Co-Registration of Ultrasound and Photoacoustic Radar Imaging and Image Improvement for Early Cancer Diagnosi

Unlike mainstream biomedical photoacoustics, mostly based on pulsed laser excitation, this work explores the alternative photoacoustic radar (PAR) modality, using intensity-modulated continuous-wave laser sources driven by frequency-swept (chirp) waveforms. A one-dimensional, axisymmetric model, and quantitative blood oxygenation analysis were developed for analyzing experimental results. Signal processing tools are investigated to enhance system parameters such as signal-to-noise ratio (SNR), dynamic range and spatial resolution. Besides applying pulse compression through matched-filtering to generate high peak power cross-correlation response, SNR can be improved by leveraging the distinct phase channel to filter the PAR amplitude channel acquired by the cross-correlation of the PA response and the reference waveform. Phase-filtering is also investigated as a spatial-resolution improvement technique. An in-vivo study of a cancer cell-injected mouse recorded a 14--15 dB SNR gain for the phase-filtered image compared to the amplitude and phase independently, while the phase PAR image produced ~340 microm spatial resolution compared to ~840 microm for the amplitude image.;Additionally, to accelerate clinical acceptance and use, the combination of the PAR system with clinically-accepted ultrasound is explored. PAR tomography is investigated toward in-vivo functional analysis and the effects of the number of scan lines on image quality, resolution and contrast, examined.;Furthermore, addressing assumptions of linear fluence dependence in conventional multispectral photoacoustic imaging is crucial for obtaining accurate spatially-resolved quantitative functional information by exploiting known chromophore-specific spectral characteristics. A study conducted introduces the non-invasive phase-filtered wavelength-modulated differential photoacoustic radar technique to address 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 with significant improvement in dynamic range, SNR and spatial resolution, as minute changes in total hemoglobin concentration and oxygenation are detectable.