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Optical microscopy suffers from multiple scattering (MS), which limits the optical imaging depth into scattering media. We previously demonstrated aberration-diverse optical coherence tomography (AD-OCT) for MS suppression, based on the principle that for datasets acquired with different aberration states of the imaging beam, MS backgrounds become decorrelated while single scattering (SS) signals remain correlated, so that a simple coherent average can be used to enhance the SS signal over the MS background. Here, we propose a space/spatial-frequency domain analysis framework for the investigation of MS in OCT, and apply the framework to compare AD-OCT (using astigmatic beams) to standard Gaussian-beam OCT via experiments in scattering tissue phantoms. Utilizing this framework, we found that increasing the astigmatic magnitude produced a large drop in both MS background and SS signal, but the decay experienced by the MS background was larger than the SS signal. Accounting for the decay in both SS signal and MS background, the overall signal-to-background ratio (SBR) of AD-OCT was similar to the Gaussian control after about 10 coherent averages, when deeper line foci was positioned at the plane-of-interest and the line foci spacing was smaller than or equal to 80 µm. For an even larger line foci spacing of 160 µm, AD-OCT resulted in a lower SBR than the Gaussian-beam control. This work provides an analysis framework to gain deeper levels of understanding and insights for the future study of MS and MS suppression in both the space and spatial-frequency domains. 

Optical coherence microscopy (OCM) uses interferometric detection to capture the complex optical field with high sensitivity, which enables computational wavefront retrieval using back-scattered light from the sample. Compared to a conventional wavefront sensor, aberration sensing with OCM via computational adaptive optics (CAO) leverages coherence and confocal gating to obtain signals from the focus with less cross-talk from other depths or transverse locations within the field-of-view. Here, we present an investigation of the performance of CAO-based aberration sensing in simulation, bead phantoms, andex vivomouse brain tissue. We demonstrate that, due to the influence of the double-pass confocal OCM imaging geometry on the shape of computed pupil functions, computational sensing of high-order aberrations can suffer from signal attenuation in certain spatial-frequency bands and shape similarity with lower order counterparts. However, by sensing and correcting only low-order aberrations (astigmatism, coma, and trefoil), we still successfully corrected tissue-induced aberrations, leading to 3× increase in OCM signal intensity at a depth of ∼0.9 mm in a freshly dissectedex vivomouse brain. 

Multiple scattering is a major barrier that limits the optical imaging depth in scattering media. In order to alleviate this effect, we demonstrate aberration-diverse optical coherence tomography (AD-OCT), which exploits the phase correlation between the deterministic signals from single-scattered photons to suppress the random background caused by multiple scattering and speckle. AD-OCT illuminates the sample volume with diverse aberrated point spread functions, and computationally removes these intentionally applied aberrations. After accumulating 12 astigmatism-diverse OCT volumes, we show a 10 dB enhancement in signal-to-background ratio via a coherent average of reconstructed signals from a USAF target located 7.2 scattering mean free paths below a thick scattering layer, and a 3× speckle contrast reduction from an incoherent average of reconstructed signals inside the scattering layer. This AD-OCT method, when implemented using astigmatic illumination, is a promising approach for ultra-deep volumetric optical coherence microscopy.