Elasto-optical refractive index modulation due to photoacoustic initial pressure transients produced significant reflection of a probe beam when the absorbing interface had an appreciable refractive index difference. This effect was harnessed in a new form of non-contact optical resolution photoacoustic microscopy called photoacoustic remote sensing microscopy. A non-interferometric system architecture with a low-coherence probe beam precludes detection of surface oscillations and other phase-modulation phenomenon. The probe beam was confocal with a scanned excitation beam to ensure detection of initial pressure-induced intensity reflections at the subsurface origin where pressures are largest. Phantom studies confirmed signal dependence on optical absorption, index contrast and excitation fluence. In vivo imaging of superficial microvasculature and melanoma tumors was demonstrated with ~2.7±0.5 μm lateral resolution.

Quantitative imaging of optical properties of biological tissues with high resolution has been a long-sought-after goal of many research groups. Photoacoustic imaging is a hybrid bio-optical imaging technique offering optical absorption contrast with ultrasonic spatial resolution. While photoacoustic methods offer significant promise for high-resolution optical imaging, quantification has thus far proved challenging. In this paper, a noniterative reconstruction technique for producing quantitative photoacoustic images of absorption perturbations is introduced for the case when the optical properties of the turbid background are known and when multiple optical illumination locations are used. Through theoretical developments and computational examples it is demonstrated that multiple-optical-source photoacoustic imaging can produce quantitative optical absorption reconstructions. The combination of optical and photoacoustic measurements is shown to yield improved reconstruction stability.

While photoacoustic methods offer significant promise for high-resolution optical contrast imaging, quantification has thus far proved challenging. In this paper, a noniterative reconstruction technique for producing quantitative photoacoustic images of both absorption and scattering perturbations is introduced for the case when the optical properties of the turbid background are known and multiple optical illumination locations are used. Through theoretical developments and computational examples, it is demonstrated that multiple-illumination photoacoustic tomography (MI-PAT) can alleviate ill- posedness due to absorption-scattering nonuniqueness and produce quantitative high-resolution reconstructions of optical absorption, scattering, and Gruneisen parameter distributions. While numerical challenges still exist, we show that the linearized MI-PAT framework that we propose has orders of magnitude improved condition number compared with CW diffuse optical tomography.

The goal of oncologic surgeries is complete tumor resection, yet positive margins are frequently found postoperatively using gold standard H&E-stained histology methods. Frozen section analysis is sometimes performed for rapid intraoperative margin evaluation, albeit with known inaccuracies. Here, we introduce a label-free histological imaging method based on an ultraviolet photoacoustic remote sensing and scattering microscope, combined with unsupervised deep learning using a cycle-consistent generative adversarial network for realistic virtual staining. Unstained tissues are scanned at rates of up to 7 mins/cm², at resolution equivalent to 400x digital histopathology. Quantitative validation suggests strong concordance with conventional histology in benign and malignant prostate and breast tissues. In diagnostic utility studies we demonstrate a mean sensitivity and specificity of 0.96 and 0.91 in breast specimens, and respectively 0.87 and 0.94 in prostate specimens. We also find virtual stain quality is preferred (P = 0.03) compared to frozen section analysis in a blinded survey of pathologists.

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