Scott Barry

Ultrahigh speed 1050nm swept source / Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second

We demonstrate ultrahigh speed swept source/Fourier domain ophthalmic OCT imaging using a short cavity swept laser at 100,000 - 400,000 axial scan rates. Several design configurations illustrate tradeoffs in imaging speed, sensitivity, axial resolution, and imaging depth. Variable rate A/D optical clocking is used to acquire linear-in-k OCT fringe data at 100 kHz axial scan rate with 5.3 um axial resolution in tissue. Fixed rate sampling at 1 GSPS achieves a 7.5mm imaging range in tissue with 6.0 um axial resolution at 100 kHz axial scan rate. A 200 kHz axial scan rate with 5.3 um axial resolution over 4mm imaging range is achieved by buffering the laser sweep. Dual spot OCT using two parallel interferometers achieves 400 kHz axial scan rate, almost 2X faster than previous 1050 nm ophthalmic results and 20X faster than current commercial instruments. Superior sensitivity roll-off performance is shown. Imaging is demonstrated in the human retina and anterior segment. Wide field 12x12 mm data sets include the macula and optic nerve head. Small area, high density imaging shows individual cone photoreceptors. The 7.5 mm imaging range configuration can show the cornea, iris, and anterior lens in a single image. These improvements in imaging speed and depth range provide important advantages for ophthalmic imaging. The ability to rapidly acquire 3D-OCT data over a wide field of view promises to simplify examination protocols. The ability to image fine structures can provide detailed information on focal pathologies. The large imaging range and improved image penetration at 1050 m wavelengths promises to improve performance for instrumentation which images both the retina and anterior eye. These advantages suggest that swept source OCT at 1050 nm wavelengths will play an important role in future ophthalmic instrumentation.

Rapid volumetric angiography of cortical microvasculature with optical coherence tomography

We describe methods and algorithms for rapid volumetric imaging of cortical vasculature with optical coherence tomography (OCT). By optimizing system design, scanning protocols, and algorithms for visualization of capillary flow, comprehensive imaging of the surface pial vasculature and capillary bed is performed in approximately 12 s. By imaging during hypercapnia and comparing with simultaneous CCD imaging, the sources of contrast of OCT angiography are investigated.

Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast

In vivo optical microscopic imaging techniques have recently emerged as important tools for the study of neurobiological development and pathophysiology. In particular, two-photon microscopy has proved to be a robust and highly flexible method for in vivo imaging in highly scattering tissue. However, two-photon imaging typically requires extrinsic dyes or contrast agents, and imaging depths are limited to a few hundred microns. Here we demonstrate Optical Coherence Microscopy (OCM) for in vivo imaging of neuronal cell bodies and cortical myelination up to depths of ~1.3 mm in the rat neocortex. Imaging does not require the administration of exogenous dyes or contrast agents, and is achieved through intrinsic scattering contrast and image processing alone. Furthermore, using OCM we demonstrate in vivo, quantitative measurements of optical properties (index of refraction and attenuation coefficient) in the cortex, and correlate these properties with laminar cellular architecture determined from the images. Lastly, we show that OCM enables direct visualization of cellular changes during cell depolarization and may therefore provide novel optical markers of cell viability.

OCT methods for capillary velocimetry

To date, two main categories of OCT techniques have been described for imaging hemodynamics: Doppler OCT and OCT angiography. Doppler OCT can measure axial velocity profiles and flow in arteries and veins, while OCT angiography can determine vascular morphology, tone, and presence or absence of red blood cell (RBC) perfusion. However, neither method can quantify RBC velocity in capillaries, where RBC flow is typically transverse to the probe beam and single-file. Here, we describe new methods that potentially address these limitations. Firstly, we describe a complex-valued OCT signal in terms of a static scattering component, dynamic scattering component, and noise. Secondly, we propose that the time scale of random fluctuations in the dynamic scattering component are related to red blood cell velocity. Analysis was performed along the slow axis of repeated B-scans to parallelize measurements. We correlate our purported velocity measurements against two-photon microscopy measurements of RBC velocity, and investigate changes during hypercapnia. Finally, we image the ischemic stroke penumbra during distal middle cerebral artery occlusion (dMCAO), where OCT velocimetry methods provide additional insight that is not afforded by either Doppler OCT or OCT angiography.

Optical coherence tomography for the quantitative study of cerebrovascular physiology

Doppler optical coherence tomography (DOCT) and OCT angiography are novel methods to investigate cerebrovascular physiology. In the rodent cortex, DOCT flow displays features characteristic of cerebral blood flow, including conservation along nonbranching vascular segments and at branch points. Moreover, DOCT flow values correlate with hydrogen clearance flow values when both are measured simultaneously. These data validate DOCT as a noninvasive quantitative method to measure tissue perfusion over a physiologic range.

Comparison of three-dimensional optical coherence tomography and high resolution photography for art conservation studies

Gold punchwork and underdrawing in Renaissance panel paintings are analyzed using both three-dimensional swept source / Fourier domain optical coherence tomography (3D-OCT) and high resolution digital photography. 3D-OCT can generate en face images with micrometer-scale resolutions at arbitrary sectioning depths, rejecting out-of-plane light by coherence gating. Therefore 3D-OCT is well suited for analyzing artwork where a surface layer obscures details of interest. 3D-OCT also enables cross-sectional imaging and quantitative measurement of 3D features such as punch depth, which is beneficial for analyzing the tools and techniques used to create works of art. High volumetric imaging speeds are enabled by the use of a Fourier domain mode locked (FDML) laser as the 3D-OCT light source. High resolution infrared (IR) digital photography is shown to be particularly useful for the analysis of underdrawing, where the materials used for the underdrawing and paint layers have significantly different IR absrption properties. In general, 3D-OCT provides a more flexible and comprehensive analysis of artwork than high resolution photography, but also requires more complex instrumentation and data analysis.

High-resolution optical coherence tomography imaging of the living kidney

Optical coherence tomography (OCT) is a rapidly emerging imaging modality that can provide non-invasive, cross-sectional, high-resolution images of tissue morphology in situ and in real-time. In the present series of studies, we used a high-speed OCT imaging system equipped with a frequency-swept laser light source (1.3 μm wavelength) to study living kidneys in situ. Adult, male Munich–Wistar rats were anesthetized, a laparotomy was performed and the living kidneys were exposed for in situ observation. We observed the kidneys prior to, during and following exposure to renal ischemia induced by clamping the renal artery. The effects of intravenous mannitol infusion (1.0 ml of 25%) prior to and during renal ischemia were also studied. Finally, living kidneys were flushed with a renal preservation solution, excised and observed while being stored at 0–4°C. Three-dimensional OCT data sets enabled visualization of the morphology of the uriniferous tubules and the renal corpuscles. When renal ischemia was induced, OCT revealed dramatic shrinkage of tubular lumens due to swelling of the lining epithelium. Three-dimensional visualization and volumetric rendering software provided an accurate evaluation of volumetric changes in tubular lumens in response to renal ischemia. Observations of kidneys flushed with a renal preservation solution and stored at 0–4°C also revealed progressive and significant loss of tubular integrity over time. Intravenous infusion of mannitol solution resulted in thinning of the tubular walls and an increase in the tubular lumen diameters. Mannitol infusion also prevented the cell swelling that otherwise resulted in shrinkage of proximal tubule lumens during ischemia. We conclude that OCT represents an exciting new approach to visualize, in real-time, pathological changes in the living kidney in a non-invasive fashion. Possible clinical applications are discussed.

Modeling and control of a fast steering mirror in imaging applications

Fast steering mirrors are used in many optical system applications, ranging from image tracking and scanning, to laser material processing, to jitter stabilization in optical communication. This paper presents a systematic approach to the modeling and feedback control design for a high performance fast steering mirror used for image scanning in a microscope. The overall approach consists of 1. definition of relevant image-based metric, 2. model identification, 3. simulation based controller optimization, and 4. experimental validation. The imaging application means that the performance metric is driven by the image quality rather than angular sensor output settling time. An output variance metric is shown to effectively capture the image quality and can be used in simulation for controller tuning. For controller development, a two-input/two-output mirror model is identified based on the small-input frequency response. In addition, amplifier nonlinearity and sensor and actuator noise models are also identified to ensure the overall model reflects the physical reality sufficiently closely to allow simulation-based controller optimization. Both Linear-Quadratic-Gaussian and Proportional-Integral-Derivative controller structures are considered. The controller parameters are tuned based on the simulated response and implemented in the experimental testbed to show the effectiveness of the proposed method.

Ultrahigh speed volumetric ophthalmic OCT imaging at 850nm and 1050nm

The performance and imaging characteristics of ultrahigh speed ophthalmic optical coherence tomography (OCT) are investigated. In vivo imaging results are obtained at 850nm and 1050nm using different configurations of spectral and swept source / Fourier domain OCT. A spectral / Fourier domain instrument using a high speed CMOS linescan camera with SLD light source centered at 850nm achieves speeds of ~91,000 axial scans per second with ~3μm axial resolution in tissue. A spectral / Fourier domain instrument using an InGaAs linescan camera with SLD light source centered at 1050nm achieves ~47,000 axial scans per second with ~7μm resolution in tissue. A swept source instrument using a novel wavelength swept laser light source centered at 1050nm achieves 100,000 axial scans per second. Retinal diseases seen in the clinical setting are imaged using the 91kHz 850nm CMOS camera and 47kHz 1050nm InGaAs camera based instruments to investigate the combined effects of varying speed, axial resolution, center wavelength, and instrument sensitivity on image quality. The novel 1050nm swept source / Fourier domain instrument using a recently developed commercially available short cavity laser source images at 100,000 axial scans per second and is demonstrated in the normal retina. The dense 3D volumetric data sets obtained with ultrahigh speed OCT promise to improve reproducibility of quantitative measurements, enabling early diagnosis as well as more sensitive assessment of disease progression and response to therapy.