We have developed a multispectral imaging technique for identifying chemical compounds in vivo in the retina with cellular-level resolution and without the use of contrast agents. We combined simultaneous multi-channels offset and confocal AO-SLO imaging, which provides isotropic images of retinal microstructures free of directionality artifacts, with spectral signature analysis of chemical compounds to identify such biomarkers at cellular-level. The new concept has been demonstrated in a model eye using commercially available Aβ. An animal study on a mouse Alzheimer’s model is ongoing. This technique may pave a path forward for better understanding of the onset of various neurodegenerative diseases.
Simultaneous dual-channel offset imaging provides isotropic images of retinal microstructures that enable phase imaging in the living eye with enhanced visualization contrast. Phase imaging is widely used in microscopy and biomedical imaging to reveal structures not visible in standard imaging due to their low scattering properties. We implement the technique in a line-scanning approach using a high-speed 2D camera to visualize microstructures in the living eye with enhanced contrast, that were only visible with other modalities, such as flying-spot scanning laser ophthalmoscopy (SLO). A simplified phase imaging system has the potential to be quantitative, with diagnostic value for retinal diseases, and may enable monitoring treatment. Methods for super-resolution reconstruction were explored to break the diffraction limit. SLO phase imaging exploits forward-scatter through phase objects in the retina and subsequent reflection (rescatter) of intensity-encoded diffuse reflections for detection; line-scan ophthalmoscopy (LSO) phase imaging works in the opposite way, in which the offset line-beam produces oblique back-illumination enabling the diffractive/refractive effects of phase objects in the inner retina to be imaged in transmission. The former scrambles optical phase information, the latter preserves it. This design has several advantages over conventional SLOs: 1) the LSO has a reduced number of optical elements, which results in a short optical path and compact design, 2) only one moving part, thus hardware and electronics are simplified, and 3) the LSO is inherently safer because the beam is focused in only one dimension on the retina.
Simultaneous multi-channels offset imaging provides isotropic images of retinal microstructures free of directionality artifacts and enables phase imaging in the living eye with enhanced visualization contrast. Phase imaging is widely used in microscopy and biomedical imaging to reveal structures not visible in standard imaging due to their low scattering properties. We introduce the technique in high-resolution retinal imaging to visualize microstructures in the living eye with enhanced contrast, that were not visible with other modalities, and without adding contrast agents. Phase imaging has the potential to be quantitative, may have diagnostic value for retinal diseases, and may enable monitoring treatment.
We developed a novel ophthalmic imaging platform that combines non-invasive measurements of retina/choroid structure and ocular blood flow based on optical coherence tomography (OCT) and wide-field semi-quantitative global flow visualization using line-scanning Doppler flowmetry (LSDF). The combination of these two imaging modalities within the same imaging platform enables comprehensive assessment of blood flow in retina and choroid and provides efficient characterization of blood flow in hemodynamic studies both in human volunteers and in small animals. The platform enables visualization of the entire posterior hemisphere vasculature, including vortex veins, using only light and without additional contrast agent in humans and rats.
A new detection scheme was developed for simultaneous multi-channel imaging that provides isotropic images of retinal structures, free of directionality artifacts. The arrangement consists of light collecting fibers that act as offset apertures. This fiber bundle configuration can be used to retrofit basically any existing AO-SLO platform. The channels can be combined to reveal additional structural and functional details and this kind of retinal imaging with cellular resolution is a valuable new tool for researchers and clinicians.
The use of a Prosthetic Replacement of the Ocular Surface Environment (PROSE) device is a revolutionary treatment for military patients that have lost their eyelids due to 3rd degree facial burns and for civilians who suffer from a host of corneal diseases. However, custom manual fitting is often a protracted painful, inexact process that requires multiple fitting sessions. Training for new practitioners is a long process. Automated methods to measure the complete corneal and scleral topology would provide a valuable tool for both clinicians and PROSE device manufacturers and would help streamline the fitting process.
PSI has developed an ocular anterior-segment profiler based on Optical Coherence Tomography (OCT), which provides a 3D measure of the surface of the sclera and cornea. This device will provide topography data that will be used to expedite and improve the fabrication process for PROSE devices. OCT has been used to image portions of the cornea and sclera and to measure surface topology for smaller contact lenses [1-3]. However, current state-of-the-art anterior eye OCT systems can only scan about 16 mm of the eye’s anterior surface, which is not sufficient for covering the sclera around the cornea. In addition, there is no systematic method for scanning and aligning/stitching the full scleral/corneal surface and commercial segmentation software is not optimized for the PROSE application.
Although preliminary, our results demonstrate the capability of PSI’s approach to generate accurate surface plots over relatively large areas of the eye, which is not currently possible with any other existing platform. Testing the technology on human volunteers is currently underway at Boston Foundation for Sight.
AO has achieved success in a range of applications in ophthalmology where microstructures need to be identified,
counted, and mapped. Multiple images are averaged to improve the SNR or analyzed for temporal dynamics. For small
patches, image registration by cross-correlation is straightforward. Larger images require more sophisticated registration
techniques. Strip-based registration has been used successfully for photoreceptor mosaic alignment in small patches;
however, if the deformations along long strips are not simple displacements, averaging will actually degrade the images.
We have applied non-rigid registration that significantly improves the quality of processed images for mapping cones
and rods, and microvasculature in dark-field imaging. Local grid deformations account for local image stretching and
compression due to a number of causes. Individual blood cells can be traced along capillaries in high-speed imaging
(130 fps) and flow dynamics can be analyzed.
We present portable preclinical low-coherence interference (LCI) instrumentation for aiding fine needle aspiration biopsies featuring the second-generation LCI-based biopsy probe and an improved scoring algorithm for tissue differentiation. Our instrument and algorithm were tested on 38 mice with cultured tumor mass and we show the specificity, sensitivity, and positive predictive value of tumor detection of over 0.89, 0.88, and 0.96, respectively.
This study aimed to evaluate the concept of using high-resolution optical coherence tomography (OCT) imaging to rapidly assess surgical specimens and determine if cancer positive margins were left behind in the surgical bed. A mouse model of breast cancer was used in this study. Surgical specimens from 30 animals were investigated with OCT and automated interpretation of the OCT images was performed and tested against histopathology findings. Specimens from 10 animals were used to build a training set of OCT images, while the remaining 20 specimens were used for a validation set of images. The validation study showed that automated interpretation of OCT images can differentiate tissue types and detect cancer positive margins with at least 81% sensitivity and 89% specificity. The findings of this pilot study suggest that OCT imaging of surgical specimens and automated interpretation of OCT data may enable in the future real-time feedback to the surgeon about margin status in patients with breast cancer, and potentially with other types of cancers. Currently, such feedback is not provided and if positive margins are left behind, patients have to undergo another surgical procedure. Therefore, this approach can have a potentially high impact on breast surgery outcome.
The performance of clinical confocal SLO and OCT imagers is limited by ocular aberrations. Adaptive optics (AO)
addresses this problem, but most research systems are large, complex, and less well suited to the clinical environment.
PSI's recently developed compact retinal imager is designed for rapid, automated generation of cone photoreceptor
density maps. The device has a compact foot-print suitable for clinical deployment. The system previously presented at
Photonics West and ARVO 2013 has been upgraded to include numerous new features that support clinical research
applications. These upgrades significantly enhance the capabilities of the imager, providing the clinician with
simultaneously-acquired (registered) en face photoreceptor images and AO-OCT retinal cross-sections.
A multifunctional line scanning ophthalmoscope (mLSO) was designed, constructed, and tested on human subjects. The mLSO could sequentially acquire wide-field, confocal, near-infrared reflectance, fluorescein angiography (FA), and indocyanine green angiography (ICGA) retinal images. The system also included a retinal tracker (RT) and a photodynamic therapy laser treatment port. The mLSO was tested in a pilot clinical study on human subjects with and without retinal disease. The instrument exhibited robust retinal tracking and high-contrast line scanning imaging. The FA and ICGA angiograms showed a similar appearance of hyper- and hypo-pigmented disease features and a nearly equivalent resolution of fine capillaries compared to a commercial flood-illumination fundus imager. An mLSO-based platform will enable researchers and clinicians to image human and animal eyes with a variety of modalities and deliver therapeutic beams from a single automated interface. This approach has the potential to improve patient comfort and reduce imaging session times, allowing clinicians to better diagnose, plan, and conduct patient procedures with improved outcomes.
We recently developed several versions of a multimodal adaptive optics (AO) retinal imager, which includes highresolution
scanning laser ophthalmoscopy (SLO) and Fourier domain optical coherence tomography (FDOCT) imaging
channels as well as an auxiliary wide-field line scanning ophthalmoscope (LSO). Some versions have also been
equipped with a fluorescence channel and a retinal tracker. We describe the performance of three key features of the
multimodal AO system including: simultaneous SLO/OCT imaging, which allows SLO/OCT co-registration; a small
animal imaging port, which adjusts the beam diameter at the pupil from 7.5 to 2.5 mm for use with small animals
ubiquitous in biological research or for extended depth-of-focus imaging in humans; and slow scan Doppler flowmetry
imaging using the wide field auxiliary LSO imaging channel. The systems are currently deployed in several
ophthalmology clinics and research laboratories and several investigations have commenced on patients with a variety
of retinal diseases and animals in vision research.
Adaptive optics ophthalmic imaging systems that rely on a standalone wave-front sensor can be costly to build and
difficult for non-technical personnel to operate. As an alternative we present a simplified wavefront sensorless adaptive
optics laser scanning ophthalmoscope. This sensorless system is based on deterministic search algorithms that utilize the
image's spatial frequency as an optimization metric. We implement this algorithm on a NVIDIA video card to take
advantage of the graphics processing unit (GPU)'s parallel architecture to reduce algorithm computation times and
approach real-time correction.
Subretinal neovascular membranes (SRNM) are a deleterious complication of laser eye injury and retinal diseases such as age-related macular degeneration (AMD), choroiditis, and myopic retinopathy. Photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) drugs are approved treatment methods. PDT acts by selective dye accumulation, activation by laser light, and disruption and clotting of the new leaky vessels. However, PDT surgery is currently not image-guided, nor does it proceed in an efficient or automated manner. This may contribute to the high rate of re-treatment. We have developed a multimodal scanning laser ophthalmoscope (SLO) for automated diagnosis and image-guided treatment of SRNMs associated with AMD. The system combines line scanning laser ophthalmoscopy (LSLO), fluorescein angiography (FA), indocyanine green angiography (ICGA), PDT laser delivery, and retinal tracking in a compact, efficient platform. This paper describes the system hardware and software design, performance characterization, and automated patient imaging and treatment session procedures and algorithms. Also, we present initial imaging and tracking measurements on normal subjects and automated lesion demarcation and sizing analysis of previously acquired angiograms. Future pre-clinical testing includes line scanning angiography and PDT treatment of AMD subjects. The automated acquisition procedure, enhanced and expedited data post-processing, and innovative image visualization and interpretation tools provided by the multimodal retinal imager may eventually aid in the diagnosis, treatment, and prognosis of AMD and other retinal diseases.
Tunable Diode Laser Absorption Spectroscopy (TDLAS) has evolved over the past decade from a laboratory specialty to an accepted, robust, and reliable technology for trace gas sensing. Some applications include improving efficiency of gas leak detection surveying, monitoring and controlling trace gases in chemical and pharmaceutical processing, and monitoring emissions in energy production plants. The recent advent of lightweight battery-powered standoff TDLAS sensors is enabling novel applications for remote gas sensing and non-contact process monitoring. This paper provides an overview of these next-generation TDLAS tools.
In this paper we discuss vibrational to electronic energy transfer as a potential method for producing a population inversion in atomic iodine. We discuss the background of this approach and a novel, high-flux F atom source integrated into a small scale supersonic reactor. We present data for energy transfer from HF(v) and H2(v) to the I atom manifold. Using a sensitive diode laser diagnostic we have probed the ground state manifold atomic iodine and observed that the absorption on the I atom line could be reduced to an immeasureably low value. We also describe a novel, diode laser based imaging diagnostic that will have important applications in future chemical or electrical laser development.
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