MAGNETIC RESONANCE AND BIOLUMINESCENCE IMAGING MONITOR QUANTITATIVE DIFFERENCES IN PANCREATIC ISLETS AND THEIR REGENERATION AFTER BETA CELL LOSS

Abstract

Many questions about the natural history of diabetes remain unanswered, since it is not yet possible to repeatedly image pancreatic islets in vivo. We evaluated whether manganese‐enhanced MRI (MEMRI) could be useful in this context. Using a 14.1T equipment, we found that MEMRI visualizes individual islets, and ex vivo quantitates their different mass in control and diabetic mice. Using a 1.5T equipment, we repeatedly monitored transgenic mice, after deletion of their insulin‐producing beta cells by diphtheria toxin. The pancreatic signal, reporting on beta cell mass, decreased in all animals exposed to the toxin. This decrease was 66% and 33% in male and female mice, respectively, paralleling the gender difference in insulin and islet content. As evaluated by bioluminescence, the pancreas signal remained unchanged, with insulin content, in diabetic males for more than a year. In contrast, these parameters progressively returned to control levels in a subset of normoglycemic females. In a retrospective clinical study, we found that MEMRI increased the pancreas signal of both normoglycemic and type 2 diabetic patients, due to high uptake by the endocrine islets. However, this enhancement was 30% lower in the latter than in the former group of patients (p < 0.01), consistent with the decrease in beta cell mass indicated by pathology. The data show that MEMRI quantitatively detects pancreatic islets, evaluates their changes in models of experimental diabetes, and could be translatable into a clinical context.