Rationale Airway smooth muscle (ASM) remodelling is a central feature of asthma pathology but cannot currently be measured in vivo with adequate coverage, limiting the development of targeted therapies. The objective of the present study was to trial bronchoscopic polarisation-sensitive optical coherence tomography (PS-OCT) to assess ASM remodelling and its distribution in vivo throughout the lungs in individuals with and without asthma. Methods Participants with (n=7) and without (n=13) doctor-diagnosed asthma undergoing bronchoscopy were recruited to obtain PS-OCT imaging data during the procedure. ASM area in large and small airways was measured and normalised for airway size (lumen perimeter). ASM remodelling was defined as ASM mass (ASM area/perimeter 2 ) >1.96 sd above a histological reference control group. Measurements and main results PS-OCT quantified ASM mass was greater in participants with asthma (median 0.0072, Q1–Q3 0.0064–0.0089) compared with the control group (0.0039, 0.0035–0.0049), (p=0.012). ASM remodelling was also more prevalent in the asthma group (44% of airways examined, 24–53%) than in the control group (0%, 0–4%) (p=0.007). ASM mass was heterogeneously distributed within airways, lungs and the sample population. Phenotypes of ASM remodelling (based on location in small or large airways) were apparent in the asthma group, compared with the control group where participants were all classified as non-remodelled. Conclusions PS-OCT is a minimally invasive, accurate, efficient and effective modality to measure ASM mass. Visualising and quantifying ASM in patients with asthma provides an opportunity to make ASM remodelling a treatable trait and may facilitate the development of novel therapeutics for the treatment of asthma.

Recent advances in artificial intelligence (AI) and deep learning (DL) are reshaping ophthalmology, particularly in the domains of image analysis and image synthesis. Optical coherence tomography (OCT) has become indispensable for diagnosing and monitoring retinal diseases, and the application of generative models such as generative adversarial networks (GANs) now enables the creation of realistic synthetic OCT data. In this systematic review, we evaluate the current state of OCT image generation using DL techniques, with emphasis on retinal applications including common pathologies such as age-related macular degeneration, diabetic retinopathy, glaucoma, diabetic retinopathy and other retinal pathologies. We provide an overview of commonly employed architectures, including GAN variants, variational autoencoders, and emerging diffusion models, and highlight how they have been applied for data augmentation, cross-modality translation, noise reduction, and rare pathology synthesis. We discuss validation strategies, performance metrics, and limitations across existing studies, and emphasize the clinical opportunities these technologies present in improving diagnostic accuracy, education, and accessibility of advanced imaging. Finally, we identify gaps in dataset diversity, external validation, and regulatory considerations, and outline future directions to ensure responsible translation of synthetic OCT imaging into clinical practice.

Skin scars remain a substantial clinical challenge because of their impact on appearance and psychological well-being. Lysyl oxidases catalyze collagen cross-linking, a key factor in scar development. Here, we report a randomized, double-blind, placebo-controlled phase 1 study to assess the safety and tolerability of PXS-6302, a topical pan-lysyl oxidase inhibitor, in treating mature scars (ACTRN12621001545853). Fifty participants were enrolled across two cohorts: Cohort 1 (open label, n = 8) applied PXS-6302 (2%) daily, and cohort 2 (n = 42) was randomized 1:1 to apply PXS-6302 (2%) or placebo three times per week to a 10-square-centimeter area of scar for 3 months. No severe adverse events (AEs) were reported. Mild to moderate localized skin reactions were the only treatment-related AEs, leading to discontinuation by six participants. Treatment with PXS-6302 three times per week reduced lysyl oxidase activity by 66% and decreased hydroxyproline (a marker for collagen) and total protein concentrations in scar biopsies compared with placebo. Optical coherence tomography showed increased microvessel density and tissue attenuation [a marker of extracellular matrix (ECM) composition] at 3 months compared with the baseline, suggesting ECM remodeling toward unscarred skin architecture. No significant differences in Patient Observer Scar Assessment Scale (POSAS) scores were observed between groups after 90 days of treatment once baseline imbalances were accounted for. Together, these data showed that topical pan-lysyl oxidase inhibition was generally well tolerated and altered some measures of the ECM in mature scars, supporting the advancement of this treatment into phase 2 trials.

Skin scars are a significant clinical challenge, with poor appearance and increased tissue stiffness affecting both physical and psychological wellbeing. Lysyl oxidases are a family of enzymes that catalyze collagen crosslinking, a key factor in scar pathophysiology. Here we report a randomized, double-blind, placebo-controlled Phase 1 clinical trial to assess the safety and tolerability of PXS-6302, a topical pan-lysyl oxidase inhibitor, in treating mature scars (ACTRN12621001545853). Fifty participants with scars were enrolled and PXS-6302 or placebo cream applied to a 10 cm2 area for three months. No severe adverse events were reported. All treatment-related adverse events (AEs) were localized skin reactions. Treatment with PXS-6302 significantly inhibited lysyl oxidase activity (66%). Hydroxyproline (a marker for collagen) and total protein concentration in the scar were significantly reduced in the PXS-6302 treatment group compared to placebo. Optical coherence tomography (OCT) was used to measure vascularity and attenuation (a marker of extracellular matrix composition). PXS-6302 treatment significantly increased vessel density at 3 months compared to baseline. Tissue attenuation was also significantly increased in PXS-6302 treated participants compared to baseline, suggesting extracellular matrix was becoming increasingly similar to normal skin. No significant differences between placebo and PXS-6302 treatment groups were observed in Patient Observer Scar Assessment Scale (POSAS) scores at study conclusion. To our knowledge, this study represents the first demonstration of a safe and effective pharmaceutical intervention that significantly improves the molecular composition of established scar extracellular matrix in humans. Pan-lysyl oxidase inhibition therefore represents a potential paradigm shift for the amelioration of scarring. ### Competing Interest Statement Wolfgang Jarolimek, Brett Charlton, Alison Findlay and Joanna Leadbetter are all employees (or previous employees) of Syntara Ltd. All other authors declare that they have no competing interests. ### Clinical Trial ACTRN12621001545853 ### Funding Statement This study was funded by Syntara ltd (formerly Pharmaxis) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The South Metropolitan Health Service Human ethics committee at Fiona Stanley Hospital gave ethical approval for this work (RGS0000004980) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

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.

Terahertz (THz) imaging and optical coherence tomography (OCT) are of great importance in non-destructive testing and medical diagnostics, offering complementary data on similar length scales. This study primarily investigates a method designed to enhance our understanding and measurement of hydrated biological samples by merging OCT and THz data through an iterative algorithm. Initially applied to a flat silicone step wedge with varying thicknesses, the method was validated and extended to gelatin samples with varying water content. By integrating multiple measurements from different sample locations, the algorithm not only confirms the expected refractive indices but also consistently determines thickness measurements. The demonstrated utility of this approach in accurately assessing biologically relevant materials highlights its potential application of interest in corneal diagnostics. Such advancements are particularly vital for improving the accuracy and reliability of measurements crucial for managing corneal diseases.

In-vivo imaging of the retina inevitably requires an image acquisition through the subject's pupil, which suffers from aberrations induced by the subject's crystalline lens and cornea, as well as scattering by tissue. Epi-illumination differential phase contrast (DPC) has demonstrated recovery phase information of cellular structures from intensity images captured with oblique back-illumination; but its image quality can still be compromised by eye movements and aberration. To overcome these challenges, we propose a computational method that compensates for the aberration in the platform of Oblique back-illumination differential phase-contrast microscopy. Our method involves asymmetric oblique-back illumination, so that phase images can be obtained with smaller number of acquisitions. The acquired images are then processed with a novel gradient decent-based algorithm to obtain aberration-corrected images and pupil aberration simultaneously. We will present the details of our experimental setup and reconstruction algorithms.

We demonstrate an adaptation of deep learning for label-free imaging of the micro-scale lymphatic vessels and aqueous veins in the eye using optical coherence tomography (OCT). The proposed deep learning-based OCT lymphangiography (DL-OCTL) method was trained, validated and tested, using OCT scans (23 volumetric scans comprising 19,736 B-scans) from 11 fresh ex vivo porcine eyes with the corresponding vessel labels generated by a conventional OCT lymphangiography (OCTL) method based on thresholding with attenuation compensation. Compared to conventional OCTL, the DL-OCTL method demonstrates comparable results for imaging lymphatics and aqueous veins in the eye, with an Intersection over Union value of 0.79 ± 0.071 (mean ± standard deviation). In addition, DL-OCTL mitigates the imaging artifacts in conventional OCTL where the OCT signal modelling was corrupted by the tissue heterogeneity, provides ~ 10 times faster processing based on a rough comparison and does not require OCT-related knowledge for correct implementation as in conventional OCTL. With these favorable features, DL-OCTL promises to improve the practicality of OCTL for label-free imaging of lymphatics and aqueous veins for preclinical and clinical imaging applications.

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

Contact lenses are widely used for correcting refractive errors and treating various ocular disorders. However, their thickness and refractive index can change over time due to dehydration and mechanical stress, which can impact their optical performance and safety. In this study, we introduce a new method to measure these parameters using a combined terahertz and optical coherence tomography system. An iterative algorithm that combines information from multiple locations within the sample can provide the depth information and refractive index measurements for both THz and OCT frequencies. We applied this method to contact lenses and measured their thickness and refractive index at different time intervals. The results revealed significant changes in these parameters over time, highlighting the importance of proper monitoring. Overall, this novel method provides accurate and reliable measurements of contact lens thickness and refractive index over time, providing essential insights into their behavior in vivo.

Birefringence, an inherent characteristic of optically anisotropic materials, is widely utilized in various imaging applications ranging from material characterizations to clinical diagnosis. Polarized light microscopy enables high-resolution, high-contrast imaging of optically anisotropic specimens, but it is associated with mechanical rotations of polarizer/analyzer and relatively complex optical designs. Here, we present a form of lens-less polarization-sensitive microscopy capable of complex and birefringence imaging of transparent objects without an optical lens and any moving parts. Our method exploits an optical mask-modulated polarization image sensor and single-input-state LED illumination design to obtain complex and birefringence images of the object via ptychographic phase retrieval. Using a camera with a pixel size of 3.45 μm, the method achieves birefringence imaging with a half-pitch resolution of 2.46 μm over a 59.74 mm 2 field-of-view, which corresponds to a space-bandwidth product of 9.9 megapixels. We demonstrate the high-resolution, large-area, phase and birefringence imaging capability of our method by presenting the phase and birefringence images of various anisotropic objects, including a monosodium urate crystal, and excised mouse eye and heart tissues.

Abstract Blood vessel walls are made of organized fibrous tissue with intrinsic birefringence. Even in its very early stages, hypertension can change the structure of a blood vessel wall. We showed that this structural change can be quantitatively measured non-invasively in the human retina using polarization-sensitive optical coherence tomography (PS-OCT). Organizational loss in vessel wall tissue was quantified in hypertensive patients and compared to data obtained from age-matched healthy subjects. The wall tissue in patients with hypertension was shown to be thicker, and exhibited lower birefringence, presumably due to a loss of tissue organization. The blood vessel wall birefringence index (BBI) combines vessel wall birefringence and thickness into one number and is introduced here to readily distinguish between blood vessel walls of hypertensive and healthy subjects. Based on receiver operating characteristic (ROC) curves, BBI showed 99% sensitivity and 100% specificity when discriminating normotensive (N = 11) and hypertensive (N = 11) subjects. Accurately determining the thickness of the blood vessel wall is not possible without polarization-sensitivity. Moreover, just blood vessel wall thickness or wall birefringence were not sufficient to achieve this high classification performance. Retinal vessel wall measurements with PS-OCT cannot be affected by a patient being anxious, by hormones or other blood values, since the measurement is intrinsic to the optical and mechanical properties of the vessel wall. Furthermore, this relatively low-cost system combines a very short imaging and analysis time with high sensitivity and specificity, making it highly suitable for low-cost screening.

Polarization-sensitive optical coherence tomography (PS-OCT) measures the polarization states of the backscattered light from tissue that can improve angiography based on conventional optical coherence tomography (OCT). We present a feasibility study on PS-OCT integrated with deep learning for PS-OCT angiography (PS-OCTA) imaging of human cutaneous microvasculature. Two neural networks were assessed for PS-OCTA, including the residual dense network (RDN), which previously showed superior performance for angiography with conventional OCT and the upgraded grouped RDN (GRDN). We also investigated different protocols to process the multiple signal channels provided by the Jones matrices from the PS-OCT system to achieve optimal PS-OCTA performance. The training and testing of the deep learning-based PS-OCTA were performed using PS-OCT scans collected from 18 skin locations comprising 16,600 B-scan pairs. The results demonstrated a moderately improved performance of GRDN over RDN, and of the use of the combined signal from the Jones matrix elements over the separate use of the elements, as well as a similar image quality to that provided by speckle decorrelation angiography. GRDN-based PS-OCTA also showed ∼2-3 times faster processing and improved mitigation of tissue motion as compared to speckle decorrelation angiography, and enabled fully automatic processing. Deep learning-based PS-OCTA can be used for imaging cutaneous microvasculature, which may enable easy adoption of PS-OCTA for preclinical and clinical applications.

Significance:Post-burn scars and scar contractures present significant challenges in burn injury management, necessitating accurate evaluation of the wound healing process to prevent or minimize complications. Non-invasive and accurate assessment of burn scar vascularity can offer valuable insights for evaluations of wound healing. Optical coherence tomography (OCT) and OCT angiography (OCTA) are promising imaging techniques that may enhance patient-centered care and satisfaction by providing detailed analyses of the healing process.Aim:Our study investigates the capabilities of OCT and OCTA for acquiring information on blood vessels in burn scars and evaluates the feasibility of utilizing this information to assess burn scars.Approach:Healthy skin and neighboring scar data from nine burn patients were obtained using OCT and processed with speckle decorrelation, Doppler OCT, and an enhanced technique based on joint spectral and time domain OCT. These methods facilitated the assessment of vascular structure and blood flow velocity in both healthy skin and scar tissues. Analyzing these parameters allowed for objective comparisons between normal skin and burn scars.Results:Our study found that blood vessel distribution in burn scars significantly differs from that in healthy skin. Burn scars exhibit increased vascularization, featuring less uniformity and lacking the intricate branching network found in healthy tissue. Specifically, the density of the vessels in burn scars is 67% higher than in healthy tissue, while axial flow velocity in burn scar vessels is 25% faster than in healthy tissue.Conclusions:Our research demonstrates the feasibility of OCT and OCTA as burn scar assessment tools. By implementing these technologies, we can distinguish between scar and healthy tissue based on its vascular structure, providing evidence of their practicality in evaluating burn scar severity and progression.

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