Analysis of strain estimation methods in phase-sensitive compression optical coherence elastography.

In compression optical coherence elastography (OCE), deformation is quantified as the local strain at each pixel in the OCT field-of-view. A range of strain estimation methods have been demonstrated, yet it is unclear which method provides the best performance. Here, we analyze the two most prevalent strain estimation methods used in phase-sensitive compression OCE, i.e., weighted least squares (WLS) and the vector method. We introduce a framework to compare strain imaging metrics, incorporating strain sensitivity, strain signal-to-noise ratio (SNR), strain resolution, and strain accuracy. In addition, we propose a new phase unwrapping algorithm in OCE, fast phase unwrapping (FPU), and combine it with WLS, termed WLSFPU. Using the framework, we compare this new strain estimation method with both a current implementation of WLS that incorporates weighted phase unwrapping (WPU), termed WLSWPU, and the vector method. Our analysis reveals that the three methods provide similar strain sensitivity, strain SNR, and strain resolution, but that WLSFPU extends the dynamic range of accurate, measurable local strain, e.g., measuring a strain of 2.5 mɛ with ∼4% error, that is ×11 and ×15 smaller than the error measured using WLSWPU and the vector method, respectively. We also demonstrate, for the first time, the capability to detect sub-resolution contrast in compression OCE, i.e., changes in strain occurring within the strain axial resolution, and how this contrast varies between the different strain estimation methods. Lastly, we compare the performance of the three strain estimation methods on mouse skeletal muscle and human breast tissue and demonstrate that WLSFPU avoids strain imaging artifacts resulting from phase unwrapping errors in WLSWPU and provides improved contrast over the other two methods.

Extraction of phase-based optoretinograms (ORG) from serial B-scans acquired over tens of seconds by mouse retinal raster scanning OCT system.

Several specialized retinal optical coherence tomography (OCT) acquisition and processing methods have been recently developed to allow in vivo probing of light-evoked photoreceptors function, focusing on measurements in individual photoreceptors (rods and cones). Recent OCT investigations in humans and experimental animals have shown that the outer segments in dark-adapted rods and cones elongate in response to the visible optical stimuli that bleach fractions of their visual photopigment. We have previously successfully contributed to these developments by implementing OCT intensity-based "optoretinograms" (ORG), the paradigm of using near-infrared OCT (NIR OCT) to measure bleaching-induced back-scattering and/or elongation changes of photoreceptors in the eye in vivo. In parallel, several groups have successfully implemented phase-based ORGs, mainly in human studies, exploiting changes in the phases of back-scattered light. This allowed more sensitive observations of tiny alterations of photoreceptors structures. Applications of the phase-based ORG have been implemented primarily in high speed and cellular resolution AO-OCT systems that can visualize photoreceptor mosaic, allowing phase measurements of path length changes in outer segments of individual photoreceptors. The phase-based ORG in standard resolution OCT systems is much more demanding to implement and has not been explored extensively. This manuscript describes our efforts to implement a phase analysis framework to retinal images acquired with a standard resolution and raster scanning OCT system, which offers much lower phase stability than line-field or full-field OCT detection schemes due to the relatively slower acquisition speed. Our initial results showcase the successful extraction of phase-based ORG signal from the B-scans acquired at ∼100 Hz rate and its favorable comparison with intensity-based ORG signal extracted from the same data sets. We implemented the calculation of phase-based ORG signals using Knox-Thompson paths and modified signal recovery by adding decorrelation weights. The phase-sensitive ORG signal analysis developed here for mouse retinal raster scanning OCT systems could be in principle extended to clinical retinal raster scanning OCT systems, potentially opening doors for clinically friendly ORG probing.

Blood flow rate estimation in optic disc capillaries and vessels using Doppler optical coherence tomography with 3D fast phase unwrapping.

The retinal volumetric flow rate contains useful information not only for ophthalmology but also for the diagnosis of common civilization diseases such as diabetes, Alzheimer's disease, or cerebrovascular diseases. Non-invasive optical methods for quantitative flow assessment, such as Doppler optical coherence tomography (OCT), have certain limitations. One is the phase wrapping that makes simultaneous calculations of the flow in all human retinal vessels impossible due to a very large span of flow velocities. We demonstrate that three-dimensional Doppler OCT combined with three-dimensional four Fourier transform fast phase unwrapping (3D 4FT FPU) allows for the calculation of the volumetric blood flow rate in real-time by the implementation of the algorithms in a graphics processing unit (GPU). The additive character of the flow at the furcations is proven using a microfluidic device with controlled flow rates as well as in the retinal veins bifurcations imaged in the optic disc area of five healthy volunteers. We show values of blood flow rates calculated for retinal capillaries and vessels with diameters in the range of 12-150 µm. The potential of quantitative measurement of retinal blood flow volume includes noninvasive detection of carotid artery stenosis or occlusion, measuring vascular reactivity and evaluation of vessel wall stiffness.

Computationally effective 2D and 3D fast phase unwrapping algorithms and their applications to Doppler optical coherence tomography.

We propose a simplification for a robust and easy to implement fast phase unwrapping (FPU) algorithm that is used to solve the phase wrapping problem encountered in various fields of optical imaging and metrology. We show that the number of necessary computations using the algorithm can be reduced compared to its original version. FPU can be easily extended from two to three spatial dimensions. We demonstrate the applicability of the two- and three-dimensional FPU algorithm for Doppler optical coherence tomography (DOCT) in numerical simulations, and in the imaging of a flow phantom and blood flow in the human retina in vivo. We introduce an FPU applicability plot for use as a guide in the selection of the most suitable version of the algorithm depending on the phase noise in the acquired data. This plot uses the circular standard deviation of the wrapped phase distribution as a measure of noise and relates it to the root-mean-square error of the recovered, unwrapped phase.

Quality improvement of OCT angiograms with elliptical directional filtering.

We present a method of OCT angiography (OCTA) data filtering for noise suppression and improved visualization of the retinal vascular networks in en face projection images. In our approach, we use a set of filters applied in three orthogonal axes in the three-dimensional (3-D) data sets. Minimization of artifacts generated in B-scan-wise data processing is accomplished by filtering the cross-sections along the slow scanning axis. A-scans are de-noised by axial filtering. The core of the method is the application of directional filtering to the C-scans, i.e. one-pixel thick sections of the 3-D data set, perpendicular to the direction of the scanning OCT beam. The method uses a concept of structuring, directional kernels of shapes matching the geometry of the image features. We use rotating ellipses to find the most likely local orientation of the vessels and use the best matching ellipses for median filtering of the C-scans. We demonstrate our approach in the imaging of a normal human eye with laboratory-grade spectral-domain OCT setup. The "field performance" is demonstrated in imaging of diabetic retinopathy cases with a commercial OCT device. The absolute complex differences method is used for the generation of OCTA images from the data collected in the most noise-wise unfavorable OCTA scanning regime-two frame scanning.