Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS) for noninvasive early cancer detection and tissue hypoxia monitoring

This study introduces a novel noninvasive differential photoacoustic method, Wavelength Modulated Differential Photoacoustic Spectroscopy (WM‐DPAS), for noninvasive early cancer detection and continuous hypoxia monitoring through ultrasensitive measurements of hemoglobin oxygenation levels (StO2). Unlike conventional photoacoustic spectroscopy, WM‐DPAS measures simultaneously two signals induced from square‐wave modulated laser beams at two different wavelengths where the absorption difference between maximum deoxy‐ and oxy‐hemoglobin is 680 nm, and minimum (zero) 808 nm (the isosbestic point). The two‐wavelength measurement efficiently suppresses background, greatly enhances the signal to noise ratio and thus enables WM‐DPAS to detect very small changes in total hemoglobin concentration (CHb) and oxygenation levels, thereby identifying pre‐malignant tumors before they are anatomically apparent. The non‐invasive nature also makes WM‐DPAS the best candidate for ICU bedside hypoxia monitoring in stroke patients. Sensitivity tunability is another special feature of the technology: WM‐DPAS can be tuned for different applications such as quick cancer screening and accurate StO2 quantification by selecting a pair of parameters, signal amplitude ratio and phase shift. The WM‐DPAS theory has been validated with sheep blood phantom measurements. Sensitivity comparison between conventional single‐ended signal and differential signal. This work describes a noninvasive differential photoacoustic technique, Wavelength Modulated Differential Photoacoustic Spectroscopy (WM‐DPAS) that can measure hemoglobin oxygenation levels with ultrahigh sensitivity. WM‐DPTAS is proposed to be used for pre‐malignant tumor detection and bedside hypoxia monitoring in stroke patients. WM‐DPAS can be tuned for different applications such as quick cancer screening and accurate StO2 quantification by selecting a pair of parameters, signal amplitude ratio and phase difference.