Empirical mathematical model for dynamic manganese-enhanced MRI of the murine pancreas for assessment of β-cell function

Autoimmune ablation of pancreatic β-cells and alteration of its microvasculature may be a predictor of Type I diabetes development. A dynamic manganese-enhanced MRI (MEMRI) approach and an empirical mathematical model were developed to monitor whole pancreatic β-cell function and vasculature modifications in mice. Normal and streptozotocin-induced diabetic FVB/N mice were imaged on a 9.4 T MRI system using a 3D magnetization prepared rapid acquisition gradient echo pulse sequence to characterize low dose manganese kinetics in the pancreas head, body and tail. Average signal enhancement in the pancreas (head, body, and tail) as a function of time was fit by a novel empirical mathematical model characterizing contrast uptake/washout rates and yielding parameters describing peak signal, initial slope, and initial area under the curve. Signal enhancement from glucose-induced manganese uptake was fit by a linear function. The results demonstrated that the diabetic pancreatic tail had a significantly lower contrast uptake rate, smaller initial slope/initial area under the curve, and a smaller rate of Mn uptake following glucose activation (p < 0.05) compared to the normal pancreatic tail. These observations parallel known patterns of β-cell loss and alteration in supportive vasculature associated with diabetes. Dynamic MEMRI is a promising technique for assessing β-cell functionality and vascular perfusion with potential applications for monitoring diabetes progression and/or therapy.