Noninvasive mapping of pancreatic inflammation in recent-onset type-1 diabetes patients

Abstract

Significance We describe a readily exportable method for noninvasive imaging of the pancreatic inflammation underlying type-1 diabetes (T1D), based on MRI of the clinically approved magnetic nanoparticle ferumoxytol. This approach, which reflects nanoparticle uptake by macrophages in the inflamed pancreatic lesion, has been validated rigorously in mouse T1D models. Methodological advances reported here include extensive optimization of image acquisition and improved MRI registration and visualization technologies. A proof-of-principle study revealed a clear difference in whole-pancreas nanoparticle accumulation in patients with recent-onset T1D versus healthy controls and pronounced intra- and interpancreatic signal heterogeneity in patients. Noninvasive generation of 3D, high-resolution maps of pancreatic inflammation should prove invaluable in assessing T1D progression and as an indicator of response to therapy.