How Can the Enhanced Sensitivity and Favourable Noise Characteristics Conferred by Electron Multiplication Improve Fluorescence-Guided Surgery?

Biomarkers are traceable substances that can be used to monitor pathological molecular processes and in particular to guide the resection of tumors. A biomarker that is currently being used clinically is the protoporphyrin IX (PpIX), which has been demonstrated to preferentially accumulate in high-grade glioma following administration of 5-aminolevulinic acid. In the case of high-grade glioma, PpIX accumulates in a sufficient manner that it can be seen through the naked eye when exposed to blue light. However, higher sensitivity is needed to detect PpIX in other types of brain tumors where PpIX levels are lower or to achieve more complete resections. Higher sensitivity has been achieved using a fiberoptics point-probe allowing surgeons to detect PpIX with an unparalleled sensitivity in vivo during gliomas surgeries. However, point-by-point detection disrupts the neurosurgical workflow and so less disrupting wide-field imaging methods with high sensitivity and rapid image acquisition are desirable. We investigate whether or not electron multiplication devices (EMCCD) can confer sensitivity and acquisition time advantages in fluorescence-guided neurosurgery when compared to scientific-grade charge-coupled devices (CCD). We present a demonstration of the sensitivity of PpIX detection that can be obtained with a new EMCCD camera that was developed by Nüvü Cameras. This device significantly reduces the noise generated during the read-out process (at least 10x) and presents a previously unreachable sensitivity in photon counting mode. Such major reduction in the noise threshold represents an opportunity to detect very faint levels of PpIX with smaller integration times than was previously achieved with CCDs. The goal of this study was to open the way to a less disruptive in vivo fluorescence detection technique to allow surgeon to perform more accurate resections on a more varied range of intracranial tumors