Noninvasive assessment of pancreatic β-cell function in vivo with manganese-enhanced magnetic resonance imaging

Abstract

Loss of β-cell function in type 1 and type 2 diabetes leads to metabolic dysregulation and inability to maintain normoglycemia. Noninvasive imaging of β-cell function in vivo would therefore provide a valuable diagnostic and research tool for quantifying progression to diabetes and response to therapeutic intervention. Because manganese (Mn2+) is a longitudinal relaxation time (T1)-shortening magnetic resonance imaging (MRI) contrast agent that enters cells such as pancreatic β-cells through voltage-gated calcium channels, we hypothesized that Mn2+-enhanced MRI of the pancreas after glucose infusion would allow for noninvasive detection of β-cell function in vivo. To test this hypothesis, we administered glucose and saline challenges intravenously to normal mice and mice given high or low doses of streptozotocin (STZ) to induce diabetes. Serial inversion recovery MRI was subsequently performed after Mn2+ injection to probe Mn2+ accumulation in the pancreas. Time-intensity curves of the pancreas (normalized to the liver) fit to a sigmoid function showed a 51% increase in signal plateau height after glucose stimulation relative to saline ( P < 0.01) in normal mice. In diabetic mice given a high dose of STZ, only a 9% increase in plateau signal intensity was observed after glucose challenge ( P = not significant); in mice given a low dose of STZ, a 20% increase in plateau signal intensity was seen after glucose challenge ( P = 0.02). Consistent with these imaging findings, the pancreatic insulin content of high- and low-dose STZ diabetic mice was reduced about 20-fold and 10-fold, respectively, compared with normal mice. We conclude that Mn2+-enhanced MRI demonstrates excellent potential as a means for noninvasively monitoring β-cell function in vivo and may have the sensitivity to detect progressive decreases in function that occur in the diabetic disease process.