title: Quantitative phase-filtered wavelength-modulated differential photoacoustic radar tumor hypoxia imaging toward early cancer detection.
abstract: Overcoming the limitations of conventional linear spectroscopy used in multispectral photoacoustic imaging, wherein a linear relationship is assumed between the absorbed optical energy and the absorption spectra of the chromophore at a specific location, is crucial for obtaining accurate spatially-resolved quantitative functional information by exploiting known chromophore-specific spectral characteristics. This study introduces a non-invasive phase-filtered differential photoacoustic technique, wavelength-modulated differential photoacoustic radar (WM-DPAR) imaging that addresses this issue by eliminating the effect of the unknown wavelength-dependent fluence. It employs two laser wavelengths modulated out-of-phase to significantly suppress background absorption while amplifying the difference between the two photoacoustic signals. This facilitates pre-malignant tumor identification and hypoxia monitoring, as minute changes in total hemoglobin concentration and hemoglobin oxygenation are detectable. The system can be tuned for specific applications such as cancer screening and SO2quantification by regulating the amplitude ratio and phase shift of the signal. The WM-DPAR imaging of a head and neck carcinoma tumor grown in the thigh of a nude rat demonstrates the functional PA imaging of small animals in vivo. The PA appearance of the tumor in relation to tumor vascularity is investigated by immunohistochemistry. Phase-filtered WM-DPAR imaging is also illustrated, maximizing quantitative SO2imaging fidelity of tissues. Oxygenation levels within a tumor grown in the thigh of a nude rat using the two-wavelength phase-filtered differential PAR method.
authors.affiliation: Center for Advanced Diffusion-Wave and Photoacoustic Technologies (CADIPT), Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada.
authors.forename: Edem
authors.initials: E
authors.lastname: Dovlo
authors.affiliation: Center for Advanced Diffusion-Wave and Photoacoustic Technologies (CADIPT), Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada.
authors.forename: Bahman
authors.initials: B
authors.lastname: Lashkari
authors.affiliation: Center for Advanced Diffusion-Wave and Photoacoustic Technologies (CADIPT), Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada.
authors.forename: Sung
authors.initials: S
authors.lastname: Soo Sean Choi
authors.affiliation: Center for Advanced Diffusion-Wave and Photoacoustic Technologies (CADIPT), Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mandelis
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, 610 University Ave, Toronto, ON, M5G 2M9, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, 610 University Ave, Toronto, ON, M5G 2M9, Canada.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
mesh_terms: D000818:Animals; D055088:Early Detection of Cancer / Q000379:methods*; D009369:Neoplasms / Q000000981:diagnostic imaging*; D061088:Photoacoustic Techniques; D011825:Radar; D011923:Rats, Nude; D013057:Spectrum Analysis; D000072258:Tumor Hypoxia
keywords: cancer diagnosis; differential imaging; frequency modulation; hypoxia; quantitative photoacoustic imaging; spectroscopy; tissue diagnostics