X-RAY IMAGING AND XAS SPECTROSCOPIC STUDIES OF GD DEPOSITS ASSOCIATED WITH NSF

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 肾病系统性纤维化（NSF）是一种使人衰弱、痛苦、往往致命的疾病。它与肾功能不全和暴露于钆基磁共振成像造影剂有关。症状包括皮肤中存在不溶性钆沉积物。据信，这些沉积物可能在NSF疾病中起关键作用。然而，其化学成分目前尚不清楚。解决这个问题对于正确理解疾病显然很重要。我们以前的特点是固定的尸检组织样本使用微XAS成像，X射线断层扫描和EXAFS光谱。这些结果显示具有基于磷酸钆的结构的Gd：Ca：P颗粒的分布。这项工作已提交出版。我们计划将这些研究扩展到几个不同患者和同一患者在不同时间的固定和冷冻组织样本。这也将我们的特点详细的差异和变化的Gd存款的结构与不同的患者和个别患者？的疾病状态。固定和冷冻组织的比较将确认固定组织的过程是否对沉积物进行了化学修饰。冷冻组织样本还将允许研究不溶性沉积物之外的任何Gd的化学性质。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Nephrotic systemic fibrosis (NSF) is a debilitating, painful, often fatal disease. It is associated with renal insufficiency and exposure to gadolinium-based magnetic resonance imaging contrast agents. Symptoms include the presence of insoluble Gadolinium deposits in the skin. It is believed that these deposits may play a key role in the NSF disease. However, their chemical composition is currently unclear. Resolving this is clearly important for a proper understanding of the disease. We have previously characterized a fixed autopsy tissue sample using micro XAS imaging, x-ray tomography and EXAFS spectroscopy. These results show a distribution of Gd:Ca:P particles with a structure based on gadolinium phosphate. This work has been submitted for publication. We plan to extend these studies to fixed and frozen tissue samples from several different patients and from the same patient at different times. This will also us to characterize detailed differences and changes in the structure of the Gd deposits with different patients and with an individual patient?s disease status. Comparisons of fixed and frozen tissues will confirm whether the process of fixing the tissue has chemically modified the deposits. Frozen tissue samples will also allow study the chemical nature of any Gd outside the insoluble deposits.