Spatiotemporal Optical Coherence Research Articles

In vivo volumetric analysis of retinal vascular hemodynamics in mice with spatio-temporal optical coherence tomography.

Microcirculation and neurovascular coupling are important parameters to study in neurological and neuro-ophthalmic conditions. As the retina shares many similarities with the cerebral cortex and is optically accessible, a special focus is directed to assessing the chorioretinal structure, microvasculature, and hemodynamics of mice, a vital animal model for vision and neuroscience research. We aim to introduce an optical imaging tool enabling in vivo volumetric mouse retinal monitoring of vascular hemodynamics with high temporal resolution. We translated the spatio-temporal optical coherence tomography (STOC-T) technique into the field of small animal imaging by designing a new optical system that could compensate for the mouse eye refractive error. We also developed post-processing algorithms, notably for the assessment of (i) localized hemodynamics from the analysis of pulse wave-induced Doppler artifact modulation and (ii) retinal tissue displacement from phase-sensitive measurements. We acquired high-quality, in vivo volumetric mouse retina images at a rate of 113Hz over a lateral field of view of . We presented high-resolution en face images of the retinal and choroidal structure and microvasculature from various layers, after digital aberration correction. We were able to measure the pulse wave velocity in capillaries of the outer plexiform layer with a mean speed of 0.35mm/s and identified venous and arterial pulsation frequency and phase delay. We quantified the modulation amplitudes of tissue displacement near major vessels (with peaks of 150nm), potentially carrying information about the biomechanical properties of the retinal layers involved. Last, we identified the delays between retinal displacements due to the passing of venous and arterial pulse waves. The developed STOC-T system provides insights into the hemodynamics of the mouse retina and choroid that could be beneficial in the study of neurovascular coupling and vasculature and flow speed anomalies in neurological and neuro-ophthalmic conditions.

Multiwavelength laser doppler holography (MLDH) in spatiotemporal optical coherence tomography (STOC-T)

Spatiotemporal optical coherence tomography (STOC-T) is the novel modality for high-speed, crosstalk- and aberration-free volumetric imaging of biological tissue in vivo. STOC-T extends the Fourier-Domain holographic Optical Coherence Tomography by the spatial phase modulation that enables the reduction of spatial coherence of the tunable laser. By reducing the spatial coherence of the laser, we suppress coherent noise, and, consequently, improve the imaging depth. Furthermore, we remove geometrical aberrations computationally in postprocessing. We recently demonstrated high-speed, high-resolution STOC-T of human retinal imaging in vivo. Here, we show that the dataset produced by STOC-T can be processed differently to reveal blood flow in the human retina in vivo. To render the blood flow, we first pre-process STOC-T holographic data to access the approximated information about the Doppler-shifted optical field backscattered from the sample. Then, we analyze it using methods from the laser Doppler flowmetry, namely, by analyzing the Doppler broadening caused by moving light scatterers (red blood cells). However, contrary to conventional approaches, we use multiple illumination wavelengths. This enables us to render the structural volumetric and blood flow images from the same dataset concurrently. Our method, denoted as multiwavelength laser Doppler holography (MLDH), links laser Doppler flowmetry with multiwavelength holographic detection to enable noninvasive visualization and possible blood flow quantification at different human retina layers at high speeds and high transverse resolution in vivo.

Imaging the retinal and choroidal vasculature using Spatio-Temporal Optical Coherence Tomography (STOC-T)

Spatio-Temporal Optical Coherence Tomography (STOC-T) is a novel imaging technique using light with controlled spatial and temporal coherence. Retinal images obtained using the STOC-T system maintain high resolution in all three dimensions, on a sample of about 700 μm, without the need for mechanical scanning. In the present work, we use known data processing algorithms for optical coherence tomography angiography (OCTA) and modify them to improve the rendering of the vasculature in the human retina at different depths by introducing the angio STOC-T method. The algorithms are primarily sensitive to the strong signal phase variance corresponding to the appearance of a wide Doppler band in STOC-T signals obtained for millisecond exposure times. After using STOC-T angiography, we can render high contrast images of the choroid.

Poster Session: Optoretinography-based frequency characterization of the retinal response to a chirped flickering light.

In this contribution, we present experimental results of in vivo characterization of the photoreceptor's response to a chirped flickering white light stimulating the retina. We acquire the ORG signal with Spatio-Temporal Optical Coherence Tomography (STOC-T) setup, which combines both temporal and coherence gating to overcome limitations present in Full Field Fourier Domain Optical Coherence Tomography. From the acquired volumes, we extract the changes in optical path length (OPL) between the inner and outer photoreceptor junction (ISOS) and the cone outer segment tips (COST). We perform the measurements for frequencies ranging from 5 Hz to 50 Hz. The chirped flickering facilitates significantly shorter data acquisition time. We present results of in vivo measurement from three volunteers. Our results show that we can measure OPL changes between ISOS and COST occurring in response to a chirped flickering stimulation in a reproducible manner and resolve the amplitude of the response in the function of flicker frequency.

Spatio-temporal optical coherence tomography provides full thickness imaging of the chorioretinal complex.

Despite the rapid development of optical imaging methods, high-resolution invivo imaging with penetration into deeper tissue layers is still a major challenge. Optical coherence tomography (OCT) has been used successfully for non-invasive human retinal volumetric imaging invivo, advancing the detection, diagnosis, and monitoring of various retinal diseases. However, there are important limitations of volumetric OCT imaging, especially coherent noise and the limited axial range over which high resolution images can be acquired. The limited range prevents simultaneous measurement of the retina and choroid with adequate lateral resolution. In this article, we address these limitations with a technique that we term spatio-temporal optical coherence tomography (STOC-T), which uses light with controlled spatial and temporal coherence and advanced signal processing methods. STOC-T enabled the acquisition of high-contrast and high-resolution coronal projection images of the retina and choroid at arbitrary depths.

Light-adapted flicker optoretinograms captured with a spatio-temporal optical coherence-tomography (STOC-T) system.

For many years electroretinography (ERG) has been used for obtaining information about the retinal physiological function. More recently, a new technique called optoretinography (ORG) has been developed. In one form of this technique, the physiological response of retinal photoreceptors to visible light, resulting in a nanometric photoreceptor optical path length change, is measured by phase-sensitive optical coherence tomography (OCT). To date, a limited number of studies with phase-based ORG measured the retinal response to a flickering light stimulation. In this work, we use a spatio-temporal optical coherence tomography (STOC-T) system to capture optoretinograms with a flickering stimulus over a 1.7 × 0.85 mm2 area of a light-adapted retina located between the fovea and the optic nerve. We show that we can detect statistically-significant differences in the photoreceptor optical path length (OPL) modulation amplitudes in response to different flicker frequencies and with better signal to noise ratios (SNRs) than for a dark-adapted eye. We also demonstrate the ability to spatially map such response to a patterned stimulus with light stripes flickering at different frequencies, highlighting the prospect of characterizing the spatially-resolved temporal-frequency response of the retina with ORG.

Computational aberration correction in spatiotemporal optical coherence (STOC) imaging.

Spatiotemporal optical coherence (STOC) imaging is a new technique for suppressing coherent cross talk noise in Fourier-domain full-field optical coherence tomography (FD-FF-OCT). In STOC imaging, the time-varying inhomogeneous phase masks modulate the incident light to alter the interferometric signal. Resulting interference images are then processed as in standard FD-FF-OCT and averaged incoherently or coherently to produce cross-talk-free volumetric optical coherence tomography (OCT) images of the sample. Here, we show that coherent averaging is suitable when phase modulation is performed for both interferometer arms simultaneously. We explain the advantages of coherent over incoherent averaging. Specifically, we show that modulated signal, after coherent averaging, preserves lateral phase stability, enabling computational phase correction to compensate for geometrical aberrations. Ultimately, we employ it to correct for aberrations present in the image of the photoreceptor layer of the human retina that reveals otherwise invisible photoreceptor mosaics.

Spatio-Temporal Optical Coherence Imaging – a new tool for in vivo microscopy

Optical Coherence Imaging (OCI) including Optical Coherence Tomography (OCT) and Optical Coherence Microscopy (OCM) uses interferometric detection to generate high-resolution volumetric images of the sample at high speeds. Such capabilities are significant for in vivo imaging, including ophthalmology, brain, intravascular imaging, as well as endoscopic examination. Instrumentation and software development allowed to create many clinical instruments. Nevertheless, most of OCI setups scan the incident light laterally. Hence, OCI can be further extended by wide-field illumination and detection. This approach, however, is very susceptible to the so-called crosstalk-generated noise. Here, we describe our novel approach to overcome this issue with spatio-temporal optical coherence manipulation (STOC), which employs spatial phase modulation of the incident light. Full Text: PDF ReferencesL. Wang, P. P. Ho, C. Liu, G. Zhang, and R. R. Alfano, "Ballistic 2-D Imaging Through Scattering Walls Using an Ultrafast Optical Kerr Gate", Science 253, 769-771 (1991). CrossRef D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and et al., "Optical coherence tomography", Science 254, 1178-1181 (1991). CrossRef J. A. Izatt, E. A. Swanson, J. G. Fujimoto, M. R. Hee, and G. M. Owen, "Optical coherence microscopy in scattering media", Opt. Lett. 19, 590-592 (1994). CrossRef D. Borycki, M. Nowakowski, and M. Wojtkowski, "Control of the optical field coherence by spatiotemporal light modulation", Opt. Lett. 38, 4817-4820 (2013). CrossRef D. Borycki, M. Hamkalo, M. Nowakowski, M. Szkulmowski, and M. Wojtkowski, "Spatiotemporal optical coherence (STOC) manipulation suppresses coherent cross-talk in full-field swept-source optical coherence tomography", Biomed. Opt. Express 10, 2032-2054 (2019). CrossRef P. Stremplewski, E. Auksorius, P. Wnuk, L. Kozon, P. Garstecki, and M. Wojtkowski, "In vivo volumetric imaging by crosstalk-free full-field OCT", Optica 6, 608-617 (2019). CrossRef L. Vabre, A. Dubois, and A. C. Boccara, "Thermal-light full-field optical coherence tomography", Opt. Lett. 27, 530-532 (2002). CrossRef M. Laubscher, M. Ducros, B. Karamata, T. Lasser, and R. Salathé, "Video-rate three-dimensional optical coherence tomography", Opt. Express 10, 429-435 (2002). CrossRef Dubois and A. C. Boccara, Full-Field Optical Coherence Tomography, (Springer Berlin Heidelberg, Berlin, Heidelberg, 2008), pp. 565-591. CrossRef O. Thouvenin, K. Grieve, P. Xiao, C. Apelian, and A. C. Boccara, "En face coherence microscopy [Invited]", Biomedical Opt. Express 8, 622-639 (2017). CrossRef F. Fercher, C. K. Hitzenberger, M. Sticker, E. Moreno-Barriuso, R. Leitgeb, W. Drexler, and H. Sattmann, "A thermal light source technique for optical coherence tomography", Optics Commun. 185, 57-64 (2000). CrossRef R. A. Leitgeb, "En face optical coherence tomography: a technology review [Invited]", Biomed Opt Express 10, 2177-2201 (2019). CrossRef J. Fujimoto and W. Drexler, Introduction to Optical Coherence Tomography, (Springer, Berlin, Heidelberg, 2008), pp. 1-45. CrossRef J. A. Izatt, M. A. Choma, and A.-H. Dhalla, Theory of Optical Coherence Tomography, (Springer International Publishing, Cham, 2015), pp. 65-94. CrossRef

Spatiotemporal optical coherence (STOC) manipulation suppresses coherent cross-talk in full-field swept-source optical coherence tomography.

Full-field swept-source optical coherence tomography (FF-SS-OCT) provides high-resolution depth-resolved images of the sample by parallel Fourier-domain interferometric detection. Although FF-SS-OCT implements high-speed volumetric imaging, it suffers from the cross-talk-generated noise from spatially coherent lasers. This noise reduces the transversal image resolution, which in turn, limits the wide adaptation of FF-SS-OCT for practical and clinical applications. Here, we introduce the novel spatiotemporal optical coherence (STOC) manipulation. In STOC the time-varying inhomogeneous phase masks are used to modulate the light incident on the sample. By properly adjusting these phase masks, the spatial coherence can be reduced. Consequently, the cross-talk-generated noise is suppressed, the transversal image resolution is improved by the factor of , and sample features become visible. STOC approach is validated by imaging 1951 USAF resolution test chart covered by the diffuser, scattering phantom and the rat skin ex vivo. In all these cases STOC suppresses the cross-talk-generated noise, and importantly, do not compromise the transversal resolution. Thus, our method provides an enhancement of FF-SS-OCT that can be beneficial for imaging biological samples.

Control of the optical field coherence by spatiotemporal light modulation

The novel spatiotemporal optical coherence manipulation technique, which allows one to tailor the second-order coherence properties of a light beam, is introduced. With the use of an interferometric setup we show that the basic measure of the contrast of interference fringes, i.e., Michelson's visibility, can be controlled across the interference pattern by modulating the phase of the spectral degree of coherence.