ASSESSMENT OF BRAIN IRON IN PATIENTS WITH PARKINSON?S DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 应用新型MRI对比剂评估帕金森病患者脑铁和神经元完整性 在帕金森氏病（PD）中，尸检证明黑质（SN）中的铁增加是一个很好的发现。铁促进自由基的产生，自由基被认为在多巴胺神经元损失中起作用。然而，迄今为止，常规MRI未能显示PD受试者与对照受试者的SN铁水平存在显著的体内差异。这可能是由于使用传统的T1和T2加权序列可实现的组织对比度的限制。随着新的旋转框架横向（T2）和纵向（T1）弛豫MRI方法的发展，似乎是敏感的铁和神经元的损失，分别，我们开始了一项研究的8个人与PD和8个年龄匹配的对照组。使用我们的4 T MRI磁体采用这些技术，我们评估了SN中的铁沉积和神经元完整性。首先，T2磁共振成像，这是反映铁相关的动态失相机制（例如，局部不同磁化率的化学交换和扩散），显示PD组和对照组之间存在统计学显著差异，而常规T2 MRI则无此差异。其次，T1测量，这似乎反映了神经元计数，表明在PD的SN神经元的损失。我们在这里表明，亚毫米分辨率T1和T2 MRI弛豫方法可以提供一个非侵入性的测量铁含量以及证据的神经元损失，在中脑的PD患者

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. Assessment of Brain Iron and Neuronal Integrity in Patients with Parkinson's Disease Using Novel MRI Contrasts Postmortem demonstration of increased iron in the substantia nigra (SN) is a well appreciated finding in Parkinson's disease (PD). Iron facilitates generation of free radicals which are thought to play a role in dopamine neuronal loss. To date, however, conventional MRI has failed to show significant in vivo differences in SN iron levels in subjects with PD versus control subjects. This may be due to the limitations in tissue contrasts achievable with conventional T1- and T2-weighted sequences that have been employed. With the recent development of novel rotating frame transverse (T2¿) and longitudinal (T1¿) relaxation MRI methods that appear to be sensitive to iron and neuronal loss, respectively, we embarked on a study of eight individuals with PD and eight age-matched control subjects. Employing these techniques using our 4T MRI magnet, we assessed iron deposits and neuronal integrity in the SN. Firstly, T2¿ MRI, which is reflective of iron-related dynamic dephasing mechanisms (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities), demonstrated a statistically significant difference between the PD and control group, while routine T2 MRI did not. Secondly, T1¿ measurements, which appear to reflect upon neuronal count, indicated neuronal loss in the SN in PD. We show here that sub-millimeter resolution T1¿ and T2¿ MRI relaxation methods can provide a non-invasive measure of iron content as well as evidence of neuronal loss in the midbrain of patients with PD