Compact NMR Relaxometry of Human Blood and Living Tissues

dc.contributor.advisorCistola, David P.
dc.contributor.committeeMemberGryczynski, Ignacy
dc.contributor.committeeMemberBerg, Rance E.
dc.contributor.committeeMemberLacko, Andras G.
dc.contributor.committeeMemberPark, InWoo
dc.creatorPatel, Vipulkumar R.
dc.date.accessioned2019-10-15T13:40:10Z
dc.date.available2019-10-15T13:40:10Z
dc.date.issued2018-08
dc.description.abstractMetabolic syndrome (MetS) is a cluster of metabolic abnormalities. The designation of MetS requires three or more of five clinical criteria: central obesity, high triglycerides, low HDL cholesterol, elevated blood pressure and high blood glucose. The main purpose of the MetS diagnosis is to prevent diabetes. However, the clinical criteria of MetS are poorly calibrated and fail to detect early metabolic abnormalities essential for diabetes prevention. Additionally, the MetS definition lacks a measure of chronic inflammation, an important driver of metabolic dysregulation. Our lab has shown that plasma and serum water T2, measured using benchtop nuclear magnetic resonance (NMR) relaxometry, are better metabolic health indicators and inclusive of inflammation. In Chapter 2 of this dissertation, we describe a broad-based, unbiased proteomic search for new biomarkers that predict plasma and serum water T2. Using a multistep statistical approach, we identified five circulatory proteins that are strongly implicated in metabolic health. In Chapter 3, we investigated whether whole blood T2 can provide similar metabolic information. Mixed blood yielded a single T2, whereas settled blood gave rise to two distinct T2 values for the cell pellet (T2P) and plasma supernatant (T2S). Supernatant T2S showed strong correlations with red blood cell count and hematocrit, and this association was due to paramagnetic relaxation enhancement. In contrast, the pellet T2P exhibited strong correlations with metabolic biomarkers. Hemoglobin glycation (HbA1C, a marker of metabolic health) is responsible for this association, as it provides water binding sites that lead to faster T2 relaxation because of increased binding and chemical exchange. The T2 value for mixed blood revealed strong associations with red blood cell count and hemoglobin. In Chapter 4, we investigated the feasibility of acquiring T2 data non-invasively from living human tissue using a custom-build NMR relaxometry device equipped with a magnet configuration to accommodate the human fingertip. Using healthy volunteers, we showed that three T2 components, corresponding primarily to different mobility domains of adipose tissue, can be measured reproducibly, with significant subject-to-subject biological variation. We propose that the source of variation is adipose tissue fluidity, which varies with lipid composition and the state of connective tissue matrix.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29709
dc.language.isoen
dc.subjectinflammation
dc.subjectinsulin resistance
dc.subjectmetabolic syndrome
dc.subjectnuclear magnetic resonance
dc.subjectrelaxometry
dc.subjecttransverse relaxation time
dc.titleCompact NMR Relaxometry of Human Blood and Living Tissues
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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