Magnetic particle imaging of transplanted islets in type 1 diabetes animal models

1型糖尿病(T1D)是一种破坏性疾病，由自身免疫破坏产生胰岛素的胰岛β细胞所致。胰岛移植(TX)是一种很有前途的恢复T1D患者正常血糖的临床方法。然而，TX后由于各种因素造成的显著胰岛移植物丢失阻碍了T1D的治疗。显然，迫切需要一种活体成像方法来监测移植的胰岛。所有主要的常规成像方式都已用于胰岛可视化和TX后的监测。这些包括(磁共振成像)磁共振成像、核成像、超声成像和生物发光成像。到目前为止，每种方式的局限性都阻碍了胰岛TX的广泛临床翻译。磁粒子成像(MPI)是一种新兴的成像方式，它利用时变磁场直接检测超顺磁性纳米氧化铁粒子示踪剂。由于示踪剂通常不存在于体内，MPI图像具有特殊的对比度、定量能力和高灵敏度。这项新的成像技术有望改变现代医学成像和活体翻译研究的格局。在这一应用中，我们建议将这一尖端成像技术应用于监测小动物模型中标记了氧化铁纳米颗粒的移植胰岛。在小鼠模型中，肝脏或肾被膜下的胰岛移植物将使用体内MPI进行纵向追踪。基于我们的初步研究，我们还将调查MPI是否可以定量检测TX后早期移植物丢失。实验设计将包括体内MPI检测糖尿病动物模型的移植物损伤，然后进行相关的全面组织学检查。胰岛移植物的MPI数据也将首次与MRI数据进行比较。这项工作的成果将包括用于监测移植胰岛的新的图像协议，从而改进T1D治疗。

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.