Browsing by Subject "transverse relaxation time"
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Item Compact NMR Relaxometry of Human Blood and Living Tissues(2018-08) Patel, Vipulkumar R.; Cistola, David P.; Gryczynski, Ignacy; Berg, Rance E.; Lacko, Andras G.; Park, InWooMetabolic 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.Item Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study(BioMed Central Ltd., 2017-12-19) Robinson, Michelle D.; Mishra, Ina; Deodhar, Sneha; Patel, Vipulkumar; Gordon, Katrina V.; Vintimilla, Raul; Brown, Kim; Johnson, Leigh A.; O'Bryant, Sid E.; Cistola, David P.BACKGROUND: Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic beta-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement. METHODS: Water T2, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. RESULTS: Plasma and serum water T2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma. CONCLUSIONS: Water T2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual's metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.