Review of Neurosurgical Fluorescence Imaging Methodologies

Abstract

Fluorescence imaging in neurosurgery has a long historical development, with several different biomarkers and biochemical agents being used, and several technological approaches. This review focuses on the different contrast agents, summarizing endogenous fluorescence, exogenously stimulated fluorescence and exogenous contrast agents, and then on tools used for imaging. It ends with a summary of key clinical trials that lead to consensus studies. The practical utility of protoporphyrin IX (PpIX) as stimulated by administration of δ-aminolevulinic acid (ALA) has had substantial pilot clinical studies and basic science research completed. Recently multi-center clinical trials using PpIx fluorescence to guide resection have shown efficacy for improved short term survival. Exogenous agents are being developed and tested pre-clinically, and hopefully hold the potential for long term survival benefit if they provide additional capabilities for resection of micro-invasive disease or certain tumor sub-types that do not produce PpIX or help delineate low grade tumors. The range of technologies used for measurement and imaging ranges widely, with most clinical trials being carried out with either point probes or modified surgical microscopes. At this point in time, optimized probe approaches are showing efficacy in clinical trials, and fully commercialized imaging systems are emerging, which will clearly help lead to adoption into neurosurgical practice.

Fluorescence and Glioma Surgery

“…Research on the benefits of using 5-ALA-induced accumulation of PpIX in tumors for photodynamic therapy and photodiagnosis have shown promising results in both fields [8][9]. Besides photodynamic therapy and photodiagnosis, 5-ALA-induced fluorescence can improve the accuracy of biopsies.…”

“…Besides 5-ALA-induced fluorescence, which is an exogenously induced fluorescence procedure, other methods (endogenous autofluorescence and exogenous contrast agents) are capable of using fluorescence to emphasize tumor tissue in real-time surgery [8]. Endogenous autofluorescence, a technique that utilizes UV and blue light excitation to emphasize tumor tissue, can also be exploited for tumor resection surgery.…”

“…After exciting tumor tissue, the emission spectra are visualized in the blue-green spectra. The fluorescent signals are derived from collagen, NADH, and FADH for unknown reasons [8]. By utilizing endogenous fluorescence signals, medical shortcomings, such as allergic reactions, are avoided.…”

“…Due to the lack of a contrasting agent, the ability to delineate tumor margins could be obscured by the lack of tumor background contrast. Unfortunately, the synergy of blood absorption, light scatter, and tissue layers obscure the neurosurgeon's ability to interpret the spectra intraoperatively [8]. Also, this method requires that the data, which takes up to 30 seconds to acquire, be analyzed postoperatively [8].…”

“…Unfortunately, the synergy of blood absorption, light scatter, and tissue layers obscure the neurosurgeon's ability to interpret the spectra intraoperatively [8]. Also, this method requires that the data, which takes up to 30 seconds to acquire, be analyzed postoperatively [8]. The pilot studies have shown promising results for autofluorescence [8,12].…”