Mathematical model to interpret localized reflectance spectra measured in the presence of a strong fluorescence marker

Document Type

Article

Publication Date

6-1-2016

Publication Title

Journal of Biomedical Optics

Department

Thayer School of Engineering

Additional Department

Geisel School of Medicine

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" role="presentation" style="margin: 0px; padding: 0px; border: 0px; font-variant-numeric: inherit; font-stretch: inherit; font-size: 15px; line-height: normal; font-family: "Museo Sans-300", Arial, "Sans Serif"; vertical-align: baseline; display: inline; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative;">μaμa and μs′" role="presentation" style="margin: 0px; padding: 0px; border: 0px; font-variant-numeric: inherit; font-stretch: inherit; font-size: 15px; line-height: normal; font-family: "Museo Sans-300", Arial, "Sans Serif"; vertical-align: baseline; display: inline; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative;">μ′sμs′ 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" role="presentation" style="margin: 0px; padding: 0px; border: 0px; font-variant-numeric: inherit; font-stretch: inherit; font-size: 15px; line-height: normal; font-family: "Museo Sans-300", Arial, "Sans Serif"; vertical-align: baseline; display: inline; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative;">1000μg/ml1000  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′" role="presentation" style="margin: 0px; padding: 0px; border: 0px; font-variant-numeric: inherit; font-stretch: inherit; font-size: 15px; line-height: normal; font-family: "Museo Sans-300", Arial, "Sans Serif"; vertical-align: baseline; display: inline; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; position: relative;">μ′sμs′ (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.

DOI

10.1117/1.JBO.21.6.061004

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