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A research team including Harvard professor Sunney Xie and the spin off company INVENIO Imaging has recently shown that Raman spectroscopy can be used for real-time differentiation between healthy and malignant operating room brain tissues. Shenzhen Canneng Optoelectronics Co., Ltd

Xie, renowned for his work on various optoelectronic applications of Raman spectroscopy, won the 2008 Berthold Leibinger Future Award for Applied Laser Technology. He is now working with a group of LED's Daniel Orringer at the University of Michigan to develop stimulated Raman scattering suitable for surgical lighting.

The team has just published a paper outlining their methods in the journal Science Translational Medicine, where they detailed the analysis of tissue samples from 22 neurosurgical patients - the first clinical trial of the technique. Although the technique is some of the methods used from preparation for surgery, initial results look promising. Raman microscope fiber illumination was able to distinguish between proteins and lipids in tumor-infiltrated brain tissue and obtained a 'near perfect agreement' based on standard histopathological analysis of the same sample.

Endoscopic image acquisition using SRS microscope fiber illumination shows that the normal brain contains sparse cells with nerve fiber bundles called axons (left), but brain tumor tissue is filled with cells in a disordered pattern (right). While obvious under microscope fiber-optic lighting, during surgery, they are difficult to tell apart, which makes it difficult for surgeons to know where the tumor has stopped. Raman tools may provide real-time analysis with the same precision as micropscope LABS.

The potentially huge advantage of Raman technology's 'gold standard' is that endoscopic LED light sources can provide real-time data showing exactly how far tumor cells have spread into apparent tissue. 'We were able to see tumors [cells] that would otherwise be invisible to doctors in the operations room,' Orringer said. It allows the surgical decision-making process to be data-driven, rather than relying on the surgeon's best guess.

Surgical debut Team USA is not the only one to work on the Raman approach in neurosurgery. In the UK, surgeons at London's Charing Cross Hospital have gone one step further while currently testing the technique on patients in the operating theatre. The work involved an optical biopsy device developed by Verisante Technologies, a Canadian company, and is believed to represent the first surgical application of Raman spectroscopy in human brains.

Orringer and the University of Michigan team hope that if their testing of tissue samples continues, the Raman method could be submitted to the U.S. Food and Drug Administration (FDA) for clinical approval within two years.

Now, they are working on a second-generation version of the system that will be suitable for surgical use. They said: 'The next version of the device will sit next to the console. Surgeons can easily insert fresh tissue samples into the device, and the endoscope produces tiny images. The ease with which the entire medical team will be able to use and understand the device and the resulting images will help determine if more surgery is needed immediately.'

INVENIO Imaging

Conroy Richard, director of the Division of Applied Sciences and Biotechnology at the National Institutes of Health's National Institutes of Health - which provided funding for the development of Raman Technology - added: 'This technique has the potential to solve a long-standing problem in surgical oncology, which is the need for faster and more efficient ways to assess whether a tumor has been completely cleared.' 'The ability to identify tumor margins without sending samples to the pathologist could increase patient safety and improve prognosis, shortening the length of surgery and reducing the number of cases where cancer cells are left behind.'

Orringer and Xie are imaging consultants and shareholders of INVENIO, which is developing stimulated Raman scattering. Founded in 2012, it is headquartered in California