Contrast agent diffusion as a CTa biomarker for articular cartilage health
Abstract/Contents
- Abstract
- Osteoarthritis (OA) is a degenerative joint disease that affects 12% of the adult population of the United States and costs the health care system $45-80 billion per year in direct and indirect costs. Currently, there is no cure for OA. One of the challenges of developing effective treatments for OA is that it cannot be detected early enough to intervene before irreversible soft tissue damage has occurred. In this dissertation, apparent diffusivity of a contrast agent measured using computed tomography arthrography (CTa) scans is introduced as a potential biomarker for early-stage cartilage degeneration. While in theory, apparent diffusivity will be elevated in cartilage with early signs of degradation compared to healthy cartilage, it is not a perfectly quantitative measurement. This is because cartilage responds to osmotic changes in its environment, so interstitial fluid flow is also occurring, which can accelerate or slow down solute transport. The first aim of this dissertation (Chapter 3) seeks to answer the question of how quantitative apparent diffusivity is by measuring it in enzymatically degraded cartilage explants and healthy, unaltered ones in the presence of different contrast agent concentrations and boundary conditions. Simulations were used to predict the effects of imaging protocol variation on diffusivity measurements with a large range of resolutions and scan times. Aims 2, 3, and 4 of this dissertation are steps towards translating this method for eventual in vivo use. In Aim 2 (Chapter 4), two different methods for making 3D voxel-wise apparent diffusivity measurements are presented. They are used to analyze a bovine explant dataset consisting of enzymatically degraded and unaltered cartilage samples to confirm that voxel-wise measurements show increases in apparent diffusivity in damaged tissue, like the bulk measurements did in Aim 1. Aim 3 (Chapter 5) details a method for identifying the cartilage surface in areas where it is in contact with cartilage or menisci, a step towards overcoming the challenge of accurate cartilage segmentation in CTa datasets. In Aim 4 (Chapter 6), simulations are used to study the effects of contrast agent solutions on cartilage mechanical properties. Solute size, bath ionic strength, and bath osmolarity are altered individually, which is not possible in the laboratory, and their effect on indentation force is quantified. The work presented in this dissertation could enable CTa-based detection of cartilage degeneration, expand access to early OA detection, and greatly increase treatment options in conjunction with the development of new interventions.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Hall, Mary Elizabeth |
|---|---|
| Degree supervisor | Levenston, Marc Elliot |
| Thesis advisor | Levenston, Marc Elliot |
| Thesis advisor | Gold, Garry E |
| Thesis advisor | Wang, Adam |
| Degree committee member | Gold, Garry E |
| Degree committee member | Wang, Adam |
| Associated with | Stanford University, Department of Mechanical Engineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Mary Elizabeth Hall. |
|---|---|
| Note | Submitted to the Department of Mechanical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/zm251pz1533 |
Access conditions
- Copyright
- © 2021 by Mary Elizabeth Hall
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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