Creating Biomedical Technologies to Improve Health

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Science Highlight: February 9, 2017

New imaging technique allows quick, automated analysis of brain tumor tissue during surgery

Brain surgery for removing cancerous tissue is a delicate and high-stakes task. Now researchers funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) have created a way to improve tumor removal surgery by distinguishing cancerous tissue from healthy tissue faster. The method, published online Feb. 6, 2017, in Nature Biomedical Engineering, makes brain tumor surgery more precise, improving safety.

technician and microscope

University of Michigan medical technician Karen Eddy prepares a sample for imaging using the stimulated Raman scattering microscopy technique. Photo by Joe Hollisy, University of Michigan.

Surgeons tread a fine line when removing a brain tumor, wanting to be sure to remove as much tumor as possible while sparing healthy brain. During surgery, a pathologist may look at a piece of tissue to better inform decisions, but prepping the tissue sample to be examined under the microscope can take 30 minutes, extending surgery time, upping the cost, and increasing risks to the patient. Furthermore, many hospitals performing brain tumor removal don’t have easy access to a neuropathologist. The new method not only decreases tenfold the time needed to examine a tissue sample, it also allows for automatic processing, enabling pathologists to confirm diagnoses from afar.

“This technology reduces tissue processing time and could significantly increase the accuracy of brain tumor surgery in operating room,” said Behrouz Shabestari, Ph.D., director of the NIBIB program in Optical Imaging and Spectroscopy. “It basically optimizes the surgical result and has the potential to improve patient outcomes by increasing safety and survival rates.”

The team from the University of Michigan Medical School, led by Daniel Orringer, M.D., a neurosurgeon and lead author of the paper, used stimulated Raman scattering (SRS), a type of microscopy that does not require tissue processing, or slicing the tissue and staining it. They adapted the procedures so they could be performed in the operating room. Previously, microscopes capable of SRS were too big and expensive for a clinical setting. But by switching to a fiber-laser microscope, which uses the same type of fiber optics as internet and phone cables, and devising a way to decrease background signals common to fiber-laser images, the team created a portable, safe, high-resolution system and validated its use in more than 100 patients.

They also created a way to quickly process the resulting images, called stimulated Raman histology (SRH). The new method takes advantage of intrinsic chemical properties of the tissue, making proteins and DNA appear purple and lipids appear pink. The resulting image is strikingly similar to the widely used hematoxylin and eosin (H&E) staining, so pathologists don’t need to be specially trained to interpret it. By eliminating the time-consuming process of sectioning and staining, SRH takes about three minutes, 10 times less than standard techniques used during surgery. When tested on 30 samples, pathologists came to similar conclusions using SRH as when using conventional techniques.

“It really provides a new vision for how pathology might be implemented in the operating room, eliminating the need for a frozen section procedure, which many surgeons rely so much on to make decisions while they’re taking care of their patients,” Orringer said.

The researchers also demonstrated that the images can be automatically classified by a computer program. In their initial study, the algorithm was able to predict the subtype of brain tumor with 90 percent accuracy. Orringer is hopeful that, in the future, an SRH machine will make a preliminary diagnosis that can be confirmed by a remote pathologist, assisting those surgical centers without pathologists on staff. “In this current era where we’re increasingly connected, this system might be the linchpin that brings the expertise to the center where the surgery is being performed,” he added.

SRS microscope in the operating room

A stimulated Raman scattering microscope helps neurosurgeons analyze tissue without the need for tissue processing and speeding the decision-making process during brain tumor surgery.

Since the SRH method provides for quicker assessment of tissue as either cancerous or healthy, surgeons can make better informed decisions about how much tissue to remove and how much to leave behind. The method may also be extended to other types of tumors, such as breast or neck cancer, in which the tumor margins are unclear.

The combination of better accuracy and speed means safer surgeries and better outcomes for patients, decreasing the time they spend on the operating table. “We’ve never had a system which makes that information available in a rapid fashion for surgeons,” Orringer said. “We’re arming surgeons with the microscopic information about the tissue that they’re operating on.”

The research was supported in part by NIH research grants EB0172254, EB010244, NS087118, and CA046592.

Orringer DA, Pandian, B, Niknafs YS, Hollon TC, Boyle J, Lewis S, Garrard M, Shawn L. Hervey-Jumper SL, Garton HJL, Maher CO, Heth JA, Sagher O, Wilkinson DA, Snuderl M, Venneti S, Ramkissoon SH, McFadden KA, Fisher-Hubbard A, Lieberman AP, Johnson TD, Xie XS, Trautman JK, Freudiger CW, Camelo-Piragua S. Rapid intraoperative histology of unprocessed surgical specimens via fiber-laser-based stimulated Raman scattering microscopy. Nature Biomedical Engineering. 06 Feb. 2017.

—Teal Burrell, special to NIBIB

Health Terms: 
Brain Disorders,
Surgical Tools