Advanced Imaging with Sound and Light: Photoacoustic Tomography and Quantum Microscopy

Optical imaging enables visualization of biological structure and function but is fundamentally limited by several physical constraints. Spatial resolution is bounded by optical diffraction, depth penetration is curtailed by strong absorption and scattering in tissue, and image contrast-to-noise ratio is often restricted by photon shot noise in low-light conditions. This thesis advances two novel directions—photoacoustic imaging and quantum imaging—to address these limitations. In photoacoustic imaging, we design and optimize high-speed photoacoustic computed tomography systems that enable deep, volumetric visualization of vasculature. By incorporating time-gated reconstruction and image-enhancement algorithms, these systems support small-animal imaging of cardiac structure, liver morphology, and brain hemodynamics non-invasively. Building on these foundations, we explore non-invasive breast photoacoustic imaging with high spatiotemporal resolution. Through integration with learning-based feature extraction, classification, and segmentation pipelines, we demonstrate the feasibility of applying photoacoustic imaging in clinical workflows to aid the characterization of breast tissue. In quantum imaging, we develop two complementary architectures that extend the state of the art in opposite but synergistic directions. The scanning quantum microscope scales up existing quantum imaging approaches, achieving the largest resolvable pixel counts to date by combining entangled-photon illumination with efficient coincidence detection. This platform enables the first demonstration of whole-organism imaging and shows potential in remote sensing and sub-shot-noise imaging. In contrast, the widefield quantum microscope scales down quantum imaging to the microscopic regime, integrating single-photon–sensitive cameras with a covariance-based coincidence estimation algorithm. This approach enables cellular-level imaging and demonstrates quantum-enhanced resolution beyond the classical diffraction limit, establishing a practical pathway for quantum microscopy in biological imaging. Across both research directions, this thesis advances system design and engineering, quantitative characterization, calibration, reconstruction, and image-enhancement methodologies. Together, these developments establish pathways from physical principles to practical imaging systems, spanning laboratory prototypes through preclinical and clinical applications in biomedical imaging.