Improving the procedure for detection of intrahepatic transplanted islets by magnetic resonance imaging

Islet transplantation is an effective therapy for restoring normoglycemia in type-1 diabetes, but long-term islet graft function is achieved only in a minority of cases. Noninvasive magnetic resonance imaging of pancreatic islets is an attractive option for "real-time" monitoring of graft evolution. So far, previous studies have been performed in the absence of a standardized labeling procedure and, besides a feasibility study in patients, the effectiveness and safety of various labeling approaches were tested only with high field magnets (4.7 T). In this study, we addressed: (a) standardization of a labeling procedure for human islets with clinically-approved contrast agent Endorem, (b) safety aspects of labeling related to inflammation and (c) quality of imaging both at 7 T and 1.5 T. We have highlighted that the ratio of Endorem/islet is crucial for reproducible labeling, with a ratio of 2.24 ug/IEQ, allowing successful in vivo imaging both with 1.5 T and 7.0 T magnets up to 143 days after intrahepatic transplant. With this standardized labeling procedure, labeled islets are neither inflamed nor more susceptible to inflammatory insults than unlabeled ones. This report represents an important contribution towards the development of a standardized and safe clinical protocol for the noninvasive imaging of transplanted islets in humans.