Type 1 diabetes (T1D) is a devastating disease that results from destruction of insulin-producing pancreatic beta cells by autoimmunity. Islet Transplantation (Tx) is a promising clinic modality to restore normalglycaemia in T1D patients. However, significant islet graft loss due to various factors post Tx hampered this treatment from curing T1D. It is clear that an in vivo imaging method to monitor transplanted islet is urgently needed. All major conventional imaging modalities have been utilized for islet visualization and monitoring post Tx. These include (Magnetic resonance imaging) MRI, nuclear imaging, ultrasound imaging and bioluminescence imaging. Limitations of each modality have so-far hindered wide clinical translation of islet Tx. Magnetic Particle Imaging (MPI) is an emerging imaging modality that directly detects superparamagnetic iron oxide nanoparticle tracers using time-varying magnetic fields. Because the tracer is not normally found in the body, MPI images have exceptional contrast, quantitative capacity and high sensitivity. This new imaging technology is promising to change the landscape of modern medical imaging and in vivo translational research. In this application, we propose to apply this cutting-edge imaging technology to monitor transplanted islets that labeled with iron oxide nanoparticles in small animal models. Islet grafts in liver or under kidney capsule in mouse models will be tracked using in vivo MPI longitudinally. Based on our preliminary studies, we will also investigate whether MPI could quantitatively detect early graft loss post Tx. The experimental design will include in vivo MPI detection of graft damages in diabetic animal models followed by correlative comprehensive histological examinations. The MPI data of islet grafts will also be compared with MRI?s data for the first time. The output of this work will include novel image protocol for monitoring transplanted islet thus improving T1D treatment.
The goal of this proposal is to longitudinally monitor islet grafts in the liver and under the kidney capsules in healthy animal using magnetic particle imaging, also to quantitatively detect early islet graft loss in diabetic animal models. This imaging method will be ultimately used for monitoring islet transplantation.
