University researchers pilot advances in microscopy

Wednesday, October 21, 2015 - 3:27pm

Brain tumor removal is the ultimate game of Operation. Remove too little of a tumor and it could be back within months. Remove too much and your patient may never speak or walk again.

A new microscope, developed in the University's Medical School, could help surgeons with the difficult task of tumor removal by showing the difference between healthy and tumorous tissue in real-time.

A team of Medical School doctors and students spent years developing the new technology, called the stimulated Raman scattering — or SRS — microscope, alongside researchers from other institutions including Harvard and New York University. It could eventually help improve the outcomes for some of the nearly 700,000 people in the United States living with brain tumors.

Third-year Medical student Spencer Lewis, an author of the paper announcing the first clinical test of this technology, said it’s difficult to tell the difference between healthy and unhealthy brain tissue using the naked eye — making the technology all the more necessary. 

“Brain tissue normally looks like a soft, tan mass with a very soft, jelly-like consistency,” Lewis said. “And tumor is often a similar color and is really only differentiated by texture. So it’s very difficult to tell by eye the difference, depending on the type of tumor.”

The SRS microscope addresses this difficulty through a technique called Raman spectroscopy, which uses a laser to shine light at a piece of brain tissue that has been biopsied from the brain. The many molecules in the tissue have chemical bonds between them that are constantly wiggling, stretching and rotating. Each type of tiny bond movement affects the light in a different way. By detecting how the light is altered and scattered, scientists can infer what kind of bonds and molecules are in the tissue. The SRS amplifies this effect, allowing doctors to see specific structural details.

Lewis, working under Daniel Orringer, assistant professor of neurological surgery, said the development team currently uses the SRS microscope to detect proteins and lipids, two major structural components of cells and tissues. While tumor tissues look similar to normal tissues to the naked eye, they organize proteins and lipids very differently at the cellular level, allowing for easier distinction between the two.

“That allows us to see the architecture of the brain in vivid detail that’s just not possible with traditional microscopy techniques,” Lewis said.

This gives doctors a potentially faster and more accurate distinguishing tool than the method that’s currently used, called the frozen-section method. By allowing doctors to shorten surgeries and confidently remove more of a tumor, Lewis said chances for relapse as well as for complications of surgery could be lessened.

Lewis said the typically used frozen-section technique has a couple of drawbacks.

“The problem is that it takes a while — 30 to 45 minutes,” he said. “And also it introduces a lot of artifacts like ice crystals that can mess with the accuracy of the pathologist’s read. SRS is done without labels and without damaging the tissue. It’s done on fresh tissue. You take it out, mount it on a slide and image it right there.”

While the SRS currently takes about the same amount of time as a frozen-section, Lewis said optimizing the technology could get imaging times down to one second.

The microscope could also help to improve the stereotactic brain surgery technique, which combines 3D models of the brain taken before surgery with probes attached to the surgeons’ instruments to show doctors exactly where their tools are during an operation.

“The problem with this is that because the brain is soft and the brain can swell, it can shift during surgery,” Lewis said. “So, during the course of an operation, you can’t always tell where you are relative to the preoperative MRI as you are dissecting the tumor. And that leads to inaccuracy.”

By identifying brain tissues in real time, Lewis said the SRS microscope could prevent these inaccuracies.

The SRS microscope, which is the first commercial version in the world, has been used on more than 60 patient brain tissue samples since June. Until the team finishes development and procures FDA approval, however, no surgeons will use it to make clinical decisions.

Lewis said that future improvements to the microscope and imaging methods, such as adapting the SRS to detect molecules that build up specifically in cancer cells, could have enormous impacts on surgery.

“Essentially, you could highlight tumor cells specifically, which would be a tremendous advance,” he said.

Next, the research team hopes to develop a probe-like model of the microscope that could examine tissues while they are still in the brain.