[show abstract][hide abstract] ABSTRACT: We demonstrate for the first time that optical coherence tomography (OCT) imaging can reliably distinguish between morphologic features of low risk pancreatic cysts (i.e., pseudocysts and serous cystadenomas) and high risk pancreatic cysts (i.e., mucinous cystic neoplasms and intraductal papillary mucinous neoplasms). In our study fresh pancreatectomy specimens (66) from patients with cystic lesions undergoing surgery were acquired and examined with OCT. A training set of 20 pathology-OCT correlated tissue specimens were used to develop criteria for differentiating between low and high risk cystic lesions. A separate (validation) set of 46 specimens were used to test the OCT criteria by three clinicians, blinded to histopathology findings. Histology was finally used as a 'gold' standard for testing OCT findings. OCT was able to reveal specific morphologic features of pancreatic cysts and thus to differentiate between low-risk and high-risk cysts with over 95% sensitivity and specificity. This pilot study suggests that OCT could be used by clinicians in the future to more reliably differentiate between benign and potentially malignant pancreatic cysts. However, in vivo use of OCT requires a probe that has to fit the bore of the pancreas biopsy needle. Therefore, we have developed such probes and planned to start an in vivo pilot study within the very near future.
[show abstract][hide abstract] ABSTRACT: A novel technology and instrumentation for fine needle aspiration (FNA) breast biopsy guidance is presented. This technology is based on spectral-domain low coherence interferometry (SD-LCI). The method, apparatus, and preliminary in vitro/in vivo results proving the viability of the method and apparatus are presented in detail. An advanced tissue classification algorithm, preliminarily tested on breast tissue specimens and a mouse model of breast cancer is presented as well. Over 80% sensitivity and specificity in differentiating all tissue types and 93% accuracy in differentiating fatty tissue from fibrous or tumor tissue was obtained with this technology and apparatus. These results suggest that SD-LCI could help for more precise needle placement during the FNA biopsy and therefore could substantially reduce the number of the nondiagnostic aspirates and improve the sensitivity and specificity of the FNA procedures.
The Review of scientific instruments 03/2009; 80(2):024302. · 1.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Real-time display of processed Fourier domain optical coherence tomography (FDOCT) images is important for applications that require instant feedback of image information, for example, systems developed for rapid screening or image-guided surgery. However, the computational requirements for high-speed FDOCT image processing usually exceeds the capabilities of most computers and therefore display rates rarely match acquisition rates for most devices. We have designed and developed an image processing system, including hardware based upon a field programmable gated array, firmware, and software that enables real-time display of processed images at rapid line rates. The system was designed to be extremely flexible and inserted in-line between any FDOCT detector and any Camera Link frame grabber. Two versions were developed for spectrometer-based and swept source-based FDOCT systems, the latter having an additional custom high-speed digitizer on the front end but using all the capabilities and features of the former. The system was tested in humans and monkeys using an adaptive optics retinal imager, in zebrafish using a dual-beam Doppler instrument, and in human tissue using a swept source microscope. A display frame rate of 27 fps for fully processed FDOCT images (1024 axial pixels x 512 lateral A-scans) was achieved in the spectrometer-based systems.
The Review of scientific instruments 12/2008; 79(11):114301. · 1.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: To describe the fine structure of the fovea in subjects with a history of mild retinopathy of prematurity (ROP) using adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT).
High-speed, high-resolution AO-FDOCT videos were recorded in subjects with a history of ROP (n = 5; age range, 14-26 years) and in control subjects (n = 5; age range, 18-25 years). Custom software was used to extract foveal pit depth and volume from three-dimensional (3-D) retinal maps. The thickness of retinal layers as a function of retinal eccentricity was measured manually. The retinal vasculature in the parafoveal region was assessed.
The foveal pit was wider and shallower in ROP than in control subjects. Mean pit depth, defined from the base to the level at which the pit reaches a lateral radius of 728 microm, was 121 microm compared with 53 microm. Intact, contiguous inner retinal layers overlay the fovea in ROP subjects but were absent in the control subjects. Mean full retinal thickness at the fovea was greater in the subjects with ROP (279.0 microm vs. 190.2 microm). The photoreceptor layer thickness did not differ between ROP and control subjects. An avascular zone was not identified in the subjects with ROP but was present in all the control subjects.
The foveas of subjects with a history of mild ROP have significant structural abnormalities that are probably a consequence of perturbations of neurovascular development.
[show abstract][hide abstract] ABSTRACT: We have developed a compact, multimodal instrument for simultaneous acquisition of en face quasi-confocal fundus images and adaptive-optics (AO) spectral-domain optical coherence tomography (SDOCT) cross-sectional images. The optical system including all AO and SDOCT components occupies a 60x60 cm breadboard that can be readily transported for clinical applications. The AO component combines a Hartmann-Shack wavefront sensor and a microelectromechanical systems-based deformable mirror to sense and correct ocular aberrations at 15 Hz with a maximum stroke of 4 microm. A broadband superluminescent diode source provides 4 mum depth resolution for SDOCT imaging. In human volunteer testing, we observed up to an 8 dB increase in OCT signal and a corresponding lateral resolution of <10 microm as a result of AO correction.
Journal of the Optical Society of America A 06/2007; 24(5):1327-36. · 1.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Spectral domain optical coherence tomography (SDOCT) is a relatively new imaging technique that allows high-speed cross-sectional scanning of retinal structures with little motion artifact. However, instrumentation for these systems is not yet fast enough to collect high-density three-dimensional retinal maps free of the adverse effects of lateral eye movements. Low coherence interferometry instruments must also contend with axial motion primarily from head movements that shift the target tissue out of the coherence detection range. Traditional SDOCT instruments suffer from inherent deficiencies that exacerbate the effect of depth motion, including limited range, depth-dependent signal attenuation, and complex conjugate overlap. We present initial results on extension of our transverse retinal tracking system to three-dimensions especially for SDOCT imagers. The design and principle of operation of two depth tracking techniques, adaptive ranging (AR) and Doppler velocity (DV) tracking, are presented. We have integrated the threedimensional tracking hardware into a hybrid line scanning laser ophthalmoscope (LSLO)/SDOCT imaging system. Imaging and tracking performance was characterized by tests involving a limited number of human subjects. The hybrid imager could switch between wide-field en-face confocal LSLO images, high-resolution cross-sectional OCT images, and an interleaved mode of sequential LSLO and OCT images. With 3-D tracking, the RMS error for axial motion decreased to
[show abstract][hide abstract] ABSTRACT: Adaptive optics (AO) is used to correct ocular aberrations primarily in the cornea, lens, and tear film of every eye. Among other applications, AO allows high lateral resolution images to be acquired with scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). Spectral domain optical coherence tomography (SDOCT) is a high-speed imaging technique that can acquire cross-sectional scans with micron-scale axial resolution at tens to hundreds of kHz line rates. We present a compact clinical AO-SDOCT system that achieves micron-scale axial and lateral resolution of retinal structures. The system includes a line scanning laser ophthalmscope (LSLO) for simultaneous wide-field retinal viewing and selection of regions-of-interest. OCT and LSLO imaging and AO correction performance are characterized. We present a case study of a single subject with hyper-reflective lesions associated with stable, resolved central serous retinopathy to compare and contrast AO as applied to scanning laser ophthalmoscopy and optical coherence tomography. The two imaging modes are found to be complementary in terms of information on structure morphology. Both provide additional information lacking in the other. This preliminary finding points to the power of combining SLO and SDOCT in a single research instrument for exploration of disease mechanisms, retinal cellular architecture, and visual psychophysics.
[show abstract][hide abstract] ABSTRACT: In this paper we demonstrate the integration of two technologies, Line-Scanning Laser Ophthalmoscopy (LSLO) and Spectral Domain Optical Coherence Tomography (SDOCT) into a single compact instrument that shares the same imaging optics and line scan camera for both LSLO and OCT imaging. Co-registered high contrast wide-field en face retinal LSLO and SDOCT images are obtained non-mydriatically with less than 600 microwatts of broadband illumination at 15 frames/sec. The hybrid instrument can work in three different modes: LSLO mode, SDOCT mode, and LSLO/SDOCT interleaved mode. This instrument could be useful in clinical ophthalmic diagnostics and emergency medicine.
[show abstract][hide abstract] ABSTRACT: We demonstrate for the first time the integration of two technologies, Spectral Domain Optical Coherence Tomography (SDOCT) and Line-Scanning Laser Ophthalmoscopy (LSLO) into a single compact instrument that shares the same imaging optics and line scan camera for both OCT and LSLO imaging. Co-registered high contrast wide-field en face retinal LSLO and SDOCT images are obtained non-mydriatically with less than 600 microwatts of broadband illumination at 15 frames/sec. The LSLO/SDOCT hybrid instrument could have important applications in clinical ophthalmic diagnostics and emergency medicine.
[show abstract][hide abstract] ABSTRACT: We demonstrate in vivo measurements in human retinal vessels of an experimental parameter, the slope of the low coherence interferometry (LCI) depth reflectivity profile, which strongly correlates with the real value of blood hematocrit. A novel instrument that combines two technologies, spectral domain low coherence interferometry (SDLCI) and retinal tracking, has been developed and used for these measurements. Retinal tracking allows a light beam to be stabilized on retinal vessels, while SDLCI is used for obtaining depth-reflectivity profiles within the investigated vessel. SDLCI backscatter extinction rates are obtained from the initial slope of the A-scan profile within the vessel lumen. The differences in the slopes of the depth reflectivity profiles for different subjects are interpreted as the difference in the scattering coefficient, which is correlated with the number density of red blood cells (RBC) in blood. With proper calibration, it is possible to determine hematocrit in retinal vessels. Ex vivo measurements at various RBC concentrations were performed to calibrate the instrument. Preliminary measurements on several healthy volunteers show estimated hematocrit values within the normal clinical range.
[show abstract][hide abstract] ABSTRACT: A retinal imaging instrument that integrates adaptive optics (AO), scanning laser ophthalmoscopy (SLO), and retinal tracking components was built and tested. The system uses a Hartmann-Shack wave-front sensor (HS-WS) and MEMS-based deformable mirror (DM) for AO-correction of high-resolution, confocal SLO images. The system includes a wide-field line-scanning laser ophthalmoscope for easy orientation of the high-magnification SLO raster. The AO system corrected ocular aberrations to <0.1 mum RMS wave-front error. An active retinal tracking with custom processing board sensed and corrected eye motion with a bandwidth exceeding 1 kHz. We demonstrate tracking accuracy down to 6 mum RMS for some subjects (typically performance: 10-15 mum RMS). The system has the potential to become an important tool to clinicians and researchers for vision studies and the early detection and treatment of retinal diseases.
[show abstract][hide abstract] ABSTRACT: Precise targeting of retinal structures including retinal pigment epithelial cells, feeder vessels, ganglion cells, photoreceptors, and other cells important for light transduction may enable earlier disease intervention with laser therapies and advanced methods for vision studies. A novel imaging system based upon scanning laser ophthalmoscopy (SLO) with adaptive optics (AO) and active image stabilization was designed, developed, and tested in humans and animals. An additional port allows delivery of aberration-corrected therapeutic/stimulus laser sources. The system design includes simultaneous presentation of non-AO, wide-field (approx. 40 deg) and AO, high-magnification (1-2 deg) retinal scans easily positioned anywhere on the retina in a drag-and-drop manner. The AO optical design achieves an error of <0.45 waves (at 800 nm) over +/- 6 deg on the retina. A MEMS-based deformable mirror (Boston Micromachines Inc.) is used for wave-front correction. The third generation retinal tracking system achieves a bandwidth of greater than 1 kHz allowing acquisition of stabilized AO images with an accuracy of approx. 10 micron. Normal adult human volunteers and animals with previously-placed lesions (cynomolgus monkeys) were tested to optimize the tracking instrumentation and to characterize AO imaging performance. Ultrafast laser pulses were delivered to monkeys to characterize the ability to precisely place lesions and stimulus beams. Other advanced features such as real-time image averaging, automatic high resolution mosaic generation, and automatic blink detection and tracking re-lock were also tested. The system has the potential to become an important tool to clinicians and researchers for early detection and treatment of retinal diseases.
[show abstract][hide abstract] ABSTRACT: Scanning laser ophthalmoscopy (SLO) is a powerful imaging tool with specialized applications limited to research and ophthalmology clinics due in part to instrument size, cost, and complexity. Conversely, low-cost retinal imaging devices have limited capabilities in screening, detection, and diagnosis of diseases. To fill the niche between these two, a hand-held, nonmydriatic line-scanning laser ophthalmoscope (LSLO) is designed, constructed, and tested on normal human subjects. The LSLO has only one moving part and uses a novel optical approach to produce wide-field confocal fundus images. Imaging modes include multiwavelength illumination and live stereoscopic imaging with a split aperture. Image processing and display functions are controlled with two stacked prototype compact printed circuit boards. With near shot-noise limited performance, the digital LSLO camera requires low illumination power (<500 microW) at near-infrared wavelengths. The line-scanning principle of operation is examined in comparison to SLO and other imaging modes. The line-scanning approach produces high-contrast confocal images with nearly the same performance as a flying-spot SLO. The LSLO may significantly enhance SLO utility for routine use by ophthalmologists, optometrists, general practitioners, and also emergency medical personnel and technicians in the field for retinal disease detection and other diverse applications.
Journal of Biomedical Optics 01/2006; 11(4):041126. · 2.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: An upgraded optical coherence tomography system with integrated retinal tracker (TOCT) was developed. The upgraded system uses improved components to extend the tracking bandwidth, fully integrates the tracking hardware into the optical head of the clinical OCT system, and operates from a single software platform. The system was able to achieve transverse scan registration with sub-pixel accuracy (~10 microm). We demonstrate several advanced scan sequences with the TOCT, including composite scans averaged (co-added) from multiple B-scans taken consecutively and several hours apart, en face images collected by summing the A-scans of circular, line, and raster scans, and three-dimensional (3D) retinal maps of the fovea and optic disc. The new system achieves highly accurate OCT scan registration yielding composite images with significantly improved spatial resolution, increased signal-to-noise ratio, and reduced speckle while maintaining well-defined boundaries and sharp fine structure compared to single scans. Precise re-registration of multiple scans over separate imaging sessions demonstrates TOCT utility for longitudinal studies. En face images and 3D data cubes generated from these data reveal high fidelity image registration with tracking, despite scan durations of more than one minute.
[show abstract][hide abstract] ABSTRACT: We have designed, developed, and tested a three-dimensional tracking and imaging system that uses a novel optical layout to acquire both en-face confocal images by scanning laser imaging (e.g. scanning laser ophthalmoscopy, SLO) and high-resolution depth sections by optical coherence tomography (OCT). The present application for this system is retinal imaging. The instrument is capable of sequentially collecting OCT and SLO images with the simple articulation of an optic affixed to a flip-mount. In addition, we have extended our mature transverse tracking system for full three-dimensional motion stabilization. The tracking component employs an innovative optical and electronic design that encodes transverse and depth tracking information on a single beam. We have demonstrated en face SLO imaging with a resolution of ~25 µm and depth-resolved OCT imaging with a resolution of ~10 µm. On artificial targets, transverse tracking was robust up to 1 m/s with a bandwidth of ~1 kHz and depth tracking was robust up to a velocity of ~15 cm/sec, a range of ~1 mm, and a bandwidth of a few hundred Hz. The details of the instrument, including optical and electronic design, are discussed. The system has the potential to provide clinicians and researchers with a wide variety of diagnostic information for the early detection and treatment of retinal diseases.
[show abstract][hide abstract] ABSTRACT: Scanning laser ophthalmoscopy is a powerful research tool with specialized but, to date, limited use in ophthalmic clinics due in part to the size, cost, and complexity of instruments. Conversely, low-cost retinal imaging devices have limited capabilities in screening, detection, and diagnosis of diseases. To fill the niche between these two, a low-cost, hand-held, line-scanning laser ophthalmoscope (LSLO) was designed, constructed, and tested on normal human subjects. The LSLO has only one moving part, multiple imaging modes, and uses low-cost but highly sensitive complimentary metal oxide semiconductor (CMOS) linear arrays for imaging with a detector dynamic range of 12-bits. The line-scanning approach produces high contrast quasi-confocal images with nearly the same performance as a flying-spot SLO. Imaging modes include simultaneous dual wavelength illumination and live stereoscopic imaging with a split aperture. Image processing and display functions are controlled with two stacked prototype compact printed circuit boards using field-programmable gated arrays (FPGA) and other digital electronic elements. With near shot-noise limited performance, the digital LSLO camera requires low illumination power (~ 100 muW) at near-infrared wavelengths. Wide field fundus images with several imaging modes have been obtained from several human subjects. The LSLO will significantly enhance confocal scanning laser ophthalmoscopy for routine use by ophthalmologist, optometrists, general practitioners and also non-specialized emergency medical personnel and technicians in the field for retinal disease detection and other diverse applications.