Cedars-Sinai animal study may lead to human trial of experimental, compact intraoperative device to aid in the removal of malignant brain tumors.
Researchers at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute and Department of Neurosurgery have created a new, unique and relatively inexpensive way of “lighting up” malignant brain tumors and other cancers.
Designed and developed at Cedars-Sinai, the experimental system consists of a special camera and a new, targeted imaging agent based on a synthetic version of a small protein found in the venom of the deathstalker scorpion. When the imaging agent is stimulated by a laser in the near-infrared part of the spectrum, it emits a glow that is captured by the camera but is invisible to the human eye.
The results of the animal studies were published as the feature article in the February issue of Neurosurgical Focus, and will provide the basis for the launch of human clinical trials. The system would be used during surgery to determine if it enables neurosurgeons to remove more tumor and spare more healthy tissue.
“We know that survival statistics increase if we can remove all of a tumor, but it is impossible to visualize with the naked eye where tumor stops and brain tissue starts, and current imaging systems don’t provide a definitive view,” said Keith Black, MD, chair and professor of the Department of Neurosurgery, the article’s senior author, and director of the Maxine Dunitz Neurosurgical Institute, director of the Johnnie L. Cochran, Jr. Brain Tumor Center and the Ruth and Lawrence Harvey Chair in Neuroscience. “Gliomas have tentacles that invade normal tissue and present big challenges for neurosurgeons: Taking out too much normal brain tissue can have catastrophic consequences, but stopping short of total removal gives remaining cancer cells a head start on growing back. That’s why we have worked to develop imaging systems that will provide a clear distinction – during surgery – between diseased tissue and normal brain,” said Black.
The new device clearly delineated tumor tissue from normal brain tissue in the studies in laboratory mice with implanted human brain tumors. Also, with near-infrared 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, PhD, research scientist and assistant professor in the Department of Neurosurgery, and the article’s first author, said that this tumor-imaging process consists of two parts: 1) deploying a fluorescent “dye” that sticks only to cancer cells, and 2) using a laser and a special camera to make an invisible image visible. “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,” said Butte.
The prototype is very compact, and the authors are looking to make it even smaller, lighter, and more portable in the next generations of it to come. This will allow it to take up minimal space in the operating room so neurosurgeons can focus more on the operating microscope rather than the imaging device. Butte adds, “We hope that eventually the camera can be transported in a small bag, but we are not sacrificing image quality for portability. 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.”
Authors: Pramod V. Butte, MBBS, PhD; Adam Mamelak, MD; Julia Parrish-Novak, PhD; Doniel Drazin, MD; Faris Shweikeh, BS; Pallavi R. Gangalum, PhD, Alexandra Chesnokova, MD; Julia Y. Ljubimova, MD, PhD; Keith Black, MD.
Image: Deathstalker Scorpion