Comparison of minimal detectable protoporphyrin IX concentrations with a loupe device and conventional 5-ALA fluorescence microscopy: an experimental study

Abstract

Significance: The 5-aminolevulinic acid (5-ALA) fluorescence technique is now widely applied for intraoperative visualization of specific central nervous system (CNS) tumors. Previous technical implementations of this technique have relied on specifically modified surgical microscopes to visualize intratumoral fluorescent protoporphyrin (PpIX). While this approach evidently allows for reliable intraoperative tumor visualization, it requires the availability of specifically modified surgical microscopes and their use even in cases where the operating neurosurgeon would prefer to use surgical loupes. Recently, a novel loupe device was introduced that is also capable of visualizing 5-ALA fluorescence.

Aim: The aim of this study was therefore to compare the detected PpIX concentrations between the conventional fluorescence microscope and the novel loupe device.

Approach: We used fluorescence phantoms of different PpIX concentrations for comparison between a conventional fluorescence microscope and the novel loupe device. For this purpose, we created fluorescence images using the excitation light sources of the conventional fluorescence microscope and the loupe device with both available background illumination modes (low and high). Subsequently, the minimal detectable PpIX concentrations according to each technique were determined by five independent neurosurgeons.

Results: Using the conventional fluorescence microscope, the median minimal detectable PpIX concentration was $0.16\mu g/\mathrm{ml}$ (range: 0.15 to $0.17\mu g/\mathrm{ml}$). By the loupe device, the median minimal detectable PpIX concentration was $0.12\mu g/\mathrm{ml}$ (range: 0.10 to $0.12\mu g/\mathrm{ml}$) and $0.08\mu g/\mathrm{ml}$ (range: 0.07 to $0.08\mu g/\mathrm{ml}$) for the high- and low-modes, respectively. Altogether, the minimal detectable PpIX concentrations were significantly lower using the loupe device compared to the conventional fluorescence microscope ($p=0.007$).

Conclusions: Our data indicate that the novel loupe device is able to visualize 5-ALA fluorescence with high sensitivity and thus might serve as a powerful tool for visualization of specific CNS tumors in the future.

Keywords: 5-aminolevulinic acid; detectable concentration; fluorescence; loupe device; protoporphyrin IX.