Intraoperative imaging is technology used by neurosurgeons and pathologists to review real-time images of the brain during surgery. This technology enables surgeons and pathologists to detect abnormal tissues from tumors during surgery resection so that the necessary tissue can be removed without damaging critical parts of the brain.
The mission of Cedars-Sinai’s intraoperative imaging research is to develop new imaging technologies that are smaller and more efficient/accurate than current technologies.
Intraoperative imaging research is based out of the Butte Laboratory and focuses on two unique projects exclusive to Cedars-Sinai: time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) and the synchronized infrared imaging system (SIRIS).
Figure 1. Intraoperative Time-Resolved Laser-Induced Fluorescence Spectroscopy System.
The TR-LIFS project is refining a technique the Butte Laboratory developed for in vivo tissue diagnosis. The system uses very short ultraviolet laser pulses (flashes of UV laser that each last for 400 trillionths of a second) to excite brain tissue during surgery. Those pulses initiate fluorescent light emission from the tissue, which is captured by a special sensor and recorded and analyzed at a high time resolution (every 120-trillionth of a second). By studying fluorescence pulse characteristics and color differences of the light coming back from tissue, the TR-LIFS system can inform neurosurgeons whether the light originates from a brain tumor or normal brain tissue.
Figure 2. Intraoperative tumor detection using suction cannula in action.
This is crucial during tumor resection because brain tissue starts to shift as the surgeons are removing the tumor. Traditional imaging guidance based on a preoperative MRI progressively loses track of tumor location. TR-LIFS allows surgeons to have immediate feedback on the type of tissue being resected, allowing them to revise their approach as required. By knowing the exact type of tissue being resected, surgeons can remove tumor mass without significant risk to adjacent healthy tissues and vital structures. This can reduce surgical complications, because resecting normal brain tissue can have catastrophic consequences, but stopping short of total tumor removal can lead to cancer cells growing back.
The Butte research team has piloted the TR-LIFS in approximately 100 patients to determine whether the TR-LIFS provides detail that can help surgeons distinguish areas of healthy brain from gliomas, which have irregular borders as they spread into normal tissue. That study has proven successful. The next step is to increase the study population to 200.
Figure 3. SIRIS device for intraoperative tumor delineation using indocyanine green (ICG) conjugated to chlorotoxin (CTX) (CTX:ICG, BLZ-100).
SIRIS is a specialized imaging device developed in the Butte Laboratory with the goal of visualizing tumors using the near-infrared spectrum of light. Although near-infrared light (which is just beyond the visual field) is not visible to naked eye, it provides deeper penetration in the tissue. Taking advantage of this, SIRIS is used to detect deeper tumors in the brain by looking at a near-infrared dye (ICG) attached to a special peptide (chlorotoxin, or CTX) that sticks only to tumor cells.
Figure 4. BLZ-100 fluorescence in a
Chlorotoxin is derived from Israeli yellow scorpion (a.k.a., Deathstalker) venom. The peptide preferentially binds to a variety of human malignancies, including brain tumors, but shows little or no binding to normal human tissue.
A synthetic version of the peptide is manufactured and covalently linked to fluorescent agents as a means of targeting and locating the tumor cells. Researchers believe the tumor-targeting ability of the peptide-dye complex could lead to accurate localization of gliomas.
SIRIS is a small, high-resolution imaging system, capable of intraoperatively detecting this fluorescent peptide at the cellular level using both near-infrared and white light. The Butte Laboratory hypothesizes that SIRIS will provide better illumination of cancer cells to help neurosurgeons distinguish cancer from normal tissue in real-time during tumor resection operations. This technology was tested in animal models of brain, lung and breast tumors.