Polarization-sensitive Optical Coherence Tomography Measurements Research Articles

Hypertension-associated changes in retinal blood vessel walls measured in vivo with polarization-sensitive optical coherence tomography

Blood vessel walls are made of organized fibrous tissue with intrinsic birefringence. Even in its very early stages, hypertension can change the structure of a blood vessel wall. In this paper, we demonstrated that this structural change associated with hypertension can be quantitatively measured non-invasively in the human retina using polarization-sensitive optical coherence tomography (PS-OCT). Measurements were performed with a relatively low-cost PS-OCT instrument in less than a minute per eye. Organizational loss in vessel wall tissue was quantified in hypertensive patients and compared to data obtained from age-matched healthy subjects. Our PS-OCT measurements showed that the vessel wall tissue in patients with hypertension is thicker, and exhibited lower birefringence, presumably due to a loss of tissue organization. The blood vessel wall birefringence index (BBI) is a newly introduced metric that combines vessel wall birefringence (decreases with hypertension) and thickness (increases with hypertension) into a single numerical value. Its purpose is to easily differentiate between the blood vessel walls of hypertensives and those of healthy subjects. Accurately determining the thickness of the blood vessel wall relies on access to polarization-sensitive data: a linear increase in retardation in the vessel wall with depth and stable retardation values below the vessel wall to determine the lower edge of the vessel wall. Based on receiver operating characteristic (ROC) curves, BBI showed 99 % sensitivity and 100 % specificity when discriminating normotensive (N = 11) and hypertensive (N = 11) subjects.

Non-Invasive Retinal Blood Vessel Wall Measurements with Polarization-Sensitive Optical Coherence Tomography for Diabetes Assessment: A Quantitative Study.

Diabetes affects the structure of the blood vessel walls. Since the blood vessel walls are made of birefringent organized tissue, any change or damage to this organization can be evaluated using polarization-sensitive optical coherence tomography (PS-OCT). In this paper, we used PS-OCT along with the blood vessel wall birefringence index (BBI = thickness/birefringence2) to non-invasively assess the structural integrity of the human retinal blood vessel walls in patients with diabetes and compared the results to those of healthy subjects. PS-OCT measurements revealed that blood vessel walls of diabetic patients exhibit a much higher birefringence while having the same wall thickness and therefore lower BBI values. Applying BBI to diagnose diabetes demonstrated high accuracy (93%), sensitivity (93%) and specificity (93%). PS-OCT measurements can quantify small changes in the polarization properties of retinal vessel walls associated with diabetes, which provides researchers with a new imaging tool to determine the effects of exercise, medication, and alternative diets on the development of diabetes.

Measuring collagen injury depth for burn severity determination using polarization sensitive optical coherence tomography

Determining the optimal treatment course for a dermatologic burn wound requires knowledge of the wound’s severity, as quantified by the depth of thermal damage. In current clinical practice, burn depth is inferred based exclusively on superficial visual assessment, a method which is subject to substantial error rates in the classification of partial thickness (second degree) burns. Here, we present methods for direct, quantitative determination of the depth extent of injury to the dermal collagen matrix using polarization-sensitive optical coherence tomography (PS-OCT). By visualizing the depth-dependence of the degree of polarization of light in the tissue, rather than cumulative retardation, we enable direct and volumetric assessment of local collagen status. We further augment our PS-OCT measurements by visualizing adnexal structures such as hair follicles to relay overall dermal viability in the wounded region. Our methods, which we have validated ex vivo with matched histology, offer an information-rich tool for precise interrogation of burn wound severity and healing potential in both research and clinical settings.

Compressive sensing for polarization sensitive optical coherence tomography

In this report, we report on the implementation of compressive sensing (CS) and sparse sampling in polarization sensitive optical coherence tomography (PS-OCT) to reduce the number of B-scans (frames consisting of an array of A-scans, where each represents a single depth profile of reflections) required for effective volumetric (3D dataset composed of an array of B-scans) PS-OCT measurements (i.e. OCT intensity, and phase retardation) reconstruction. Sparse sampling of PS-OCT is achieved through randomization of step sizes along the slow-axis of PS-OCT imaging, covering the same spatial ranges as those with equal slow-axis step sizes, but with a reduced number of B-scans. Tested on missing B-scan rates of 25%, 50% and 75%, we found CS could reconstruct reasonably good (as evidenced by a correlation coefficient >0.6) PS-OCT measurements with a maximum reduced B-scan rate of 50%, thereby accelerating and doubling the rate of volumetric PS-OCT measurements.

Correlation between Lesion Progression and Depolarization Assessed by Polarization-Sensitive Optical Coherence Tomography

The detection of early stages of caries is still one of the major challenges in preservative dentistry. Since it is known from polarized light microscopy (PLM) that intrinsic enamel birefringence is affected by demineralization, polarization-sensitive optical coherence tomography (PSOCT) could facilitate the noninvasive detection and assessment of early carious lesions. The present study aims to correlate enamel lesion progression and depolarization measurements based on PSOCT in an artificial demineralization model. A total of 18 enamel slabs were prepared from bovine incisor teeth and demineralized in an acetic buffer solution for up to 49 days. The degree of polarization (DOP)—indicating depolarization and thus, demineralization—was calculated from PSOCT measurements and compared to lesion depth which was measured from PLM images. Artificial lesions showed characteristic zones of natural enamel demineralization in PLM images. DOP representations showed no depolarization for sound, nondemineralized enamel, whereas significant changes were found after 15 days of acid-exposition. The linear regression analysis of the DOP and the measured lesion depth showed a substantial correlation ( R 2 = 0.71 ). The results indicate that PSOCT-based depolarization imaging provides an unambiguous contrast for initial enamel demineralization which is correlated to the lesion progression.

Three-dimensional volumetric human meibomian gland investigation using polarization-sensitive optical coherence tomography

In this study, polarization-sensitive optical coherence tomography (PS-OCT) capable of providing polarization contrasts such as phase retardation and degree of polarization uniformity (DOPU) was used for visualizing human meibomian glands (MGs) and investigating morphological characteristics of them. Especially, with the help of the DOPU contrast, MGs were exclusively extracted from the volumetric OCT image. In vivo PS-OCT measurements were performed on the upper eyelids of different age groups. From these measurements, different age-dependent aspects of the MG structure were also observed. Based on these observations, it can be inferred that the PS-OCT system has the potential for clinical diagnosis and investigation of MG-related dry eye diseases like MG dysfunction (MGD) and acinar atrophy.

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

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). 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. 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). 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.

Polarimetric analysis of the human cornea measured by polarization-sensitive optical coherence tomography

Corneal polarimetry measurement has been the object of several papers. The results of techniques like polarization-sensitive optical coherence tomography (PS-OCT), scanning laser polarimetry, or polarization microscopy are contradictory. Some studies propose a biaxial-like birefringence pattern, while others postulate that birefringence grows at corneal periphery. Several theoretical approaches were proposed for the interpretation of these measurements, but they usually lack accuracy and an adequate consideration of the nonnormal incidence on the tissue. We analyze corneal polarization effects measured by PS-OCT. In vivo and in vitro PS-OCT images of the human cornea are acquired. PS-OCT measurements are apparently not in agreement with the biaxial-like birefringence pattern. We present a polarimetric model of the human cornea based on the extended Jones matrix formalism applied to multilayered systems. We also apply the Poincaré equivalence theorem to extract optic axis orientation and birefringence. The results show that for a fibrils orientation pattern composed by alternating circular and radial fibrils, the birefringence is biaxial-like at the corneal center, and there is an almost circularly symmetric high-birefringence area at corneal periphery. The model could be useful for diagnosis of corneal diseases or corneal compensation in retinal polarimetric imaging.

High-resolution PS-OCT of Enamel Remineralization.

Previous studies have demonstrated that Polarization Sensitive Optical Coherence Tomography (PS-OCT) can be used to image the remineralization of early artificial caries lesions. However, the depth resolution of the imaging system employed in those previous studies was limited and the outer surface structure of the lesions were not resolved as clearly as desired. The purpose of this study was to repeat the earlier remineralization study using a broadband light-source of higher resolution to determine if there can be improved resolution of the remineralized surface zones of the lesions. An all polarization-maintaining fiber based PS-OCT system operating at 1310-nm was used to acquire polarization resolved images of bovine enamel surfaces exposed to a demineralizing solution at pH-4.9 followed by a fluoride containing remineralizing solution at pH-7.0 containing 2-ppm fluoride. The structure of the surface zones could be clearly resolved using PS-OCT in the samples that underwent remineralization. The PS-OCT measurements indicated a significant (p<0.05) reduction in the integrated reflectivity between the severity of the lesions that were exposed to the remineralization solution and those that were not. The lesion depth and mineral loss were also measured with polarized light microscopy and transverse microradiography after sectioning the enamel blocks. These results show that PS-OCT can be used to non-destructively monitor the remineralization potential of anti-caries agents.

Measurement of Collagen and Smooth Muscle Cell Content in Atherosclerotic Plaques Using Polarization-Sensitive Optical Coherence Tomography

The purpose of this study was to investigate the measurement of collagen and smooth muscle cell (SMC) content in atherosclerotic plaques using polarization-sensitive optical coherence tomography (PSOCT). A method capable of evaluating plaque collagen content and SMC density can provide a measure of the mechanical fidelity of the fibrous cap and can enable the identification of high-risk lesions. Optical coherence tomography has been demonstrated to provide cross-sectional images of tissue microstructure with a resolution of 10 mum. A recently developed technique, PSOCT measures birefringence, a material property that is elevated in tissues such as collagen and SMCs. We acquired PSOCT images of 87 aortic plaques obtained from 20 human cadavers. Spatially averaged PSOCT birefringence, Phi, was measured and compared with plaque collagen and SMC content, quantified morphometrically by picrosirius red and smooth muscle actin staining at the corresponding locations. There was a high positive correlation between PSOCT measurements of Phi and total collagen content in all plaques (r = 0.67, p < 0.001) and in fibrous caps of necrotic core fibroatheromas (r = 0.68, p < 0.001). Polarization-sensitive optical coherence tomography measurements of Phi demonstrated a strong positive correlation with thick collagen fiber content (r = 0.76, p < 0.001) and SMC density (r = 0.74, p < 0.01). Our results demonstrate that PSOCT enables the measurement of birefringence in plaques and in fibrous caps of necrotic core fibroatheromas. Given its potential to evaluate collagen content, collagen fiber thickness, and SMC density, we anticipate that PSOCT will significantly improve our ability to evaluate plaque stability in patients.

Collagen denaturation can be quantified in burned human skin using polarization-sensitive optical coherence tomography

Quantifiable prognostic indicators are of considerable practical value following thermal injury. Collagen is a major component of the skin, and is known to undergo denaturation at the elevated temperatures associated with burns. The purpose of this study was to determine whether a recently developed, non-invasive imaging technique could detect and quantify collagen denaturation in burned human skin. Polarization-sensitive optical coherence tomography (PS-OCT) imaging was used to quantify collagen birefringence in normal human skin, and in skin excised from burn patients. Images were acquired and displayed in 1 s, and demonstrated qualitative differences between normal and partial-thickness burned human skin. Birefringence loss due to thermal denaturation of collagen was quantified, with mean phase retardation rates for samples of 26 normal and 26 burned skin sites determined to be 0.401±0.020 and 0.249±0.017°/μm, respectively (mean±S.E.M.), with this difference in sample means shown to be statistically significant ( P<0.000001). Analysis of the accuracy of the technique indicated that PS-OCT measurements may be made with resolution sufficient to distinguish between burns of varying severity. In conclusion, PS-OCT is capable of imaging and quantifying collagen denaturation in burned human skin, providing a new parameter against which post-injury outcome may be compared.