Valentina Pirro, a research scientist in Purdue’s Department of Chemistry, works in the operating room with a newly developed technology that within minutes could tell surgeons if a cancerous tumor is still present in a tissue sample and estimate the percentage of infiltration. The technology is patented through the Purdue Research Foundation Office of Technology Commercialization and is available for license. (Valentina Pirro Image)

Originally pioneered three years ago in R. Graham Cook’s Purdue lab, a mass spectrometry-based tool is finally making inroads in the clinical setting by helping brain surgeons test and more precisely remove cancerous tissue from tumors.

The tool sprays a microscopic stream of charged solvent onto a tissue surface to gather information about its molecular makeup, and produces a color-coded image that reveals the location, nature and concentration of tumor cells. The morphologically friendly method relies on an ambient mass spec analysis technique developed by Cooks called desorption electrospray ionization, or DESI.

DESI eliminates the need for time-consuming sample prep by performing the ionization step directly on surfaces outside of mass spectrometers. This makes the technique faster, simpler and much more applicable to surgical settings.

An initial pilot program with Brigham and Women’s Hospital (BWH) in 2014 was successful; since then, the technique has been used in the operating room 18 times in preclinical assessments—without influencing the surgical process itself.

Normally, preoperative MRIs are used to guide surgeons during brain surgery, but technical issues abound. For one, when the brain is first opened, the pressure changes and the brain gently shifts, rendering the MRI less accurate. And the more the surgeon removes of the tumor, the less accurate the original MRI becomes. Additionally, there may be high infiltration of the tumor beyond what the MRI image is able to see. To make matters even more complicated, a tumor looks exactly like normal brain.

“Brain tumors are specifically complicated because they infiltrate into the brain and don’t make clear borders,” explained Valentina Pirro, a research scientist in Purdue’s department of chemistry. “In order to make sure the patient has the highest chance of survival, it’s imperative that as much cancer tissue as possible is removed while trying to minimize neurological damages.”

In its preclinical assessments, the technique has proven feasible, rapid and robust.

The analysis is simple and straightforward with no sample preparation and the ability to validate results with standard histopathology. Essentially, the charged solvent is used as a spray that is directed onto a small area of a sample to extract molecules contained within.

Once a surgeon resects a small biopsy, the researchers smear it on a glass slide and analyze as is. The modified DESI-MS instrument sits on top of a cart as a standalone system, so it can be easily wheeled into the operating room when needed.

After a few analysis minutes, the team can tell the surgeon if the tumor is still present in the tissue sample and estimate the percentage of infiltration. These objective measures can guide a surgeon in the resection, and help them make quick decisions on whether or not to remove more tissue.

According to Pirro, a clinical trial is the next step.

“Through a clinical trial the technology could influence the decision strategy. Ideally you would compare surgeries done with and without this technology and see if there is an improvement in the survival rate,” she said. “We imagine a company licensing this technology to take these next steps before eventually bringing it to market and provide this supplemental tool to surgeons everywhere.”