NIR imaging system singles out malignant brain tumors

Researchers at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute and Department of Neurosurgery (Los Angeles, CA) have developed a compact, relatively inexpensive imaging device to distinguish malignant brain tumors and other cancers from normal, healthy tissue.

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The experimental system consists of a camera designed and developed at Cedars-Sinai and a new, targeted imaging agent based on a synthetic version of a small protein—a peptide—found in the venom of the deathstalker scorpion. The agent, Tumor Paint BLZ-100 from Blaze Bioscience (Seattle, WA), homes to brain tumor cells. When stimulated by a laser in the near-infrared (NIR) part of the spectrum, it emits a glow that is invisible to the eye but can be captured by the camera.

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In studies in laboratory mice with implanted human brain tumors, the new device clearly delineated tumor tissue from normal brain tissue. Also, with NIR light's ability to penetrate deep into the tissue, the system identified tumors that had migrated away from the main tumor and would have evaded detection.

Pramod Butte, MBBS, Ph.D., research scientist and assistant professor in the Department of Neurosurgery, the article’s first author, says the tumor-imaging process consists of two parts: deploying a fluorescent "dye" that sticks only to cancer cells, and using a laser and a special camera to make an invisible image visible. To get the dye to the tumor, it is linked to a peptide called chlorotoxin, which, contrary to its name, is not toxic. It completely ignores normal tissue, but seeks out and binds to a variety of malignant tumor cells. It first was derived from the venom of the yellow Israeli scorpion, also called the deathstalker.

"Injected intravenously, the chlorotoxin seeks out the brain tumor, carrying with it indocyanine green, which has been used in a variety of medical imaging applications. When we shine a near-infrared laser on the tissue, the tumor glows. But the glow emitted by the tumor is invisible to the human eye," says Butte. The camera device, designed in his lab, solves this problem by capturing two images and combining them on a high-definition monitor.

"Other experimental systems we have seen—which use different tumor-targeting methods—are larger and bulkier because they consist of two cameras," Butte says. "Our single-camera device takes both near-infrared and white light images simultaneously. This is achieved by alternately strobing the laser and normal white lights at very high speeds. The eye just sees normal light, but the camera is capturing white light once, near-infrared light next, over and over. We then superimpose the two HD images. The image from the laser shows the tumor, and the image produced from white light shows the visible 'landscape' so we can see where the tumor is in context to what we actually can see."

The prototype is compact, but the authors said they are working to make the next generations even smaller, lighter, and portable so the device will require very little space in operating room, allowing the neurosurgeon to focus on the operating microscope and give little attention on the imaging system. "We hope that eventually the camera can be transported in a small bag, but we are not sacrificing image quality for portability,” Butte says. “In fact, most systems that use two cameras lose a lot of light. But because of the special filters we use and the way we arrange them, we lose very little light. And from what we have seen and tested, our device provides about 10 times greater sensitivity and contrast than others."

In an editorial accompanying the journal article, David W. Roberts, MD, from the Section of Neurosurgery at the Geisel School of Medicine at Dartmouth College (Hanover, NH), says the Cedars-Sinai "paper presents a newer direction in which fluorescence-guided surgery may well be headed." He also notes that the researchers overcame one of the limitations of NIR technology—that it is outside of the visible portion of the spectrum.

For full details on the team's work, please visit http://thejns.org/doi/full/10.3171/2013.11.FOCUS13497.

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