Bingqing Wang

Optimal Power Settings for Holmium:YAG Lithotripsy

PURPOSE We determined the optimal Ho:YAG lithotripsy power settings to achieve maximal fragmentation, minimal fragment size and minimal retropulsion. MATERIALS AND METHODS Stone phantoms were irradiated in water with a Ho:YAG laser using a 365 μm optical fiber. Six distinct power settings were tested, including 0.2 to 2.0 J and 10 to 40 Hz. For all cohorts 500 J total radiant energy were delivered. A seventh cohort (0.2 J 40 Hz) was tested post hoc to a total energy of 1,250 J. Two experimental conditions were tested, including with and without phantom stabilization. Total fragmentation, fragment size and retropulsion were characterized. In mechanism experiments using human calculi we measured crater volume by optical coherence tomography and pressure transients by needle hydrophone across similar power settings. RESULTS Without stabilization increased pulse energy settings produced increased total fragmentation and increased retropulsion (each p <0.0001). Fragment size was smallest for the 0.2 J cohorts (p <0.02). With stabilization increased pulse energy settings produced increased total fragmentation and increased retropulsion but also increased fragment size (each p <0.0001). Craters remained symmetrical and volume increased as pulse energy increased. Pressure transients remained modest at less than 30 bars even at 2.0 J pulse energy. CONCLUSIONS Holmium:YAG lithotripsy varies as pulse energy settings vary. At low pulse energy (0.2 J) less fragmentation and retropulsion occur and small fragments are produced. At high pulse energy (2.0 J) more fragmentation and retropulsion occur with larger fragments. Anti-retropulsion devices produce more efficient lithotripsy, particularly at high pulse energy. Optimal lithotripsy laser dosimetry depends on the desired outcome.

Thickness, Phase Retardation, Birefringence, and Reflectance of the Retinal Nerve Fiber Layer in Normal and Glaucomatous Non-Human Primates

PURPOSE We identified candidate optical coherence tomography (OCT) markers for early glaucoma diagnosis. Time variation of retinal nerve fiber layer (RNFL) thickness, phase retardation, birefringence, and reflectance using polarization sensitive optical coherence tomography (PS-OCT) were measured in three non-human primates with induced glaucoma in one eye. We characterized time variation of RNFL thickness, phase retardation, birefringence, and reflectance with elevated intraocular pressure (IOP). METHODS One eye of each of three non-human primates was laser treated to increase IOP. Each primate was followed for a 30-week period. PS-OCT measurements were recorded at weekly intervals. Reflectance index (RI) is introduced to characterize RNFL reflectance. Associations between elevated IOP and RNFL thickness, phase retardation, birefringence, and reflectance were characterized in seven regions (entire retina, inner and outer rings, and nasal, temporal, superior and inferior quadrants) by linear and non-linear mixed-effects models. RESULTS Elevated IOP was achieved in three non-human primate eyes with an average increase of 13 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in the nasal region (P = 0.0002), decreased RNFL phase retardation in the superior (P = 0.046) and inferior (P = 0.021) regions, decreased RNFL birefringence in the nasal (P = 0.002) and inferior (P = 0.029) regions, and loss of RNFL reflectance in the outer rings (P = 0.018). When averaged over the entire retinal area, only RNFL reflectance showed a significant decrease (P = 0.028). CONCLUSIONS Of the measured parameters, decreased RNFL reflectance was the most robust correlate with glaucomatous damage. Candidate cellular mechanisms are considered for decreased RNFL reflectance, including mitochondrial dysfunction and retinal ganglion cell apoptosis.

Birefringence measurement of the retinal nerve fiber layer by swept source polarization sensitive optical coherence tomography

A Swept Source Polarization-Sensitive Optical Coherence Tomography (SS-PS-OCT) instrument has been designed, constructed, and verified to provide high sensitivity depth-resolved birefringence and phase retardation measurements of the retinal nerve fiber layer. The swept-source laser had a center wavelength of 1059 nm, a full-width-half-max spectral bandwidth of 58 nm and an A-line scan rate of 34 KHz. Power incident on the cornea was 440 µW and measured axial resolution was 17 µm in air. A multiple polarization state nonlinear fitting algorithm was used to measure retinal birefringence with low uncertainty. Maps of RNFL phase retardation in a subject measured with SS-PS-OCT compare well with those generated using a commercial scanning laser polarimetry instrument. Peak-to-valley variation of RNFL birefringence given here is less than values previously reported at 840nm.

Retinal nerve fiber layer reflectance for early glaucoma diagnosis.

Purpose:Compare performance of normalized reflectance index (NRI) and retinal nerve fiber layer thickness (RNFLT) parameters determined from optical coherence tomography (OCT) images for glaucoma and glaucoma suspect diagnosis. Methods:Seventy-five eyes from 71 human subjects were studied: 33 controls, 24 glaucomatous, and 18 glaucoma-suspects. RNFLT and NRI maps were measured using 2 custom-built OCT systems and the commercial instrument RTVue. Using area under the receiver operating characteristic curve, RNFLT and NRI measured in 7 RNFL locations were analyzed to distinguish between control, glaucomatous, and glaucoma-suspect eyes. Results:The mean NRI of the control group was significantly larger than the means of glaucomatous and glaucoma-suspect groups in most RNFL locations for all 3 OCT systems (P<0.05 for all comparisons). NRI performs significantly better than RNFLT at distinguishing between glaucoma-suspect and control eyes using RTVue OCT (P=0.008). The performances of NRI and RNFLT for classifying glaucoma-suspect versus control eyes were statistically indistinguishable for PS-OCT-EIA (P=0.101) and PS-OCT-DEC (P=0.227). The performances of NRI and RNFLT for classifying glaucomatous versus control eyes were statistically indistinguishable (PS-OCT-EIA: P=0.379; PS-OCT-DEC: P=0.338; RTVue OCT: P=0.877). Conclusions:NRI is a promising measure for distinguishing between glaucoma-suspect and control eyes and may indicate disease in the preperimetric stage. Results of this pilot clinical study warrant a larger study to confirm the diagnostic power of NRI for diagnosing preperimetric glaucoma.

Path-length-multiplexed scattering-angle-diverse optical coherence tomography for retinal imaging.

A low-resolution path-length-multiplexed scattering angle diverse optical coherence tomography (PM-SAD-OCT) is constructed to investigate the scattering properties of the retinal nerve fiber layer (RNFL). Low-resolution PM-SAD-OCT retinal images acquired from a healthy human subject show the variation of RNFL scattering properties at retinal locations around the optic nerve head. The results are consistent with known retinal ganglion cell neural anatomy and principles of light scattering. Application of PM-SAD-OCT may provide potentially valuable diagnostic information for clinical retinal imaging.

Dual-modality fiber-based OCT-TPL imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques

New optical imaging techniques that provide contrast to study both the anatomy and composition of atherosclerotic plaques can be utilized to better understand the formation, progression and clinical complications of human coronary artery disease. We present a dual-modality fiber-based optical imaging system for simultaneous microstructural and molecular analysis of atherosclerotic plaques that combines optical coherence tomography (OCT) and two-photon luminescence (TPL) imaging. Experimental results from ex vivo human coronary arteries show that OCT and TPL optical contrast in recorded OCT-TPL images is complimentary and in agreement with histological analysis. Molecular composition (e.g., lipid and oxidized-LDL) detected by TPL imaging can be overlaid onto plaque microstructure depicted by OCT, providing new opportunities for atherosclerotic plaque identification and characterization.

Detection of plaque structure and composition using OCT combined with two-photon luminescence (TPL) imaging

Atherosclerosis and plaque rupture leads to myocardial infarction and stroke. A novel hybrid optical coherence tomography (OCT) and two‐photon luminescence (TPL) fiber‐based imaging system was developed to characterize tissue constituents in the context of plaque morphology.

Fourier optics analysis of phase-mask-based path-length-multiplexed optical coherence tomography

Optical coherence tomography (OCT) is an imaging technique that constructs a depth-resolved image by measuring the optical path-length difference between broadband light backscattered from a sample and a reference surface. For many OCT sample arm optical configurations, sample illumination and backscattered light detection share a common path. When a phase mask is placed in the sample path, features in the detected signal are observed, which suggests that an analysis of a generic common path OCT imaging system is warranted. In this study, we present a Fourier optics analysis using a Fresnel diffraction approximation of an OCT system with a path-length-multiplexing element (PME) inserted in the sample arm optics. The analysis may be generalized for most phase-mask-based OCT systems. A radial-angle-diverse PME is analyzed in detail, and the point spread function, coherent transfer function, sensitivity of backscattering angular diversity detection, and signal formation in terms of sample spatial frequency are simulated and discussed. The analysis reveals important imaging features and application limitations of OCT imaging systems with a phase mask in the sample path optics.

Degradation in the degree of polarization in human retinal nerve fiber layer

Abstract. Using a fiber-based swept-source (SS) polarization-sensitive optical coherence tomography (PS-OCT) system, we investigate the degree of polarization (DOP) of light backscattered from the retinal nerve fiber layer (RNFL) in normal human subjects. Algorithms for processing data were developed to analyze the deviation in phase retardation and intensity of backscattered light in directions parallel and perpendicular to the nerve fiber axis (fast and slow axes of RNFL). Considering superior, inferior, and nasal quadrants, we observe the strongest degradation in the DOP with increasing RNFL depth in the temporal quadrant. Retinal ganglion cell axons in normal human subjects are known to have the smallest diameter in the temporal quadrant, and the greater degradation observed in the DOP suggests that higher polarimetric noise may be associated with neural structure in the temporal RNFL. The association between depth degradation in the DOP and RNFL structural properties may broaden the utility of PS-OCT as a functional imaging technique.

Optimized Retinal Nerve Fiber Layer Segmentation Based On Optical Reflectivity And Birefringence For Polarization-Sensitive Optical Coherence Tomography

Segmentation of the retinal nerve fiber layer (RNFL) from swept source polarization-sensitive optical coherence tomography (SS-PSOCT) images is required to determine RNFL thickness and calculate birefringence. Traditional RNFL segmentation methods based on image processing and boundary detection algorithms utilize only optical reflectivity contrast information, which is strongly affected by speckle noise. We present a novel approach to segment the retinal nerve fiber layer (RNFL) using SS-PSOCT images including both optical reflectivity and phase retardation information. The RNFL anterior boundary is detected based on optical reflectivity change due to refractive index difference between the vitreous and inner limiting membrane. The posterior boundary of the RNFL is a transition zone composed of birefringent axons extending from retinal ganglion cells and may be detected by a change in birefringence. A posterior boundary detection method is presented that segments the RNFL by minimizing the uncertainty of RNFL birefringence determined by a Levenberg-Marquardt nonlinear fitting algorithm. Clinical results from a healthy volunteer show that the proposed segmentation method estimates RNFL birefringence and phase retardation with lower uncertainty and higher continuity than traditional intensity-based approaches.