A new type of laser microscope may dramatically improve the accuracy of brain tumor surgery, according to a study reported this week in Science Translational Medicine. The new tool helps surgeons see clearly, while operating, where tumor tissue ends and healthy tissue begins.

Surgeons face many challenges when removing brain tumors, including how to remove all of the tumor without leaving behind any cells that could start a new one, as well as not damaging healthy tissue so as to minimize the risk of causing disability in the patient.

Researchers have tested the new tool, which is based on a technology called SRS microscopy, in live mice and in brain tissue removed from a human patient with glioblastoma multiforme, one of the most deadly brain tumors.

They found they could distinguish healthy tissue from tumor tissue in both cases: the new laser-based tool allowed them to see even the tiniest areas of tumor cells in brain tissue.

The team, from University of Michigan (UM) Medical School and Harvard University, says the next step is to fine-tune the approach so they can go ahead with a small human trial.

Co-lead author Dr. Daniel Orringer, a lecturer in the UM Department of Neurosurgery, says:

“Though brain tumor surgery has advanced in many ways, survival for many patients is still poor, in part because surgeons can’t be sure that they’ve removed all tumor tissue before the operation is over.”

We need better tools for visualizing tumor[s] during surgery, and SRS microscopy is highly promising. With SRS we can see something that’s invisible through conventional surgical microscopy.”

SRS is short for stimulated Raman scattering, a method that shines a light onto a target area and identifies the materials present by analyzing the colors that are reflected back.

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A normal view of a mouse brain neurosurgeons see with bright-field microscopy (left), next to an SRS microscopy view of the same area of brain (right).
Source: The Xie Laboratory at Harvard University

Senior author Dr. Sunney Xie, of the Department of Chemistry and Chemical Biology at Harvard University, has been perfecting SRS for use with live tissue for over a decade.

The result is that for this study, the team could see colorful SRS images of living tissue, at a rate of 30 per second – the rate needed to make videos in real time.

In 2010, in the journal Science, Xie and colleagues reported how they had developed SRS microscopy to the point where they could make label-free chemical movies, with streaming footage at the subcellular level, to see blood cells squeezing through capillaries and even observe proteins, lipids and water moving within cells.

This latest paper is the first to report using SRS microscopy on a living organism to see the margin of a tumor – the hardest area to operate on.

The images were clear enough for the team to see where brain tumor tissue ended and healthy tissue began. The SRS microscope distinguished between dense brain tumor tissue and the normal healthy grey and white matter of the brain.

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The same areas of brain, viewed with SRS microscopy (left) and H&E staining (right). SRS microscopy allows doctors to see tumors without having to remove tissue or inject dyes.
Source: The Xie Laboratory at Harvard University

The authors say the tool may be as accurate as hematoxylin and eosin (H&E) staining, the current method for diagnosing brain tumors. In their paper, they recount how they tested the two methods against each other to arrive at this conclusion.

The advantage of SRS microscopy over H&E staining is that it can be done in real time, during the brain operation, without having to remove and process tissue, and without dyeing or marking it.

The team now wants to make the technology smaller and more stable so it can be used in an operating room. They are working with a start-up company called Invenio Imaging Inc., formed by some of Xie’s group. One of the things they are working on is how to make the device more affordable, for example by using fiber optics.

They hope to start a validation study next year, using brain tissue from volunteer patients.

Funds from the National Institutes of Health helped finance the study.