Sepideh Hariri

Limiting factors to the OCT axial resolution for in-vivo imaging of human and rodent retina in the 1060nm wavelength range

A computational model was developed to evaluate the limitations to the highest axial resolution, achievable with ultrahigh resolution optical coherence tomography (UHROCT) in the 1060 nm wavelength region for in-vivo imaging of the human and rodent retina. The model considers parameters such as the wavelength dependent water absorption, the average length of the human and rodent eyes, and the power limitations for the imaging beam as defined in the ANSI standard. A custom-built light source with re-shaped spectrum was used to verify experimentally the results from the computational model. Axial OCT resolution of 4.2 microm and 7.7 microm was measured from a mirror reflection with the custom light source by propagating the imaging beam through water cells with 5 mm and 25 mm thickness, corresponding to the average axial length of the rodent and human eye respectively. Assuming an average refractive index of 1.38 for retinal tissue, the expected axial OCT resolution in the rodent and human retina is 3 microm and 5.7 microm respectively. Retinal tomograms acquired in-vivo from the rat eye with the modified light source show clear visualization of all intraretinal layers, as well as a network of capillaries (approximately 10 microm in diameter) in the inner- and outer plexiform layers of the retina.

In vivo imaging of intrinsic optical signals in chicken retina with functional optical coherence tomography.

Visually evoked intrinsic optical signals (IOSs) were measured in vivo for the first time to our knowledge from all retina layers of the chicken retina with a combined functional optical coherence tomography and electroretinography (ERG) system. IOS traces were recorded from a small volume in the retina with 3.5 μm axial resolution and 7 ms time resolution. Comparison of the IOS and ERG traces shows a correlation between the positive and negative IOS measured from different retinal layers and the timing of the a and b waves in the ERG recording.

In vivo volumetric imaging of chicken retina with ultrahigh-resolution spectral domain optical coherence tomography

The chicken retina is an established animal model for myopia and light-associated growth studies. It has a unique morphology: it is afoveate and avascular; oxygen and nutrition to the inner retina is delivered by a vascular tissue (pecten) that protrudes into the vitreous. Here we present, to the best of our knowledge, the first in vivo, volumetric high-resolution images of the chicken retina. Images were acquired with an ultrahigh-resolution optical coherence tomography (UHROCT) system with 3.5 µm axial resolution in the retina, at the rate of 47,000 A-scans/s. Spatial variations in the thickness of the nerve fiber and ganglion cell layers were mapped by segmenting and measuring the layer thickness with a semi-automatic segmentation algorithm. Volumetric visualization of the morphology and morphometric analysis of the chicken retina could aid significantly studies with chicken retinal models of ophthalmic diseases.

Noninvasive imaging of the early effect of sodium iodate toxicity in a rat model of outer retina degeneration with spectral domain optical coherence tomography

Abstract. An ultrahigh resolution spectral domain optical coherence tomography (SD-OCT) system is used to observe for the first time in vivo the early effect of sodium iodate (NaIO3) toxicity on retinal morphology. Retinal degeneration is induced in rats via tail vein injection of NaIO3 and structural changes in the outer retina are assessed longitudinally at baseline and 1, 2, 3, 6, 8, and 10 h, and 12 post drug administration with OCT, H&E histology, and IgG immunochemistry. Disruption of the structural integrity and changes in the optical reflectivity of the photoreceptor inner (IS) and outer segment (OS) layers are observed as early as 1 h post NaIO3 injection. A new layer is observed in the OCT tomograms to form between the retinal pigmented epithelium and the photoreceptors OS a few hours post NaIO3 injection. The dynamics and the low optical reflectivity of this layer, as well as cell swelling and disruption of the blood-retina barrier observed in the histological and immunohistochemistry cross-sections suggest that the layer corresponds to temporary fluid accumulation in the retina. Results from this study demonstrate the effectiveness of OCT technology for monitoring dynamic changes in the retinal morphology and provide better understanding of the early stages of outer retina degeneration induced by NaIO3 toxicity.

Correlation of visually evoked intrinsic optical signals and electroretinograms recorded from chicken retina with a combined functional optical coherence tomography and electroretinography system

Visually evoked fast intrinsic optical signals (IOSs) were recorded for the first time in vivo from all layers of healthy chicken retina by using a combined functional optical coherence tomography (fOCT) and electroretinography (ERG) system. The fast IOSs were observed to develop within ∼5 ms from the on-set of the visual stimulus, whereas slow IOSs were measured up to 1 s later. The visually evoked IOSs and ERG traces were recorded simultaneously, and a clear correlation was observed between them. The ability to measure visually evoked fast IOSs non-invasively and in vivo from individual retinal layers could significantly improve the understanding of the complex communication between different retinal cell types in healthy and diseased retinas.

Combined optical coherence tomography and electroretinography system for in vivo simultaneous morphological and functional imaging of the rodent retina.

A combined ultrahigh resolution optical coherence tomography (UHROCT) and a electroretinography (ERG) system is presented for simultaneous imaging of the retinal structure and physiological response to light stimulation in the rodent eye. The 1060-nm UHROCT system provides approximately 3x5 microm (axialxlateral) resolution in the rat retina and time resolution of 22 micros. A custom-designed light stimulator integrated into the UHROCT imaging probe provides light stimuli with user-selected color, duration, and intensity. The performance of the combined system is demonstrated in vivo in healthy rats, and in a rat model of drug-induced outer retinal degeneration. Experimental results show correlation between the observed structural and physiological changes in the healthy and degenerated retina.

Evaluation of hypoxic swelling of human cornea with high speed, ultrahigh resolution optical coherence tomography

Hypoxia induced corneal swelling was observed and evaluated in healthy human volunteers by use of high speed, ultrahigh resolution optical coherence tomography (UHROCT). Two dimensional corneal images were acquired at a speed of 47,000 A-scans/s with 3µm x 10µm (axial x lateral) resolution in corneal tissue. The UHROCT tomograms showed clear visualization of all corneal layers, including the Bowmans layer and the Descemets membrane - Endothelium complex. A segmentation algorithm was developed and used for automatic detection of the boundaries of the different corneal layers and evaluation the individual layer thickness as a function of location. Corneal hypoxia was induced by wear of a soft contact lens (SCL) and an eye patch by 2 healthy volunteers for duration of 3 hours. The thickness of all corneal layers was measured as a function of time, prior to, with and after removal of the SCL. Results from the hypoxia study showed different rates of swelling and de-swelling of the individual corneal layers. About 10% increase in the total cornea thickness was observed, similar to the changes in the stroma, the Bowmans membrane swelled by 20%, while no significant change in the thickness was observed in the Descemets - Endothelium complex.

In-vivo human retina imaging with 5μm axial resolution, at 92000 A-scans/s with 1μm spectral domain OCT system

We have outfitted a 1060nm Spectral Domain Optical Coherence Tomography system with a prototype, high speed infrared linear array camera and a custom spectrally reshaped superluminescent diode to achieve 5μm axial resolution at 91,911 A-scans/s image acquisition rate in-vivo in the human retina. 4dB loss of sensitivity was observed as a result of the reduced integration time (7μs) of the fast camera as compared to similar commercially available cameras with 14μs integration time and 47kHz readout rate. Fewer motion artefacts were observed in the retinal images acquired with the fast camera, while the higher axial resolution along with deeper penetration allowed for improved visualization of fine morphological details such as retinal and choroidal capillaries and the deep choroidal structure.

Tensor total variation approach to optical coherence tomography reconstruction for improved visualization of retinal microvasculature

A novel optical coherence tomography (OCT) reconstruction approach is introduced for improved visualization of inner-retina capillaries in retinal OCT tomograms. The proposed method utilizes a minimization framework based on a tensor total variation (TTV) energy functional, to enforce capillary structural characteristics in the spatial domain. By accounting for structure tensor characteristics, the TTV reconstruction method allows for contrast enhancement of capillary structural characteristics. The novel TTV method was tested on high resolution OCT images acquired in-vivo from the foveal region of the retina of a healthy human subject. Experimental results demonstrate significant contrast and visibility enhancement of the inner retina capillaries in the retinal OCT tomograms, achieved by use of the TTV reconstruction method. Therefore, the TTV method has a strong potential for improved disease progression analysis based on the study of disease-induced changes in the inner retina vasculature.

A cellular automata based semi-automatic algorithm for segmentation of choroidal blood vessels from ultrahigh resolution optical coherence images of rat retina

Abnormal changes in choroidal blood flow have been linked to various retinal diseases, such as Diabetic Retinopathy (DR) and Age related Macular Degeneration (AMD), which at later stages can lead to blindness. Therefore non-invasive and precise evaluation of choroidal blood flow can aid the diagnosis, treatment and monitoring of retinal disease progression. Doppler Optical Coherence Tomography is an imaging technique capable of measuring blood flow velocity and visualization of retinal and choroidal blood vessles. However accurate assesment of retinal and choroidal blood flow requires precise measurement of the blood vessel thickness. The presence of speckle noise and low image contrast of OCT tomograms makes this task very challenging. This paper proposes a cellular automata based semi-automatic algorithm for the segmentation of choroidal blood vessels. The proposed approach propagates user-defined points in order to identify the vessel boundaries, allowing a thickness profile to be extracted. The performance of the algorithm was tested on a series of retinal images acquired from living rats with a high speed, ultrahigh resolution OCT system (UHROCT). Experimental results show that the proposed approach provides precise thickness profiles even in the suboptimal conditions of low image contrast in the UHROCT images.