Polarization sensitive spectroscopic optical coherence tomography for multimodal imaging

Spontaneous preterm birth (sPTB) is one of the most serious causes of neonatal death. However, sPTB is unpredictable at present due to simplistic research. That cervix remodels progressively through collagen alterations plays an important role during gestation, but the study of cervical collagen structure has been limited by the lack of suitable observational method. Polarization-sensitive optical coherence tomography (PSOCT) is a functional extension of intensity-based OCT, which can noninvasively offer additional information, i.e., the light’s polarization state. Thus, the collagen properties of birefringence and depolarization can be obtained by a PSOCT in vivo. A PSOCT has been developed from our in-house swept-source (SS) OCT. In the PS-SS-OCT, a circularly polarized light is used to interact tissue and the backscattered light which carries sample’s polarization information is detected by two channels for measuring the horizontal and vertical polarization state respectively. Several human cervix tissues have been investigated by the PS-SS-OCT in vitro. The birefringence and depolarization information of cervical collagen can be obtained by processing the intensity and phase value of the two channels. Besides the birefringence and depolarization information, a conical beam scan strategy has been applied for exploring orientation of the collagen structure of human cervix. In the conical scan, the illumination beam streams into sample at a 45° of incidence angle, and the sample is imaged by acquiring successive B-scan over sample-rotation spans of 0-360°. Since probe of PSOCT can be easily integrated into a catheter or a hand-held probe, PSSS-OCT with a conical beam scan is an excellent candidate to identify cervical structure in clinical practice.

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.

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.

Optical Coherence Tomography Measurements and Analysis Methods in Optical Coherence Tomography Studies of Diabetic Macular Edema

Minimally Invasive Polarization Sensitive Optical Coherence Tomography (PS-OCT) for assessing Pre-OA, a pilot study on technical feasibility

Sequential phases of RGC axonal and somatic injury in EAE mice examined using DTI and OCT

Objective:To evaluate the anatomical and functional outcome in eyes with indocyanine green (ICG)-assisted idiopathic epiretinal membrane (ERM) peeling by optical coherence tomography (OCT) and multifocal electroretinogram (MFERG).Design:Prospective, interventional, noncomparative case series.Methods:Twenty eyes of 20 patients with idiopathic ERM underwent pars plana vitrectomy and ICG-assisted ERM and internal limiting membrane (ILM) removal. Visual acuity (VA), OCT, and MFERG measurements were performed preoperatively and postoperatively at 1, 3, 6, and 12 months.Results:Best-corrected VA (BCVA) improved ≥2 Snellen lines in 70% of our patients at the 12th postoperative month. Mean VA increased from 20/100 preoperatively to 20/40 at 12 months. VA increased significantly at all postoperative examinations, compared to preoperative VA. Foveal thickness measured by OCT decreased significantly at all postoperative examinations. OCT mean values dropped from 472.3 μm preoperatively, to 249.2 μm at 12 months. Preoperative MFERG values significantly improved only at 12 months. OCT measurements and MFERG values did not correlate at any time. OCT values correlated with VA values only preoperatively while MFERG measurements correlated with VA at 12 months.Conclusions:In our series of eyes with ERM surgery, OCT measurements and VA improved gradually throughout the first postoperative year, while MFERG values showed significant improvement at 12 months.

Non-vascularized pigment epithelial detachments (PED) are usually associated with dry age-related macular degeneration (AMD). In this study, we aimed to investigate the correlation between visual function and morphologic parameters. Seventeen eyes of eleven patients with non-vascularized AMD were enrolled. In addition to conventional optical coherence tomography (OCT), polarization-sensitive optical coherence tomography (PS-OCT) measurements were performed by evaluating the regularity of retinal pigment epithelium (RPE) entropy within the PED area. Retinal sensitivity was measured with MP-3 microperimetry, and retinal sensitivities within (RSin) and outside (RSout) the PED area were calculated. The relationship between OCT parameters and visual function was analyzed. As a result, there was a significant difference between the RSin and RSout (p < 0.001, Wilcoxon signed rank test). Moreover, RSin was significantly related to logMAR VA (p = 0.033, linear mixed model). The regularity of RPE entropy was significantly related to visual acuity and RSin (p = 0.00038, p = 0.031, linear mixed model), although neither the height nor area of PED correlated with visual function. Our results suggest that retinal sensitivity is significantly deteriorated within the PED area and RPE entropy measured with PS-OCT was closely related to visual function in eyes with non-vascularized PED.

ObjectiveTo study the association between serum neurofilament light chain (sNfL) and multiple optical coherence tomography (OCT) measures in patients with MS and healthy controls (HCs).MethodsIn this prospective study, 110 patients with MS were recruited, together with 52 age- and sex-matched HCs. Clinical evaluation and spectral domain OCT and sNfL were obtained at baseline and after 5.5 years of follow-up. Nested linear mixed models were used to assess differences between MS vs HC and associations between sNfL and OCT measures. Partial correlation coefficients are reported, and p values were adjusted for the false discovery rate.ResultsAt baseline, peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular ganglion cell and inner plexiform layer thickness (mGCIP) were significantly lower in MS than HC both in MS-associated optic neuritis (MSON) (p = 0.007, p = 0.001) and nonaffected MSON (n-MSON) eyes (p = 0.003, p = 0.018), along with total macular volume (TMV) in n-MSON eyes (p = 0.011). At follow-up, MS showed significantly lower pRNFLT, mGCIP, and TMV both in MSON and n-MSON eyes (p < 0.001) compared with HC. In MS n-MSON eyes, sNfL was significantly associated with baseline pRNFLT and mGCIP (q = 0.019). No significant associations were found in MSON eyes.ConclusionsThis study confirms the ability of sNfL to detect neurodegeneration in MS and advocates for the inclusion of sNfL and OCT measures in clinical trials.Classification of evidenceThis study provides Class III evidence that sNfL levels were associated with MS neurodegeneration measured by OCT.

Comparison between retinal thickness analyzer and optical coherence tomography for assessment of foveal thickness in eyes with macular disease

An animal study was designed to explore the potentially damaging effects of electrical overstimulation on peripheral nerves using a polarization‐sensitive optical coherence tomography (PS‐OCT) imaging and stimulation platform. Lewis rats (n = 15) were divided into 3 groups with 2 different levels of stimulation applied to the exposed sciatic nerve: Group 1 (sham control): 0.0 mA/0 Hz, Group 2: 3.4 mA/50 Hz, and Group 3: 6.8 mA/100 Hz. On day 1, the protocol contains Von Frey and walking track behavioral tests, followed by sciatic nerve exposure surgery (left leg). Electrical stimulation of the nerve was performed for one hour, with a one‐hour recovery period. PS‐OCT and optical coherence tomography angiography (OCT‐A) imaging were performed both prior to and during these periods. On day 7, this protocol was repeated without stimulation. OCT imaging was performed along a 5‐mm length of the sciatic nerve, including sites proximal and distal to injury. Both the stimulated and contralateral sciatic nerves were then resected and processed for histology. Image analysis quantified the effects of electrical stimulation at the two time points and allows comparison between stimulation levels. In all cohort groups, PS‐OCT image features remained consistent on day 1. On day 7, we observed relatively few PS‐OCT or OCT‐A changes compared to day 1 in the sham control animals. Groups 2 and 3 showed a clear increase in OCT‐A perfusion in the stimulated region, while there is a drop in PS‐OCT signal in the same area. The PS‐OCT signal drop‐out appears more pronounced in Group 2 compared to Group 3. It is not yet clear if the PS‐OCT signal drop‐out is related to demyelination or from shadowing from hyperperfused tissue. Walking track video was analyzed frame‐by‐frame for animal foot spread to determine sciatic and tibial function indices. This data, along with Von Frey withdrawal forces, were analyzed with statistical comparison tests (ANOVA) and indicated no significant differences between the groups nor significant interactions when compared across stimulation group, pre‐ and post‐exposure, and ipsilateral‐contralateral leg. Histological samples were processed for histomorphometry and axonal damage proximal and distal to the injury, as well as for immunohistochemistry of axons, macrophages, and nuclei in the stimulated and unstimulated regions in all groups. PS‐OCT and OCT‐A proffer real‐time observation of nerve changes with overstimulation that are undetectable by behavioral testing. Support or Funding Information NIH SPARC

Leveraging the polarization property of light to evaluate the birefringence of tissues as well as changes due to pathological conditions has been gaining interest over the past two decades with the introduction of different variants of optical coherence tomography (OCT) including polarization-sensitive OCT (PS-OCT) and cross-polarization OCT (CP-OCT). Because OCT sources are partially polarized, PS-OCT and CP-OCT generally require a linear polarizer and polarization-maintaining fibers to enable a linearly polarized input beam into the interferometer. While recent studies have suggested using an unpolarized input beam to reduce the system's complexity, the effect of unpolarized light on the point spread function (PSF) of OCT has not been fully studied. This work proposed a mathematical framework to evaluate the contribution of unpolarized light to the PSF of OCT. Simulation and experiments were performed for three OCT sources to assess the validity of the proposed model. Overall, simulations were in good agreement with experiments and revealed that unpolarized light introduced two additional reflectors into the reflectivity profile of the source, which were more pronounced in the cross-polarization configuration. This additional information can lead to misinterpretation of the birefringence of tissues in PS-OCT and CP-OCT. Their effect on image quality was evaluated in ex vivo corneal imaging of porcine eyeballs.

The zebrafish has shown to be an essential preclinical animal model, especially in the field of oncology. A non-invasive, high-resolution, and three-dimensional imaging modality is required to identify disease related changes in this model organism. The presented polarization-sensitive Jones matrix optical coherence tomography (JM-OCT) prototype was utilized in three different studies, covering in vivo imaging of wildtype zebrafish, an adult postmortem tumor model and a longitudinal xenograft tumor zebrafish investigation. This work highlights the potential of JM-OCT as a non-invasive, label-free, and three-dimensional imaging tool for preclinical cancer research based on zebrafish models.

High-Definition and 3-dimensional Imaging of Macular Pathologies with High-speed Ultrahigh-Resolution Optical Coherence Tomography

Polarization sensitive optical coherence tomography for technical materials investigation