title: Design and validation of a fiber optic point probe instrument for therapy guidance and monitoring.
abstract: Optical techniques for tissue diagnostics currently are experiencing tremendous growth in biomedical applications, mainly due to their noninvasive, inexpensive, and real-time functionality. Here, we demonstrate a hand-held fiber optic probe instrument based on fluorescence/reflectance spectroscopy for precise tumor delineation. It is mainly aimed for brain tumor resection guidance with clinical adaptation to minimize the disruption of the standard surgical workflow and is meant as a complement to the state-of-the-art fluorescence surgical microscopy technique. Multiple light sources with fast pulse modulation and detection enable precise quantification of protoporphyrin IX (PpIX), tissue optical properties, and ambient light suppression. Laboratory measurements show the system is insensitive to strong ambient light. Validation measurements of tissue phantoms using nonlinear least squares support vector machines (LS-SVM) regression analysis demonstrate an error of <5% for PpIX concentration ranging from 400 to 1000 nM, even in the presence of large variations in phantom optical properties. The mean error is 3% for reduced scattering coefficient and 5% for blood concentration. Diagnostic precision of 100% was obtained by LS-SVM classification for in vivo skin tumors with topically applied 5-aminolevulinic acid during photodynamic therapy. The probe could easily be generalized to other tissue types and fluorophores for therapy guidance and monitoring.
authors.affiliation: Lund University, Department of Physics, P.O. Box 118, SE-221 00 Lund, Sweden.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xie
authors.affiliation: Lund University, Department of Physics, P.O. Box 118, SE-221 00 Lund, Sweden.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Lund University, Department of Physics, P.O. Box 118, SE-221 00 Lund, Sweden.
authors.forename: Monirehalsadat
authors.initials: M
authors.lastname: Mousavi
authors.affiliation: Skåne University Hospital, Department of Dermatology and Venereology, Lasarettsgatan 15, SE-221 85 Lund, Sweden.
authors.forename: Niels
authors.initials: N
authors.lastname: Bendsoe
authors.affiliation: Lund University, Department of Physics, P.O. Box 118, SE-221 00 Lund, Sweden.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Brydegaard
authors.affiliation: Lund University, Department of Physics, P.O. Box 118, SE-221 00 Lund, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Axelsson
authors.affiliation: Lund University, Department of Physics, P.O. Box 118, SE-221 00 Lund, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Andersson-Engels
mesh_terms: D000622:Aminolevulinic Acid / Q000737:chemistry; D000818:Animals; D002138:Calibration; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000473:pathology; D004867:Equipment Design; D005336:Fiber Optic Technology / Q000295:instrumentation*; D006801:Humans; D016018:Least-Squares Analysis; D008027:Light; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055100:Optical Fibers; D019047:Phantoms, Imaging; D010778:Photochemotherapy / Q000379:methods; D011524:Protoporphyrins / Q000737:chemistry; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D012878:Skin Neoplasms / Q000175:diagnosis / Q000473:pathology; D013053:Spectrophotometry / Q000379:methods; D060388:Support Vector Machine
chemical_list: D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX