Abstract
Quantification of multiple fluorescence markers during neurosurgery has the potential to provide complementary contrast mechanisms between normal and malignant tissues, and one potential combination involves fluorescein sodium (FS) and aminolevulinic acid-induced protoporphyrin IX (PpIX). We focus on the interpretation of reflectance spectra containing contributions from elastically scattered (reflected) photons as well as fluorescence emissions from a strong fluorophore (i.e., FS). A model-based approach to extract μa and μ′s in the presence of FS emission is validated in optical phantoms constructed with Intralipid (1% to 2% lipid) and whole blood (1% to 3% volume fraction), over a wide range of FS concentrations (0 to 1000 μg/ml 1000 μg/ml ). The results show that modeling reflectance as a combination of elastically scattered light and attenuation-corrected FS-based emission yielded more accurate tissue parameter estimates when compared with a nonmodified reflectance model, with reduced maximum errors for blood volume (22% versus 90%), microvascular saturation (21% versus 100%), and μs′ (13% versus 207%). Additionally, quantitative PpIX fluorescence sampled in the same phantom as FS showed significant differences depending on the reflectance model used to estimate optical properties (i.e., maximum error 29% versus 86%). These data represent a first step toward using quantitative optical spectroscopy to guide surgeries through simultaneous assessment of FS and PpIX.
Highlights
Fluorescence guidance during neurosurgical tumor resection has been shown to enhance contrast between normal and malignant tissues.1 Fluorescein sodium (FS) is a vascular-targeted marker, which accumulates in areas of blood–brain barrier breakdown, making it useful for marking malignant gliomas.2,3 While FS has high sensitivity,4 it has low tumor specificity, and vascular leakage into areas of peritumoral edema or surgical trauma limits its role as a unique tumor biomarker during neurosurgery
This study investigates the use of white light reflectance spectroscopy to accurately estimate the tissue optical properties necessary to quantify the biodistribution of the multiplexed fluorophores FS and protoporphyrin IX (PpIX)
This study focuses on the development of a spectral analysis algorithm to quantify optical properties from white light reflectance spectra in the presence of emission from a strong fluorescence marker (i.e., FS)
Summary
Fluorescence guidance during neurosurgical tumor resection has been shown to enhance contrast between normal and malignant tissues. Fluorescein sodium (FS) is a vascular-targeted marker, which accumulates in areas of blood–brain barrier breakdown, making it useful for marking malignant gliomas. While FS has high sensitivity, it has low tumor specificity, and vascular leakage into areas of peritumoral edema or surgical trauma limits its role as a unique tumor biomarker during neurosurgery. Fluorescence guidance during neurosurgical tumor resection has been shown to enhance contrast between normal and malignant tissues.. Fluorescein sodium (FS) is a vascular-targeted marker, which accumulates in areas of blood–brain barrier breakdown, making it useful for marking malignant gliomas.. FS may provide complementary tissue contrast when coupled with other tumor-targeting fluorophores to guide surgeries. One potential multiplexed approach involves the coupled administration of FS with aminolevulinic acid, which is a nonfluorescent prodrug that serves to bypass the negative feedback controls of heme, leading to a temporary enhanced accumulation of the endogenous fluorophore protoporphyrin IX (PpIX).. Tumor selectivity is a result of altered metabolic turnover of heme biosynthesis in diseased cells, providing tumor-tonormal-tissue contrast.. One potential multiplexed approach involves the coupled administration of FS with aminolevulinic acid, which is a nonfluorescent prodrug that serves to bypass the negative feedback controls of heme, leading to a temporary enhanced accumulation of the endogenous fluorophore protoporphyrin IX (PpIX). Tumor selectivity is a result of altered metabolic turnover of heme biosynthesis in diseased cells, providing tumor-tonormal-tissue contrast. This study investigates the use of white light reflectance spectroscopy to accurately estimate the tissue optical properties necessary to quantify the biodistribution of the multiplexed fluorophores FS and PpIX
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