Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy

Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy

Bibliographic Details
Main Author: Pinkl, Joseph T.
Language:English
Published: University of Cincinnati / OhioLINK 2021
Subjects:
Audiology
cholesteatoma
oncolytic herpes simplex virus
virotherapy
bone mineral density
bone resorption
micro computed tomography
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1627663262820533
id ndltd-OhioLink-oai-etd.ohiolink.edu-ucin1627663262820533
record_format oai_dc
collection NDLTD
language English
sources NDLTD
topic Audiology
cholesteatoma
oncolytic herpes simplex virus
virotherapy
bone mineral density
bone resorption
micro computed tomography
spellingShingle Audiology
cholesteatoma
oncolytic herpes simplex virus
virotherapy
bone mineral density
bone resorption
micro computed tomography
Pinkl, Joseph T.
Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy
author Pinkl, Joseph T.
author_facet Pinkl, Joseph T.
author_sort Pinkl, Joseph T.
title Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy
title_short Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy
title_full Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy
title_fullStr Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy
title_full_unstemmed Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy
title_sort characterizing osteologic effects of cholesteatoma and oncolytic virotherapy
publisher University of Cincinnati / OhioLINK
publishDate 2021
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1627663262820533
work_keys_str_mv AT pinkljosepht characterizingosteologiceffectsofcholesteatomaandoncolyticvirotherapy
_version_ 1719474159157772288
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin16276632628205332021-09-02T05:10:44Z Characterizing Osteologic Effects of Cholesteatoma and Oncolytic Virotherapy Pinkl, Joseph T. Audiology cholesteatoma oncolytic herpes simplex virus virotherapy bone mineral density bone resorption micro computed tomography The purpose of this study was to quantify and compare the degree of bone erosion of middle ear bone structures in response to middle ear cholesteatoma (CHST); and to measure the recovery of bone integrity post oncolytic herpes simplex virus (oHSV) treatment for CHST in the gerbil model. Data was collected from previously acquired micro-computed tomography (CT) scans of 12 total Mongolian gerbils (Samy et al., 2019a). 10 experimental gerbils (n = 20 ears) received Pseudomonas aeruginosa (PA) inoculations plus double ligation of the external auditory canal to expedite CHST growth. Two weeks post PA inoculation, the 10 gerbils (n = 20 ears) received intrabullar injections of oHSV. Of those animals, five (n = 10 ears) received a second intrabullar oHSV injection. And of those animals, two (n = 4 ears) received a third injection. All oHSV treatments were administered biweekly. Micro-CT scans were obtained two weeks post CHST induction and 2-4 weeks after each oHSV treatment. Micro-CT scans of two unoperated gerbils were included as controls. Micro-CT analyses included two regions of interest (ROIs): a cross section of the auditory bulla, and the ossicular chain. ROIs were manually traced and filtered (based on Hounsfield units, HU) using a voxel labeling tool from Siemens Inveon Research Workplace software. Micro-CT analyses included volumetric measurements of the ossicle ROIs (measured in mm3), the perimeter of the auditory bulla ROIs (measured in mm), and bone mineral density (BMD) estimations of the ossicle and bulla ROIs (measured as the average HU-per-voxel).At two weeks post CHST induction, the mean bullar perimeter of experimental animals was significantly lower than the control animals (p = 0.044), indicating bone erosion of the auditory bulla. There were no significant differences in volume and estimated BMD for any of the ossicle ROIs. When treated with oHSV, animals exhibited a significant increase in estimated BMD of the bulla after the first two injections (p < 0.001). Post third oHSV injection, the bullar BMD was significantly higher compared to the control group (p < 0.001) and the bullar perimeter significantly increased from pre oHSV treatment to post third oHSV injection (p = 0.017) with no statistically significant difference in mean perimeter between animals that received three oHSV injections and the control group. Of the three ossicle bones (malleus, incus, and stapes), the malleus was the only structure that significantly decreased in volume after each oHSV injection (p = 0.021), indicating that bone erosion occurs at this site even during oHSV treatment. However, a significant increase in estimated BMD of the malleus was noted from pre oHSV treatment to post third oHSV injection (p < 0.004). The ossicular chain ROIs were refiltered at HU ranges of 3000-8000 HU, 4000-8000 HU, and 5000-8000 HU to account for variations in BMD across different bone regions. When refiltered at 5000-8000 HU, the mean volume of the ossicular chain ROIs significantly increased from the second oHSV treatment to the third oHSV treatment (p < 0.003). Findings suggest that the gerbil auditory bulla is more prone than the ossicular chain to resorption two weeks after CHST induction. Bone erosion recovery was indicated at the level of the auditory bulla following oHSV treatment, however, there was a significant increase in estimated BMD post treatment compared to controls. The malleus exhibited a significant reduction in volume while the estimated BMD increased throughout oHSV treatment. Further investigation detected a significant increase in volume within the densest region of the bone. This suggests that different regions of the ossicular chain are responding differently to oHSV. These results support further investigation to determine if changes in bullar density are permanent, and if recovery of integrity of the ossicular chain requires a longer time course. 2021-08-29 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1627663262820533 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1627663262820533 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

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