title: Quantitative pancreatic β cell MRI using manganese-enhanced Look-Locker imaging and two-site water exchange analysis.
abstract: Pancreatic β-cell imaging would be useful in monitoring the progression of and therapies for diabetes. The purpose of this study was to develop and evaluate quantitative β-cell MRI using manganese (Mn(2+)) labeling of β cells, T1 mapping, and a two-site water exchange model. Normal, pharmacologically-treated, and severely diabetic mice underwent injection of MnCl(2). Pancreatic water proton T1 relaxation was measured using Look-Locker MRI, and two-site water exchange analysis was used to estimate model parameters including the intracellular water proton relaxation rate constant (R1(ic)) and the intracellular fraction as indicators of β-cell function and mass, respectively. Logarithmic plots of T1 relaxation revealed two distinct proton pools relaxing with different T1s, and the two-site water exchange model fit the measured T1 relaxation data better than a monoexponential model. The intracellular R1(ic) time course revealed the kinetics of β-cell Mn(2+) labeling. Pharmacological treatments with nifedipine, tolbutamide, and diazoxide altered R1(ic), indicating that beta cell function was a determinant of Mn(2+) uptake. Intracellular fraction was significantly higher in mice with normal β cell mass than in diabetic mice (14.9% vs. 14.4%, P < 0.05). Two-site water exchange analysis of T1 relaxation of the Mn(2+)-enhanced pancreas is a promising method for quantifying β cell volume fraction and function.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Antkowiak
authors.forename: Moriel H
authors.initials: MH
authors.lastname: Vandsburger
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Epstein
mesh_terms: D000465:Algorithms; D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology*; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese; D051379:Mice; D008810:Mice, Inbred C57BL; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014867:Water / Q000378:metabolism
chemical_list: D003287:Contrast Media; D014867:Water; D008345:Manganese