Measurement of retinal vascular permeability in a rat model using spectroscopic optical coherence tomography

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.Cataloged from PDF version of thesis.Includes bibliographical references.Optical coherence tomography (OCT), a diagnostic tool which can perform non-contact, noninvasive, cross-sectional imaging of the retina and anterior eye in real time, has dramatically improved in its resolution and speed in the recent years. In addition to the advancement in hardware, different OCT methods for functional measurements, such as Doppler OCT for quantifying blood flow and generating angiography using OCT phase information, polarization sensitive OCT for measuring intrinsic mechanical / optical tissue property using light of different polarizations, and spectroscopic OCT for measuring blood oxygenation using multiple wavelengths, have been demonstrated and developed. In this thesis, a dual-wavelength spectroscopic OCT technique is investigated to detect and quantify retinal vascular permeability changes in a small animal model. By injecting an intravascular dye that can act as a wavelength-dependent absorbing contrast agent into the bloodstream of a small animal, retinal vascular permeability changes induced by retinal diseases or external agents directly injected into the vitreous could be measured using spectroscopic OCT. Because OCT enables depth-resolved imaging of the retina, this technique may enable quantitative mapping of vascular permeability in vivo, which may have a significant impact on understanding the mechanisms of diseases that alter retinal vascular permeability, such as diabetic retinopathy. In this study, an OCT system with a diffraction-limited small animal imaging interface and a dual-wavelength OCT spectrometer for spectroscopic measurements was designed and built. Using this dual-wavelength spectroscopic OCT system, the rat retina could be imaged at two different wavelength bands simultaneously, and methods for analyzing spectroscopic OCT data were investigated for retinal vascular permeability measurement.by Woo Jhon Choi.S.M

Parafoveal Retinal Vascular Response to Pattern Visual Stimulation Assessed with OCT Angiography

We used optical coherence tomography (OCT) angiography with a high-speed swept-source OCT system to investigate retinal blood flow changes induced by visual stimulation with a reversing checkerboard pattern. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to quantify blood flow as measured with parafoveal flow index (PFI), which is proportional to the density of blood vessels and the velocity of blood flow in the parafoveal region of the macula. PFI measurements were taken in 15 second intervals during a 4 minute period consisting of 1 minute of baseline, 2 minutes with an 8 Hz reversing checkerboard pattern stimulation, and 1 minute without stimulation. PFI measurements increased 6.1±4.7% (p = .001) during the first minute of stimulation, with the most significant increase in PFI occurring 30 seconds into stimulation (p<0.001). These results suggest that pattern stimulation induces a change to retinal blood flow that can be reliably measured with OCT angiography.National Institutes of Health (U.S.) (Grant R01 EY013516)National Institutes of Health (U.S.) (Grant Rosenbaum's P30EY010572)Research to Prevent Blindness, Inc. (United States) (Grant R01-Ey11289-26)United States. Air Force Office of Scientific Research (FA9550-10-1-0551

Wideband Electrically Pumped 1050-nm MEMS-Tunable VCSEL for Ophthalmic Imaging

In this paper, we present a 1050-nm electrically pumped microelectromechanically tunable vertical cavity surface-emitting laser (MEMS-VCSEL) with a record dynamic tuning bandwidth of 63.8 nm, suitable for swept-source optical coherence tomography (SS-OCT) imaging. These devices provide reduced cost and complexity relative to previously demonstrated optically pumped devices by obviating the need for a pump laser and associated hardware. We demonstrate ophthalmic SS-OCT imaging with the electrically-pumped MEMS-VCSEL at a 400 kHz axial scan rate for wide-field imaging of the in vivo human retina over a 12 mm × 12 mm field and for OCT angiography of the macula over 6 mm × 6 mm and 3 mm × 3 mm fields to show retinal vasculature and capillary structure near the fovea. These results demonstrate the feasibility of electrically pumped MEMS-VCSELs in ophthalmic instrumentation, the largest clinical application of OCT. In addition, we estimate that the 3 dB coherence length in air is 225 ± 51 m, far greater than required for ophthalmic SS-OCT and suggestive of other distance ranging applications.National Eye InstituteNational Institutes of Health (U.S.) (Grant R01-EY011289-28)National Institutes of Health (U.S.) (Grant R44-EY022864-02)National Institutes of Health (U.S.) (Grant R44-EY022864-03)National Institutes of Health (U.S.) (Grant R01-CA075289-17)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-12-1-0499

Structural and functional imaging of the human and small animal eyes using ultrahigh speed Fourier domain optical coherence tomography

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2014.Cataloged from PDF version of thesis.Includes bibliographical references.Optical coherence tomography (OCT) is a non-invasive optical imaging technique that allows the three-dimensional structure of biological tissue to be visualized with micrometer resolution. In ophthalmology OCT has the unique advantage that it provides cross-sectional images of the retina and choroid noninvasively and in vivo, which have led OCT to be a clinical standard for the diagnosis of a variety of retinal diseases. Although current commercial Fourier domain OCT systems have high imaging speeds of 20-100kHz A-scan rates, these imaging speeds are not sufficient for more advanced structural and functional imaging techniques. Current state-of-the-art spectral domain and swept source OCT provide ultrahigh imaging speeds of >200kHz A-scan rates. These speeds enable functional imaging of retinal blood flow, OCT angiography of the retinal and choroidal microvasculature, and wide field volumetric structural imaging of the retina and choroid. In this thesis, advances in structural and functional ophthalmic imaging techniques for the human and small animal eyes are investigated using ultrahigh speed Fourier domain OCT. The following topics are discussed: (1) a method for numerically extracting and compensating dispersion mismatch in ultrahigh resolution spectral domain OCT, (2) ultrahigh speed spectral domain imaging in the small animal eye for measuring total retinal blood flow, (3) development of ultrahigh speed phase stable swept source OCT system for human retinal imaging, (4) OCT angiography of the choriocapillaris in the human eye, (5) clinical applications of OCT angiography in retinal diseases, including diabetic retinopathy and age-related macular degeneration, (6) small animal anesthesia protocol for functional hemodynamic imaging, and (7) imaging of neurovascular coupling in small animals using ultrahigh speed OCT.by Woo Jhon Choi.Ph. D

A sub-0.5 V operating RF low noise amplifier using tunneling-FET

60 nm tunneling FET (TFET) based low noise amplifier (LNA) with a sub-0.5 V supply voltage for 2.4GHz WSN application has been evaluated systematically from device level up to circuit level design. With the help of TFET&apos;s unique property of high subthreshold swing, it shows that substantial increase of gain performance was confirmed compared to that of conventional LNA using 60nm bulk MOSFET at ultra-low voltage (ULV) condition. From the simulation study, TFET LNA at 0.4 V operating voltage has the gain of 15.1 dB and noise figure 50 of 3.5 dB while dissipating DC power consumption of 0.41 mW. (C) 2017 The Japan Society of Applied PhysicsN

On-current Modeling of 70-nm PMOSFETs Dependent on Hot-carrier Stress Bias Conditions

Based on the drain-avalanche-hot-carrier (DAHC-) mechanism, a stress-bias-dependent on-current model is proposed for 70-nm p-channel metal-oxide-semiconductor field-effect transistors (PMOSFETs) by using only one device parameter: channel length variation (Delta L-ch). The proposed model describes the influence of drain and gate stress bias on the on-current of PMOSFETs successfully. It is a simple and effective method of predicting the on-current variation for more reliable circuit operation.N

Drain-current Modeling of Sub-70-nm PMOSFETs Dependent on Hot- carrier Stress Bias Conditions

Stress drain bias dependent current model is proposed for sub-70-nm p-channel metal-oxide semiconductor field-effect transistors (pMOSFETs) under drain-avalanche-hot-carrier (DAHC-) mechanism. The proposed model describes the both on-current and off-current degradation by using two device parameters: channel length variation (triangle L-ch) and threshold voltage shift (triangle V-th). Also, it is a simple and effective model of predicting reliable circuit operation and standby power consumption.N

Functional imaging of hemodynamic stimulus response in the rat retina with ultrahigh-speed spectral / Fourier domain OCT

Measuring retinal hemodynamics in response to flicker stimulus is important for investigating pathophysiology in small animal models of diabetic retinopathy, because a reduction in the hyperemic response is thought to be one of the earliest changes in diabetic retinopathy. In this study, we investigated functional imaging of retinal hemodynamics in response to flicker stimulus in the rat retina using an ultrahigh speed spectral / Fourier domain OCT system at 840nm with an axial scan rate of 244kHz. At 244kHz the nominal axial velocity range that could be measured without phase wrapping was +/-37.7mm/s. Pulsatile total retinal arterial blood flow as a function of time was measured using an en face Doppler approach where a 200μm × 200μm area centered at the central retinal artery was repeatedly raster scanned at a volume acquisition rate of 55Hz. Three-dimensional capillary imaging was performed using speckle decorrelation which has minimal angle dependency compared to other angiography techniques based on OCT phase information. During OCT imaging, a flicker stimulus could be applied to the retina synchronously by inserting a dichroic mirror in the imaging interface. An acute transient increase in total retinal blood flow could be detected. At the capillary level, an increase in the degree of speckle decorrelation in capillary OCT angiography images could also be observed, which indicates an increase in the velocity of blood at the capillary level. This method promises to be useful for the investigation of small animal models of ocular diseases. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.United States. Air Force Office of Scientific Research (AFOSR FA9550-10-1-0551)National Institutes of Health (U.S.) (NIH R01-EY011289-26)National Institutes of Health (U.S.) (NIH R01-EY013516-09)National Institutes of Health (U.S.) (NIH R01-EY019029-04)National Institutes of Health (U.S.) (NIH R01-EY013178-12)National Institutes of Health (U.S.) (NIH R01-NS057476-05)National Institutes of Health (U.S.) (NIH R01-HL095717-04)National Institutes of Health (U.S.) (NIH R01-CA075289-15)National Institutes of Health (U.S.) (NIH R44-EY022864-01)Samsung Scholarship Foundatio