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 SO 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 SO 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.

The application of frequency-domain photoacoustics to temperature-dependent measurements of the Grüneisen parameter in lipids

“…We employ frequency-domain (or Fourier-domain, FD) PA to evaluate the absorption coefficient and the Grüneisen parameter of lipids. The methodology and various techniques of FD-PA for spectroscopic probing and imaging have been discussed before, where the main subject was the evaluation of the blood oxygenation level [ [33] , [34] , [35] , [36] , [37] ]. Furthermore, we report the Grüneisen parameter of some lipids such as mineral oil, castor oil, olive oil, glycerin as well as cholesterol and cholesteryl oleate.…”

Frequency wavelength multiplexed optoacoustic tomography

“…Therefore, despite the potential advantages over TD 17 – 19 , 23 , 24 , FD has had little impact in the field of optoacoustics. Frequency chirp has also been investigated as a hybrid TD-FD method, by modulating light at a continuously varying frequency 17 , 25 , thus encoding time in frequency. Detection is carried out in the TD using time-correlation techniques.…”

Frequency Comb Optoacoustic Tomography

“…Frequency chirp has also been investigated as a hybrid TD-FD method, by modulating light at a continuously varying frequency 22,24 , thus encoding time in frequency. Detection is carried out in the TD using time-correlation techniques.…”