? The rapid rise of diabetes (Type 1 and Type 2) to the estimated level of 230 million sufferers worldwide during the last 20 years has global implications and requires paradigm-shifting approaches to diagnosis, treatment and prevention. The development of type 1 and type 2 diabetes share one common trait. Both distinct pathologies include the early onset of local vascular dysfunction including (but not limited to) the increase of vascular permeability and functional changes in islet capillaries in Type 1 diabetes and changing in blood flow and local permeability increase in Type 2 diabetes. The prominent role of vascular component in pathogenesis of both types of diabetes suggests that a focused multidisciplinary systematic approach to study islet vasculature is critically needed. Currently, studies on islet vasculature are generally limited to histological post-mortem findings, which suffer from inevitable tissue processing and inability to study the dynamics of blood flow. Therefore, we propose to establish a collaborative multidisciplinary research team of investigators with backgrounds in in vivo imaging, islet biology and chemistry to provide a comprehensive characterization of islet vasculature using state-of-the-art in vivo magnetic resonance imaging (MRI) technique in combination with a novel nanocarrier delivery system. Specifically, we propose to utilize high field functional MRI (fMRI) technology to obtain a high-resolution longitudinal and comprehensive assessment of the critical vascular parameters relating to blood flow, blood volume, vascular permeability and extravasation. We will use a nano-sized protected graft co-polymer (PGC) as an imaging blood pool agent for delivery of paramagnetic elements to image vascular compartment. The obtained imaging parameters will be then correlated with ex vivo immunohistological evaluation, which will serve as a validation tool for our in vivo imaging studies. Finally, using PGC as a carrier as well as an imaging agent, we will attempt to deliver therapeutic moieties to the islets and image the effect of this delivery on pancreatic vascular endothelium in models of Type 1 and Type 2 diabetes. To our knowledge, no comprehensive studies on in vivo imaging of islet vasculature have been performed to date. We believe that this proposal will provide valuable information on islet vasculature during diabetes progression that could serve not only as a scientific research tool but also as a practical way to stage islet inflammation and vascular dysfunction. ?
| Medarova, Zdravka; Greiner, Dale L; Ifediba, Marytheresa et al. (2011) Imaging the pancreatic vasculature in diabetes models. Diabetes Metab Res Rev 27:767-72 |
