title: Simplified and optimized multispectral imaging for 5-ALA-based fluorescence diagnosis of malignant lesions.
abstract: 5-aminolevulinic acid (5-ALA)-based fluorescence diagnosis is now clinically applied for accurate and ultrarapid diagnosis of malignant lesions such as lymph node metastasis during surgery. 5-ALA-based diagnosis evaluates fluorescence intensity of a fluorescent metabolite of 5-ALA, protoporphyrin IX (PPIX); however, the fluorescence of PPIX is often affected by autofluorescence of tissue chromophores, such as collagen and flavins. In this study, we demonstrated PPIX fluorescence estimation with autofluorescence elimination for 5-ALA-based fluorescence diagnosis of malignant lesions by simplified and optimized multispectral imaging. We computationally optimized observation wavelength regions for the estimation of PPIX fluorescence in terms of minimizing prediction error of PPIX fluorescence intensity in the presence of typical chromophores, collagen and flavins. By using the fluorescence intensities of the optimized wavelength regions, we verified quantitative detection of PPIX fluorescence by using chemical mixtures of PPIX, flavins, and collagen. Furthermore, we demonstrated detection capability by using metastatic and non-metastatic lymph nodes of colorectal cancer patients. These results suggest the potential and usefulness of the background-free estimation method of PPIX fluorescence for 5-ALA-based fluorescence diagnosis of malignant lesions, and we expect this method to be beneficial for intraoperative and rapid cancer diagnosis.
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Minamikawa
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.|Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Ushio Inc., 6409 Moto-Ishikawa-cho, Aoba-ku, Yokohama, Kanagawa 225-0004, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
authors.affiliation: Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Yanagisawa
authors.affiliation: Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Medical Photonics, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Takamatsu
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000378:metabolism*; D001711:Biotransformation; D045744:Cell Line, Tumor; D003094:Collagen / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D005415:Flavins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D061848:Optical Imaging; D011524:Protoporphyrins / Q000737:chemistry* / Q000378:metabolism; D059629:Signal-To-Noise Ratio; D012984:Software
chemical_list: D005415:Flavins; D005456:Fluorescent Dyes; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; D003094:Collagen; C028025:protoporphyrin IX