- Title Information
- Title
- Investigating Long-term, Progressive Cerebrovascular Alterations Using Optical Coherence Tomography in Alzheimer’s Disease
- Type of Resource (primo)
- dissertations
- Name:
Personal
- Name Part
- Lee, Jang-Hoon
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Lee, Jonghwan
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Borton, David
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Plavicki, Jessica
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Salloway, Stephen
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biomedical Engineering
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2022
- Physical Description
- Extent
- xii, 137 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Ph. D.)--Brown University, 2022
- Genre (aat)
- theses
- Abstract
- Alzheimer's Disease (AD) is an irreversible neurodegenerative disorder with a decades long clinically asymptomatic phase which makes the early and accurate detection of the disease challenging. Cerebrovascular alterations, evidently showing a strong association with AD, and considered as one of the earliest events in AD pathogenesis. However, there has not been any in vivo imaging study conducted to investigate vascular alterations in longitudinal manner. This thesis, for the first time, conducts a study with a 1-year longitudinal imaging experiment to investigate microvascular alterations in APOE4 carrying mice, the strongest known genetic risk factor for late-onset AD which accounts for ~97% of all AD cases. First, we have validated the technical feasibility of our optical coherence tomography (OCT) imaging system in a 1-year timespan using one of familial AD mouse models (3xTg). We have acquired the almost 1-year data using OCT techniques such as OCT-Angiogram (OCTA) and Doppler-OCT (DOCT) to investigate both structural and functional alterations in pial and penetrating arterioles and venules. We detect early vascular alterations around 20 weeks of age (WOA) compared to late cognitive decline (40 WOA) observed from 3xTg mice. Second, we have addressed the limitations of the first study by investigating the isoflurane-induced effect in an age-related manner and have confirmed the vasodilating effect of isoflurane. The effect of aging is significant only in pial vessel diameter change (but not in penetrating vessels). In addition, we have quantified the sensitivity of our OCT approach in detecting changes in diameter (6%) and blood flow (24%) of pial and penetrating vessels. Lastly, we have conducted the longitudinal 1-year awake imaging study using APOE4 mice and acquired OCTA and DOCT data to investigate temporal dynamics of microvascular alterations along with the behavioral test for determining cognitive decline. As a result, early vascular alterations (starting from 26 WOA) are observed in pial and penetrating vessels when compared to cognitive decline (51 WOA observed only in the female APOE4). Overall, the characterization of time courses of these vascular alterations can provide good insights on which vascular properties would be crucial when developing novel retinal-based vascular biomarkers to detect AD earlier.
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00806532")
- Topic
- Alzheimer's disease
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01739425")
- Topic
- Optical coherence tomography
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00837583")
- Topic
- Brain--Blood-vessels
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20230602