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1.
J Biomed Opt ; 29(4): 046004, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38690122

RESUMEN

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


Asunto(s)
Oro , Moco , Nanotubos , Tomografía de Coherencia Óptica , Tomografía de Coherencia Óptica/métodos , Humanos , Nanotubos/química , Oro/química , Moco/química , Moco/metabolismo , Difusión , Bronquios/diagnóstico por imagen , Células Epiteliales/química , Células Epiteliales/metabolismo , Solución Salina Hipertónica/farmacología , Solución Salina Hipertónica/química , Células Cultivadas
2.
Phys Med Biol ; 67(15)2022 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-35790176

RESUMEN

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.


Asunto(s)
Acústica , Trombosis , Humanos , Fantasmas de Imagen , Análisis Espectral , Ultrasonografía/métodos
3.
Adv Mater ; 34(40): e2203366, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35679599

RESUMEN

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 Fe3 O4 nanoparticles (NPs) are deposited on the surface of anionic gold nanorods coated with bovine serum albumin. The magnetic gold nanorods (MagGNRs) obtained through mixing maintain the distinct optical properties of plasmonic gold nanorods that are minimally perturbed by the magnetic overcoating. Magnetic alignment of the MagGNRs arising from magnetic dipolar interactions on the anisotropic gold nanorod core is comprehensively characterized, including structural characterization and enhancement (suppression) of the longitudinal surface plasmon resonance and suppression (enhancement) of the transverse surface plasmon resonance for light polarized parallel (orthogonal) to the magnetic field. The MagGNRs can also be driven in rotating magnetic fields to rotate at frequencies of at least 17 Hz. For suitably large gold nanorods (148 nm long) and Fe3 O4 NPs (13.4 nm diameter), significant alignment is possible even in modest (<500 Oe) magnetic fields. An analytical model provides a unified understanding of the magnetic alignment of MagGNRs.


Asunto(s)
Oro , Nanotubos , Oro/química , Campos Magnéticos , Nanopartículas Magnéticas de Óxido de Hierro , Nanotubos/química , Polietileneimina , Albúmina Sérica Bovina
4.
Laryngoscope ; 132(11): 2148-2156, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34894356

RESUMEN

OBJECTIVES/HYPOTHESIS: To establish the utility of anatomic optical coherence tomography (aOCT) in evaluating internal nasal valve (INV). STUDY DESIGN: Anatomic specimen imaging study. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2148-2156, 2022.


Asunto(s)
Obstrucción Nasal , Rinoplastia , Humanos , Hidrodinámica , Obstrucción Nasal/cirugía , Tabique Nasal/diagnóstico por imagen , Tabique Nasal/cirugía , Nariz/cirugía , Rinoplastia/métodos , Tomografía de Coherencia Óptica/métodos , Tomografía Computarizada por Rayos X/métodos
5.
Appl Opt ; 60(22): 6385-6392, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34612872

RESUMEN

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.


Asunto(s)
Endoscopía/instrumentación , Lentes , Fibras Ópticas , Tomografía de Coherencia Óptica/instrumentación , Manejo de la Vía Aérea/instrumentación , Diseño de Equipo , Humanos , Distribución Normal , Refractometría
6.
Artículo en Inglés | MEDLINE | ID: mdl-33844629

RESUMEN

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 R2 ≥ 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.


Asunto(s)
Nanopartículas de Magnetita , Medios de Contraste , Fenómenos Magnéticos , Fantasmas de Imagen , Ultrasonografía
7.
J Mammary Gland Biol Neoplasia ; 26(2): 89-99, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33439408

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama/patología , Transformación Celular Neoplásica/patología , Proteína p53 Supresora de Tumor/deficiencia , Línea Celular Tumoral , Técnicas de Cocultivo , Células Epiteliales/patología , Femenino , Fibroblastos , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Invasividad Neoplásica/patología , Células del Estroma/patología , Proteína p53 Supresora de Tumor/genética
8.
IEEE Trans Biomed Eng ; 68(8): 2360-2367, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33175676

RESUMEN

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.


Asunto(s)
Quemaduras , Diagnóstico por Imagen de Elasticidad , Enfermedades Pulmonares , Animales , Porcinos , Tomografía de Coherencia Óptica , Tráquea
9.
Biomed Opt Express ; 11(6): 3181-3194, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32637249

RESUMEN

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.

10.
Quant Imaging Med Surg ; 10(1): 76-85, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31956531

RESUMEN

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<0.001), and a significant decrease only in α for MCF7 organoids after 48 hours of exposure (P<0.0001). We also observed a significant decrease in both M and α of MCF7 organoids at the longest exposure time of 6 days to Blebbistatin (P<0.0001), and a significant decrease only in M for MCF10DCIS.com organoids after 24 hours of exposure (P<0.01). CONCLUSIONS: OCT-SFS revealed cell line-specific response patterns, in terms of intracellular motility, to different motility suppression mechanisms. This provides a foundation for future OCT-SFS studies of longitudinal responses of the mammary gland in toxicology and drug research.

11.
Opt Express ; 27(12): 16751-16766, 2019 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-31252896

RESUMEN

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.

12.
Phys Med Biol ; 64(12): 125019, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-31051477

RESUMEN

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.


Asunto(s)
Módulo de Elasticidad/fisiología , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Fantasmas de Imagen , Procesamiento de Señales Asistido por Computador/instrumentación , Ultrasonografía/instrumentación , Medios de Contraste , Dextranos/química , Humanos , Procesamiento de Imagen Asistido por Computador , Fenómenos Magnéticos , Ultrasonografía/métodos
13.
IEEE Trans Med Imaging ; 38(4): 1005-1015, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30334787

RESUMEN

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 mm2 for aOCT, and -3.4 ± 4.3 and -1.9 ± 1.2 mm2 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.


Asunto(s)
Imagenología Tridimensional/métodos , Sistema Respiratorio/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Tomografía Computarizada por Rayos X/métodos , Endoscopía , Humanos , Modelación Específica para el Paciente , Fantasmas de Imagen , Impresión Tridimensional , Sistema Respiratorio/anatomía & histología
14.
J Biomed Opt ; 23(10): 1-4, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30350490

RESUMEN

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.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Pulmón/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Tráquea/diagnóstico por imagen , Animales , Fenómenos Biomecánicos/fisiología , Elasticidad/fisiología , Diseño de Equipo , Pulmón/fisiología , Presión , Respiración , Porcinos , Tomografía Computarizada por Rayos X , Tráquea/fisiología
15.
IEEE Trans Med Imaging ; 37(10): 2356-2366, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29994656

RESUMEN

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 ( -off) from on ( -on) data. Shortcomings to this approach include long tracking ensembles and the requirement for -off data. In this paper, a novel blind source separation-based FPL (BSS-FPL) algorithm is presented for detecting motion using a shorter ensemble length (EL) than FPL and without -off data. MMUS imaging of two phantoms containing an SPIO-laden cubical inclusion and one 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 EL < 3.5 s. However, contrast and CNR were similar for BSS-FPL and FPL for EL ≥ 3.5 s. When only -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 ELs. 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 paper is an important step toward translating MMUS imaging to in vivo application, where long tracking ensembles would increase acquisition time and -off data may be misaligned with -on due to physiological motion.


Asunto(s)
Nanopartículas de Magnetita/química , Ultrasonografía/métodos , Algoritmos , Diseño de Equipo , Fantasmas de Imagen , Análisis de Componente Principal , Ultrasonografía/instrumentación
16.
Artículo en Inglés | MEDLINE | ID: mdl-29993541

RESUMEN

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 ( ) and decreasing elastic modulus ( ), 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.


Asunto(s)
Vasos Sanguíneos/diagnóstico por imagen , Módulo de Elasticidad/fisiología , Flujo Pulsátil/fisiología , Trombosis/diagnóstico por imagen , Ultrasonografía , Angiografía , Humanos , Nanopartículas de Magnetita/química , Modelos Cardiovasculares , Fantasmas de Imagen , Ultrasonografía/instrumentación , Ultrasonografía/métodos
17.
Phys Med Biol ; 63(2): 025007, 2018 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-29176039

RESUMEN

In situ measurements of diffusive particle transport provide insight into tissue architecture, drug delivery, and cellular function. Analogous to diffusion-tensor magnetic resonance imaging (DT-MRI), where the anisotropic diffusion of water molecules is mapped on the millimeter scale to elucidate the fibrous structure of tissue, here we propose diffusion-tensor optical coherence tomography (DT-OCT) for measuring directional diffusivity and flow of optically scattering particles within tissue. Because DT-OCT is sensitive to the sub-resolution motion of Brownian particles as they are constrained by tissue macromolecules, it has the potential to quantify nanoporous anisotropic tissue structure at micrometer resolution as relevant to extracellular matrices, neurons, and capillaries. Here we derive the principles of DT-OCT, relating the detected optical signal from a minimum of six probe beams with the six unique diffusion tensor and three flow vector components. The optimal geometry of the probe beams is determined given a finite numerical aperture, and a high-speed hardware implementation is proposed. Finally, Monte Carlo simulations are employed to assess the ability of the proposed DT-OCT system to quantify anisotropic diffusion of nanoparticles in a collagen matrix, an extracellular constituent that is known to become highly aligned during tumor development.


Asunto(s)
Colágeno/química , Imagen de Difusión Tensora/métodos , Matriz Extracelular/química , Fibroblastos/citología , Método de Montecarlo , Anisotropía , Células Cultivadas , Humanos
18.
Toxicol Sci ; 162(1): 234-240, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29140506

RESUMEN

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 17ß-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.


Asunto(s)
Doxorrubicina/toxicidad , Disruptores Endocrinos/toxicidad , Glándulas Mamarias Humanas/patología , Organoides/efectos de los fármacos , Lesiones Precancerosas/patología , Neoplasias de la Mama Triple Negativas/patología , Técnicas de Cultivo de Célula , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estradiol/toxicidad , Humanos , Células MCF-7 , Glándulas Mamarias Humanas/metabolismo , Organoides/patología , Lesiones Precancerosas/metabolismo , Receptores de Estrógenos/metabolismo , Tamoxifeno/análogos & derivados , Tamoxifeno/toxicidad , Factores de Tiempo , Tomografía de Coherencia Óptica , Neoplasias de la Mama Triple Negativas/metabolismo
19.
Artículo en Inglés | MEDLINE | ID: mdl-29056811

RESUMEN

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.

20.
Biomed Opt Express ; 8(4): 2195-2209, 2017 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-28736665

RESUMEN

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.

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