Quantitative phase‐filtered wavelength‐modulated differential photoacoustic radar tumor hypoxia imaging toward early cancer detection

• Published in: Journal of biophotonics Vol. 10; no. 9; pp. 1134 - 1142
• Main Authors: Dovlo, Edem, Lashkari, Bahman, Sean Choi, Sung, Mandelis, Andreas, Shi, Wei, Liu, Fei‐Fei
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01-09-2017; Wiley Subscription Services, Inc
• Subjects: Absorption spectra; Animals; Cancer; cancer diagnosis; Cancer screening; differential imaging; Early Detection of Cancer - methods; Fluence; frequency modulation; Head; Head & neck cancer; Hemoglobin; Hypoxia; Immunohistochemistry; Medical screening; Neoplasms - diagnostic imaging; Oxygenation; Phase shift; Photoacoustic Techniques; quantitative photoacoustic imaging; Radar; Radar imaging; Rats, Nude; Spectroscopy; Spectrum Analysis; Thigh; tissue diagnostics; Tumor Hypoxia; Wavelength; hypoxia; differential imaging; quantitative photoacoustic imaging; spectroscopy; cancer diagnosis; frequency modulation; tissue diagnostics
• ISSN: 1864-063X; 1864-0648
• DOI: 10.1002/jbio.201600168

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 SO2 quantification 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 SO2 imaging 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.
Wavelength‐modulated differential photoacoustic radar (WM‐DPAR) imaging utilizes chirp modulated laser beams at two distinct wavelengths for non‐invasive early cancer detection via the sensitive characterization of functional information such as hemoglobin oxygenation (SO2) levels and total hemoglobin concentration (tHb). Due to the out‐of‐phase modulation of the lasers, background absorption is highly suppressed while the difference between the two photoacoustic signals is amplified. Minute changes in tHb and SO2 are thereby detectable, allowing for pre‐malignant tumor identification (before becoming anatomically apparent) and hypoxia monitoring.