA is used—more than double the rate seen without it. 5-ALA also likely allows the surgeon to resect malignant tumor cells that are not yet visible or enhancing on MRI. That higher rate of complete resection has a meaningful effect: when more of the tumor is removed surgically, the burden placed on chemotherapy and radiation is reduced.

“We believe this technology has the potential to improve the detection of malignant tumors in the operating room and improve the surgical workflow,” Dr Pucci said. “ We are proud that UIC is at the forefront of that innovation and that we can provide our patients with the latest technology”.