Wavelength-Modulated Differential Photoacoustic (WM-DPA) imaging: a high dynamic range modality towards noninvasive diagnosis of cancer

Abstract

This study explores wavelength-modulated differential photoacoustic (WM-DPA) imaging for non-invasive early cancer detection via sensitive characterization of functional information such as hemoglobin oxygenation (sO 2 ) levels. Wellknown benchmarks of tumor formation such as angiogenesis and hypoxia can be addressed this way. While most conventional photoacoustic imaging has almost entirely employed high-power pulsed lasers, frequency-domain photoacoustic radar (FD-PAR) has seen significant development as an alternative technique. It employs a continuous wave laser source intensity-modulated and driven by frequency-swept waveforms. WM-DPA imaging utilizes chirp modulated laser beams at two distinct wavelengths for which absorption differences between oxy-and deoxygenated hemoglobin are minimum (isosbestic point, 805 nm) and maximum (680 nm) to simultaneously generate two signals detected using a standard commercial array transducer as well as a single-element transducer that scans the sample. Signal processing is performed using Lab View and Matlab software developed in-house.Minute changes in total hemoglobin concentration (tHb) and oxygenation levels are detectable using this method since background absorption is suppressed due to the out-of-phase modulation of the laser sources while the difference between the two signals is amplified, thus allowing pre-malignant tumors to become identifiable. By regulating the signal amplitude ratio and phase shift the system can be tuned to applications like cancer screening, sO 2 quantification and hypoxia monitoring in stroke patients. Experimental results presented demonstrate WM-DPA imaging of sheep blood phantoms in comparison to single-wavelength FD-PAR imaging. Future work includes the functional PA imaging of small animals in vivo.