title: Photoacoustic signal characterization of cancer treatment response: Correlation with changes in tumor oxygenation.
abstract: Frequency analysis of the photoacoustic radiofrequency signals and oxygen saturation estimates were used to monitor the in-vivo response of a novel, thermosensitive liposome treatment. The liposome encapsulated doxorubicin (HaT-DOX) releasing it rapidly (<20 s) when the tumor was exposed to mild hyperthermia (43 °C). Photoacoustic imaging (VevoLAZR, 750/850 nm, 40 MHz) of EMT-6 breast cancer tumors was performed 30 min pre- and post-treatment and up to 7 days post-treatment (at 2/5/24 h timepoints). HaT-DOX-treatment responders exhibited on average a 22% drop in oxygen saturation 2 h post-treatment and a decrease (45% at 750 nm and 73% at 850 nm) in the slope of the normalized PA frequency spectra. The spectral slope parameter correlated with treatment-induced hemorrhaging which increased the optical absorber effective size via interstitial red blood cell leakage. Combining frequency analysis and oxygen saturation estimates differentiated treatment responders from non-responders/control animals by probing the treatment-induced structural changes of blood vessel.
authors.affiliation: Department of Physics, Ryerson University, Toronto, M5 B 2K3, Canada; Institute for Biomedical Engineering, Science and Technology, Li Ka Shing Knowledge Institute, Keenan Research Center, St. Michael's Hospital, Toronto, M5 B 1T8, Canada.
authors.forename: Eno
authors.initials: E
authors.lastname: Hysi
authors.affiliation: Department of Physics, Ryerson University, Toronto, M5 B 2K3, Canada; Institute for Biomedical Engineering, Science and Technology, Li Ka Shing Knowledge Institute, Keenan Research Center, St. Michael's Hospital, Toronto, M5 B 1T8, Canada.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Wirtzfeld
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Colombia, Vancouver, V6T 1Z3, Canada.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: May
authors.affiliation: Drug Delivery and Formulation Group, Ontario Institute for Cancer Research, Toronto, M5G 0A3, Canada.
authors.forename: Elijus
authors.initials: E
authors.lastname: Undzys
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Colombia, Vancouver, V6T 1Z3, Canada.
authors.forename: Shyh-Dar
authors.initials: SD
authors.lastname: Li
authors.affiliation: Department of Physics, Ryerson University, Toronto, M5 B 2K3, Canada; Institute for Biomedical Engineering, Science and Technology, Li Ka Shing Knowledge Institute, Keenan Research Center, St. Michael's Hospital, Toronto, M5 B 1T8, Canada.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Kolios
keywords: Cancer treatment monitoring; Oxygen saturation; Photoacoustic and ultrasound tissue characterization; Radiofrequency analysis; Tumor blood vessels