Abstract

A wide variety of hearing problems can potentially be treated with local drug delivery systems capable of delivering drugs directly to the cochlea over extended periods of time. Developing and testing such systems requires accurate quantification of drug concentration over time. A variety of techniques have been proposed for both direct and indirect measurement of drug pharmacokinetics; direct techniques are invasive, whereas many indirect techniques are imprecise because they rely on assumptions about the relationship between physiological response and drug concentrations. One indirect technique, however, is capable of quantifying drug pharmacokinetics very precisely: Micro-Computed tomography (micro-CT) can provide a non-invasive way to measure the concentration of a contrast agent in the cochlea over time. In this thesis, we propose a systematic approach for analyzing micro-CT images to measure concentrations of the contrast agent ioversol in mouse cochlea. This approach requires segmenting and classifying the intra-cochlea structures from micro-CT images, which is done via 3D atlas-subject registration to a published atlas of the mouse cochlea. Labels of each intra-cochlear structure in the atlas are propagated through the registration transformation to the corresponding structures in the micro-CT images. Pixel intensities are extracted from three key intra-cochlea structures: scala tympani (ST), scala vestibuli (SV), scala media (SM) in the micro-CT images, and these intensities are mapped into concentrations using a linear model between solution concentration and image intensity that is determined in a previous calibration step. To localize this analysis, the ST, SV, SM are divided into several discrete components, and the concentrations are estimated in each component using a weighted average with weights determined by solving a nonhomogeneous Poisson equation with Dirichlet boundary conditions on the component boundaries. We illustrate this entire system on a series of micro-CT images of an anesthetized mouse that include a baseline scan (with no contrast agent) and a series of scans after injection of ioversol into the cochlea.

Library of Congress Subject Headings

Drug delivery systems--Imaging; Image registration; Veterinary tomography; Cochlea--Imaging

Publication Date

12-8-2016

Document Type

Thesis

Student Type

Graduate

Degree Name

Imaging Science (MS)

Department, Program, or Center

Chester F. Carlson Center for Imaging Science (COS)

Advisor

Nathan D. Cahill

Advisor/Committee Member

David Borkholder

Advisor/Committee Member

John Kerekes

Comments

Physical copy available from RIT's Wallace Library at RS199.5 .X8 2016

Campus

RIT – Main Campus

Plan Codes

IMGS-MS

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