title: Hemodynamic monitoring of Chlorin e6-mediated photodynamic therapy using diffuse optical measurements.
abstract: Tumor response during photodynamic therapy (PDT) is heavily dependent on treatment parameters such as light dose, photosensitizer concentration, and tissue oxygenation. Therefore, it is desirable to have a real-time hemodynamic monitoring device in order to fine-tune the parameters and improve PDT efficacy. In this paper, such a tumor response monitoring system was built incorporating both frequency domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS), which enables concurrent monitoring of tissue oxygenation (StO₂), total hemoglobin concentration (THC) and relative blood flow (rBF). The tumor metabolic rate of oxygen (TMRO₂) was calculated by using the hemodynamic parameters. Mouse models bearing xenograft tumors were subjected to chlorin e6 (Ce6)-mediated PDT, and the four parameters were monitored with varying treatment conditions. The results show (1) At 3 h post-PDT, rStO₂, rBF and rTMRO₂ exhibited sharp PDT-induced decreases in responders (>40% reduction in tumor volume). Statistically significant difference between responders and non-responders were observed in rStO₂ and rBF, but not in rTMRO₂. (2) Non-responders show gradual recovery of rStO₂, rBF and rTMRO₂ from ∼24 h post-PDT, while responder group did not show recovery up until 48 h post-PDT. Long-term study results up to 2 weeks are also shown. It suggests the hybrid diffuse optical system is not only capable of real-time treatment monitoring, but also able to extract tumor metabolic rate of oxygen to provide more insights about therapy mechanism. Translation of this technique to the clinic will make a quick prognosis feasible and help with treatment optimization.
authors.affiliation: Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, 637457, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, 169610, Singapore.
authors.forename: Hui Jin
authors.initials: HJ
authors.lastname: Toh
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, 169610, Singapore.
authors.forename: Patricia S P
authors.initials: PS
authors.lastname: Thong
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, 169610, Singapore.
authors.forename: Chuan Sia
authors.initials: CS
authors.lastname: Tee
authors.affiliation: Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, 637457, Singapore.
authors.forename: Renzhe
authors.initials: R
authors.lastname: Bi
authors.affiliation: Division of Medical Sciences, National Cancer Centre Singapore, 169610, Singapore.
authors.forename: Khee-Chee
authors.initials: KC
authors.lastname: Soo
authors.affiliation: Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, 637457, Singapore; School of Basic Science, Daegu Gyeongbuk Institute of Science & Technology, Daegu 711-873, Republic of Korea. Electronic address: kjlee@dgist.ac.kr.
authors.forename: Kijoon
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D055620:Optical Phenomena; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011166:Porphyrins / Q000494:pharmacology* / Q000627:therapeutic use; D013057:Spectrum Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; C062985:phytochlorin; D010100:Oxygen
keywords: Diffuse correlation spectroscopy (DCS); Diffuse optical spectroscopy (DOS); Photodynamic therapy (PDT); Relative blood flow (rBF); Tissue oxygenation (StO(2)); Tumor metabolic rate of oxygen (TMRO(2))