The use of micro-magnetic resonance imaging (micro-MRI) to study morphological changes in the cochlea of conditional connexin26 (cCx26) null mice Público

Abstract

Sensorineural hearing loss (SNHL) is the most common type of hearing loss worldwide, effecting one in every 500 newborns. Yet, the underlying cause is typically unknown. One important reason is that the inner ear cannot be biopsied directly without compromising hearing. Furthermore, intracochlear cells have not been imaged with resolution sufficient to establish diagnosis. Imaging cells within the cochlea is technologically difficult because of the cochlea's small size and encasement in bone (the cochlear shell is among the densest bones in the body). Magnetic resonance imaging (MRI) enables non-invasive imaging of tissues in biological specimens ranging from mice to human beings. There is growing interest in performing high-resolution MRI studies at the scale of resolving individual cells. Few studies have reported successful visualization of the structures of the inner ear. None have investigated morphological changes in mouse models of genetic deafness. In this work, we aimed to compare high-resolution MRI examinations of inner ear structures at 9.4T with high-power evaluation of osmium- stained plastic-embedded, serial sections through the inner ear. Our results suggest that the MRI results we currently obtained have sufficient resolution to resolve major landmarks of the cochlear and vestibular structures (e.g., scala media, scala tympani, spiral osseous laminar, etc). However, the protocol we used so far was not sufficient to resolve individual cochlear cells for a diagnosis at the cellular level for the cCx26 null mouse model. I will discuss possible improvements and future development of optical tools and techniques (such as those based on two-photon micro-endoscopy) to better study morphological changes associated with SNHL.

Table of Contents

Introduction……………………………………………………………………………………………………1

Overview of Sound Processing/Anatomy of the Mammalian Ear…………………3

GJB2 (Cx26) ………………………………………………………………………………………...…5

Cx26 Expression in the Inner Ear……………………………………………………………..6

Cx26 Function in the Inner Ear…………………………………………………………………7

Conditional Cx26 (cCx26) Null Mouse Model and

Cochlear Development.………………............................................................................8

Magnetic Resonance Imaging…………………………………………………………………..9

Methods……………………………………………………………………………………………………......11

Animal Groups and Sample Preparation………………………………………………….11

Magnetic Resonance Imaging Experiments……………………………………………..13

Morphological Study……………………………………………………………………………..13

Results……………………………………………………………………………………………………........14

Discussion……………………………………………………………………………………………………..15

The gold standard: Plastic sectioning……………………………………………………...15

MRI: Is it good enough for cellular diagnosis? …………………………………………16

Signal-to-Noise Ratio…………………………………………………………………………….18

The use of contrast agents……………………………………………………………………..19

Other Imaging Methods…………………………………………………………………………20

References…………………………………………………………………………………………………….22

Figures…………………………………………………………………………………………………………..26

Figure 1. Cross-section of a Cochlear Turn.……………………………………………..26

Figure 2. Cx26 Expression in the Organ of Corti……………………………………....27

Figure 3. Description of MRI…………………………………………………………………..28

Figure 4. Schematic of Research methods…………………………………………….…29

Figure 5. Plastic section of normal and cCx26 KO mouse…………………………..29

Figure 6. MRI scans……………………………………………………………………………….30

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	BS
Submission	Honors Thesis
Language	English
Research Field	Biology, Anatomy Health Sciences, Audiology Health Sciences, Radiology
Palabra Clave	Auditory Magnetic Resonance Imaging Mammalian Cochlea Connexin 26
Committee Chair / Thesis Advisor	Lin, Xi Erick, Emory University
Committee Members	Newby, Wendy, Emory University Lennard, Paul R, Emory University Todd Jr., Norman Wendell, Emory University

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