Polarization-sensitive Optical Coherence Tomography Research Articles

Aging of deep venous thrombosis in-vivo using polarization sensitive optical coherence tomography

Deep venous thrombosis (DVT) is a medical condition with significant post-event morbidity and mortality coupled with limited treatment options. Treatment strategy and efficacy are highly dependent on the structural composition of the thrombus, which evolves over time from initial formation and is currently unevaluable with standard clinical testing. Here, we investigate the use of intravascular polarization-sensitive optical coherence tomography (PS-OCT) to assess thrombus morphology and composition in a rat DVT model in-vivo, including changes that occur over the thrombus aging process. PS-OCT measures tissue birefringence, which provides contrast for collagen and smooth muscle cells that are present in older, chronic clots. Thrombi in the inferior vena cava of two cohorts of rats were imaged in-vivo with intravascular PS-OCT at 24 hours (acute, nrats = 3, 73 cross-sections) or 28 days (chronic, nrats = 4, 41 cross-sections) after thrombus formation. Co-registered histology was labelled by an independent pathologist to establish ground-truth clot composition. Automated analysis of OCT cross-sectional images differentiated acute and chronic thrombi with 97.6% sensitivity and 98.6% specificity using a linear discriminant model comprised of both polarization and conventional OCT metrics. These results support PS-OCT as a highly sensitive imaging modality for the assessment of DVT composition to differentiate acute and chronic thrombi. Intravascular PS-OCT imaging could be integrated with advanced catheter-based treatment strategies and serve to guide therapeutic decision-making and deployment, by offering an accurate assessment of DVT patients in real time.

Retinal Nerve Fiber Layer Damage Assessment in Glaucomatous Eyes Using Retinal Retardance Measured by Polarization-Sensitive Optical Coherence Tomography.

To assess the diagnostic performance and structure-function association of retinal retardance (RR), a customized metric measured by a prototype polarization-sensitive optical coherence tomography (PS-OCT), across various stages of glaucoma. This cross-sectional pilot study analyzed 170eyes from 49 healthy individuals and 68 patients with glaucoma. The patients underwent PS-OCT imaging and conventional spectral-domain optical coherence tomography (SD-OCT), as well as visual field (VF) tests. Parameters including RR and retinal nerve fiber layer thickness (RNFLT) were extracted from identical circumpapillary regions of the fundus. Glaucomatous eyes were categorized into early, moderate, or severe stages based on VF mean deviation (MD). The diagnostic performance of RR and RNFLT in discriminating glaucoma from controls was assessed using receiver operating characteristic (ROC) curves. Correlations among VF-MD, RR, and RNFLT were evaluated and compared within different groups of disease severity. The diagnostic performance of both RR and RNFLT was comparable for glaucoma detection (RR AUC = 0.98, RNFLT AUC = 0.97; P = 0.553). RR showed better structure-function association with VF-MD than RNFLT (RR VF-MD = 0.68, RNFLT VF-MD = 0.58; z = 1.99; P = 0.047) in glaucoma cases, especially in severe glaucoma, where the correlation between VF-MD and RR (r = 0.73) was significantly stronger than with RNFLT (r = 0.43, z = 1.96, P = 0.050). In eyes with early and moderate glaucoma, the structure-function association was similar when using RNFLT and RR. RR and RNFLT have similar performance in glaucoma diagnosis. However, in patients with glaucoma especially severe glaucoma, RR showed a stronger correlation with VF test results. Further research is needed to validate RR as an indicator for severe glaucoma evaluation and to explore the benefits of using PS-OCT in clinical practice. We demonstrated that PS-OCT has the potential to evaluate the status of RNFL structural damage in eyes with severe glaucoma, which is currently challenging in clinics.

Observation on the changes of visual field and optic nerve fiber layer thickness in patients with early diabetic retinopathy

BackgroundDiabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) and is a leading cause of vision loss. Early detection of DR-related neurodegenerative changes is crucial for effective management and prevention of vision loss in diabetic patients. MethodsIn this study, we employed spectral-domain polarization-sensitive optical coherence tomography (SD PS-OCT) to assess retinal nerve fiber layer (RNFL) changes in 120 eyes from 60 types 1 DM patients without clinical DR and 60 age-matched healthy controls. Visual field testing was performed to evaluate mean sensitivity (MS) and mean defect (MD) as indicators of visual function. ResultsSD PS-OCT measurements revealed significant reductions in RNFL birefringence, retardation, and thickness in type 1 DM patients compared to healthy controls. Visual field testing showed decreased MS and increased MD in DM patients, indicating functional impairment correlated with RNFL alterations. ConclusionOur findings demonstrate early neurodegenerative changes in the RNFL of type 1 DM patients without clinical DR, highlighting the potential of SD PS-OCT as a sensitive tool for early detection of subclinical DR-related neurodegeneration. These results underscore the importance of regular ophthalmic screenings in diabetic patients to enable timely intervention and prevent vision-threatening complications.

In situ pulmonary mucus hydration assay using rotational and translational diffusion of gold nanorods with polarization-sensitive optical coherence tomography.

Assessing the nanostructure of polymer solutions and biofluids is broadly useful for understanding drug delivery and disease progression and for monitoring therapy. Our objective is to quantify bronchial mucus solids concentration (wt. %) during hypertonic saline (HTS) treatment in vitro via nanostructurally constrained diffusion of gold nanorods (GNRs) monitored by polarization-sensitive optical coherence tomography (PS-OCT). Using PS-OCT, we quantified GNR translational () and rotational () diffusion coefficients within polyethylene oxide solutions (0 to 3wt. %) and human bronchial epithelial cell (hBEC) mucus (0 to 6.4wt. %). Interpolation of and data is used to develop an assay to quantify mucus concentration. The assay is demonstrated on the mucus layer of an air-liquid interface hBEC culture during HTS treatment. In polymer solutions and mucus, and monotonically decrease with increasing concentration. is more sensitive than to changes above 1.5wt. % of mucus and exhibits less intrasample variability. Mucus on HTS-treated hBEC cultures exhibits dynamic mixing from cilia. A region of hard-packed mucus is revealed by measurements. The extended dynamic range afforded by simultaneous measurement of and of GNRs using PS-OCT enables resolving concentration of the bronchial mucus layer over a range from healthy to disease in depth and time during HTS treatment in vitro.

Digital calibration method to enable depth-resolved all-fiber polarization sensitive optical coherence tomography with an arbitrary input polarization state

We present a fully integrated depth-resolved all fiber-based polarization sensitive optical coherence tomography (PSOCT). In contrast to conventional fiber-based PSOCT systems, which require additional modules to generate two or more input polarization states, or a pre-adjustment procedure to generate a circularly polarized light, the proposed all-fiber PSOCT system can provide depth-resolved birefringent imaging using an arbitrary single input polarization state. Utilizing the discrete differential geometry (DDG)-based polarization state tracing (PST) method, combined with several geometric rotations and transformations in the Stokes space, two problems induced by the optical fibers can be mitigated: 1) The change in the polarization state introduced by the optical fibers can be effectively compensated using a calibration target at the distal end of the probe, and the computations of the local axis orientation and local phase retardation can be achieved with a single arbitrary input polarization state, eliminating the need for a pre-defined input polarization state, allowing a flexible system design and user-friendly experimental procedure; 2) The polarization mode dispersion (PMD) induced by the optical fibers can be compensated digitally without the requirement of additional input polarization states, providing an accurate PSOCT imaging result. To demonstrate the performance of the proposed method, the depth resolved PSOCT results of a plastic phantom and in vivo skin imaging are obtained using the proposed all-fiber PSOCT system.

Reducing noise in polarization-sensitive optical coherence tomography for high-quality local phase retardation imaging

Local phase retardation (LPR) is increasingly recognized as a crucial biomarker for assessing disease progression. However, the presence of speckle noise significantly challenges its accuracy and polarization contrast. To address this challenge, we propose a signal-processing strategy aimed at reducing the impact of noise on LPR measurements. In this approach, the LPR is reconstructed by polar decomposition after averaging multiple Mueller matrices from different overlapping sub-spectra. To optimize measurement accuracy, we systematically combined and traversed different sub-spectral numbers and bandwidths. By examining the quarter-wave plate and glass slide, high-accuracy phase retardation measurements were successfully verified, and the maximum polarization contrast was improved by 23%. Moreover, experimental results from multi-tissue imaging vividly illustrate that the equivalent number of looks (ENL) and polarization contrast were improved by 18% and 19%, respectively. This outcome indicates that our proposed strategy can effectively reduce the noise spikes, enhancing tissue discrimination capabilities.

Current Status and Future Perspectives of Optic Nerve Imaging in Glaucoma.

Being the primary site of degeneration, the optic nerve has always been the focus of structural glaucoma assessment. The technical advancements, mainly of optical coherence tomography (OCT), now allow for a very precise quantification of the optic nerve head and peripapillary retina morphology. By far the most commonly used structural optic nerve parameter is the thickness of the parapapillary retinal nerve fiber, which has great clinical utility but also suffers from significant limitations, mainly in advanced glaucoma. Emerging novel imaging technologies, such as OCT angiography, polarization-sensitive or visible-light OCT and adaptive optics, offer new biomarkers that have the potential to significantly improve structural glaucoma diagnostics. Another great potential lies in the processing of the data already available. Artificial intelligence does not only help increase the reliability of current biomarkers but can also integrate data from various imaging modalities and other clinical measures to increase diagnostic accuracy. And it can, in a more efficient way, draw information from available datasets, such as an OCT scan, compared to the current concept of biomarkers, which only use a fraction of the whole dataset.

High-Sensitivity Polarization Sensitive Optical Coherence Tomography Based on Numerical Correction for Perfect Circularly Polarized Light

Polarization sensitive optical coherence tomography (PSOCT) makes use of the birefringence information of the sample to compensate for the lack of internal tissue-specific contrast in conventional optical coherence tomography (OCT). Circularly polarized light is always used as an incident beam in PSOCT, but it is difficult to have perfect in practice. The manual calibration method of circularly polarized light suffers from the problems of complicated calibration operation and lack of stability. This study proposes a simple method to enhance the imaging of PSOCT without altering the system. A numerical calibration of circularly polarized light can be implemented using the original system setup, ensuring that the system’s complexity remains unchanged. Enhancements in imaging quality can be achieved through an algorithmic analysis of the captured interference fringe data. This calibration is applied in the field map of interference data before being quadrature-assembled. Notably, the proposed approach achieves high sensitivity in PSOCT. The birefringence image shows a more obvious layered structure. Improvements in the signal-to-noise ratio (SNR) were demonstrated for chicken breast, pork, and beef imaging at about 20 dB.

Skin characterization of diabetes mellitus revealed by polarization-sensitive optical coherence tomography imaging.

Diabetes can lead to the glycation of proteins and dysfunction of skin collagen. Skin lesions are a prevalent clinical symptom of diabetes mellitus (DM). Early diagnosis and assessing the efficacy of treatment for DM are crucial for patient health management. However, performing a non-invasive skin assessment in the early stages of DM is challenging. By using the polarization-sensitive optical coherent tomography (PS-OCT) imaging technique, it is possible to noninvasively assess the skin changes caused by diabetes. The PS-OCT was used to monitor the polarization characteristics of mouse skin at different stages of diabetes. Based on a multi-layered adhesive tape model, we found that the polarization characteristics (retardation, optic axis, and polarization uniformity) were sensitive to the microstructure changes in the samples. Through this method, we observed significant changes in the polarization states of the skin as diabetes progressed. This was in line with the detected microstructure changes in skin collagen fibers using scanning electron microscopy. This study presents a highly useful approach for non-invasive skin assessment of diabetes.

Polarization-Sensitive OCT Imaging of Scleral Abnormalities in Eyes With High Myopia and Dome-Shaped Macula

The relevance of visualizing scleral fiber orientation may offer insights into the pathogenesis of pathologic myopia, including dome-shaped maculopathy (DSM). To investigate the orientation and density of scleral collagen fibers in highly myopic eyes with and without DSM by polarization-sensitive optical coherence tomography (PS-OCT). This case series included patients with highly myopic eyes (defined as a refractive error ≥6 diopters or an axial length ≥26.5 mm) with and without a DSM examined at a single site in May and June 2019. Analysis was performed from September 2019 to October 2023. The PS-OCT was used to study the birefringence and optic axis of the scleral collagen fibers. The orientation and optic axis of scleral fibers in inner and outer layers of highly myopic eyes were assessed, and the results were compared between eyes with and without a DSM. A total of 72 patients (51 [70.8%] female; mean [SD] age, 61.5 [12.8] years) were included, and 89 highly myopic eyes were examined (mean [SD] axial length, 30.4 [1.7] mm); 52 (58.4%) did not have a DSM and 37 (41.6%) had a DSM (10 bidirectional [27.0%] and 27 horizontal [73.0%]). Among the 52 eyes without DSM, the 13 eyes with simple high myopia had primarily inner sclera visible, displaying radially oriented fibers in optic axis images. In contrast, the entire thickness of the sclera was visible in 39 eyes with pathologic myopia. In these eyes, the optic axis images showed vertically oriented fibers within the outer sclera. Eyes presenting with both horizontal and bidirectional DSMs had clusters of fibers with low birefringence at the site of the DSM. In the optic axis images, horizontally or obliquely oriented scleral fibers were aggregated in the inner layer at the DSM. The vertical fibers located posterior to the inner fiber aggregation were not thickened and appeared thin compared with the surrounding areas. This study using PS-OCT revealed inner scleral fiber aggregation without outer scleral thickening at the site of the DSM in highly myopic eyes. Given the common occurrence of scleral pathologies, such as DSM, and staphylomas in eyes with pathologic myopia, recognizing these fiber patterns could be important. These insights may be relevant to developing targeted therapies to address scleral abnormalities early and, thus, mitigate potential damage to the overlying neural tissue.

Dual modality intravascular catheter system combining pulse-sampling fluorescence lifetime imaging and polarization-sensitive optical coherence tomography.

The clinical management of coronary artery disease and the prevention of acute coronary syndromes require knowledge of the underlying atherosclerotic plaque pathobiology. Hybrid imaging modalities capable of comprehensive assessment of biochemical and morphological plaques features can address this need. Here we report the first implementation of an intravascular catheter system combining fluorescence lifetime imaging (FLIm) with polarization-sensitive optical coherence tomography (PSOCT). This system provides multi-scale assessment of plaque structure and composition via high spatial resolution morphology from OCT, polarimetry-derived tissue microstructure, and biochemical composition from FLIm, without requiring any molecular contrast agent. This result was achieved with a low profile (2.7 Fr) double-clad fiber (DCF) catheter and high speed (100 fps B-scan rate, 40 mm/s pullback speed) console. Use of a DCF and broadband rotary junction required extensive optimization to mitigate the reduction in OCT performance originating from additional reflections and multipath artifacts. This challenge was addressed by the development of a broad-band (UV-visible-IR), high return loss (47 dB) rotary junction. We demonstrate in phantoms, ex vivo swine coronary specimens and in vivo swine heart (percutaneous coronary access) that the FLIm-PSOCT catheter system can simultaneously acquire co-registered FLIm data over four distinct spectral bands (380/20 nm, 400/20 nm, 452/45 nm, 540/45 nm) and PSOCT backscattered intensity, birefringence, and depolarization. The unique ability to collect complementary information from tissue (e.g., morphology, extracellular matrix composition, inflammation) with a device suitable for percutaneous coronary intervention offers new opportunities for cardiovascular research and clinical diagnosis.

Full-range depth-encoded swept source polarization sensitive optical coherence tomography.

To realize the high sensitivity polarization sensitive optical coherence tomography (PS-OCT) imaging, a fiber-based full-range depth-encoded swept source PS-OCT (SS-PS-OCT) method is proposed. The two OCT images corresponding to the orthogonal polarized input light are located on the high sensitivity imaging region of the opposite sides relative to the zero optical path difference position. The full-range OCT images can be obtained by implementing the spatial phase modulation in the reference arm. The detection sensitivity of the system was measured experimentally to be 67 dB when the imaging depth approaching to 2 mm. The imaging of the biological tissue verifies that the proposed full-range depth-encoded SS-PS-OCT system has the higher detection sensitivity compared with the conventional depth encoded SS-PS-OCT system. Finally, we demonstrated the full-range high sensitivity phase retardation image of the bovine tendon and skin of human fingertip. The fiber-based full-range depth-encoded SS-PS-OCT method can realize the high sensitivity birefringence imaging in the medical diagnosis scenes with the requirements for long imaging range and high detection sensitivity.

Segmentation of anatomical layers and imaging artifacts in intravascular polarization sensitive optical coherence tomography using attending physician and boundary cardinality losses.

Intravascular ultrasound and optical coherence tomography are widely available for assessing coronary stenoses and provide critical information to optimize percutaneous coronary intervention. Intravascular polarization-sensitive optical coherence tomography (PS-OCT) measures the polarization state of the light scattered by the vessel wall in addition to conventional cross-sectional images of subsurface microstructure. This affords reconstruction of tissue polarization properties and reveals improved contrast between the layers of the vessel wall along with insight into collagen and smooth muscle content. Here, we propose a convolutional neural network model, optimized using two new loss terms (Boundary Cardinality and Attending Physician), that takes advantage of the additional polarization contrast and classifies the lumen, intima, and media layers in addition to guidewire and plaque shadows. Our model segments the media boundaries through fibrotic plaques and continues to estimate the outer media boundary behind shadows of lipid-rich plaques. We demonstrate that our multi-class classification model outperforms existing methods that exclusively use conventional OCT data, predominantly segment the lumen, and consider subsurface layers at most in regions of minimal disease. Segmentation of all anatomical layers throughout diseased vessels may facilitate stent sizing and will enable automated characterization of plaque polarization properties for investigation of the natural history and significance of coronary atheromas.

Polarization-Sensitive Optical Coherence Tomography for Monitoring De- and Remineralization of Bovine Enamel In Vitro.

Early caries diagnosis still challenges dentistry. Polarization-sensitive optical coherence tomography (PS-OCT) is promising to detect initial lesions non-invasively in depth-resolved cross-sectional visualization. PS-OCT with determined degree of polarization (DOP) imaging provides an intuitive demineralization contrast. The aim of this study is to evaluate the suitability of DOP-based PS-OCT imaging to monitor controlled de- and remineralization progression for the first time and to introduce it as a valid, non-destructive in vitro detection method. Twelve standardized bovine enamel specimens were divided in different groups and demineralized with hydrochloric acid (HCl) as well as partly remineralized with fluoride over a 14-day pH-cycling experiment. The specimens were stored in artificial saliva and sodium chloride (NaCl), respectively. Progress measurements with PS-OCT were made with polarization-sensitive en faceand B-scan mode for qualitative evaluation. The specimens demineralized in HCl showed the most pronounced surface change (lowest DOP) and the most significant increase in depolarization. Additional fluoride treatment and the storage in artificial saliva resulted in the opposite (highest DOP). Therefore, DOP-based PS-OCT imaging appears to be a valuable technique for visualization and monitoring of enamel demineralization and remineralization processes in vitro. However, these findings need to be confirmed in human teeth ex vivo or in situ.

Quantification of smooth muscle in human airways by polarization-sensitive optical coherence tomography requires correction for perichondrium.

Quantifying airway smooth muscle (ASM) in patients with asthma raises the possibility of improved and personalized disease management. Endobronchial polarization-sensitive optical coherence tomography (PS-OCT) is a promising quantitative imaging approach that is in the early stages of clinical translation. To date, only animal tissues have been used to assess the accuracy of PS-OCT to quantify absolute (rather than relative) ASM in cross sections with directly matched histological cross sections as validation. We report the use of whole fresh human and pig airways to perform a detailed side-by-side qualitative and quantitative validation of PS-OCT against gold-standard histology. We matched and quantified 120 sections from five human and seven pig (small and large) airways and linked PS-OCT signatures of ASM to the tissue structural appearance in histology. Notably, we found that human cartilage perichondrium can share with ASM the properties of birefringence and circumferential alignment of fibers, making it a significant confounder for ASM detection. Measurements not corrected for perichondrium overestimated ASM content several-fold (P < 0.001, paired t test). After careful exclusion of perichondrium, we found a strong positive correlation (r = 0.96, P < 0.00001) of ASM area measured by PS-OCT and histology, supporting the method's application in human subjects. Matching human histology further indicated that PS-OCT allows conclusions on the intralayer composition and in turn potential contractile capacity of ASM bands. Together these results form a reliable basis for future clinical studies.NEW & NOTEWORTHY Polarization-sensitive optical coherence tomography (PS-OCT) may facilitate in vivo measurement of airway smooth muscle (ASM). We present a quantitative validation correlating absolute ASM area from PS-OCT to directly matched histological cross sections using human tissue. A major confounder for ASM quantification was observed and resolved: fibrous perichondrium surrounding hyaline cartilage in human airways presents a PS-OCT signature similar to ASM for birefringence and optic axis orientation. Findings impact the development of automated methods for ASM segmentation.

Revealing stress-induced changes equivalence between polarization-sensitive optical coherence tomography and polarimetric camera measurements

Polarization-Sensitive Optical Coherence Tomography (PS-OCT) is a widely-used technique for high-resolution material characterization since it allows for real-time structural analysis and imperfections identification. Nevertheless, when the sample is too big or imperfections are not on the micrometric scale, PS-OCT imaging can become too complex to be performed on a regular basis. Alternatively, polarimetric camera (PCam) imaging can obtain polarization measurements of a sample at a macroscopic scale, allowing for a faster and cheaper inspection of the sample. In doing so, the depth-profiling capabilities of PS-OCT would be forfeited, as well as the ability to measure other than the linear polarization qualities of the light beam. This paper compares the data that can be easily extracted from a PCam, with the complete and more complex characterization of the polarization of light that can be obtained with a PS-OCT device. The comparison of both systems is assessed through the evaluation of their performance when measuring different stress states of a sample.

Optical coherence tomography ‐ Additional contrast mechanisms, future trends, and cutting‐edge technological developments

In ophthalmology, structural OCT measurements are now used routinely in the clinic to help with the diagnosis and management of anterior‐segment and retinal disorders. More recently, the development of additional or complementary contrast mechanisms, as well as novel approaches targeted at enhancing resolution, have opened up new opportunities for ophthalmic OCT applications. For example, different algorithms have been proposed to contrast the retinal and choroidal vasculature and analyse blood flow, which extend clinical spectral‐domain OCT (SD‐OCT) from structural to functional imaging capabilities. Such OCT‐based angiography (OCT‐A) relies on sequential capture of SD‐OCT images at the same tissue region and the subsequent analysis of temporal variations in the OCT signal. OCT‐A algorithms differ in this analysis, specifically in how they create contrast between flow and static tissue (i.e. how they distinguish vascular from other structures). Common is the assumption that the change in the OCT signal over time is mainly due to the motion of backscattering particles, such as erythrocytes. With so‐called polarization‐sensitive OCT (PS‐OCT), polarized light has also been employed to create tissue‐specific contrast. PS‐OCT has shown great potential for functional and quantitative imaging and exploits the fact that various tissues, particularly birefringent structures in the cornea and retina (e.g. corneal collagen fibrils and the retinal nerve fibre layer), can change the state of polarization of incident light. Other technological developments have focused on enhancing OCT's resolution. Note that while OCT enables high‐resolution cross‐sectional views (where the axial resolution is determined by the spectral bandwidth of the light source), it has a limited lateral or en‐face resolution. Integrating adaptive optics (AO) is one method to improve the lateral resolution of retinal OCT. This lecture will discuss recent technological advances and cutting‐edge developments, leading to additional contrast mechanisms and functional extensions (e.g. OCT‐A, PS‐OCT) or improved lateral resolution (e.g. AO‐OCT).

Geometric phase for investigation of nanostructures in approaches of polarization-sensitive optical coherence tomography

Proposed paper presents the latest results in the framework of polarization-sensitive low-coherence interferometry related to new approaches for using the geometric phase to reproduce the polarization structure of a biological transparent anisotropic micro (nano) object. The polarization parameters of an anisotropic object are measured in real time on the basis of a modified Mach-Zehnder interferometer. The advantage of using the geometric phase is the diagnostic of polarization anisotropic surface (subsurface) nanosized layers in a non-contact, non-invasive manner.

Polarization-artifact reduction and accuracy improvement of Jones-matrix polarization-sensitive optical coherence tomography by multi-focus-averaging based multiple scattering reduction.

Polarization-sensitive optical coherence tomography (PS-OCT) is a promising biomedical imaging tool for the differentiation of various tissue properties. However, the presence of multiple-scattering (MS) signals can degrade the quantitative polarization measurement accuracy. We demonstrate a method to reduce MS signals and increase the measurement accuracy of Jones matrix PS-OCT. This method suppresses MS signals by averaging multiple Jones matrix volumes measured using different focal positions. The MS signals are decorrelated among the volumes by focus position modulation and are thus reduced by averaging. However, the single scattering signals are kept consistent among the focus-modulated volumes by computational refocusing. We validated the proposed method using a scattering phantom and a postmortem medaka fish. The results showed reduced artifacts in birefringence and degree-of-polarization uniformity measurements, particularly in deeper regions in the samples. This method offers a practical solution to mitigate MS-induced artifacts in PS-OCT imaging and improves quantitative polarization measurement accuracy.

Multi-Scale Label-Free Human Brain Imaging with Integrated Serial Sectioning Polarization Sensitive Optical Coherence Tomography and Two-Photon Microscopy.

The study of aging and neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation-free reconstruction. Here, the authorsdescribe an integrated serial sectioning polarization-sensitive optical coherence tomography (PSOCT) and two photon microscopy (2PM) system to provide label-free multi-contrast imaging of intact brain structures, including scattering, birefringence, and autofluorescence of human brain tissue. The authors demonstrate high-throughput reconstruction of 4 × 4 × 2cm3 sample blocks and simple registration between PSOCT and 2PM images that enablecomprehensive analysis of myelin content, vascular structure, and cellular information. The high-resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical properties on the same sample, revealing the densely packed fibers, capillaries, and lipofuscin-filled cell bodies in the cortex and white matter. It is shown that theimaging system enables quantitative characterization of various pathological features in aging process, including myelin degradation, lipofuscin accumulation, and microvascular changes, which opens up numerous opportunities in the study of neurodegenerative diseases in the future.