Optical coherence elastography (OCE) can provide clinically valuable information based on local measurements of tissue stiffness. Improved light sources and scanning methods in optical coherence tomography (OCT) have led to rapid growth in systems for high-resolution, quantitative elastography using imaged displacements and strains within soft tissue to infer local mechanical properties. We describe in some detail the physical processes underlying tissue mechanical response based on static and dynamic displacement methods. Namely, the assumptions commonly used to interpret displacement and strain measurements in terms of tissue elasticity for static OCE and propagating wave modes in dynamic OCE are discussed with the ultimate focus on OCT system design for ophthalmic applications. Practical OCT motion-tracking methods used to map tissue elasticity are also presented to fully describe technical developments in OCE, particularly noting those focused on the anterior segment of the eye. Clinical issues and future directions are discussed in the hope that OCE techniques will rapidly move forward to translational studies and clinical applications.

Elastography plays a key role in characterizing soft media such as biological tissue. Although this technology has found widespread use in both clinical diagnostics and basic science research, nearly all methods require direct physical contact with the object of interest and can even be invasive. For a number of applications, such as diagnostic measurements on the anterior segment of the eye, physical contact is not desired and may even be prohibited. Here we present a fundamentally new approach to dynamic elastography using non-contact mechanical stimulation of soft media with precise spatial and temporal shaping. We call it acoustic micro-tapping (AμT) because it employs focused, air-coupled ultrasound to induce significant mechanical displacement at the boundary of a soft material using reflection-based radiation force. Combining it with high-speed, four-dimensional (three space dimensions plus time) phase-sensitive optical coherence tomography creates a non-contact tool for high-resolution and quantitative dynamic elastography of soft tissue at near real-time imaging rates. The overall approach is demonstrated in ex-vivo porcine cornea.

We propose an integrated method combining low-frequency mechanics with optical imaging to map the shear modulus within the biological tissue. Induced shear wave propagating in tissue is tracked in space and time using phase-sensitive optical coherence tomography (PhS-OCT). Local estimates of the shear-wave speed obtained from tracking results can image the local shear modulus. A PhS-OCT system remotely records depth-resolved, dynamic mechanical waves at an equivalent frame rate of ∼47  kHz with the high spatial resolution. The proposed method was validated by examining tissue-mimicking phantoms made of agar and light scattering material. Results demonstrate that the shear wave imaging can accurately map the elastic moduli of these phantoms.

We describe theoretical and experimental investigations of motion artifacts that can arise in the detection of shear wave propagating within tissue with phase-sensitive optical coherence tomography. We find that the motion artifact is a combined product of sample surface motion and refractive index difference between sample and air, which cannot be neglected when estimating the tissue motion within tissue. A method of compensating the motion artifact is demonstrated, the results of which emphasize the need for surface motion compensation when measuring the mechanical response for elastography or other biomedical applications.

PurposeThe purpose of this study was to estimate human trabecular meshwork (hTM) stiffness, thought to be elevated in glaucoma, using a novel indirect approach, and to compare results with direct en face atomic force microscopy (AFM) measurements.MethodsPostmortem human eyes were perfused to measure outflow facility and identify high- and low-flow regions (HF, LF) by tracer. Optical coherence tomography (OCT) images were obtained as Schlemm's canal luminal pressure was directly manipulated. TM stiffness was deduced by an inverse finite element modeling (FEM) approach. A series of AFM forcemaps was acquired along a line traversing the anterior angle on a radially cut flat-mount corneoscleral wedge with TM facing upward.ResultsThe elastic modulus of normal hTM estimated by inverse FEM was 70 ± 20 kPa (mean ± SD), whereas glaucomatous hTM was slightly stiffer (98 ± 19 kPa). This trend was consistent with TM stiffnesses measured by AFM: normal hTM stiffness = 1.37 ± 0.56 kPa, which was lower than glaucomatous hTM stiffness (2.75 ± 1.19 kPa). None of these differences were statistically significant. TM in HF wedges was softer than that in LF wedges for both normal and glaucomatous eyes based on the inverse FEM approach but not by AFM. Outflow facility was significantly correlated with TM stiffness estimated by FEM in six human eyes (P = 0.018).ConclusionsTM stiffness is higher, but only modestly so, in glaucomatous patients. Outflow facility in both normal and glaucomatous human eyes appears to associate with TM stiffness. This evidence motivates further studies to investigate factors underlying TM biomechanical property regulation.

We report on the use of phase-sensitive optical coherence tomography (PhS-OCT) to detect and track temporally and spatially shear wave propagation within tissue induced by ultrasound radiation force. Kilohertz-range shear waves are remotely generated in sample using focused ultrasound emission and their propagation is tracked using PhS-OCT. Cross-sectional maps of the local shear modulus are reconstructed from local estimates of shear wave speed in tissue-mimicking phantoms. We demonstrate the feasibility of combining ultrasound radiation force and PhS-OCT to perform high-resolution mapping of the shear modulus.

Normal aging is associated with significant alterations in brain's vascular structure and function, which can lead to compromised cerebral circulation and increased risk of neurodegeneration. The in vivo examination of cerebral blood flow (CBF), including capillary beds, in aging brains with sufficient spatial detail remains challenging with current imaging modalities. In the present study, we use 3-dimensional (3-D) quantitative optical coherence tomography angiography (OCTA) to examine characteristic differences of the cerebral vasculatures and hemodynamics at the somatosensory cortex between old (16 months old) and young mice (2 months old) in vivo. The quantitative metrics include cortical vascular morphology, CBF, and capillary flow velocity. We show that compared with young mice, the pial arterial tortuosity increases by 14%, the capillary vessel density decreases by 15%, and the CBF reduces by 33% in the old mice. Most importantly, changes in capillary velocity and heterogeneity with aging are quantified for the first time with sufficiently high statistical power between young and old populations, with a 21% (p < 0.05) increase in capillary mean velocity and 19% (p ≤ 0.05) increase in velocity heterogeneity in the latter. Our findings through noninvasive imaging are in line with previous studies of vascular structure modification with aging, with additional quantitative assessment in capillary velocity enabled by advanced OCTA algorithms on a single imaging platform. The results offer OCTA as a promising neuroimaging tool to study vascular aging, which may shed new light on the investigations of vascular factors contributing to the pathophysiology of age-related neurodegenerative disorders.

Current optical coherence tomography (OCT) imaging suffers from short ranging distance and narrow imaging field of view (FOV). There is growing interest in searching for solutions to these limitations in order to expand further in vivo OCT applications. This paper describes a solution where we utilize an akinetic swept source for OCT implementation to enable ~10 cm ranging distance, associated with the use of a wide-angle camera lens in the sample arm to provide a FOV of ~20 x 20 cm 2 . The akinetic swept source operates at 1300 nm central wavelength with a bandwidth of 100 nm. We propose an adaptive calibration procedure to the programmable akinetic light source so that the sensitivity of the OCT system over ~10 cm ranging distance is substantially improved for imaging of large volume samples. We demonstrate the proposed swept source OCT system for in vivo imaging of entire human hands and faces with an unprecedented FOV (up to 400 cm 2 ). The capability of large-volume OCT imaging with ultra-long ranging and ultra-wide FOV is expected to bring new opportunities for in vivo biomedical applications. phase-stability of ultrafast swept source optical coherence tomography for single shot imaging of transient mechanical waves at 16 kHz frame rate," Appl.