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.

With the impending ‘retirement’ of bronchial thermoplasty (BT) for the treatment of patients with asthma, there is much to learn from this real-world experiment that will help us develop more effective future therapies with the same primary target i.e., airway smooth muscle (ASM) remodelling. This viewpoint discusses initial controversy surrounding BT (lack of an effect on forced expiratory volume in 1 s), its underutilisation, and importantly how non-standard diagnostics successfully demonstrated therapeutic response which escaped traditional lung function metrics. It is anticipated that the next iteration of BT (likely in a drug form) will have an overall greater effect on the health care system by virtue of evoking ASM remodelling as a treatable trait, and after appropriately drawing on lessons learned from the ∼fifteen-year BT saga.

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.

Breast density is a strong intermediate endpoint to investigate the association between early-life exposures and breast cancer risk. This study investigates the association between early-life growth and breast density in young adult women measured using Optical Breast Spectroscopy (OBS) and Dual X-ray Absorptiometry (DXA). OBS measurements were obtained for 536 female Raine Cohort Study participants at ages 27–28, with 268 completing DXA measurements. Participants with three or more height and weight measurements from ages 8 to 22 were used to generate linear growth curves for height, weight and body mass index (BMI) using SITAR modelling. Three growth parameters (size, velocity and timing) were examined for association with breast density measures, adjusting for potential confounders. Women who reached their peak height rapidly (velocity) and later in adolescence (timing) had lower OBS-breast density. Overall, women who were taller (size) had higher OBS-breast density. For weight, women who grew quickly (velocity) and later in adolescence (timing) had higher absolute DXA-breast density. Overall, weight (size) was also inversely associated with absolute DXA-breast density, as was BMI. These findings provide new evidence that adolescent growth is associated with breast density measures in young adult women, suggesting potential mediation pathways for breast cancer risk in later life.

Purpose Age and body mass index (BMI) are critical considerations when assessing individual breast cancer risk, particularly for women with dense breasts. However, age- and BMI-standardized estimates of breast density are not available for screen-aged women, and little is known about the distribution of breast density in women aged < 40. This cross-sectional study uses three different modalities: optical breast spectroscopy (OBS), dual-energy X-ray absorptiometry (DXA), and mammography, to describe the distributions of breast density across categories of age and BMI. Methods Breast density measures were estimated for 1,961 Australian women aged 18–97 years using OBS (%water and %water + %collagen). Of these, 935 women had DXA measures (percent and absolute fibroglandular dense volume, %FGV and FGV, respectively) and 354 had conventional mammographic measures (percent and absolute dense area). The distributions for each breast density measure were described across categories of age and BMI. Results The mean age was 38 years (standard deviation = 15). Median breast density measures decreased with age and BMI for all three modalities, except for DXA-FGV, which increased with BMI and decreased after age 30. The variation in breast density measures was largest for younger women and decreased with increasing age and BMI. Conclusion This unique study describes the distribution of breast density measures for women aged 18–97 using alternative and conventional modalities of measurement. While this study is the largest of its kind, larger sample sizes are needed to provide clinically useful age-standardized measures to identify women with high breast density for their age or BMI.

[This corrects the article on p. 1386 in vol. 13, PMID: 35414965.].

All-fiber-optic imaging microendoscopes are emerging as an important tool in bioimaging studies, including those conducted with optical coherence tomography, but physical limitations constrain the achievable beam characteristics of designs using a single focusing element. These constraints are especially relevant for applications that require a long working distance, high resolution, and/or minimal probe diameter. Through detailed analysis based on ABCD matrix modelling, we show that side-viewing probes combining a graded-index (GRIN) fiber with a ball lens – GRIN-ball-lens probes (GBLPs) – offer superior performance over a range of numerical apertures and pave the way for a broader range of imaging applications. The performance of side-viewing GBLPs designed for 1300-nm optical coherence tomography imaging is compared against commonly used single-focusing-element all-fiber side-viewing probe designs, namely, ball-lens probes (BLPs) and GRIN-fiber probes (GFPs). All possible realizations of this novel probe design and their impact on the requisite design tradeoffs are investigated, including the impact on probe performance of fabrication error and the refractive index of the surrounding medium. Applications of GBLPs, including ultra-high-resolution (sub-2 micrometer) miniature probes for micro-endomicroscopy, are discussed.

Polarization-sensitive optical coherence tomography (PS-OCT) derived birefringence values effectively identify skeletal muscle structural disruption due to muscular dystrophy and exercise-related muscle damage in animal models in ex vivo tissue. The purpose of this investigation was to determine if a PS-OCT needle probe inserted into the leg of a human subject could accurately identify various anatomical structures with implications for use as a diagnostic tool for the determination of skeletal muscle pathology. A healthy middle-aged subject participated in this study. A custom-built PS-OCT system was interfaced with a side-viewing fiber-optic needle probe inserted into the subject's vastus lateralis muscle via a motorized stage for 3D data acquisition via rotation and stepwise pullback. The deepest recorded PS-OCT images correspond to a depth of 6 mm beneath the dermis with structural images showing uniform, striated muscle tissue. Multiple highly birefringent band-like structures with definite orientation representing connective tissue of the superficial aponeurosis appeared as the depth of the needle decreased. Superficial to these structures the dominating appearance was that of adipose tissue and low birefringent but homogeneous scattering tissue. The data indicate that a PS-OCT needle probe can be inserted into live human skeletal muscle for the identification of relevant anatomical structures that could be utilized to diagnose significant skeletal muscle pathology.

Mammographic breast density is a strong breast cancer risk factor, and its routine clinical measurement could potentially be used to identify women at higher risk of breast cancer and/or monitor primary prevention strategies. Previous reports of optical breast spectroscopy (OBS), a novel approach to measuring breast density, demonstrated that it is safe (no ionizing radiation), portable, low-cost, and does not require image interpretation but have been limited to small, single-center studies. Reference measurements taken on a phantom breast prior to and after each woman's OBS assessment are required for the calibration of the system transfer function as a part of processing participant data. To inform the validity of participant data, a detailed description of the reference measurements and a repeatability analysis of these measurements taken before and after participant assessment is presented. Reference measurements for OBS from 539 women aged 18-40 years were obtained as a part of a high-throughput epidemiological pilot study. Of these, measurements from 20 women with no useable data due to device failure (3.7%) were excluded and from another 12 women due to user error. The intra-class correlation (ICC) within complete pairs of reference data (taken before and after assessment) was high (all ICC > 0.84). The analysis presented here confirms the OBS participant data as valid for use in ongoing epidemiological research, providing further supporting evidence of OBS as a measure of breast density. A novel method of measuring breast density is needed to bridge large gaps in the knowledge of breast density in younger women and its relation to later-life breast cancer risk.

This publisher's notes amends the reference citations and the reference list of [Biomed. Opt. Express 13, 1386 (2022)]. (C) 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement

Clinical visualization and quantification of the amount and distribution of airway smooth muscle (ASM) in the lungs of individuals with asthma has major implications for our understanding of airway wall remodeling as well as treatments targeted at the ASM. This paper theoretically investigates the feasibility of quantifying airway wall thickness (focusing on the ASM) throughout the lung in vivo by means of bronchoscopic polarization-sensitive optical coherence tomography (PS-OCT). Using extensive human biobank data from subjects with and without asthma in conjunction with a mathematical model of airway compliance, we define constraints that airways of various sizes pose to any endoscopic imaging technique and how this is impacted by physiologically relevant processes such as constriction, inflation and deflation. We identify critical PS-OCT system parameters and pinpoint parts of the airway tree that are conducive to successful quantification of ASM. We further quantify the impact of breathing and ASM contraction on the measurement error and recommend strategies for standardization and normalization

Thickness and birefringence properties of the vein and artery walls of healthy subjects were quantified following retinal imaging with polarization-sensitive optical coherence tomography and the integrity and structure of vessel walls were assessed.

A new method based on polarization-sensitive optical coherence tomography (PS-OCT) is introduced to determine the polarization properties of human retinal vessel walls, in vivo. Measurements were obtained near the optic nerve head of three healthy human subjects. The double pass phase retardation per unit depth (DPPR/UD), which is proportional to the birefringence, is higher in artery walls, presumably because of the presence of muscle tissue. Measurements in surrounding retinal nerve fiber layer tissue yielded lower DPPR/UD values, suggesting that the retinal vessel wall tissue near the optic nerve is not covered by retinal nerve fiber layer tissue (0.43°/µm vs. 0.77°/µm, respectively). Measurements were obtained from multiple artery-vein pairs, to quantify the different polarization properties. Measurements were taken along a section of the vessel wall, with changes in DPPR/UD up to 15%, while the vessel wall thickness remained relatively constant. A stationary scan pattern was applied to determine the influence of involuntary eye motion on the measurement, which was significant. Measurements were also analyzed by two examiners, with high inter-observer agreement. The measurement repeatability was determined with measurements that were acquired during multiple visits. An improvement in accuracy can be achieved with an ultra-broad-bandwidth PS-OCT system since it will provide more data points in-depth, which reduces the influence of discretization and helps to facilitate better fitting of the birefringence data.

Terahertz (THz) imaging and optical coherence tomography (OCT) provide complementary information with similar length scales. In addition to OCT's extensive use in ophthalmology, both methods have shown some promise for other medical applications and non-destructive testing. In this paper, we present an iterative algorithm that combines the information from OCT and THz imaging at two different measurement locations within an object to determine both the depth of the reflecting layers at the two locations and the unknown refractive index of the medium for both the OCT wavelengths and THz frequencies. We validate this algorithm using a silicone test object with embedded layers and show that the depths and refractive index values obtained from the algorithm agreed with the measured values to within 3.3%. We further demonstrate for the first time that OCT and THz images can be co-registered and aligned using unsupervised image registration. Hence we show that a combined OCT/THz system can provide unique information beyond the capability of the separate modalities alone, with possible applications in the medical, industrial and pharmaceutical sectors.

Tissue with fibrillar architecture, such as collagen or muscle fiber, exhibits birefringence. In addition to the scalar amount of birefringence, the orientation of the birefringence axis, i.e. the fast optic axis, provides important information on the physical orientation of the fibrillar tissue components. We have previously demonstrated local optic axis mapping using bench-top fiber-based polarization-sensitive optical coherence tomography (PS-OCT), by compensating for the transmission through fiber and system elements, imperfect system alignment, and preceding tissue layers. Using depth-multiplexed PS-OCT, the compensation considers both retardation and diattenuation and is applied in the wavenumber domain, preserving the full axial resolution of the system. Here, we extend our approach to catheter-based imaging. Analyzing a reflection signal from the distal tip of the optical probe, we decompose the recovered system transmission into a static component and a varying catheter transmission to accurately correct for the rotation-dependent transmission through the catheter. Catheter-based local optic axis mapping is validated with a custom-made birefringence phantom. Imaging ex-vivo human bronchus demonstrates the utility of reconstructing the local optic axis orientation to assess airway smooth muscle (ASM), which is oriented approximately orthogonal from the surrounding tissue, offering strong optic axis orientation contrast. Thickening and contraction of the ASM is considered a primary cause of breathing difficulties, and the capacity to clearly image the ASM could lead to an improved understanding of diseases such as asthma.

Non-Gaussian beams can provide extended depth of focus (DOF) at constant and potentially uncompromised transverse resolution, as well as a degree of self-reconstruction after beam shadowing, which may be present in tissue imaging. Hence such beams are being developed for imaging systems throughout many disciplines, including endoscopic imaging, where they hold great potential. General possibilities include up to more than 20-fold extension of DOF, tunable working distance, imaging around obstacles and integrated all-fiber designs. In all-fiber based optical imaging systems; however, these advantages are limited by system design considerations. Trade-offs between miniaturization, extended DOF, SNR, and fiber availability arise, and estimating the effects of design modifications can be difficult and time consuming. We model zero-order quasi-Bessel illumination and detection for a range of common probe and sample materials based on an analytic solution of the Fresnel diffraction integral and compare the results to Gaussian beams. We show that these beams, on scales that match optical fiber dimensions, generally have an upper limit for the spot size above which their distinct advantages over Gaussian beams fade. Similarly, we show the existence of a lower limit of practical performance of quasi-Bessel beams, where the imaging SNR penalty compared to a Gaussian beam becomes significant. Additionally to general theoretic considerations we discuss designs, modeling and characterization of all-fiber imaging probes. This work provides an accessible overview for researchers to estimate what potential benefit non-Gaussian beams can introduce into their optical imaging system.