ISLET OF LANGERHANS GRAFT MONITORING BY MAGNETIC RESONANCE IMAGING

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DESCRIPTION (provided by applicant): The overall goal of this project is to develop an islet imaging method in order to visualize islet grafts in vivo and to monitor damage to the islet graft early enough to allow intervention to salvage the graft. Specific aims: 1. To determine optimal conditions for labelling isolated islets with iron nanoparticles. 2. To develop a quantitative method for the determination of MRI signal intensity. 3. To show the feasibility of islet graft monitoring by magnetic resonance imaging (MRI) in clinical islet transplant recipients. 4. To attempt salvage of islet grafts in the time lag between MRI signal alterations and islet graft loss. Experimental design: This project will apply the method of MRI imaging of islet grafts previously incubated with iron nanoparticles. In a first set of experiments performed in vitro, we will try to optimize islet labeling by determining the labeling efficiency of various amounts of iron nanoparticles. In a second set of experiments, in a model of rat islet transplantation, we will develop a method to quantify the transplanted islet mass on MRI images. In a third set of experiments in a rat model of islet graft rejection, we will attempt to detect islet graft damage by MRI before the islets are lost in order to salvage the graft by timely antirejection therapy. Finally, the method of MRI imaging of islet transplants will be applied to a small series of islet transplant recipients in a pilot study. Relevance of the project: Islet transplantation is one of the most promising therapeutic methods for restoring insulin secretion in patients with type 1 diabetes. The development of novel methods of measuring islet mass, such as islet graft imaging, to be used in the investigation and clinical follow-up of islet transplant recipients is critically needed. This project should allow to obtain sustained visualization of the islet grafts over the 1-year period of the study, and the development of islet graft dysfunction that might occur in some islet transplant recipients should be preceded by an alteration of the MRI signal, making timely graft salvage possible.