Abstract
In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX sensitivity in wide-field fluorescence imaging may improve the residual tumor detection during surgery with consequent impact on survival.
Highlights
The goal of neurosurgery in brain tumor management is to maximize the extent of tumor resection while minimizing functional impairment secondary to surgery
The calibration factor allows the x and y axis to be expressed in the same units, while the attenuation correction factor brings the data points closer together along the y-axis [30]. These plots indicate that the quantified fluorescence varies linearly with concentration to the lowest protoporphyrin IX (PpIX) level (8 ng/ml) for the electron-multiplying charge-coupled device (EMCCD) system, but the linearity breaks down at around 40 ng/ml for the scientific CMOS (sCMOS) system at a 20 ms exposure time
Since the noise floor of the EMCCD system was not reached at the lowest concentration, its sensitivity is at least 1-2 orders of magnitude greater than that of the sCMOS system, which is the current state-of-the-art for aminolevulinic acid (ALA)-PpIX fluorescence detection in neurosurgical guidance
Summary
The goal of neurosurgery in brain tumor management is to maximize the extent of tumor resection while minimizing functional impairment secondary to surgery. Standard surgical equipment comprises a white-light neurosurgical microscope and a neuronavigation unit to guide surgery based on preoperative magnetic resonance imaging (MRI). The use of preoperative MRI improves the accuracy and safety of surgical resections using spatial coregistration of MRI scans with intraoperative magnified bright-field images taken in real time during surgery. Image-guided neurosurgery has increased the completeness of tumor resection as determined by comparing tumor tissue visible in preoperative relative to postoperative MRI [1]. Preferential accumulation of PpIX in tumor cells results in part from differences in heme biosynthesis and pro-drug uptake. Glioblastoma resection surgery guided by the red fluorescence of PpIX upon violet light excitation has been demonstrated in controlled clinical trials to improve the completeness of tumor resection relative to resections based solely on bright-field, white-light visualization [3]
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