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Optical elastography offers a rich body of imaging capabilities that can serve as a bridge between organ-level medical elastography and single-molecule biophysics. We review the methodologies and recent developments in optical coherence elastography, Brillouin microscopy, optical microrheology, and photoacoustic elastography. With an outlook toward maximizing the basic science and translational clinical impact of optical elastography technologies, we discuss potential ways that these techniques can integrate not only with each other, but also with supporting technologies and capabilities in other biomedical fields. By embracing cross-modality and cross-disciplinary interactions with these parallel fields, optical elastography can greatly increase its potential to drive new discoveries in the biomedical sciences as well as the development of novel biomechanics-based clinical diagnostics and therapeutics.

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.