ISLET OF LANGERHANS GRAFT MONITORING BY MAGNETIC RESONANCE IMAGING

描述（由申请人提供）： 该项目的总体目标是开发一种胰岛成像方法，以便在体内可视化胰岛移植物，并尽早监测胰岛移植物的损伤，以便进行干预以挽救移植物。 具体目标： 1.确定用铁纳米颗粒标记分离的胰岛的最佳条件。 2.建立一种定量测定MRI信号强度的方法。 3.目的：探讨磁共振成像（MRI）在胰岛移植受者临床监测中的可行性。 4.在MRI信号改变和胰岛移植物丢失之间的时间间隔内尝试挽救胰岛移植物。 实验设计：本项目将应用MRI成像的方法，胰岛移植物预先孵育铁纳米粒子。 在体外进行的第一组实验中，我们将尝试通过确定各种量的铁纳米颗粒的标记效率来优化胰岛标记。 在第二组实验中，在大鼠胰岛移植模型中，我们将开发一种方法来量化MRI图像上移植的胰岛质量。 在第三组实验中，在大鼠胰岛移植排斥模型中，我们将尝试在胰岛丢失之前通过MRI检测胰岛移植物损伤，以便通过及时的抗排斥治疗挽救移植物。 最后，胰岛移植的MRI成像方法将在一项初步研究中应用于一小批胰岛移植受者。 项目的相关性：胰岛移植是恢复1型糖尿病患者胰岛素分泌的最有前途的治疗方法之一。迫切需要开发测量胰岛质量的新方法，如胰岛移植物成像，用于胰岛移植受者的研究和临床随访。 该项目应允许在1年的研究期间获得胰岛移植物的持续可视化，并且在某些胰岛移植受者中可能发生的胰岛移植物功能障碍的发展之前，应通过改变MRI信号，使及时的移植物挽救成为可能。

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.