Development of Swept Source Optical Coherence Tomography and Adaptive Optics Scanning Laser Ophthalmoscopy: Improved Imaging Speed and Handheld Applications

Optical coherence tomography (OCT) is a noninvasive three-dimensional interferometric imaging technique capable of achieving micrometer scale resolution. It is now a standard of care in ophthalmology, where it is used to improve the accuracy of early diagnosis, to better understand the source of pathophysiology, and to monitor disease progression and response to therapy. In particular, retinal imaging has been the most prevalent clinical application of OCT, but researchers and companies alike are developing OCT systems for cardiology, dermatology, dentistry, and many other medical and industrial applications.

Adaptive optics (AO) is a technique used to reduce monochromatic aberrations in optical instruments. It is used in astronomical telescopes, laser communications, high-power lasers, retinal imaging, optical fabrication and microscopy to improve system performance. Scanning laser ophthalmoscopy (SLO) is a noninvasive confocal imaging technique that produces high contrast two-dimensional retinal images. AO is combined with SLO (AOSLO) to compensate for the wavefront distortions caused by the optics of the eye, providing the ability to visualize the living retina with cellular resolution. AOSLO has shown great promise to advance the understanding of the etiology of retinal diseases on a cellular level.

Broadly, we endeavor to enhance the vision outcome of ophthalmic patients through improved diagnostics and personalized therapy. Toward this end, the objective of the work presented herein was the development of advanced techniques for increasing the imaging speed, reducing the form factor, and broadening the versatility of OCT and AOSLO. Despite our focus on applications in ophthalmology, the techniques developed could be applied to other medical and industrial applications. In this dissertation, a technique to quadruple the imaging speed of OCT was developed. This technique was demonstrated by imaging the retinas of healthy human subjects. A handheld, dual depth OCT system was developed. This system enabled sequential imaging of the anterior segment and retina of human eyes. Finally, handheld SLO/OCT systems were developed, culminating in the design of a handheld AOSLO system. This system has the potential to provide cellular level imaging of the human retina, resolving even the most densely packed foveal cones.

Guided Wave based Damage Detection in a Composite T-joint using 3D Scanning Laser Doppler Vibrometer

Composite T-joints are commonly used in modern composite airframe, pressure vessels and piping structures, mainly to increase the bending strength of the joint and prevents buckling of plates and shells, and in multi-cell thin-walled structures. Here we report a detailed study on the propagation of guided ultrasonic wave modes in a composite T-joint and their interactions with delamination in the co-cured co-bonded flange. A well designed guiding path is employed wherein the waves undergo a two step mode conversion process, one is due to the web and joint filler on the back face of the flange and the other is due to the delamination edges close to underneath the accessible surface of the flange. A 3D Laser Doppler Vibrometer is used to obtain the three components of surface displacements/velocities of the accessible face of the flange of the T-joint. The waves are launched by a piezo ceramic wafer bonded on to the back surface of the flange. What is novel in the proposed method is that the location of any change in material/geometric properties can be traced by computing a frequency domain power flow along a scan line. The scan line can be chosen over a grid either during scan or during post-processing of the scan data off-line. The proposed technique eliminates the necessity of baseline data and disassembly of structure for structural interrogation.

Guided-wave-based damage detection in a composite T-joint using 3D scanning laser Doppler vibrometer

Composite T-joints are commonly used in modern composite airframe, pressure vessels and piping structures, mainly to increase the bending strength of the joint and prevents buckling of plates and shells, and in multi-cell thin-walled structures. Here we report a detailed study on the propagation of guided ultrasonic wave modes in a composite T-joint and their interactions with delamination in the co-cured co-bonded flange. A well designed guiding path is employed wherein the waves undergo a two step mode conversion process, one is due to the web and joint filler on the back face of the flange and the other is due to the delamination edges close to underneath the accessible surface of the flange. A 3D Laser Doppler Vibrometer is used to obtain the three components of surface displacements/velocities of the accessible face of the flange of the T-joint. The waves are launched by a piezo ceramic wafer bonded on to the back surface of the flange. What is novel in the proposed method is that the location of any change in material/geometric properties can be traced by computing a frequency domain power flow along a scan line. The scan line can be chosen over a grid either during scan or during post-processing of the scan data off-line. The proposed technique eliminates the necessity of baseline data and disassembly of structure for structural interrogation.

Super-resolution scanning laser microscopy with a third-order optical nonlinear thin film

In a configuration of optical far-field scanning microscopy, super-resolution achieved by inserting a third-order optical nonlinear thin film is demonstrated and analyzed in terms of the frequency response function. Without the thin film the microscopy is diffraction limited; thus, subwavelength features cannot be resolved. With the nonlinear thin film inserted, the resolution is dramatically improved and thus the microscopy resolves features significantly smaller than the smallest spacing allowed by the diffraction limit. A theoretical model is established and the device is analyzed for the frequency response function. The results show that the frequency response function exceeds the cutoff spatial frequency of the microscopy defined by the laser wavelength and the numerical aperture of the convergent lens. The main contribution to the improvement of the cutoff spatial frequency is from the phase change induced by the complex transmission of the nonlinear thin film. Experimental results are presented and are shown to be consistent with the results of theoretical simulations.

Evaluation of leukocyte dynamic in mouse retinal circulation with scanning laser ophthalmoloscopy (Video report)

http://bjo.bmj.com/content/suppl/2001/06/20/85.7.DC1 Leukocyte-endothelial cell interactions play an important role in the pathogenesis of various types of retinal vascular diseases, including diabetes, uveitis, and ischemic lesions. Over the last few years, several methods have been devised in which the scanning laser ophthalmoscope (SLO) is used to study leukocyte-endothelial interactions in vivo [1,2]. Previously we reported a noninvasive in vivo leukocyte tracking method using the SLO in rat. In this method, a nontoxic fluorescent agent (6-carboxyfluorescein diacetate, CFDA) was used to label leukocytes in vitro. Leukocyte velocities within the retinal and choroidal circulations were be quantified simultaneously [3]. None of the previous methods has been developed for imaging the murine fundus, mainly due to problems arising from the small size of the mouse eye. However, there are many advantages of using a murine model to study retinal vascular diseases such as enhanced genetic definition, increased range of reagents available for immunological studies and cost reduction. We have developed our SLO method such that we can track leukocytes in the mouse retinal and choroidal circulations.

Reproducibility of fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope

Aim - To evaluate the reproducibility of the background fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope. Methods - 10 normal volunteers and 10 patients with retinal disease were included in the study. One eye per subject was chosen randomly. Five images of the same eye of each individual were obtained, after pupillary dilatation, by two investigators using a confocal scanning laser ophthalmoscope. Background fundus autofluorescence was measured at 7 degrees temporal to the fovea in normal volunteers and between 7 and 15 degrees temporal to the fovea in patients. Within session reproducibility of the measurements obtained by each investigator and interobserver reproducibility were evaluated. Results - For investigator 1 the median values of fundus autofluorescence obtained were 31.9 units for normal volunteers and 27.3 units for patients. The median largest difference in readings in normal volunteers was 5.7 units (range 1.4-13.5 units) and in patients 4.2 units (1.5-15.1 units). For investigator 2 the median values of fundus autofluorescence obtained were 28.9 units for normal volunteers and 27.4 units for patients. The median largest difference in readings in normal volunteers was 3.6 units (2.7-11.7 units), and in patients 4.1 units (1.5-9.3 units). The median interobserver difference in readings in normal volunteers was 3.3 units and for patients 6.6 units. The median greatest interobserver difference in measurements obtained for normal volunteers was 8.8 units (8.4-23.0 units) and for patients 11.1 units (7.1-40.8 units). Conclusion - Within session reproducibility of the measurements of background fundus autofluorescence was satisfactory. Although interobserver reproducibility was moderate, the variability of the measurements of fundus autofluorescence between observers appears to be small when compared with variation in fundus autofluorescence with age and disease.

The quality of reporting of diagnostic accuracy studies in glaucoma using scanning laser polarimetry

PURPOSE: Scanning laser polarimetry (SLP) has been proposed as a useful diagnostic test for glaucoma. This study was conducted to evaluate the quality of reporting of published studies using the SLP for diagnosing glaucoma. METHODS: A validated Medline and hand search of English-language articles reporting on measures of diagnostic accuracy of the SLP for glaucoma was performed. Two reviewers independently selected and appraised the manuscripts. The Standards for Reporting of Diagnostic Accuracy (STARD) checklist was used to evaluate the quality of each publication. RESULTS: A total of 47 papers were identified of which the first 10 (from 1997 to 2000) and the last 10 articles (from 2004 to 2005) were appraised. Interobserver rating agreement of STARD items was high (85.5% agreement, ?=0.796). The number of STARD items properly reported ranged from 3/25 to 19/25. Only a quarter of studies (5/20) explicitly reported more than half of the STARD items. Important aspects of the methodology were often missing such as participant sampling (reported in 40% of manuscripts), masking of the readers of the index test and reference standard (reported in 20% of manuscripts), and estimation of uncertainty (eg, 95% confidence intervals, reported in 25% of manuscripts). There was a slight increase in the number of STARD items reported with time. CONCLUSIONS: The quality of reporting of diagnostic accuracy tests for glaucoma with SLP is suboptimal. The STARD initiative may be a useful tool for appraising the strengths and weaknesses of diagnostic accuracy studies. © 2007 Lippincott Williams & Wilkins, Inc.

Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph

Objective: To detect and quantitate changes in optic nerve morphology after glaucoma surgery using the Heidelberg Retina Tomograph (HRT, Heidelberg Instruments, Heidelberg, Germany). Design: Nonconsecutive observational case series. Participants and Intervention: The authors prospectively enrolled 21 adult patients undergoing incisional glaucoma surgery for progressive glaucoma damage. Quantitative analysis of the optic nerve head by scanning laser tomography and automated perimetry were performed before and after glaucoma surgery. Main Outcome Measures: Changes in optic nerve parameters were subjected to linear regression analysis with respect to percent of postoperative reduction of intraocular pressure (IOP), as well as with respect to age, refraction, preoperative cup:disc ratio, and change in visual field parameters. Results: Seventeen patients had pre- and postoperative images suitable for analysis. Mean IOP at the time of image acquisition before surgery was 30.5 ± 12 mmHg, and after surgery 11.8 ± 5.2 mmHg (mean follow-up, 26 ± 7 weeks). Eleven of 13 (85%) patients having IOP reduction of greater than 40% showed improvement in optic disc parameters. All four patients with less than 25% reduction in IOP showed worsening of most parameters. Changes in optic disc parameters were highly correlated with percent IOP reduction and with age. The parameters in which change most strongly correlated with percent change of IOP were cup area, rim area, cup:disc ratio, and mean cup depth (each, P <0.005). The age of the patient correlated highly with change in maximum cup depth (P <0.005). Refraction and clinically determined cup:disc ratio correlated poorly with changes in measured optic disc parameters. Clinical improvement in visual fields was correlated with the degree of improvement of cup:disc ratio (P = 0.025). Conclusion: Most patients showing a 40% lowering of IOP after glaucoma surgery show improved optic nerve morphology as measured by the HRT. The amount of improvement correlated highly with the percent reduction of IOP.

Use of fused airborne scanning laser altimetry and digital map data for urban flood modelling

Flood modelling of urban areas is still at an early stage, partly because until recently topographic data of sufficiently high resolution and accuracy have been lacking in urban areas. However, Digital Surface Models (DSMs) generated from airborne scanning laser altimetry (LiDAR) having sub-metre spatial resolution have now become available, and these are able to represent the complexities of urban topography. The paper describes the development of a LiDAR post-processor for urban flood modelling based on the fusion of LiDAR and digital map data. The map data are used in conjunction with LiDAR data to identify different object types in urban areas, though pattern recognition techniques are also employed. Post-processing produces a Digital Terrain Model (DTM) for use as model bathymetry, and also a friction parameter map for use in estimating spatially-distributed friction coefficients. In vegetated areas, friction is estimated from LiDAR-derived vegetation height, and (unlike most vegetation removal software) the method copes with short vegetation less than ~1m high, which may occupy a substantial fraction of even an urban floodplain. The DTM and friction parameter map may also be used to help to generate an unstructured mesh of a vegetated urban floodplain for use by a 2D finite element model. The mesh is decomposed to reflect floodplain features having different frictional properties to their surroundings, including urban features such as buildings and roads as well as taller vegetation features such as trees and hedges. This allows a more accurate estimation of local friction. The method produces a substantial node density due to the small dimensions of many urban features.