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dc.contributor.advisorTaylor, Matthew R.
dc.contributor.advisorLovell, Mark A.
dc.contributor.authorWartchow, Eric P.
dc.contributor.committeememberDeterding, Robin
dc.contributor.committeememberHokanson, John
dc.contributor.committeememberReynolds, Susan
dc.date.accessioned2020-06-29T10:03:06Z
dc.date.available2020-06-29T10:03:06Z
dc.date.submitted2020
dc.descriptionIncludes bibliographical references.
dc.descriptionSpring
dc.description.abstractPrimary ciliary dyskinesia (PCD) is a congenital disease of the respiratory airways characterized by abnormal cilia structure and function. Clinical symptoms of the disease may include situs inversus, bronchiectasis, and chronic upper and lower airway infections. Transmission electron microscopic (TEM) evaluation of ciliary ultrastructure and genetic testing are the two most important components of the multimodal approach used in the diagnosis of this disease and are the only two techniques which can positively confirm a diagnosis in children under the age of 5 years old. Unlike the continuous search for PCD-associated genetic variants, few attempts been made to similarly improve the performance of the TEM analysis of ciliary biopsies. In this thesis, enhancement of the TEM examination by implementation of single-axis electron tomography for improved visualization of ciliary fine structure is explored. The analytic validity (technical performance of the test), clinical validity (power of the test to detect disease), and clinical utility (probability the test will result in improved patient outcomes) of the technique are evaluated through a multi-reader study comparing the 3D tomographic technique to conventional TEM. The study presents an analysis and discussion of data designed to thoroughly assess the role of single-axis 3D tomography in a clinical electron microscopic laboratory. The 3D technique is shown to be equal to conventional electron microscopy in recognizing disease. Readers report enhanced visualization of the inner dynein arms, a key ultrastructural feature within cilia for the identification of a specific PCD variant. The proportion of cases reported as inconclusive is reduced when comparing the 3D technique to the 2D technique, particularly in cases with suboptimal tissue available for evaluation. These findings have clinical relevance and prove the ability to perform single-axis 3D tomography can be a valued enhancement to the conventional 2D electron microscopic technique.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierWartchow_ucdenveramc_1639D_10733.pdf
dc.identifier.urihttps://hdl.handle.net/10968/5500
dc.languageEnglish
dc.publisherUniversity of Colorado at Denver, Anschutz Medical Campus. Health Sciences Library
dc.relation.ispartof2017 to Current
dc.rightsCopyright of the original work is retained by the author.
dc.subjectdiagnostics
dc.subject.meshMicroscopy, Electron
dc.subject.meshCiliary Motility Disorders
dc.subject.meshPathology
dc.titleClinical utility of incorporating single-axis 3D tomography to the electron microscopic examination of ciliary biopsies, The
dc.typeText
thesis.degree.disciplineClinical Sciences
thesis.degree.grantorUniversity of Colorado at Denver, Anschutz Medical Campus
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)


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