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Magnetomotive Ultrasound (MMUS) is an emerging imaging modality, in which magnetic nanoparticles (MNPs) are used as contrast agents. MNPs are driven by a time-varying magnetic force, and the resulting movement of the surrounding tissue is detected with a signal processing algorithm. However, there is currently no analytical model to quantitatively predict this magnetically-induced displacement. Toward the goal of predicting motion due to forces on the distribution of MNPs, in this work, a model originally derived from the Navier–Stokes equation for the motion of a single magnetic particle subject to a magnetic gradient force is presented and validated. Displacement amplitudes for a spatially inhomogeneous and temporally sinusoidal force were measured as a function of force amplitude and Young’s modulus, and the predicted linear and inverse relationships were confirmed in gelatin phantoms, respectively, with three out of four data sets exhibiting ${R}^{{2}} \ge {0.88}$ . The mean absolute uncertainty between the predicted displacement magnitude and experimental results was 14%. These findings provide a means by which the performance of MMUS systems may be predicted to verify that systems are working to theoretical limits and to compare results across laboratories.

Quantitative methods for assessing the severity of inhalation (burn) injury are needed to aid in treatment decisions. We hypothesize that it is possible to assess the severity of injuries on the basis of differences in the compliance of the airway wall. Here, we demonstrate the use of a custom-built, endoscopic, anatomic optical coherence elastography (aOCE) system to measure airway wall compliance. The method was first validated using airway phantoms, then performed on ex vivo porcine tracheas under varying degrees of inhalation (steam) injury. A negative correlation between aOCE-derived compliance and severity of steam injuries is found, and spatially-resolved compliance maps reveal regional heterogeneity in airway properties.

The organization of plasmonic nanoparticles (NPs) determines the strength and polarization dependence of coupling of their surface plasmons. In this study, plasmon coupling of spherical Au NPs with...

Objective. An ultrasound-based system capable of both imaging thrombi against a dark field and performing quantitative elastometry could allow for fast and cost-effective thrombosis diagnosis, staging, and treatment monitoring. This study investigates a contrast-enhanced approach for measuring the Young’s moduli of thrombus-mimicking phantoms. Approach. Magnetomotive ultrasound (MMUS) has shown promise for lending specific contrast to thrombi by applying a temporally modulated force to magnetic nanoparticle (MNP) contrast agents and measuring resulting tissue displacements. However, quantitative elastometry has not yet been demonstrated in MMUS, largely due to difficulties inherent in measuring applied magnetic forces and MNP densities. To avoid these issues, in this work magnetomotive resonant acoustic spectroscopy (MRAS) is demonstrated for the first time in ultrasound. Main results. The resonance frequencies of gelatin thrombus-mimicking phantoms are shown to agree within one standard deviation with finite element simulations over a range of phantom sizes and Young’s moduli with less than 16% error. Then, in a proof-of-concept study, the Young’s moduli of three phantoms are measured using MRAS and are shown to agree with independent compression testing results. Significance. The MRAS results were sufficiently precise to differentiate between thrombus phantoms with clinically relevant Young’s moduli. These findings demonstrate that MRAS has potential for thrombus staging.

Tissue mechanical properties determine the relationship between an applied mechanical load and the resulting deformation of the sample. In optical coherence elastography (OCE), the objective is to spatially resolve tissue mechanical properties from often incomplete and noisy measurements of the load and deformation. This is achieved by solving an inverse problem, using a model of elasticity that reasonably describes the behavior of tissue. Incorporating more parameters into the model (such as heterogeneity, anisotropy, nonlinearity, or viscoelasticity) than are needed in a given application can unnecessarily complicate the inverse problem. Also, how the load is applied can enhance certain tissue responses, and the validity of an elasticity model, and, thus, allow for the characterization of tissue in different regimes. A successful OCE technique offers a good match between the load application method, and the tissue mechanical properties of interest, and employs a reasonably complete but simplified mechanical model that provides a noise-robust inversion. OCE techniques can be classified into two broad categories: those inducing and subsequently tracking propagating mechanical waves, and those applying and assuming a uniaxial load, and tracking the deformation in response. With a brief introduction to the former, this chapter focuses on the latter group, describes the most prominent of these techniques, and presents an overview of studies that have successfully extracted mechanical properties in tissue-like media.

To establish the utility of anatomic optical coherence tomography (aOCT) in evaluating internal nasal valve (INV).Anatomic specimen imaging study.Fresh-harvested human specimen heads were evaluated using both computed tomography (CT) imaging as well as using aOCT. Scans were performed at three time points: 1) After septoplasty for cartilage harvest, 2) after placement of butterfly graft (BFG), and 3) after placement of bilateral spreader grafts (SG). Imaging data were then converted into 3D models of the nasal airway. CT- and aOCT-generated models were compared by both static volumetric analysis and computational fluid dynamics (CFD) to predict nasal resistance and pressure.Scans using aOCT showed comparable results to CT in terms of volumetric parameters both before and after intervention. Analysis of aOCT data by CFD demonstrated decrease in pressure after SG or BFG intervention. No statistically significant difference was observed when comparing CT- and aOCT-generated calculations of pressure or resistance.The INV can be imaged in a static fashion using aOCT technology. Advantages over traditional CT imaging include lack of exposure to radiation and rapid scan time. In addition, in-office use is possible as aOCT technology develops. Further investigation will be necessary to define the role of aOCT in the dynamic evaluation of this vital component of the nasal airway.3 Laryngoscope, 132:2148-2156, 2022.

Significance: Imaging biofluid flow under physiologic conditions aids in understanding disease processes and health complications. We present a method employing a microparallel plate strain induction chamber (MPPSIC) amenable to optical coherence tomography to track depth-resolved lateral displacement in fluids in real time while under constant and sinusoidal shear. Aim: Our objective is to track biofluid motion under shearing conditions found in the respiratory epithelium, first validating methods in Newtonian fluids and subsequently assessing the capability of motion-tracking in bronchial mucus. Approach: The motion of polystyrene microspheres in aqueous glycerol is tracked under constant and sinusoidal applied shear rates in the MPPSIC and is compared with theory. Then 1.5 wt. % bronchial mucus samples considered to be in a normal hydrated state are studied under sinusoidal shear rates of amplitudes 0.7 to 3.2 s−1. Results: Newtonian fluids under low Reynolds conditions (Re∼10−4) exhibit velocity decreases directly proportional to the distance from the plate driven at both constant and oscillating velocities, consistent with Navier–Stokes’s first and second problems at finite depths. A 1.5 wt. % mucus sample also exhibits a uniform shear strain profile. Conclusions: The MPPSIC provides a new capability for studying biofluids, such as mucus, to assess potentially non-linear or strain-rate-dependent properties in a regime that is relevant to the mucus layer in the lung epithelium.

Endoscopic optical coherence tomography of large airways poses unique challenges. A hybrid lens is described that consists of a section of coreless fiber and graded index fiber (GIF), followed by a ball lens section. This design produces low numerical aperture beams better suited for large airway imaging. The performance of this lens is compared against conventional GIF and ball lens designs. Forward- and side-viewing probes were modeled, fabricated, and tested. The impact of a sheath on the beam profile was also investigated. Probes with working distances larger than 10 mm and depth-of-focus exceeding 12 mm are demonstrated with the proposed design.

Plasmonic nanoparticles that can be manipulated with magnetic fields are of interest for advanced optical applications, diagnostics, imaging, and therapy. Alignment of gold nanorods yields strong polarization-dependent extinction, and use of magnetic fields is appealing because they act through space and can be quickly switched. In this work, cationic polyethyleneimine-functionalized superparamagnetic Fe

Basal-like breast cancers (BBC) exhibit subtype-specific phenotypic and transcriptional responses to stroma, but little research has addressed how stromal-epithelial interactions evolve during early BBC carcinogenesis. It is also unclear how common genetic defects, such as p53 mutations, modify these stromal-epithelial interactions. To address these knowledge gaps, we leveraged the MCF10 progression series of breast cell lines (MCF10A, MCF10AT1, and MCF10DCIS) to develop a longitudinal, tissue-contextualized model of p53-deficient, pre-malignant breast. Acinus asphericity, a morphogenetic correlate of cell invasive potential, was quantified with optical coherence tomography imaging, and gene expression microarrays were performed to identify transcriptional changes associated with p53 depletion and stromal context. Co-culture with stromal fibroblasts significantly increased the asphericity of acini derived from all three p53-deficient, but not p53-sufficient, cell lines, and was associated with the upregulation of 38 genes. When considered as a multigene score, these genes were upregulated in co-culture models of invasive BBC with increasing stromal content, as well as in basal-like relative to luminal breast cancers in two large human datasets. Taken together, stromal-epithelial interactions during early BBC carcinogenesis are dependent upon epithelial p53 status, and may play important roles in the acquisition of an invasive morphologic phenotype.

We present a micro-parallel plate rheometer amenable to OCT to track depth-resolved lateral displacement in fluids in real-time while under dynamic shear. Newtonian fluid experiments show direct proportionality between lateral velocity of particles and depth.

BACKGROUND: An understanding of how the mammary gland responds to toxicant and drug exposures can shed light on mechanisms of breast cancer initiation/progression and therapeutic effectiveness, respectively. In this study, we employed noninvasive, label-free and high-throughput optical coherence tomography speckle fluctuation spectroscopy (OCT-SFS) to track exposure-response relationships in three-dimensional (3D) mammary epithelial organoid models. METHODS: OCT-SFS is sensitive to relatively high speed (~0.16–8 µm/min) motions of subcellular light scattering components occurring over short (~2–114 s) time scales, termed “intracellular motility.” In this study, OCT speckle fluctuation spectra are quantified by two metrics: the intracellular motility amplitude, M, and frequency-dependent motility roll-off, α. OCT-SFS was performed on human mammary organoid models comprised of pre-malignant MCF10DCIS.com cells or MCF7 adenocarcinoma cells over 6 days of exposure to either a microtubule inhibitor (Paclitaxel, Taxol) or a myosin II inhibitor (Blebbistatin). Raw values of α and M were normalized to a dynamic range corresponding to fixed (0%) and live/homeostatic (100%) organoids for each cell line. RESULTS: In this work, we observed a significant decrease in both M and α of MCF10DCIS.com organoids after 24 hours of exposure to Taxol (P

Direct ultrasonic imaging of arterial and venous thrombi could aid in diagnosis and treatment planning by providing rapid and cost-effective measurements of thrombus volume and elastic modulus. Toward this end, it was demonstrated that open-air magnetomotive ultrasound (MMUS) provides specific contrast to superparamagnetic iron oxide-labeled model thrombi embedded in gelatin-based blood vessel-mimicking flow phantoms. MMUS was performed on model thrombi in the presence of pulsatile flow that mimics cardiac-induced motion found in real vasculature. The MMUS signal and contrast-to-noise ratio (CNR) were measured across a range of physiologically relevant thrombus volumes and elastic moduli. Model thrombus volumes as small as 0.5 ml were shown to be detectable (CNR > 1) over the entire range of elastic moduli tested (3.5–40 kPa). It was also found that MMUS signal and CNR are increased with increasing thrombus volume ( $r = 0.99$ ) and decreasing elastic modulus ( $r = -0.81$ ), while variations in pulsatile flow rate had little effect. These findings demonstrate that MMUS has promise as a direct in vivo thrombosis imaging modality for quantifying thrombus volume and stiffness.

The ability to assess toxicant exposures of 3D in vitro mammary models that recapitulate the tissue microenvironment can aid in our understanding of environmental exposure risk over time. Longitudinal studies of 3D model systems, however, are cumbersome and suffer from a lack of high-throughput toxicological assays. In this study, we establish a noninvasive and label-free optical coherence tomography (OCT)-based imaging platform for tracking exposure-response relationships in 3D human mammary epithelial organoid models. The OCT-based assay includes metrics that quantify organoid intracellular kinetic energy and cross-sectional area (CSA). We compare the results to those obtained using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) mitochondrial dye conversion assay. Both estrogen receptor (ER)-positive (MCF7) and ER-negative (MCF10DCIS.com) breast cell lines were studied, beginning one hour after exposure and continuing for several days. Six days of exposure to 17β-estradiol or the selective ER modulator 4-hydroxytamoxifen respectively increased or decreased MCF7 organoid CSA (p < .01), consistent with the role of estrogen signaling in ER-positive mammary epithelial cell proliferation. We also observed a significant decrease in the intracellular kinetic energy of MCF10DCIS.com organoids after 24 h of exposure to doxorubicin, a cytotoxic intercalating agent that causes DNA double-strand breaks (p < .01). MTT-based metabolic activity of MCF10DCIS.com organoids after 48 h of doxorubicin exposure decreased with dose in a similar manner as OCT-based energy metrics. These results demonstrate the feasibility of an OCT-based assay to quantify mammary epithelial cell toxicant response in vitro, noninvasively, longitudinally, and in the context of tissue microenvironments, providing a new high-throughput screening tool for toxicological studies.

The solid concentration of pulmonary mucus (wt%) is critical to respiratory health. In patients with respiratory disease, such as Cystic Fibrosis (CF) and Chronic Obstructive Pulmonary Disorder (COPD), mucus hydration is impaired, resulting in high wt%. Mucus with high wt% is a hallmark of pulmonary disease that leads to obstructed airways, inflammation, and infection. Methods to measure mucus hydration in situ and in real-time are needed for drug development and personalized therapy. We employed plasmonic gold nanorod (GNR) biosensors that intermittently collide with macromolecules comprising the mucus mesh as they self-diffuse, such that GNR translational diffusion (DT) is sensitive to wt%. GNRs are attractive candidates for bioprobes due to their anisotropic optical scattering that makes them easily distinguishable from native tissue using polarization-sensitive OCT. Using principles of heterodyne dynamic light scattering, we developed diffusion-sensitive optical coherence tomography (DS-OCT) to spatially-resolve changing DT in real-time. DS-OCT enables, for the first time, direct monitoring of changes in nanoparticle diffusion rates that are sensitive to nanoporosity with spatial and temporal resolutions of 4.7 μm and 0.2 s. DS-OCT therefore enables us to measure spatially-resolved changes in mucus wt% over time. In this study, we demonstrate the applicability of DS-OCT on well-differentiated primary human bronchial epithelial cells during a clinical mucus-hydrating therapy, hypertonic saline treatment (HST), to reveal, for the first time, mucus mixing, cellular secretions, and mucus hydration on the micrometer scale that translate to long-term therapeutic effects.

Objective measurement of the nasal valve region is valuable for the assessment of functional rhinoplasty surgical outcomes. Anatomical optical coherence tomography (aOCT) is an imaging modality that may be used to obtain real-time, quantitative, and volumetric scans of the nasal airway. We aim to evaluate if volumetric aOCT imaging is useful for the examination of the nasal valve region before and after functional rhinoplasty procedures. aOCT scans of the nasal valves were performed on four cadaveric heads before and after spreader graft and butterfly graft procedures. The resulting aOCT images were compared against video endoscopy images, and the segmented volumes of the nasal airway obtained from aOCT scans were compared with computed tomography (CT) derived volumes acquired under the same conditions. The aOCT-derived volumes match the CT volumes closely, with a mean Dice similarity coefficient of 0.88 and a mean Hausdorff distance of 2.3 mm. Furthermore, the aOCT images were found to represent the shape of the nasal cavity accurately. Due to its ability to perform real-time, quantitative, and accurate evaluation of the nasal airway, aOCT imaging is a promising modality for the objective assessment of the nasal valves before and after functional rhinoplasty procedures.

We describe an elastographic method to circumferentially-resolve airway wall compliance using endoscopic, anatomic optical coherence tomography (aOCT) combined with an intraluminal pressure catheter. The method was first demonstrated on notched silicone phantoms of known elastic modulus under respiratory ventilation, where localized compliance measurements were validated against those predicted by finite element modeling. Then, ex vivo porcine tracheas were scanned, and the pattern of compliance was found to be consistent with histological identification of the locations of (stiff) cartilage and (soft) muscle. This quantitative method may aid in diagnosis and monitoring of collapsible airway wall tissues in obstructive respiratory disorders.

The eyes of scallops form images using a concave spherical mirror and contain two separate retinas, one layered on top of the other. Behavioral and electrophysiological studies indicate that the images formed by these eyes have angular resolutions of about 2°. Based on previous ray-tracing models, it has been thought that the more distal of the two retinas lies near the focal point of the mirror and that the proximal retina, positioned closer to the mirror at the back of the eye, receives light that is out-of-focus. Here, we propose three mechanisms through which both retinas may receive focused light: (1) chromatic aberration produced by the lens may cause the focal points for longer and shorter wavelengths to fall near the distal and proximal retinas, respectively; (2) focused light from near and far objects may fall on the distal and proximal retinas, respectively; and (3) the eyes of scallops may be dynamic structures that change shape to determine which retina receives focused light. To test our hypotheses, we used optical coherence tomography (OCT), a method of near-infrared optical depth-ranging, to acquire virtual cross-sections of live, intact eyes from the bay scallop Argopecten irradians . Next, we used a custom-built ray-tracing model to estimate the qualities of the images that fall on an eye’s distal and proximal retinas as functions of the wavelengths of light entering the eye (400–700 nm), object distances (0.01–1 m), and the overall shape of the eye. When we assume 550 nm wavelength light and object distances greater than 0.01 m, our model predicts that the angular resolutions of the distal and proximal retinas are 2° and 7°, respectively. Our model also predicts that neither chromatic aberration nor differences in object distance lead to focused light falling on the distal and proximal retinas simultaneously. However, if scallops can manipulate the shapes of their eyes, perhaps through muscle contractions, we speculate that they may be able to influence the qualities of the images that fall on their proximal retinas and—to a lesser extent—those that fall on their distal retinas as well.

3D paper-based cultures (PBCs) are easy-to-use and provide a biologically representative microenvironment. By stacking a sheet of cell-laden paper below sheets containing cell-free hydrogel, we form an assay capable of segmenting cells by the distance they invaded from the original cell-seeded layer. These invasion assays are limited to end-point analyses with fluorescence-based readouts due to the highly scattering nature of the paper scaffolds. Here we demonstrate that optical coherence tomography (OCT) can distinguish living cells from the surrounding extracellular matrix (ECM) or paper fibers based upon their intracellular motility amplitude (M). M is computed from fluctuation statistics of the sample, rejects shot noise, and is invariant to OCT signal attenuation. Using OCT motility analysis, we tracked the invasion of breast cancer cells over a 3-day period in 4-layer PBCs (160–300 µm thick) in situ. The cell population distributions determined with OCT are highly correlated with those obtained by fluorescence imaging, with an intraclass correlation coefficient (ICC) of 0.903. The ability of OCT motility analysis to visualize live cells and quantify cell distributions in PBC assays in situ and longitudinally provides a novel means for understanding how chemical gradients within the tumor microenvironment affect cellular invasion.

Identification and treatment of obstructive airway disorders (OADs) are greatly aided by imaging of the geometry of the airway lumen. Anatomical optical coherence tomography (aOCT) is a promising high-speed and minimally invasive endoscopic imaging modality for providing micrometer-resolution scans of the upper airway. Resistance to airflow in OADs is directly caused by the reduction in luminal cross-sectional area (CSA). It is hypothesized that aOCT can produce airway CSA measurements as accurate as that from computed tomography (CT). Scans of machine hollowed cylindrical tubes were used to develop methods for segmentation and measurement of airway lumen in CT and aOCT. Simulated scans of virtual cones were used to validate 3-D resampling and reconstruction methods in aOCT. Then, measurements of two segments of a 3-D printed pediatric airway phantom from aOCT and CT independently were compared to ground truth CSA. In continuous unobstructed regions, the mean CSA difference for each phantom segment was 2.2 ± 3.5 and 1.5 ± 5.3 mm(2) for aOCT, and −3.4 ± 4.3 and −1.9 ± 1.2 mm(2) for CT. Because of the similar magnitude of these differences, these results support the hypotheses and underscore the potential for aOCT as a viable alternative to CT in airway imaging, while offering greater potential to capture respiratory dynamics.

In magnetomotive ultrasound (MMUS) imaging, an oscillating external magnetic field displaces tissue loaded with super-paramagnetic iron oxide (SPIO) particles. The induced motion is on the nanometer scale, which makes its detection and its isolation from background motion challenging. Previously, a frequency and phase locking (FPL) algorithm was used to suppress background motion by subtracting magnetic field off (B-off) from on (B-on) data. Shortcomings to this approach include long tracking ensembles and the requirement for B-off data. In this article, a novel blind source separation based FPL (BSS-FPL) algorithm is presented for detecting motion using a shorter ensemble length than FPL and without B-off data. MMUS imaging of 2 phantoms containing an SPIO-laden cubical inclusion and 1 control phantom was performed using an open-air MMUS system. When background subtraction was used, contrast, and contrast to noise ratio (CNR) were respectively 1.20 ± 0.20 and 1.56 ± 0.34 times higher in BSS-FPL as compared to FPL-derived images for ensemble lengths < 3.5s. However, contrast and CNR were similar for BSS-FPL and FPL for ensemble lengths ≥ 3.5s. When only B-on data was used, contrast and CNR were 1.94 ± 0.21 and 1.56 ± 0.28 times higher respectively in BSS-FPL as compared to FPL-derived images for all ensemble lengths. Percent error in the estimated width and height was 39.30 ± 19.98 % and 110.37 ± 6.5 % for FPL and was 7.30 ± 7.6 % and 16.21 ± 10.29 % for BSS-FPL algorithm. This study is an important step toward translating MMUS imaging to in vivo application, where long tracking ensembles would increase acquisition time and B-off data may be misaligned with B-on due to physiological motion.

It is hypothesized that the local, viscoelastic (time-dependent) properties of the airway are important to accurately model and ultimately predict dynamic airway collapse in airway obstruction. Toward this end, we present a portable, endoscopic, swept-source anatomical optical coherence tomography (aOCT) system combined with a pressure catheter to capture local airway dynamics in vivo during respiration. aOCT scans were performed in the airways of a mechanically ventilated pig under paralysis with dynamic and static ventilation protocols. Validation of dynamic aOCT luminal cross-sectional area (CSA) measurements against Cine CT, obtained during the same exam, showed an aggregate difference of 15 % ± 3 % . aOCT-derived CSA obtained in the in vivo trachea also exhibited hysteresis as a function of pressure, depicting the viscoelastic nature of the airway wall. The volumetric imaging capabilities were validated by comparing aOCT- and CT-derived geometries of the porcine airway spanning nine generations from the trachea to the bronchioles. The ability to delineate regional differences in airway viscoelastic properties, by measuring airway deformation using aOCT combined with intraluminal pressure, paves the way to patient-specific models of dynamic airway collapse.

WELCOME to the IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS (JSTQE) Issue on Biophotonics. Biophotonics is a truly exciting multidisciplinary field as it combines state-of-the-art photonics technologies in quantum electronics, lasers, fiber optics, and electro-optics to the study of life sciences and medicine. Since the invention of the microscope, light has played a crucial role in the discovery of phenomena in all forms of life, from single-celled organisms to humans. The modern field of biophotonics represents a truly broad spectrum of research spanning from basic science studies in botany and zoology, to biomedicine and clinical technologies. Yet, all of these research themes have in common the use of photons on living cells and organisms, which leads to insights being shared and used to inspire new directions across the spectrum of applications. In the biomedical domain, biophotonics approaches often initiate at the “bench,” where promising technologies eventually lead to clinically relevant “bedside” diagnostics and therapeutics. Because of the low cost associated with biomedical technologies, and increasing use of integrated photonics in mobile technologies, this field is rapidly transforming our approach to health care by providing increasingly rapid, accurate, point-of-care, and cost-efficient diagnostics and surgical guidance techniques.

Sub-micrometer, periodic motion detection using blind source separation (BSS) via principal component analysis (PCA) is presented in the context of magnetomotive ultrasound (MMUS) imaging and Shearwave Dispersion Ultrasound Vibrometry (SDUV). In MMUS, an oscillating external magnetic field displaces tissue loaded with superparamagnetic iron oxide (SPIO) particles, whereas in SDUV, periodic tissue motion is induced using acoustic radiation force (ARF) to measure visco-elastic properties. BSS motion detection performance in MMUS imaging and SDUV was compared against frequency-phase locked (FPL) and normalized cross-correlation (NCC) motion detectors, respectively, in silico and in experimental phantoms. Parametric MMUS phantom images constructed using the BSS method had nearly twice the SNR of the corresponding images constructed using FPL method when a 0.043 mm or smaller kernel size was used. In FEM models of SDUV, the error in the BSS-estimated viscoelastic properties of simulated materials was < 10%, whereas the error was > 20% using NCC when the simulated SNR was 15 dB. In a calibrated elasticity phantom, the amplitude of the motion was ≤ 0.5 μm for a scanner power level ≤ 20%. The median percent error in BSS-derived shear modulus of the phantom was −6.8%, −1.55%, −17.11% for power level of 20%, 15%, and 10%, respectively. The corresponding NCC-derived errors were 29.90%, 127.1%, and 244.70%. These results suggest the relevance of using BSS for the detection of sub-micrometer, periodic motion in MMUS and SDUV imaging, particularly when SNR is less than 15 dB and/or induced displacements are less than 0.5 μm.

To evaluate the presence and length of microcracks in resin-based materials finished with different techniques, using optical coherence tomography (OCT).Standardized Class V preparations (3x2x2mm) were made in the facial and lingual surfaces of 20 recently-extracted human third molars. 20 preparations were restored with a resin-based composite material (RBC; Filtek Supreme Ultra) and the other 20 with a resin-modified glass-ionomer material (RMGI; Ketac Nano). After final polymerization, specimens were further stratified by finishing system: aluminum oxide discs (Sof-Lex) or spiral fluted carbide bur series (H48L). By random allocation, each extracted tooth therefore received one RBC and one RMGI restoration, and equal numbers of restorations from each material were finished using each finishing system (n= 10). After 24 hours of storage in 100% humidity at room temperature, the specimens were evaluated at x20 to x600 under environmental SEM. Cross-sectional occlusal-cervical B-mode images were obtained in increments of 25 mm from the mesial margin to the distal margin of the restoration using a spectral-domain (SD) OCT system and analyzed using Image J software to identify and measure microcrack penetration into each restoration. The total length (mm) at the point of the deepest microcrack penetration in each specimen was recorded. Data were statistically analyzed using a t-test.No microcracks were observed in the RBC samples. However, microcrack presence was identified in all of the RMGI specimens. The t-test showed a statistically significant difference (P0.05) in mean microcrack length values based on the finishing technique used for the RMGI samples. [SofLex: 0.67 (± 0.28) mm; carbide: 1.26 (± 0.30)] mm. Two-way ANOVA showed significant differences in the factors "finishing technique" and "restorative material" (P0.001). The interaction of these two factors was also statistically significant (P0.001). For the tested RMGI, Tukey post-hoc test revealed that the finishing with aluminum oxide groups resulted in statistically significant lower mean microcrack length when compared to spiral fluted carbide burs (P0.001).Resin-modified glass-ionomer (RMGI) is more susceptible to microcrack presence than resin-based composites. Also, aluminum oxide discs produced lower values of mean microcrack length than spiral fluted carbide burs after the finishing procedure of RMGI restorations.

We describe a novel, multi-modal imaging protocol for validating quantitative dynamic airway imaging performed using anatomical Optical Coherence Tomography (aOCT). The aOCT system consists of a catheter-based aOCT probe that is deployed via a bronchoscope, while a programmable ventilator is used to control airway pressure. This setup is employed on the bed of a Siemens Biograph CT system capable of performing respiratory-gated acquisitions. In this arrangement the position of the aOCT catheter may be visualized with CT to aid in co-registration. Utilizing this setup we investigate multiple respiratory pressure parameters with aOCT, and respiratory-gated CT, on both ex vivo porcine trachea and live, anesthetized pigs. This acquisition protocol has enabled real-time measurement of airway deformation with simultaneous measurement of pressure under physiologically relevant static and dynamic conditions- inspiratory peak or peak positive airway pressures of 10–40 cm H2O, and 20–30 breaths per minute for dynamic studies. We subsequently compare the airway cross sectional areas (CSA) obtained from aOCT and CT, including the change in CSA at different stages of the breathing cycle for dynamic studies, and the CSA at different peak positive airway pressures for static studies. This approach has allowed us to improve our acquisition methodology and to validate aOCT measurements of the dynamic airway for the first time. We believe that this protocol will prove invaluable for aOCT system development and greatly facilitate translation of OCT systems for airway imaging into the clinical setting.

To aid in diagnosis and treatment of upper airway obstructive disorders (UAOD), we propose anatomic Optical Coherence Tomography (aOCT) for endoscopic imaging of the upper airway lumen with high speed and resolution. aOCT and CT scans are performed sequentially on in vivo swine to compare dynamic airway imaging data. The aOCT system is capable of capturing the dynamic deformation of the airway during respiration. This may lead to methods for airway elastography and aid in our understanding of dynamic collapse in UAOD.

OCT fluctuation spectroscopy provides a quantitative and non-invasive tool to monitor 3D mammary epithelial cell (MEC) models which recapitulate features of breast cancer in vivo. Cellular dynamic fluctuation measurements allow for assessing drug responses due to different mechanisms of inhibition in 3D models in vitro. Here we report on pre-malignant MEC responses to two toxicants: Taxol, which stabilizes microtubules against depolymerization, and has emerged as an important chemotherapeutic agent in the treatment of breast cancer, and blebbistatin, a small molecule inhibitor with high affinity and selectivity toward Myosin II. Here we propose a quantitative method for measuring toxicant responses of MECs in 3D cultures from OCT speckle fluctuation spectroscopy. OCT fluctuation spectra were quantified within the 9-440 mHz band, from which the inverse power-law exponent (α) and the fractional modulation amplitude (M) were extracted. Pre-malignant MECs treated with Taxol (0, 10 μM and 20 μM) exhibit an increase (p 0.05) in α, since myosin II isn’t highly expressed in non-migratory pre-malignant MECs. We demonstrated the feasibility of OCT fluctuation spectroscopy to quantify MEC toxicant response. Microtubule stabilization was found to be a major contributor to pre-malignant MEC fluctuation signals, while myosin II inhibition was not.

While traditional, flying-spot, spectral domain OCT systems can achieve MHz linerates, they are limited by the need for mechanical scanning to produce a B-mode image. Line-field OCT (LF OCT) removes the need for mechanical scanning by simultaneously recording all A-lines on a 2D CMOS sensor. Our LF OCT system operates at the highest A-line rate of any spectral domain (SD) LF OCT system reported to date (1,024,000 A-lines/s). This is comparable with the fastest flying-spot SDOCT system reported. Additionally, all OCT systems face a tradeoff between imaging speed and sensitivity. Long exposure times improve sensitivity but can lead to undesirable motion artifacts. LF OCT has the potential to relax this tradeoff between sensitivity and imaging speed because all A-lines are exposed during the entire frame acquisition time. However, this advantage has not yet been realized due to the loss of power-per-A-line by spreading the illumination light across all A-lines on the sample. Here we use a supercontinuum source to illuminate the sample with 500mW of light in the 605-950 nm wavelength band, effectively providing 480 µW of power-per-A-line, with axial and lateral resolutions of 1.8 µm and 14 µm, respectively. With this system we achieve the highest reported sensitivity (113 dB) of any LF OCT system. We then demonstrate the capability of this system by capturing the rapidly beating cilia of human bronchial-epithelial cells in vitro. The combination of high speed and high sensitivity offered by supercontinuum-based LF SD OCT offers new opportunities for studying cell and tissue dynamics.

Quantification of airway compliance can aid in the diagnosis and treatment of obstructive airway disorders by detecting regions vulnerable to collapse. Here we evaluate the ability of a swept-source anatomic optical coherence tomography (SSaOCT) system to quantify airway cross-sectional compliance (CC) by measuring changes in the luminal cross-sectional area (CSA) under physiologically relevant pressures of 10–40 cmH2O. The accuracy and precision of CC measurements are determined using simulations of non-uniform rotation distortion (NURD) endemic to endoscopic scanning, and experiments performed in a simplified tube phantom and ex vivo porcine tracheas. NURD simulations show that CC measurements are typically more accurate than that of the CSAs from which they are derived. Phantom measurements of CSA versus pressure exhibit high linearity (R2>0.99), validating the dynamic range of the SSaOCT system. Tracheas also exhibited high linearity (R2 = 0.98) suggestive of linear elasticity, while CC measurements were obtained with typically ± 12% standard error.

We describe a novel, multi-modal imaging protocol for validating quantitative dynamic airway imaging performed using anatomical Optical Coherence Tomography (aOCT). The aOCT system consists of a catheter-based aOCT probe that is deployed via a bronchoscope, while a programmable ventilator is used to control airway pressure. This setup is employed on the bed of a Siemens Biograph CT system capable of performing respiratory-gated acquisitions. In this arrangement the position of the aOCT catheter may be visualized with CT to aid in co-registration. Utilizing this setup we investigate multiple respiratory pressure parameters with aOCT, and respiratory-gated CT, on both ex vivo porcine trachea and live, anesthetized pigs. This acquisition protocol has enabled real-time measurement of airway deformation with simultaneous measurement of pressure under physiologically relevant static and dynamic conditions- inspiratory peak or peak positive airway pressures of 10-40 cm H2O, and 20-30 breaths per minute for dynamic studies. We subsequently compare the airway cross sectional areas (CSA) obtained from aOCT and CT, including the change in CSA at different stages of the breathing cycle for dynamic studies, and the CSA at different peak positive airway pressures for static studies. This approach has allowed us to improve our acquisition methodology and to validate aOCT measurements of the dynamic airway for the first time. We believe that this protocol will prove invaluable for aOCT system development and greatly facilitate translation of OCT systems for airway imaging into the clinical setting.

Emerging supercontinuum (SC) light sources suitable for optical coherence tomography (OCT) offer greater illumination power than conventional sources, and large optical bandwidths for ultrahigh-resolution imaging. Because there is a tradeoff between power and sensitivity, by distributing the power across a line for sample illumination, we can avoid perturbing cellular behavior while increasing imaging sensitivity. Here we demonstrate an SC-based, spectral-domain, parallel line-field OCT system, and show that it exhibits an unprecedented combination of resolution, speed, and sensitivity for capturing cellular dynamics. We employ the system for imaging of human bronchial epithelial cells in vitro which exhibit rapid ciliary motion that is highly spatially localized.

Magnetomotive ultrasound (MMUS) contrasts superparamagnetic iron-oxide nanoparticles (SPIOs) that undergo submicrometer-scale displacements in response to a magnetic gradient force applied to an imaging sample. Typically, MMUS signals are defined in a way that is proportional to the medium displacement, rendering an indirect measure of the density distribution of SPIOs embedded within. Displacement-based MMUS, however, suffers from 'halo effects' that extend into regions without SPIOs due to their inherent mechanical coupling with the medium. To reduce such effects and to provide a more accurate representation of the SPIO density distribution, we propose a model-based inversion of MMUS displacement fields by reconstructing the body force distribution. Displacement fields are modelled using the static Navier-Cauchy equation for linear, homogeneous, and isotropic media, and the body force fields are, in turn, reconstructed by minimizing a regularized least-squares error functional between the modelled and the measured displacement fields. This reconstruction, when performed on displacement fields of two tissue-mimicking phantoms with cuboidal SPIO-laden inclusions, improved the range of errors in measured heights and widths of the inclusions from 54%-282% pre-inversion to-15%-20%. Likewise, the post-inversion contrast to noise ratios (CNRs) of the images were significantly larger than displacement-derived CNRs alone (p = 0.0078, Wilcoxon signed rank test). Qualitatively, it was found that inversion ameliorates halo effects and increases overall detectability of the inclusion. These findings highlight the utility of model-based inversion as a tool for both signal processing and accurate characterization of the number density distribution of SPIOs in magnetomotive imaging.

Mammary epithelial cell (MEC) organoids in 3D culture recapitulate features of breast ducts in vivo. OCT has the ability to monitor the evolution of MEC organoids non-invasively and longitudinally. The anti-cancer drug Doxorubicin (Dox) is able to inhibit proliferation of cancer cells and has been widely used for chemotherapy of breast cancers; while environmental toxins implicated in breast cancer such as estrogen regulates mammary tumor growth and stimulates the proliferation and metastatic potential of breast cancers. Here we propose a quantitative method for measuring motility of breast cells in 3D cultures based upon OCT speckle fluctuation spectroscopy. The metrics of the inverse power-law exponent (α) and fractional modulation amplitude (M) were extracted from speckle fluctuation spectra. These were used to quantify the responses of MEC organoids to Dox, and estrogen. We investigated MEC organoids comprised of two different MEC lines: MCF10DCIS.com exposed to Dox, and MCF7 exposed to estrogen. We found an increase (p

The progression of breast cancer is known to be affected by stromal cells within the local microenvironment. Here we study the effect of stromal fibroblasts on the in-place motions (motility) of mammary epithelial cells within organoids in 3D co-culture, inferred from the speckle fluctuation spectrum using optical coherence tomography (OCT). In contrast to Brownian motion, mammary cell motions exhibit an inverse power-law fluctuation spectrum. We introduce two complementary metrics for quantifying fluctuation spectra: the power-law exponent and a novel definition of the motility amplitude, both of which are signal- and position-independent. We find that the power-law exponent and motility amplitude are positively (p

Quantitative endoscopic imaging is at the vanguard of novel techniques in the assessment upper airway obstruction. Anatomic optical coherence tomography (aOCT) has the potential to provide the geometry of the airway lumen with high-resolution and in 4 dimensions. By coupling aOCT with measurements of pressure, optical coherence elastography (OCE) can be performed to characterize airway wall stiffness. This can aid in identifying regions of dynamic collapse as well as informing computational fluid dynamics modeling to aid in surgical decision-making. Toward this end, here we report on an anatomic optical coherence tomography (aOCT) system powered by a wavelength-swept laser source. The system employs a fiber-optic catheter with outer diameter of 0.82 mm deployed via the bore of a commercial, flexible bronchoscope. Helical scans are performed to measure the airway geometry and to quantify the cross-sectional-area (CSA) of the airway. We report on a preliminary validation of aOCT for elastography, in which aOCT-derived CSA was obtained as a function of pressure to estimate airway wall compliance. Experiments performed on a Latex rubber tube resulted in a compliance measurement of 0.68±0.02 mm2/cmH2O, with R2=0.98 over the pressure range from 10 to 40 cmH2O. Next, ex vivo porcine trachea was studied, resulting in a measured compliance from 1.06±0.12 to 3.34±0.44 mm2/cmH2O, (R2>0.81). The linearity of the data confirms the elastic nature of the airway. The compliance values are within the same order-of-magnitude as previous measurements of human upper airways, suggesting that this system is capable of assessing airway wall compliance in future human studies.

Mucus hydration (wt%) has become an increasingly useful metric in real-time assessment of respiratory health in diseases like cystic fibrosis and COPD, with higher wt% indicative of diseased states. However, available in vivo rheological techniques are lacking. Gold nanorods (GNRs) are attractive biological probes whose diffusion through tissue is sensitive to the correlation length of comprising biopolymers. Through employment of dynamic light scattering theory on OCT signals from GNRs, we find that weakly-constrained GNR diffusion predictably decreases with increasing wt% (more disease-like) mucus. Previously, we determined this method is robust against mucus transport on human bronchial epithelial (hBE) air-liquid interface cultures (R2=0.976). Here we introduce diffusion-sensitive OCT (DS-OCT), where we collect M-mode image ensembles, from which we derive depth- and temporally-resolved GNR diffusion rates. DS-OCT allows for real-time monitoring of changing GNR diffusion as a result of topically applied mucus-thinning agents, enabling monitoring of the dynamics of mucus hydration never before seen. Cultured human airway epithelial cells (Calu-3) with a layer of endogenous mucus were doped with topically deposited GNRs (80×22nm), and subsequently treated with hypertonic saline (HS) or isotonic saline (IS). DS-OCT provided imaging of the mucus thinning response up to a depth of 600μm with 4.65μm resolution, over a total of 8 minutes in increments of ≥3 seconds. For both IS and HS conditions, DS-OCT captured changes in the pattern of mucus hydration over time. DS-OCT opens a new window into understanding mechanisms of mucus thinning during treatment, enabling real-time efficacy feedback needed to optimize and tailor treatments for individual patients.

A portable device for measuring Young's modulus of 150uL blood samples offers 3Pa-27kPa dynamic range and small-strain (

Optical coherence tomography (OCT) has gained widespread application for many biomedical applications, yet the traditional array of contrast agents used in incoherent imaging modalities do not provide contrast in OCT. Owing to the high biocompatibility of iron oxides and noble metals, magnetic and plasmonic nanoparticles, respectively, have been developed as OCT contrast agents to enable a range of biological and pre-clinical studies. Here, we provide a review of these developments within the past decade, including an overview of the physical contrast mechanisms and classes of OCT system hardware add-ons needed for magnetic and plasmonic nanoparticle contrast. A comparison of the wide variety of nanoparticle systems is also presented, where the figures of merit depend strongly upon the choice of biological application.