High performance OCTA enabled by combining features of shape, intensity, and complex decorrelation.

Motion contrast optical coherence tomography angiography (OCTA) entails a precise identification of dynamic flow signals from the static background, but an intermediate region with voxels exhibiting a mixed distribution of dynamic and static scatterers is almost inevitable in practice, which degrades the vascular contrast and connectivity. In this work, the static-dynamic intermediate region was pre-defined according to the asymptotic relation between inverse signal-to-noise ratio (iSNR) and decorrelation, which was theoretically derived for signals with different flow rates based on a multi-variate time series (MVTS) model. Then the ambiguous voxels in the intermediate region were further differentiated using a shape mask with adaptive threshold. Finally, an improved OCTA classifier was built by combining shape, iSNR, and decorrelation features, termed as SID-OCTA, and the performance of the proposed SID-OCTA was validated experimentally through mouse retinal imaging.

Light-evoked deformations in rod photoreceptors, pigment epithelium and subretinal space revealed by prolonged and multilayered optoretinography.

Phototransduction involves changes in concentration of ions and other solutes within photoreceptors and in subretinal space, which affect osmotic pressure and the associated water flow. Corresponding expansion and contraction of cellular layers can be imaged using optoretinography (ORG), based on phase-resolved optical coherence tomography (OCT). Until now, ORG could reliably detect only photoisomerization and phototransduction in photoreceptors, primarily in cones under bright stimuli. Here, by employing a phase-restoring subpixel motion correction algorithm, which enables imaging of the nanometer-scale tissue dynamics during minute-long recordings, and unsupervised learning of spatiotemporal patterns, we discover optical signatures of the other retinal structures' response to visual stimuli. These include inner and outer segments of rod photoreceptors, retinal pigment epithelium, and subretinal space in general. The high sensitivity of our technique enables detection of the retinal responses to dim stimuli: down to 0.01% bleach level, corresponding to natural levels of scotopic illumination. We also demonstrate that with a single flash, the optoretinogram can map retinal responses across a 12° field of view, potentially replacing multifocal electroretinography. This technique expands the diagnostic capabilities and practical applicability of optoretinography, providing an alternative to electroretinography, while combining structural and functional retinal imaging in the same OCT machine.

Endoscopic optical coherence tomography angiography using inverse SNR-amplitude decorrelation features and electrothermal micro-electro-mechanical system raster scan.

Background: Angiogenesis is closely associated with tumor development and progression. Endoscopic optical coherence tomography angiography (OCTA) enables rapid inspection of mucosal 3D vasculature of inner organs in the early-stage tumor diagnosis; however, it is limited by instabilities of the optical signal and beam scanning. Methods: In the phase-unstable swept source OCTA (SS-OCTA), amplitude decorrelation was used to compute the motion-induced changes as motion contrast. The influence of the random noise-induced amplitude fluctuations on decorrelation was characterized as a function of inverse signal-to-noise ratio (SNR) with a multi-variate time series (MVTS) model and statistical analysis. Then, the noise-induced decorrelation artifacts in static tissue regions were eliminated by applying a flow mask based on the statistical relation between inverse SNR (iSNR) and amplitude decorrelation (IDa), which was named IDa-OCTA. In addition, a distal stepwise raster scan was realized with a low-voltage electrothermal micro-electro-mechanical system (ET-MEMS)-based catheter for endoscopic imaging, whereby the stable and repeatable B-scans at each step suppressed the decorrelation noise induced by the spatial mismatch between paired scans. Results: The derived IDa relation was validated through numerical simulation and flow phantom experiments. In vivo human buccal mucosa imaging was performed to demonstrate the endoscopic IDa-OCTA imaging. In this, the subsurface structure and vasculature were visualized in a rapid and depth-resolved manner. Conclusions: The rapid 3D vasculature visualization realized by the endoscopic IDa-OCTA improves the diagnosis of early tumors in internal organs.

Noninvasive OCT angiography-based blood attenuation measurements correlate with blood glucose level in the mouse retina.

In this study, we investigated the correlation of the blood optical attenuation coefficient (OAC) and the blood glucose concentration (BGC). The blood OAC was measured in mouse retina in vivo by analyzing the depth attenuation of backscattered light under the guidance of OCT angiography (OCTA) vascular mapping, and then its correlation to the BGC was further investigated. The optical attenuation of the blood components presented a more reliable correlation to BGC than that of the background tissues. The arteries and veins presented a blood OAC change of ∼0.05-0.07 mm-1 per 10 mg/dl and a significant (P < 0.001) elevation of blood OAC in diabetic mice was observed. Furthermore, different kinds of vessels also presented different performances. The veins had a higher correlation coefficient (R=0.86) between the measured blood OAC and BGC than that of the arteries (R=0.73). Besides, the blood OAC changes of the specific vessels occur without any obvious change in the vascular morphology in the retina. The blood OAC-BGC correlation suggests a concept of non-invasive OCTA-based glucometry, allowing a fast assessment of the blood glucose of specific vessels with superior motion immunity. A direct glucometry of the retina would be helpful for accurately monitoring the progression of diabetic retinopathy.

Automatic 3D adaptive vessel segmentation based on linear relationship between intensity and complex-decorrelation in optical coherence tomography angiography.

BACKGROUND: Vascular quantitative metrics have been widely used in the preclinical studies and clinical applications (e.g., the diagnosis and treatment of port wine stain, PWS), which require accurate vessel segmentation. An automatic 3D adaptive vessel segmentation is in need for a reproducible and objective quantification of the optical coherence tomography angiography (OCTA) image. METHODS: Human skin imaging was performed with a lab-built optical coherence tomography (OCT) system. Rather than separately applying the conventional 2-step (intensity and binarization) thresholding in the decorrelation-contrast OCTA, we proposed a 3D adaptive threshold using the linear relationship between the local intensity and complex-decorrelation which was termed as inverse SNR-decorrelation (ID) threshold. Furthermore, the ID threshold was automatically determined by defining a binary image similarity (BISIM) index as the feedback and searching the ID threshold with the minimal BISIM value. The proposed ID-BISIM threshold was applied to the acquired OCTA skin images for further vessel quantification. RESULTS: The proposed ID-BISIM threshold enabled a 3D adaptive binarization and presented superior sensitivity and specificity in vessel segmentation over conventional 2-step thresholding method in the decorrelation-contrast OCTA and a 37-65% improvement of the Youden's index in human skin experiments. The 3D binarization enabled a depth-resolved vessel skeleton and enhanced the differentiation of the overlapping vessels in the depth direction. Using ID-BISIM, the quantitative OCTA image presented a significant increase of vessel diameter index (P=0.0015) and vessel area density (VAD) (P=0.0485) as well as a significant decrease of vessel complexity index (VCI) (P=0.0094) in PWS lesion skin compared with normal skin. CONCLUSIONS: The proposed ID-BISIM method enables an automatic 3D adaptive vessel segmentation with enhanced performance in quantitative OCTA. The vascular quantitative metrics would be a useful tool for improving the diagnosis and the treatment of PWS.

Improvement of Decorrelation-Based OCT Angiography by an Adaptive Spatial-Temporal Kernel in Monitoring Stimulus-Evoked Hemodynamic Responses.

Complex decorrelation-based OCT angiography (OCTA) has the potential for monitoring hemodynamic activities in a label-free, high-resolution, and quantitative manner. To improve the measurement dynamic range and uncertainty of blood flow, an adaptive spatial-temporal (ST) kernel was proposed for decorrelation estimation and it was validated through a theoretical simulation and experimental measurements. The ensemble size in the decorrelation computation was effectively enlarged by collecting samples of the phasor pair in both the spatial and temporal dimensions. The spatial sub-kernel size was adaptively changed to suppress the influence of bulk motion in the temporal dimension by solving a maximum entropy model. Using the flow phantom, it was observed that the decorrelation dynamic range presented an increase of ~49% and the uncertainty exhibited a decrease of ~40% and ~38% in the saturation and background limits, respectively. In monitoring the stimulus-evoked hemodynamic response, the extended dynamic range enabled an improvement of ~180% in the separability between different stimulation modes. Furthermore, the suppressed uncertainty and motion artifacts allowed a reliable temporal analysis of the hemodynamic response. The proposed adaptive ST-kernel will greatly promote the development of decorrelation-based quantitative OCTA in hemodynamic studies.