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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肾病全身性纤维化(NSF)是一种衰弱、痛苦、通常是致命的疾病。它与肾功能不全和暴露于基于Gd的磁共振成像造影剂有关。症状包括皮肤中存在不溶性Gd沉淀物。据认为，这些沉积可能在NSF疾病中起关键作用。然而，它们的化学成分目前尚不清楚。解决这一问题对于正确理解这种疾病显然很重要。我们之前已经使用显微XAS成像、X射线断层成像和EXAFS光谱表征了固定的尸检组织样本。这些结果表明，Gd：Ca：P颗粒的分布具有以磷酸Gd为基础的结构。这部作品已提交出版。我们计划将这些研究扩展到几个不同患者的固定和冷冻组织样本，以及同一患者在不同时间的样本。这也将使我们能够详细地刻画出不同患者与单个患者之间Gd沉积结构的差异和变化？S病的病情。固定组织和冷冻组织的比较将证实固定组织的过程是否对沉积物进行了化学修饰。冰冻的组织样本还可以研究不溶沉积物以外的任何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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.