Evaluation of osteoarthritis progression using polarization-sensitive optical coherence tomography

Previous studies have demonstrated that optical coherence tomography (OCT) could be used to delineate alterations in the microstructure of cartilage, and have suggested that changes in the polarization state of light as detected by OCT could provide information on the birefringence properties of articular cartilage as influenced by disease. In this study we have used both OCT and polarization sensitive optical coherence tomography (PS-OCT) technologies to evaluate normal and abnormal bovine articular cartilage according to established structural, organizational, and birefringent characteristics of degenerative joint disease (DJD) in order to determine if this technology can be used to differentiate various stages of DJD as a minimally invasive imaging tool. Fresh bovine femoral-tibial joints were obtained from an abattoir, and 45 cartilage specimens were harvested from 8 tibial plateaus. Whole ex vivo specimens of normal and degenerative articular cartilage were imaged by both OCT and PS-OCT, then fixed and processed for histological evaluation. OCT/PS-OCT images and corresponding histology sections of each specimen were scored according to a modified Mankin structural grading scale and compared. OCT and PS-OCT imaging allowed structural evaluation of intact articular cartilage along a 6 mm surface length to a depth of 2 mm with a transverse resolution of 12 microm and an axial resolution of 10 microm. The OCT and PS-OCT images demonstrated characteristic alterations in the structure of articular cartilage with a high correlation to histological evaluation (kappa = 0.776). The OCT images were able to demonstrate early to advanced structural changes of articular cartilage while the optical phase retardation images obtained by PS-OCT imaging were able to discriminate areas where disorganization of the cartilage matrix was present, however, these characteristics are much different than those reported where OCT images alone were used to characterize tissue birefringence. No evidence of differences in OCT or PS-OCT images were detected between specimens of similar structural characteristics where proteoglycan was judged present or absent by safranin-O Fast Green staining. The combined use of OCT and PS-OCT technologies to obtain images from a single system is able to demonstrate and discriminate between characteristics of very early stages of surface irregularities not previously reported for OCT imaging, to deep clefts and collagen matrix disorganization for tissue at depths of up to 2 mm with good correlation to histology. PS-OCT and accumulated optical phase retardation images of articular cartilage as constructed from alterations in Stokes vector parameters appear to give a valuable but different assessment of alterations in tissue birefringence and organization than have been reported for OCT images obtained with the use of polarized or non-polarized light sources. This is the first time that alterations in the polarization state of light reflected from within the tissue have been demonstrated to be consistent with changes observed in the orientation and organization of the collagen matrix in advanced stages of DJD. The degree of phase transformation of light reflected from within the tissue as determined by PS-OCT imaging does not appear to be altered by the presence or absence of proteoglycan.

Current evidence indicates that most plaques classified as vulnerable or ruptured plaques do not lead to unstable angina or myocardial infarction. Improved methods are needed to risk stratify plaques to identify those which lead to most acute coronary syndromes. Collagen depletion in the intima overlying lipid collections appears to be a critical component of unstable plaques. In this study, we use polarization sensitive optical coherence tomography (PS-OCT) for the assessment of coronary plaque collagen. Collagen is birefringent, meaning that different polarization states travel through it at different velocities. Changes in PS-OCT images are a measure of tissue birefringence. Twenty-two coronary artery segments were imaged with PS-OCT and analyzed by picrosirius staining (a measure of collagen intensity and fiber size) and trichrome blue. The regression plot between PS-OCT changes and measured collagen yielded a correlation coefficient value of 0.475 (p<0.002). Good correlation was noted between two blinded investigators both with respect to PS-OCT measurements as well as luminosity as assessed by picrosirius. The predictive value of a PS-OCT measurement of negligible birefringence (less than 33% change) for minimal collagen was 93% while the predictive value of high birefringence (greater than 66% change) for high collagen concentrations was 89%. The effect of fiber type (chemical composition) was minimal relative to the effect due to fiber concentration. The capability of PS-OCT to assess plaque collagen content, in addition to its ability to generate high resolution structural assessments, make it a potentially powerful technology for identifying high risk plaques.

Polarization-sensitive optical coherence tomography (PS-OCT) is a high-resolution label-free optical biomedical imaging modality that is sensitive to the microstructural architecture in tissue that gives rise to form birefringence, such as collagen or muscle fibers. To enable polarization sensitivity in an OCT system, however, requires additional hardware and complexity. We developed a deep-learning method to synthesize PS-OCT images by training a generative adversarial network (GAN) on OCT intensity and PS-OCT images. The synthesis accuracy was first evaluated by the structural similarity index (SSIM) between the synthetic and real PS-OCT images. Furthermore, the effectiveness of the computational PS-OCT images was validated by separately training two image classifiers using the real and synthetic PS-OCT images for cancer/normal classification. The similar classification results of the two trained classifiers demonstrate that the predicted PS-OCT images can be potentially used interchangeably in cancer diagnosis applications. In addition, we applied the trained GAN models on OCT images collected from a separate OCT imaging system, and the synthetic PS-OCT images correlate well with the real PS-OCT image collected from the same sample sites using the PS-OCT imaging system. This computational PS-OCT imaging method has the potential to reduce the cost, complexity, and need for hardware-based PS-OCT imaging systems.

Polarization sensitive optical coherence tomography (PS-OCT) is a functional extension of OCT. In addition to imaging based on tissue reflectivity, PS-OCT also enables depth-resolved mapping of sample polarization properties such as phase-retardation, birefringent axis orientation, Stokes vectors, and degree of polarization uniformity (DOPU). In this study, PS-OCT was used to investigate the polarization properties of melanin. In-vitro measurements in samples with varying melanin concentrations revealed polarization scrambling, i.e. depolarization of backscattered light. Polarization scrambling in the PS-OCT images was more pronounced for higher melanin concentrations and correlated with the concentration of the melanin granules in the phantoms. Moreover, in-vivo PS-OCT was performed in the retinas of normal subjects and individuals with albinism. Unlike in the normal eye, polarization scrambling in the retinal pigment epithelium (RPE) was less pronounced or even not observable in PS-OCT images of albinos. These results indicate that the depolarizing appearance of pigmented structures like, for instance, the RPE is likely to be caused by the melanin granules contained in these cells.

Assessing tissue birefringence with imaging modality polarization-sensitive optical coherence tomography (PS-OCT) could improve the characterization of in vivo tissue pathology. Among the birefringent components, collagen may provide invaluable clinical information because of its alteration in disorders ranging from myocardial infarction to arthritis. But the features required of clinical imaging modality in these areas usually include the ability to assess the parameter of interest rapidly and without extensive data analysis, the characteristics that single-detector PS-OCT demonstrates. But beyond detecting organized collagen, which has been previously demonstrated and confirmed with the appropriate histological techniques, additional information can potentially be gained with PS-OCT, including collagen type, form versus intrinsic birefringence, the collagen angle, and the presence of multiple birefringence materials. In part I, we apply the simple but powerful fast-Fourier transform (FFT) to both PS-OCT mathematical modeling and in vitro bovine meniscus for improved PS-OCT data analysis. The FFT analysis yields, in a rapid, straightforward, and easily interpreted manner, information on the presence of multiple birefringent materials, distinguishing the true anatomical structure from patterns in image resulting from alterations in the polarization state and identifying the tissue/phantom optical axes. Therefore the use of the FFT analysis of PS-OCT data provides information on tissue composition beyond identifying the presence of organized collagen in real time and directly from the image without extensive mathematical manipulation or data analysis. In part II, Helistat phantoms (collagen type I) are analyzed with the ultimate goal of improved tissue characterization. This study, along with the data in part I, advance the insights gained from PS-OCT images beyond simply determining the presence or absence of birefringence.

Radiofrequency ablation (RFA) is an important standard therapy for cardiac arrhythmias, but direct monitoring of tissue treatment is currently lacking. We demonstrate an RFA catheter integrated with polarization sensitive optical coherence tomography (PSOCT) for directly monitoring the RFA process in real time. The integrated RFA/OCT catheter was modified from a standard clinical RFA catheter and includes a miniature forward-viewing cone-scanning OCT probe. The PSOCT system was validated with a quarter-wave plate while the RFA function of the integrated catheter was validated by comparing lesion sizes with those made with an unmodified RFA catheter. Additionally, the integrated catheter guided catheter-tissue apposition and monitored RFA lesion formation in cardiac tissue in real time. The results show that catheter-tissue contact can be characterized by observing the features of the blood and tissue in the acquired OCT images and that RFA lesion formation can be confirmed by monitoring the change in phase retardance in the acquired PSOCT images. This system demonstrates the feasibility of an integrated RFA/OCT catheter to deliver RF energy and image the cardiac wall simultaneously and justifies further research into use of this technology to aid RFA therapy for cardiac arrhythmias.

We present in-vivo 3D human vocal fold images with polarization sensitive optical coherence tomography (PS-OCT). Characterizing the extent and location of vocal fold lesions provides useful information in guiding surgeons during phonomicrosurgery. Previous studies showed that PS-OCT imaging can distinguish vocal fold lesions from normal tissue, but these studies were limited to 2D cross-sectional imaging and were susceptible to sampling error. In-vivo 3D endoscopic imaging was performed by using a recently developed 2-axis MEMS scanning catheter and a spectral domain OCT (SD-OCT), running at 18.5 frames/s. Imaging was performed in the operating room with patients under general anesthesia and 3D images were acquired either by 2D scanning of the scanner on the sites of interest or by combining 1D scanning and manual sliding to capture whole length of the vocal fold. Vocal fold scar, polyps, nodules, papilloma and malignant lesions were imaged and characteristics of individual lesions were analyzed in terms of spatial distribution and variation of tissue structure and birefringence. The 3D large sectional PS-OCT imaging showed that the spatial extent of vocal fold lesions can be found non-invasively with good contrast from normal tissue.

This Letter presents a spectral-domain, polarization-sensitive optical coherence tomography (PS-OCT) system, where the light collection from the two arms of the interferometer is performed exclusively using single-mode fibers and couplers, and the two orthogonal polarization components are sequentially detected by a single line camera. Retardance measurements can be affected by polarimetric effects because of fiber birefringence and diattenuation in fiber couplers. This configuration bypasses such issues by performing polarization selection before the collection fiber through the combination of a polarization rotator and a linear polarizer. Retardance calibration is achieved with a Berek compensator. Similar net retardance maps of a birefringent phantom are obtained for two different settings of induced fiber birefringence, effectively demonstrating the tolerance of the configuration to fiber-based disturbances.

Polarization-sensitive optical coherence tomography (PS-OCT) combines the advantages of OCT with image contrast enhancement, which is based on its ability to detect phase retardation and the fast-axis angle. Both PS-OCT images and histopathology have demonstrated similar features that allowed differentiation of atherosclerotic structures (i.e., plaques) from normal tissue. Moreover, the picrosirius polarization method was used to confirm PS-OCT assessment of collagen in the fibrous cap of atherosclerotic plaques, and high-frequency (40 MHz) ultrasound images were used to identify calcium in the vessel wall. Our preliminary ex vivo investigation of human aortic specimens indicated that PS-OCT might help to identify atherosclerotic lesions.

The purpose of this study was to demonstrate polarization-sensitive optical coherence tomography (PS-OCT) for imaging pigmented structures in the posterior eye segments of albino and pigmented rats and to correlate depolarization contrast of the retinal pigment epithelium (RPE) and choroid in in vivo PS-OCT to melanin pigmentation detected in postmortem histologic serial sections. In vivo three-dimensional PS-OCT imaging was performed in adult albino and pigmented rat eyes at 70-kHz A-line rate. Degree of polarization uniformity (DOPU) fundus maps and radial DOPU profiles were generated. Postmortem histomorphologic analysis was performed in order to investigate melanin pigmentation of the RPE and choroid. Fundus pigmentation maps were extracted from histologic serial sections. Pigmentation profiles were correlated to DOPU profiles of the same eyes. Strong depolarization was found in the RPE/choroid complex of pigmented rats, whereas the same structures exhibited uniform polarization in albino rats. The difference between the depolarization characteristics between albino and pigmented animals was statistically significant. In the fundus pigmentation maps, optical pigment density was zero in albino rat eyes. In pigmented rat eyes, a strong negative correlation between optical pigment density and DOPU was observed. This in vivo and ex vivo investigation of posterior rat eyes indicates that melanin is the cause of depolarization in retinal PS-OCT images. It further demonstrates that melanin pigmentation in the RPE and choroid can be quantified via depolarization imaging and therefore suggests that PS-OCT is a useful tool for the noninvasive quantitative assessment of pigmentary changes in vision-threatening diseases such as age-related macular degeneration.

A polarization sensitive optical coherence tomography (PS-OCT) instrument was used to investigate the retinal pigment epithelium (RPE). The instrument uses the polarization properties of light to record backscattered intensity, retardation and fast axis orientation simultaneously and needs only one measurement per sample location to retrieve these parameters. The polarization state of light backscattered from within the RPE was found to be random. This can be observed in PS-OCT images by random retardation and axis orientation values within the RPE layer. In diseased eyes where the normal retinal structure is corrupted (e.g. RPE atrophy, RPE detachment) the localization of the RPE within OCT images which do not provide polarization information (standard OCT) is rather difficult. Since the RPE is the only structure within the retina to cause this polarization scrambling, PS-OCT can be used for contrast enhancement and enables the exact localization of the RPE in these pathologies. Therefore it is possible to determine if the RPE is still preserved in regions of interest. Furthermore, in patients with RPE atrophy an enhanced penetration depth into the choroid and even into the sclera was observed. Because of birefringence introduced by the sclera the border between choroid and sclera could easily be determined.

In swept source polarization depth encoding polarization sensitive optical coherence tomography (PS-OCT), the laser jitter induces additional noise to the polarization sensitive measurement. In this Letter, we developed a numerical algorithm to correct the jitter phases based on the image data using the Mueller matrix calculus. The algorithm was demonstrated on in vivo retina imaging of a guinea pig with a custom-built PS-OCT system. The performance of the proposed algorithm was almost comparable to the conventional method of using a physical calibration signal. By not requiring a hardware generated calibration signal and k-clock, the proposed algorithm is useful to reduce the complexity and the cost of a polarization depth encoding PS-OCT system.

Optical coherence tomography (OCT) technology can generate cross-sectional images of the scattering media such as biological tissues with spatial resolution as low as 1 ~ 10 mum. OCT uses a partial coherence Michelson interferometry that produces images similar to the ultrasound B-scans. There are many types of functional OCT technologies including polarization-sensitive OCT (PS-OCT), spectroscopic OCT, Optical Doppler Tomography (ODT), etc.PS-OCT produces not only the structural cross-sectional images but the functional images related to the tissue birefringence, phase retardation and depolarization of light reflected from deep tissue regions. Because the PS-OCT is sensitive to birefringent materials such as collagen, the PS-OCT has been studied as an optical diagnosis tool in skin, bone, cartilage, and tooth. In dermatology, OCT can generate useful images such as skin topology and basement membranes. It also can produce other useful images related to skin collagen morphologies and photoaging. We have also demonstrated that the PS-OCT can be applied to clinical problems such as wound healing monitoring of skin. Light depolarization due to multiple scattering is often considered as a negative effect during OCT image acquisition which prevents imaging of deep regions. In our study, we show that the scattering changes can be quantified using PS-OCT by measuring the axial variations of degree of polarization (DOP). Therefore, we suggest that the depolarization process can be used in a positive way. We have tested our hypothesis using various optical phantoms. Scattering changes often occur in pathologic conditions of human cervical tissues. We successfully applied our technique to in vitro diagnosis of cervical interepithelial neoplasm (CIN). It was found that the high-grade squamous intraepithelial lesions (H-SIL) including CIN-II, CIN-III, and Carcinoma in situ (CIS) can be diagnosed by DOP quantification with high sensitivity and specificity.

PurposeTo determine the structural characteristics of the peripapillary sclera in myopic eyes using polarization-sensitive optical coherence tomography (PS-OCT).MethodsPatients with myopia who underwent PS-OCT imaging between April and June 2023 were studied. The intensity, optic axis, and birefringence of PS-OCT images were analyzed to determine the surface of the lamina cribrosa (LC). The direction and arrangement of the scleral collagen fibers in the peripapillary region and scleral ridge were determined.ResultsOne hundred and ten eyes of 59 patients with myopia (mean axial length, 30.00 ± 1.98 mm) were studied. The scleral fibers around the optic nerve were arranged circularly in all eyes regardless of the presence or size of the peripapillary atrophy. Inner scleral fibers that penetrated beneath this circular arrangement were detected in 98 eyes (89.1%). There was a Y-shaped split at the point of penetration in 77 eyes (70.0%). The integrity of the circular arrangement and penetrating scleral fiber complexes remained intact even in cases of severe peripapillary scleral deformation. A scleral ridge was identified in 27 eyes (24.5%), and it appeared as a full-thickness protrusion composed primarily of outer scleral fibers. The ridge was consistently located outside the circular arrangement.ConclusionsThe penetration of the radial inner scleral fibers into the circular arrangement and extension to the LC suggest that they act as stabilizing anchors for the circular structure. The differences of the scleral ridges from those in eyes with dome-shaped macula suggest that unique mechanisms cause the scleral differences.

We developed a tissue discrimination algorithm of polarization sensitive optical coherence tomography (PS-OCT) based on the optical properties of tissues. We calculated the three-dimensional (3D) feature vector from the parameters intensity, extinction coefficient, birefringence, which were obtained by PS-OCT. The tissue type of each pixel was determined according to the position of the feature vector in the 3D feature space. The algorithm was applied for discriminating tissues of the human anterior eye segment. The conjunctiva, sclera, trabecular meshwork (TM), cornea, and uvea were well separated in the 3D feature space, and we observed them with good contrast. The TM line can be observed in the 3D discriminated volume, as observed by gonioscopy.We validated our method by applying our algorithm and histological data to porcine eyes. A marker was injected into sub-Tenon's space and the tissues that were anterior to the marker and posterior to the marker were successfully segmented by our algorithm.