Current embodiments of photoacoustic imaging require either serial detection with a singleelement ultrasonic transducer or parallel detection with an ultrasonic array, necessitating a tradeoff between cost and throughput. Here, we present photoacoustic topography through an ergodic relay (PATER) for low-cost high-throughput snapshot widefield imaging. Encoding spatial information with randomized temporal signatures through ergodicity, PATER requires only a single-element ultrasonic transducer to capture a widefield image with a single laser shot. We applied PATER to demonstrate both functional imaging of hemodynamic responses and highspeed imaging of blood pulse wave propagation in mice in vivo. Leveraging the high frame rate of 2 kHz, PATER tracked and localized moving melanoma tumor cells in the mouse brain in vivo, which enabled flow velocity quantification and super-resolution imaging. Among the potential biomedical applications of PATER, wearable monitoring of human vital signs in particular is envisaged.Optical imaging reveals structures and molecular information in biological tissues. Tomographic optical microscopy technologies, such as confocal microscopy, multiphoton

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Diagnosis of corneal disease and challenges in corneal transplantation require comprehensive understanding of corneal anatomy, particularly that of the posterior cornea. Micro-optical coherence tomography (µOCT) is a potentially suitable tool to meet this need, owing to its ultrahigh isotropic spatial resolution, high image acquisition rate and depth priority scanning mode. In this study, we explored the ability of µOCT to visualize micro-anatomical structures of the posterior cornea ex vivo and in vivo using small and large animals. µOCT clearly delineated cornea layers and revealed micro-anatomical structures, including not only polygonal endothelial cells, stellate keratocytes, collagen fibres and corneal nerve fibres but also new structures such as the dome-shaped basolateral side of endothelial cells and lattice structures at the interface between endothelium and Descemet’s membrane. Based on these observations, a short post-harvest longitudinal study was conducted on rat cornea to test the feasibility of using µOCT to monitor the quality of endothelial cells. This study successfully reveals a series of morphological features and pathological changes in the posterior cornea at the cellular level in situ and in real time with µOCT. These findings enrich knowledge of corneal anatomy and suggest that µOCT may be a promising imaging tool in corneal transplantation.

Imaging nuclei of keratinocytes in the stratified squamous epithelium has been a subject of intense research since nucleus associated cellular atypia is the key criteria for the screening and diagnosis of epithelial cancers and their precursors. However, keratinocyte nuclei have been reported to be either low scattering or high scattering, so that these inconsistent reports might have led to misinterpretations of optical images, and more importantly, hindered the establishment of optical diagnostic criteria. We disclose that they are generally low scattering in the core using Micro‐optical coherence tomography (μOCT) of 1.28‐μm axial resolution in vivo; those previously reported “high scattering” or “bright” signals from nuclei are likely from the nucleocytoplasmic boundary, and the low‐scattering nuclear cores were missed possibly due to insufficient axial resolutions (~4μm). It is further demonstrated that the high scattering signals may be associated with flattening of nuclei and cytoplasmic glycogen accumulation, which are valuable cytologic hallmarks of cell maturation.

Our ability to detect neoplastic changes in gastrointestinal (GI) tracts is limited by the lack of an endomicroscopic imaging tool that provides cellular-level structural details of GI mucosa over a large tissue area. In this article, we report a fiber-optic-based micro-optical coherence tomography (μOCT) system and demonstrate its capability to acquire cellular-level details of GI tissue through circumferential scanning. The system achieves an axial resolution of 2.48 μm in air and a transverse resolution of 4.8 μm with a depth-of-focus (DOF) of ~150 μm. To mitigate the issue of limited DOF, we used a rigid sheath to maintain a circular lumen and center the distal-end optics. The sensitivity is tested to be 98.8 dB with an illumination power of 15.6 mW on the sample. With fresh swine colon tissues imaged ex vivo, detailed structures such as crypt lumens and goblet cells can be clearly resolved, demonstrating that this fiber-optic μOCT system is capable of visualizing cellular-level morphological features. We also demonstrate that time-lapsed frame averaging and imaging speckle reduction are essential for clearly visualizing cellular-level details. Further development of a clinically viable μOCT endomicroscope is likely to improve the diagnostic outcome of GI cancers.