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.

Erratum: In vivo PS-OCT needle probe scan of human skeletal muscle: publisher's note.

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

In vivo PS-OCT needle probe scan of human skeletal muscle.

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.

Assessment of repeated reference measurements to inform the validity of optical breast spectroscopy.

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.

Requirements and limitations of imaging airway smooth muscle throughout the lung in vivo.

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.

Polarization properties of retinal blood vessel walls measured with polarization sensitive optical coherence tomography.

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.