Research ArticleCancer Imaging

Intraoperative brain cancer detection with Raman spectroscopy in humans

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Science Translational Medicine  11 Feb 2015:
Vol. 7, Issue 274, pp. 274ra19
DOI: 10.1126/scitranslmed.aaa2384

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Probing for brain tumors

Gliomas are invasive cancers, spreading quietly throughout the brain. They pose a formidable challenge to surgeons who try to remove all cancer cells during resection; leaving any cancer behind can lower the patient’s prospects for survival. Jermyn et al. adapted Raman spectroscopy for the operating room by developing an imaging technique that uses a commercially available, handheld contact fiber optic probe. The probe’s optic cables were connected to a near-infrared laser, for stimulating tissue molecules; in turn, these components were linked to a computer to visualize resulting spectra in real time. When held against human brain tissue, the probe measured the Raman scattering signal, which was separated from background signals and differentiated from “normal” tissues using certain algorithms. The authors tested the probe in 17 patients with grade 2 to 4 gliomas who were undergoing surgery and compared imaging results with 161 biopsy samples. Intraoperative Raman imaging allowed the authors to detect both invasive and dense cancer cells with an accuracy of 92%. By comparison, the surgeon, using standard surgical tools like the bright-field microscope and magnetic resonance imaging, identified cancer with 73% accuracy. Such label-free, portable, intraoperative imaging technologies will be important in improving the efficiency of tumor resections and, in turn, for extending survival times of glioma patients.


Cancers are often impossible to visually distinguish from normal tissue. This is critical for brain cancer where residual invasive cancer cells frequently remain after surgery, leading to disease recurrence and a negative impact on overall survival. No preoperative or intraoperative technology exists to identify all cancer cells that have invaded normal brain. To address this problem, we developed a handheld contact Raman spectroscopy probe technique for live, local detection of cancer cells in the human brain. Using this probe intraoperatively, we were able to accurately differentiate normal brain from dense cancer and normal brain invaded by cancer cells, with a sensitivity of 93% and a specificity of 91%. This Raman-based probe enabled detection of the previously undetectable diffusely invasive brain cancer cells at cellular resolution in patients with grade 2 to 4 gliomas. This intraoperative technology may therefore be able to classify cell populations in real time, making it an ideal guide for surgical resection and decision-making.

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