1. Articles from Susan E. Birket

    1-9 of 9
    1. Excess mucus viscosity and airway dehydration impact COPD airway clearance

      Excess mucus viscosity and airway dehydration impact COPD airway clearance

      The mechanisms by which cigarette smoking impairs airway mucus clearance are not well understood. We recently established a ferret model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) exhibiting chronic bronchitis. We investigated the effects of cigarette smoke on mucociliary transport (MCT). Adult ferrets were exposed to cigarette smoke for 6 months, with in vivo mucociliary clearance (MCC) measured by Tc-labeled DTPA (Tc-DTPA) retention. Excised tracheae were imaged with micro-optical coherence tomography. Mucus changes in primary human airway epithelial cells and ex vivo ferret airways were assessed by histology and particle tracking microrheology. Linear mixed models for repeated measures identified ...

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    2. Intranasal micro-optical coherence tomography imaging for cystic fibrosis studies

      Intranasal micro-optical coherence tomography imaging for cystic fibrosis studies

      Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Although impairment of mucociliary clearance contributes to severe morbidity and mortality in people with CF, a clear understanding of the pathophysiology is lacking. This is, in part, due to the absence of clinical imaging techniques capable of capturing CFTR-dependent functional metrics at the cellular level. Here, we report the clinical translation of a 1-μm resolution micro-optical coherence tomography (μOCT) technology to quantitatively characterize the functional microanatomy of human upper airways. Using a minimally invasive intranasal imaging approach, we performed a clinical ...

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    3. Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography

      Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography

      Ciliary motion defects cause defective mucociliary transport (MCT) in primary ciliary dyskinesia (PCD). Current diagnostic tests do not assess how MCT is affected by perturbation of ciliary motion. In this study, we sought to use micro-optical coherence tomography (μOCT) to delineate the mechanistic basis of cilia motion defects of PCD genes by functional categorization of cilia motion. Tracheae from three PCD mouse models were analyzed using μOCT to characterize ciliary motion and measure MCT. We developed multiple measures of ciliary activity, integrated these measures, and quantified dyskinesia by the angular range of the cilia effective stroke (ARC). Ccdc39 –/– mice, with ...

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    4. Flexible, high-resolution micro-optical coherence tomography endobronchial probe toward in vivo imaging of cilia

      Flexible, high-resolution micro-optical coherence tomography endobronchial probe toward in vivo imaging of cilia

      We report the design and fabrication of a flexible, longitudinally scanning high-resolution micro-optical coherence tomography (μOCT) endobronchial probe, optimized for micro-anatomical imaging in airways. The 2.4 mm diameter and flexibility of the probe allows it to be inserted into the instrument channel of a standard bronchoscope, enabling real-time video guidance of probe placement. To generate a depth-of-focus enhancing annular beam, we utilized a new fabrication method, whereby a hollow glass ferrule was angle-polished and gold-coated to produce an elongated annular reflector. We present validation data that verifies the preservation of linear scanning, despite the use of flexible materials. When ...

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    5. Particle-Tracking Microrheology Using Micro-Optical Coherence Tomography

      Particle-Tracking Microrheology Using Micro-Optical Coherence Tomography

      Clinical manifestations of cystic fibrosis (CF) result from an increase in the viscosity of the mucus secreted by epithelial cells that line the airways. Particle-tracking microrheology (PTM) is a widely accepted means of determining the viscoelastic properties of CF mucus, providing an improved understanding of this disease as well as an avenue to assess the efficacies of pharmacologic therapies aimed at decreasing mucus viscosity. Among its advantages, PTM allows the measurement of small volumes, which was recently utilized for an in situ study of CF mucus formed by airway cell cultures. Typically, particle tracks are obtained from fluorescence microscopy video ...

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    6. In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography

      In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography

      We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (µOCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 μm and 1.7 μm, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting ...

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    7. Combination Therapy with Cystic Fibrosis Transmembrane Conductance Regulator Modulators Augment the Airway Functional Microanatomy

      Combination Therapy with Cystic Fibrosis Transmembrane Conductance Regulator Modulators Augment the Airway Functional Microanatomy

      Recently approved therapies that modulate CFTR function have shown significant clinical benefit, but recent investigations regarding their molecular mechanism when used in combination have not been consistent with clinical results. We employed Micro-Optical Coherence Tomography (µOCT) as a novel means to assess the mechanism of action of CFTR modulators, focusing on the effects on mucociliary clearance. Primary human airway monolayers from patients with a G551D mutation responded to ivacaftor treatment with increased ion transport, airway surface liquid depth, ciliary beat frequency, and mucociliary transport rate, in addition to decreased effective viscosity of the mucus layer, a unique mechanism established by ...

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    8. A Functional Anatomic Defect of the Cystic Fibrosis Airway

      A Functional Anatomic Defect of the Cystic Fibrosis Airway

      Rationale: The mechanisms underlying cystic fibrosis (CF) lung disease pathogenesis are unknown. Objective: To establish mechanisms linking anion transport with the functional microanatomy, we evaluated normal and CF piglet trachea, as well as adult swine trachea in the presence of selective anion inhibitors. Methods: We investigated airway functional microanatomy using micro-optical coherence tomography, a new imaging modality that concurrently quantifies multiple functional parameters of airway epithelium in a co-localized fashion. Main Results: Tracheal explants from wild type swine demonstrated a direct link between periciliary liquid (PCL) hydration and mucociliary transport (MCT) rates, a relationship frequently invoked but never experimentally confirmed ...

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    9. Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

      Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

      We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised ...

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    1-9 of 9
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  2. Topics in the News

    1. (9 articles) Harvard University
    2. (9 articles) Massachusetts General Hospital
    3. (7 articles) University of Alabama
    4. (3 articles) Johns Hopkins University
    5. (3 articles) Nanyang Technological University
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    Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography A Functional Anatomic Defect of the Cystic Fibrosis Airway Combination Therapy with Cystic Fibrosis Transmembrane Conductance Regulator Modulators Augment the Airway Functional Microanatomy In vivo imaging of airway cilia and mucus clearance with micro-optical coherence tomography Particle-Tracking Microrheology Using Micro-Optical Coherence Tomography Flexible, high-resolution micro-optical coherence tomography endobronchial probe toward in vivo imaging of cilia Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography Intranasal micro-optical coherence tomography imaging for cystic fibrosis studies Excess mucus viscosity and airway dehydration impact COPD airway clearance Vascular and Structural Alterations of the Choroid Evaluated by Optical Coherence Tomography Angiography and Enhanced-Depth Imaging Optical Coherence Tomography in Eyes with Reticular Pseudodrusen and Soft Drusen Total venous nature of retinal deep capillary plexus inferred by continuity of prominent middle limiting membrane sign in optical coherence tomography Evaluating Onychomycosis Outcomes 2 Months into an 11-month-long Efinaconazole Regimen: The Role of Optical Coherence Tomography