title: Mathematical model to interpret localized reflectance spectra measured in the presence of a strong fluorescence marker.
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.
authors.affiliation: Dartmouth College, Thayer School of Engineering, 14 Engineering Drive, Hanover, New Hampshire 03755, United States.
authors.forename: Jaime J
authors.initials: JJ
authors.lastname: Bravo
authors.affiliation: Dartmouth College, Thayer School of Engineering, 14 Engineering Drive, Hanover, New Hampshire 03755, United StatesbDartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, United States.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Davis
authors.affiliation: Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, United StatescGeisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, New Hampshire 03755, United StatesdDartmouth-Hitchcock.
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.affiliation: Dartmouth College, Thayer School of Engineering, 14 Engineering Drive, Hanover, New Hampshire 03755, United StatesbDartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, United StatescGeisel.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Paulsen
authors.affiliation: Dartmouth College, Thayer School of Engineering, 14 Engineering Drive, Hanover, New Hampshire 03755, United StatesbDartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, 1 Medical Center Drive, Lebanon, New Hampshire 03756, United States.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Kanick
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D005456:Fluorescent Dyes / Q000032:analysis* / Q000737:chemistry*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008027:Light; D008856:Microscopy, Fluorescence / Q000295:instrumentation / Q000379:methods*; D008956:Models, Chemical; D019047:Phantoms, Imaging; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes
references.citation: Acta Neurochir (Wien). 2013 Jul;155(7):1277-86
references.pmid: 23661063
references.citation: Neurosurgery. 1998 Mar;42(3):518-25; discussion 525-6
references.pmid: 9526986
references.citation: Opt Express. 2008 Apr 14;16(8):5907-25
references.pmid: 18542702
references.citation: BMC Public Health. 2012;12:439
references.pmid: 22709383
references.citation: J Neurosurg. 2003 Sep;99(3):597-603
references.pmid: 12959452
references.citation: Med Phys. 1992 Jul-Aug;19(4):879-88
references.pmid: 1518476
references.citation: Lasers Surg Med. 2010 Sep;42(7):680-8
references.pmid: 20740619
references.citation: Curr Med Chem Anticancer Agents. 2004 May;4(3):301-16
references.pmid: 15134506
references.citation: J Neurosurg. 2011 Jul;115(1):11-7
references.pmid: 21438658
references.citation: Acta Neurochir (Wien). 2013 Apr;155(4):693-9
references.pmid: 23430234
references.citation: J Biomed Opt. 2014;19(7):75002
references.pmid: 24996661
references.citation: Appl Opt. 1999 Aug 1;38(22):4939-50
references.pmid: 18323984
references.citation: J Appl Phys. 2009 May 15;105(10):102024
references.pmid: 20157444
references.citation: J R Soc Interface. 2006 Feb 22;3(6):1-13
references.pmid: 16849213
references.citation: J Biomed Opt. 2010 Nov-Dec;15(6):067006
references.pmid: 21198210
references.citation: IEEE Trans Biomed Eng. 1989 Dec;36(12):1162-8
references.pmid: 2606490
references.citation: J Biomed Opt. 2011 Nov;16(11):116007
references.pmid: 22112112
references.citation: Phys Med Biol. 1999 Apr;44(4):967-81
references.pmid: 10232809
references.citation: Opt Express. 2010 Mar 15;18(6):5580-94
references.pmid: 20389574
references.citation: Surg Neurol Int. 2014 Apr 28;5:60
references.pmid: 24872922
references.citation: Surg Neurol. 1998 Jul;50(1):41-8; discussion 48-9
references.pmid: 9657492
references.citation: IEEE J Sel Top Quantum Electron. 2010 May;16(3):493-505
references.pmid: 20671936
references.citation: J Clin Neurosci. 2012 Dec;19(12):1719-22
references.pmid: 23036170
references.citation: Neurosurg Rev. 2014 Oct;37(4):547-57
references.pmid: 24756415
references.citation: Obes Surg. 2006 Jun;16(6):773-6
references.pmid: 16756741