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Chemical Exchange Saturation Transfer and Quantitative MRI Methods: Applications for Osteoarthritis and Cartilage Injury

Clark, Daniel James
http://orcid.org/0000-0002-4633-7886
http://rave.ohiolink.edu/etdc/view?acc_num=osu1431016691

Abstract Details

2015, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
Osteoarthritis (OA) is a huge disease burden in United States, affecting almost 30 million Americans, and is the leading cause of disability in the elderly. Knee and hip replacements cost over $40 billion annually, but may be avoided through early detection of at risk cartilage and early intervention. There are abundant MRI tools for non-invasive, quantitative imaging that reveal characteristics of cartilage structure and physiology such as collagen alignment, molecular content, and health of subchondral bone vasculature. However, no quantitative MRI technique has been added to clinical standard of care for cartilage imaging because of lack of specificity and technical difficulty. Chemical exchange saturation transfer (CEST) MRI is a promising technique to detect small metabolites such as glutamate, creatine and glucose, as well as large soluble molecules such as protein, proteoglycans, and glycogen. It has been demonstrated that CEST MRI can detect glycosaminoglycan (GAG), a proteoglycan crucial to the functioning of healthy articular cartilage, however only with high-field non-clinical scanners (> 3 Tesla). In osteoarthritis development, reduction in GAG content is a preliminary step before gross changes in cartilage thickness and joint space, and therefore clinical methods to detect GAG may have a tremendous impact on OA prevention. In this dissertation, we discuss multiple quantitative MRI techniques used to characterize articular cartilage, but then focus on CEST MRI. A miniature horse model of cartilage injury is used to evaluate several MRI techniques through serial imaging of the healing process over the course of one year. While promising, the techniques lack specificity and are technically challenging to perform, especially delayed gadolinium enchance MRI of cartilage (dGEMRIC), a technique used to detect GAG content. To meet the challenge of GAG detection at 3 Tesla, we hypothesized that a variant of CEST, using a novel variable saturation power (vCEST) scheme could detect the hydroxyl protons of the GAG molecule. We show through phantom studies that vCEST robustly detects glycogen and glucose (hydroxyl rich molecules) in multiple environments (aqueous, multiple solutes, and within semi-solid tissue), an improvement over typical CEST MRI. We offer in vivo imaging that shows contrast between lesions and normal cartilage using vCEST that is not apparent in typical CEST imaging. Finally, we propose an extension of vCEST that combines it with quantitative magnetization transfer (qMT). We use in vivo imaging of a healthy brain to show that vCEST/qMT can produce hydroxyl, amine/amide, and NOE maps that are consistent with results achieved at higher field-strengths. Since GAG molecules, in addition to hydroxyl moieties, also have an amine proton in each disaccharide unit, we hypothesize that the vCEST/qMT combine technique might further specify GAG detection at 3 T, which will be included in future work. The theme of this work is cartilage imaging, but it focuses on developing a novel technology for molecular imaging at 3 T. High resolution, non-invasive spatial mapping of molecular content using clinical scanners can have a tremendous benefit to evaluate many diseases. We hope that this work provides a step towards clinical application.
Michael Knopp, MD, PhD (Advisor)
Seth Smith, PhD (Committee Member)
Orlando Simonetti, PhD (Committee Member)
Jun Liu, PhD (Committee Member)
180 p.
Biomedical Engineering; Medical Imaging
chemical exchange; CEST; magnetization transfer; MRI; cartilage; glycosaminoglycan

Recommended Citations

Citations

  • Clark, D. J. (2015). Chemical Exchange Saturation Transfer and Quantitative MRI Methods: Applications for Osteoarthritis and Cartilage Injury [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1431016691

    APA Style (7th edition)

  • Clark, Daniel. Chemical Exchange Saturation Transfer and Quantitative MRI Methods: Applications for Osteoarthritis and Cartilage Injury. 2015. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1431016691.

    MLA Style (8th edition)

  • Clark, Daniel. "Chemical Exchange Saturation Transfer and Quantitative MRI Methods: Applications for Osteoarthritis and Cartilage Injury." Doctoral dissertation, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1431016691

    Chicago Manual of Style (17th edition)

osu1431016691
451
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This open access ETD is published by The Ohio State University and OhioLINK.