Polarization-sensitive Optical Coherence Tomography Images Research Articles

Improved accuracy of quantitative birefringence imaging by polarization sensitive OCT with simple noise correction and its application to neuroimaging.

Polarization-sensitive optical coherence tomography (PS-OCT) enables three-dimensional imaging of biological tissues based on the inherent contrast provided by scattering and polarization properties. In fibrous tissue such as the white matter of the brain, PS-OCT allows quantitative mapping of tissue birefringence. For the popular PS-OCT layout using a single circular input state, birefringence measurements are based on a straight-forward evaluation of phase retardation data. However, the accuracy of these measurements strongly depends on the signal-to-noise ratio (SNR) and is prone to mapping artifacts when the SNR is low. Here we present a simple yet effective approach for improving the accuracy of PS-OCT phase retardation and birefringence measurements. By performing a noise bias correction of the detected OCT signal amplitudes, the impact of the noise floor on retardation measurements can be markedly reduced. We present simulation data to illustrate the influence of the noise bias correction on phase retardation measurements and support our analysis with real-world PS-OCT image data.

Application of Polarization Sensitive-Optical Coherence Tomography to the Assessment of Phase Retardation in Subpleural Cancer in Rabbits.

Polarization sensitive-optical coherence tomography (PS-OCT) provides the unique advantage of being able to measure the optical characteristics of tissues by using polarized light. Although the well-organized fibers of healthy muscle can change the polarization states of passing light, damaged tissue has different behaviors. There are studies on optical imaging methods applied to the respiratory organs; however, they are restricted to structural imaging. In particular, the intercostal muscle situated under the pleura is very challenging to visualize due to the difficulty of access. In this study, PS-OCT was used to identify subpleural cancer in male New Zealand white rabbits (3.2-3.4kg) and to assess the phase retardation changes in normal and cancerous chest walls. VX2 cell suspension was injected between the intercostal muscle and parietal pleura and a tented area was observed by thoracic scope. A group of rabbits (n = 3) were sacrificed at day 7 after injection and another group (n = 3) at day 14. In the PS-OCT images, pleura thickness changes and muscle damage were criteria to understand the stages of the disease. The results of image and phase retardation analysis matched well with the pathologic examinations. We were able to visualize and analyze subpleural cancer by PS-OCT, which provided structural and functional information. The measured phase retardation could help to identify the margin of the tumor. For further studies, various approaches into other diseases using polarization light are expected to have positive results.

Investigation of the Clinical Potential of Polarization-Sensitive Optical Coherence Tomography in a Laryngeal Tumor Model.

The vocal cord tissue consists of three anatomical layers from the surface to deep inside: the epithelium that contains almost no collagen, the lamina propria that is composed of abundant collagen, and the vocalis muscle layer. It is clinically important to visualize the tissue microstructure using a non-invasive method, especially in the case of vocal cord nodules or cancer, since histological changes in each layer of the vocal cord cause changes in the voice. Polarization-sensitive optical coherence tomography (PS-OCT) enables phase retardation measurement to evaluate birefringence of tissue with varied organization of collagen fibers in different tissue layers. Therefore, PS-OCT can visualize structural changes between normal and abnormal vocal cord tissue. A rabbit laryngeal tumor model with different stages of tumor progression was investigated ex-vivo by PS-OCT. A phase retardation slope-based analysis, which quantifies the birefringence in different layers, was conducted to distinguish the epithelium, lamina propria, and muscle layers. The PS-OCT images showed a gradual decrease in birefringence from normal tissue to advanced tumor tissue. The quantitative analysis provided a more detailed comparison among different stages of the rabbit laryngeal tumor model, which was validated by the corresponding histological findings. Differences in tissue birefringence was evaluated by PS-OCT phase retardation measurement. It is also possible to indirectly infer the dysplastic changes based on the mucosal and submucosal alterations.

Stable fiber-based polarization-sensitive optical coherence tomography using polarization maintaining common-path interferometer.

.Significance: Our work advances the development of fiber-based polarization-sensitive optical coherence tomography (PS-OCT) by stabilizing the output polarization state of the light beam when the system is under environmental disturbance. While the fiber-based PS-OCT has been demonstrated previously, it remains a challenge for the traditional fiber-based PS-OCT to obtain a stable measurement when the optic fibers are disturbed by the environment. This important issue is addressed, paving the path for clinical translation of PS-OCT, which can provide a unique perspective of the biological samples.Aim: Polarization maintaining common-path (CP) interferometer is fabricated with the goal of providing a stable fiber-based PS-OCT imaging system that is only responsive to the polarization changes generated by the sample, immune to environmental conditions.Approach: The system is implemented by incorporating a CP interferometer together with polarization maintaining (PM) fibers. The PM fibers are used to preserve the two orthogonal linearly polarized components of the light during propagation. By sharing the CP in the sample and reference arms, any variations in phase retardation can be eliminated between the two channels in the PM fibers. The combination of the PM fiber and the CP interferometer ensures the stability of the output polarization state.Results: The stability of the proposed PS-OCT system is tested when a periodically stressed disturbance is applied to the fibers within the system. Stable in vivo PS-OCT images of the mouse thigh are demonstrated.Conclusions: We have demonstrated a stable fiber-based PS-OCT system that combined the PM fiber and the CP configuration together. We have shown that the output polarization states and the system sensitivity can keep stable over time under the environmental disturbances to the system.

In Vivo 3D Determination of Peripapillary Scleral and Retinal Layer Architecture Using Polarization-Sensitive Optical Coherence Tomography.

PurposeThe purpose of this paper was to determine the architecture of the collagen fibers of the peripapillary sclera, the retinal nerve fiber layer (RNFL), and Henle's fiber layer in vivo in 3D using polarization-sensitive optical coherence tomography (PS-OCT).MethodsSeven healthy volunteers were imaged with our in-house built PS-OCT system. PS-OCT imaging included intensity, local phase retardation, relative optic axis, and optic axis uniformity (OAxU). Differential Mueller matrix calculus was used for the first time in ocular tissues to visualize local orientations that varied with depth, incorporating a correction method for the fiber orientation in preceding layers.ResultsScleral collagen fiber orientation images clearly showed an inner layer with an orientation parallel to the RNFL orientation, and a deeper layer where the collagen was circularly oriented. RNFL orientation images visualized the nerve fibers leaving the optic nerve head (ONH) in a radial pattern. The phase retardation and orientation of Henle's fiber layer were visualized locally for the first time.ConclusionsPS-OCT successfully showed the orientation of the retinal nerve fibers, sclera, and Henle's fiber layer, and is to the extent of our knowledge the only technique able to do so in 3D in vivo.Translational RelevanceIn vivo 3D imaging of scleral collagen architecture and the retinal neural fibrous structures can improve our understanding of retinal biomechanics and structural alterations in different disease stages of myopia and glaucoma.

High-resolution polarization-sensitive optical coherence tomography for zebrafish muscle imaging.

Zebrafish are an important animal model, whose structure and function information can be used to study development, pathologic changes and genetic mutations. However, limited by the penetration depth, the available optical methods are difficult to image the whole-body zebrafish in juvenile and adult stages. Based on a home-made high-resolution polarization-sensitive optical coherence tomography (PS-OCT) system, we finished in vivo volumetric imaging for zebrafish, and various muscles can be clearly discerned by scanning from dorsal, ventral, and lateral directions. Besides structure information, polarization properties extracted from PS-OCT images provide abundant function information to distinguish different muscles. Furthermore, we found local retardation and local optic axis of zebrafish muscle are related to their composition and fiber orientation. We think high-resolution PS-OCT will be a promising tool in studying myopathy models of zebrafish.

Detection of Oral Dysplastic and Early Cancerous Lesions by Polarization-Sensitive Optical Coherence Tomography.

Detection of oral dysplastic and early-stage cancerous lesions is difficult with the current tools. Half of oral cancers are diagnosed in a late stage. Detection of early stromal change to predict malignant transformation is a new direction in the diagnosis of early-stage oral cancer. The application of new optical tools to image stroma in vivo is under investigation, and polarization-sensitive optical coherence tomography (PS-OCT) is potentially one of those tools. This is a preliminary study to sequentially image oral stromal changes from normal, hyperplasia, and dysplasia to early-stage cancer by PS-OCT in vivo. We used 4-Nitroquinoline-1-oxide drinking water to induce dysplasia and early-stage oral cancer in 19 K14-EGFP-miR-211-GFP transgenic mice. A total of 8 normal, 12 hyperplastic, 11 dysplastic, and 4 early-stage cancerous lesions were enrolled. A new analytic process of PS-OCT imaging was proposed, called an en-face birefringence map. From the birefringence map, the sensitivity, specificity, positive predictive value, and negative predictive values to detect dysplasia and early-stage cancer were 100.00%, 95.00%, 93.75%, and 100.00%, respectively, and the kappa value of these images between two investigators was 0.942. The mean size of malignant lesions detected in this study is 1.66 ± 0.93 mm. This pilot animal study validates the use of PS-OCT to detect small and early-stage oral malignancy with high accuracy and consistency.

Intracardiac radiofrequency ablation in living swine guided by polarization-sensitive optical coherence tomography.

Significance: Pulmonary vein isolation with catheter-based radiofrequency ablation (RFA) is carried out frequently to treat atrial fibrillation. However, RFA lesion creation is only guided by indirect information (e.g., temperature, impedance, and contact force), which may result in poor lesion quality (e.g., nontransmural) and can lead to reoccurrence or complications.Aim: The feasibility of guiding intracardiac RFA with an integrated polarization-sensitive optical coherence tomography (PSOCT)-RFA catheter in the right atria (RA) of living swine is demonstrated.Approach: In total, 12 sparse lesions were created in the RA of three living swine using an integrated PSOCT-RFA catheter with standard ablation protocol. PSOCT images were displayed in real time to guide catheter-tissue apposition. After experiments, post-processed PSOCT images were analyzed to assess lesion quality and were compared with triphenyltetrazolium chloride (TTC) lesion quality analysis.Results: Five successful lesions identified with PSOCT images were all confirmed by TTC analysis. In two ablations, PSOCT imaging detected gas bubble formation, indicating overtreatment. Unsuccessful lesions observed with PSOCT imaging were confirmed by TTC analysis.Conclusions: The results demonstrate that the PSOCT-RFA catheter provides real-time feedback to guide catheter-tissue apposition, monitor lesion quality, and possibly help avoid complications due to overtreatment, which may enable more effective and safer RFA treatment.

Polarization-sensitive Optical Coherence Tomography Imaging of Pleural Reaction Caused by Talc in an ex vivo Rabbit Model

Polarization-sensitive Optical Coherence Tomography Imaging of Pleural Reaction Caused by Talc in an ex vivo Rabbit Model

Detecting human articular cartilage degeneration in its early stage with polarization-sensitive optical coherence tomography.

Detecting articular cartilage (AC) degeneration in its early stage plays a critical role in the diagnosis and treatment of osteoarthritis (OA). Polarization-sensitive optical coherence tomography (PS-OCT) is sensitive to the alteration and disruption of collagen organization that happens during OA progression. This study proposes an effective OA evaluating method based on PS-OCT imaging. A slope-based analysis is applied on the phase retardation images to segment articular cartilage into three zones along the depth direction. The boundaries and birefringence coefficients (BRCs) of each zone are quantified. Two parameters, namely phase homogeneity index (PHI) and zonal distinguishability (Dz), are further developed to quantify the fluctuation within each zone and the zone-to-zone variation of the tissue birefringence properties. The PS-OCT based evaluating method then combines PHI and Dz to provide a G PS score for the severity of OA. The proposed method is applied to human hip joint samples and the results are compared with the grading by histology images. The G PS score shows very strong statistical significance in differentiating different stages of OA. Compared to using the BRC of each zone or a single BRC for the entire depth, the G PS score shows great improvement in differentiating early-stage OA. The proposed method is shown to have great potential to be developed as a clinical tool for detecting OA.

Temporal dynamics of muscle optical properties during degeneration and regeneration in a canine muscle xenograft model.

We studied time-dependent changes in muscle optical properties during degeneration and regeneration using polarization-sensitive optical coherence tomography (PSOCT). Excised canine muscle transplants in a xenograft mouse model were imaged ex vivo from 3- to 112-day post-transplantation. PSOCT images were quantified to evaluate post-transplantation changes of three optical/structural properties: attenuation, birefringence and fiber alignment. The birefringence and fiber alignment decreased after transplantation until 20∼30-day and recovered thereafter. The attenuation coefficient showed a reversed trend over the same period of time. These results suggest that optical properties could be used for monitoring skeletal muscle degeneration and regeneration.

Subretinal Fibrosis Detection Using Polarization Sensitive Optical Coherence Tomography.

PurposeSubretinal fibrosis (SRFib) is an important cause of permanent loss-of-vision diseases with submacular neovascularization, but a reliable diagnostic method is currently missing. This study uses polarization-sensitive optical coherence tomography (PS-OCT) to detect SRFib within retinal lesions by measurement of its birefringent collagen fibers.MethodsTwenty-five patients were enrolled with retinal pathology in one or both eyes containing (1) suspected SRFib, (2) lesions suspected not to be fibrotic, or (3) lesions with doubtful presence of SRFib. All eyes were evaluated for SRFIb using conventional diagnostics by three retinal specialists. PS-OCT images were visually evaluated for SRFib based on cumulative phase retardation, local birefringence, and optic axis uniformity.ResultsTwenty-nine eyes from 22 patients were scanned successfully. In 13 eyes, SRFib was diagnosed by all retinal specialists; of these, 12 were confirmed by PS-OCT and one was inconclusive. In nine eyes, the retinal specialists expected no SRFib, which was confirmed by PS-OCT in all cases. In seven eyes, the retinal specialists’ evaluations were inconsistent with regard to the presence of SRFib. PS-OCT confirmed the presence of SRFib in four of these eyes and the absence of SRFib in two eyes and was inconclusive in one eye.ConclusionsIn 21 out of 22 eyes, PS-OCT confirmed the evaluation of retinal specialists regarding the presence of SRFib. PS-OCT provided additional information to distinguish SRFib from other tissues within subretinal neovascular lesions in 6 out of 7 eyes.Translational RelevancePS-OCT can identify and quantify SRFib in doubtful cases for which a reliable diagnosis is currently lacking.

Fiber-based polarization-sensitive optical coherence tomography of a minimalistic system configuration.

We present a very simple method of constructing a polarization-sensitive optical coherence tomography (PS-OCT) system. An ordinary fiber-based swept-source OCT system was reconfigured for PS-OCT by adding a long section of polarization-maintaining fiber in the sample arm. Two polarization modes of a large group-delay difference formed spatially distinguished polarization channels. The depth-encoded information on the polarization states was retrieved by an amplitude-based analysis. We found that our method provides an economic scheme of PS-OCT. It demonstrates that an ordinary OCT system can be easily reconfigured for PS-OCT imaging if it has sufficient margins in the imaging range.

Large Field of View Corneal Epithelium and Bowman's Layer Thickness Maps in Keratoconic and Healthy Eyes

To assess differences between epithelium thickness (ET) and Bowman's layer thickness (BLT) maps in keratoconic eyes and healthy eyes. Cross-sectional study. Setting: institutional. 47 patients (1 eye) with keratoconus (KC) and 20 healthy subjects (1 eye). epithelium and Bowman's layer measurements were performed by using custom-designed polarization-sensitive optical coherence tomography (PS-OCT) with a conical scanning optics design. En face corneal ET and BLT maps with a diameter of 11mm were computed. Main outcome measurements were mean ET and BLT of 25 sectors; the thinnest (minET, minBLT) and thickest sectors (maxET, maxBLT) were assessed. Ratios between thinnest/thickest sectors (R1) and between mean ET and BLT of the inferior temporal quadrant/superior nasal quadrant (R2) were calculated (R1ET, R1BLT; R2ET, R2BLT). Receiver operator characteristic (ROC) curve analysis was used to assess the diagnostic power of statistically different parameters. In healthy eyes, smooth ET maps were observed. KC eyes showed a "doughnut pattern." The BLT maps of healthy eyes had a smooth appearance, but highly irregular "moth"-like damage pattern could be observed in keratoconic eyes. Highest area under the curve values were found for the thinnest sector of the BLT map, the R1ET, and the thinnest sector of the ET map. PS-OCT imaging enables the visualization of significant differences of the corneal epithelium and the Bowman's layer in en face maps covering almost the entire cornea. ET and BLT profiles could clearly show their diagnostic importance for the distinguishing of keratoconic eyes and healthy eyes.

Slope-based segmentation of articular cartilage using polarization-sensitive optical coherence tomography phase retardation image.

.A segmentation method based on phase retardation measurements from polarization-sensitive optical coherence tomography (PS-OCT) is developed to differentiate the structural zones of articular cartilage. The organization of collagen matrix in articular cartilage varies over the different structural zones, generating different tissue birefringence. Analyzing the slope of the accumulated phase retardation at different depths can detect the variation in tissue birefringence and be used to segment the structural zones. The method is validated on phantoms composed of layers of different materials. Articular cartilage samples from adult swine are segmented with the method. The characteristics in each segmented zone are also examined by histology and high-resolution second-harmonic generation imaging, showing distinctive properties that match with the anatomical structure of articular cartilage. The segmentation algorithm is also applied on PS-OCT images acquired at multiple illumination angles, where the angular dependence of tissue birefringence in the deep zone is detected. This method offers a noninvasive imaging approach to differentiating the structural zones of articular cartilage, as well as a quantification approach based on the phase retardation measurements of PS-OCT. This method has great potential in studying depth-related progression of cartilage degeneration.

Identification and Quantification of the Angiofibrotic Switch in Neovascular AMD.

We quantify volumetric changes of subretinal hyperreflective material (SHRM) and determine the conversion toward subretinal fibrosis, the angiofibrotic switch, under anti-VEGF therapy using polarization-sensitive optical coherence tomography (PS-OCT). A total of 50 eyes of 50 patients with treatment-naïve neovascular age-related macular degeneration (AMD) were included in this prospective observational study: 26 diagnosed with type 1 choroidal neovascularization (CNV), seven with type 2 CNV, 11 with mixed type CNV, three with a retinal angiomatous proliferation (RAP) lesion and three with a polypoidal choroidal vasculopathy (PCV). Patients were imaged at baseline and at the end of the loading phase (after treatment with three intravitreal anti-VEGF injections) using a PS-OCT system with a scanning angle of 30° × 30° and a scan pattern of 1024 × 250 A-scans. The device is capable of detecting fibrosis based on birefringence and the RPE based on depolarization. The volume of SHRM was quantified by manual delineation in each PS-OCT B-scan and interpolation between B-scans using proprietary reading center certified software. The occurrence of fibrosis detected by PS-OCT was compared to the clinical presentation of subretinal fibrosis. Of 50 eyes, 28 had SHRM at baseline. Seven of these eyes had subretinal fibrosis within 3 months, six of which could be detected unambiguously based on PS-OCT imaging. SHRM thickness and volume at month 3 (P = 0.001 and P = 0.02) were significantly larger and the reduction of SHRM thickness and volume (P = 0.002 and P = 0.027) in response to therapy were significantly less pronounced in eyes with fibrosis. SHRM volume decreases significantly under anti-VEGF therapy. However, lesions unresponsive to therapy may progress to fibrosis as early as 3 months. Reduction in SHRM thickness may be a prognostic marker for treatment response.

偏振敏感光学相干层析成像系统中样品光偏振对样品双折射相位延迟测量的影响

偏振敏感光学相干层析成像系统中样品光偏振对样品双折射相位延迟测量的影响

Imaging and visualization of the polarization state of the probing beam in polarization-sensitive optical coherence tomography

We propose a simple and efficient method of color-encoded Stokes parameters to visualize the polarization states for polarization-sensitive optical coherence tomography (PS-OCT) of biological tissue. In this method, polarization states of the probing light are detected and described in the Stokes domain. Three primary colors of red, green, and blue are used to code Stokes parameters of Q, U, and V, respectively, which can be used to represent and visualize each unique polarization state. A strategy that uses the polarization state as the PS-OCT imaging parameter is first introduced to obtain high contrast images of the birefringent samples. Then, color-based automatic segmentation of birefringent components from 3D scanned tissue volume is proposed to isolate the network of the 3D nerve bundles in a mouse brain without cutting the brain into slices. Experimental validation and demonstrations are given by imaging ex vivo mouse tail and brain tissues to show the usefulness of proposed polarization state imaging and segmentation methods.

Complementary use of polarization-sensitive and standard OCT metrics for enhanced intraoperative differentiation of breast cancer.

We report the development and implementation of an intraoperative polarization-sensitive optical coherence tomography (PS-OCT) system for enhancing breast cancer detection. A total of 3440 PS-OCT images were intraoperatively acquired from 9 human breast specimens diagnosed by H&E histology as healthy fibro-adipose tissue (n = 2), healthy stroma (n = 2), or invasive ductal carcinoma (IDC, n = 5). A standard OCT-based metric (coefficient of variation (CV)) and PS-OCT-based metrics sensitive to biological tissue from birefringence (i.e., retardation and degree of polarization uniformity (DOPU)) were derived from 398 statistically different and independent images selected by correlation coefficient analysis. We found the standard OCT-based metric and PS-OCT-based metrics were complementary for the differentiation of healthy fibro-adipose tissue, healthy stroma, and IDC. While the CV of fibro-adipose tissue was significantly higher (p<0.001) than those of either stroma or IDC, the CV difference between stroma and IDC was minimal. On the other hand, stroma was associated with significantly higher (p<0.001) retardation and significantly lower (p<0.001) DOPU as compared to IDC. By leveraging the complementary information acquired by the intraoperative PS-OCT system, healthy fibro-adipose tissue, healthy stroma, and IDC can be differentiated with an accuracy of 89.4%, demonstrating the potential of PS-OCT as an adjunct modality for enhanced intraoperative differentiation of human breast cancer.

Integrated RFA/PSOCT catheter for real-time guidance of cardiac radio-frequency ablation.

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.