ASSESSMENT OF BRAIN IRON IN PATIENTS WITH PARKINSON?S DISEASE

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。 用新的MRI对比剂评估帕金森病患者的脑铁和神经元完整性 尸检显示黑质(SN)中铁含量增加是帕金森氏病(PD)的常见发现。铁促进了自由基的产生，而自由基被认为是多巴胺神经元丧失的原因之一。然而，到目前为止，常规MRI还没有显示帕金森病患者与对照组患者体内SN铁水平的显著差异。这可能是由于已采用的常规T1和T2加权序列在组织对比方面的局限性。随着新的旋转框架横向(T2？)和纵向(T1？)松弛MRI方法的发展，它们似乎分别对铁和神经元丢失敏感，我们开始了一项针对8名帕金森病患者和8名年龄匹配的对照受试者的研究。使用我们的4T磁共振磁体使用这些技术，我们评估了SN中的铁沉积和神经元的完整性。首先，T2？MRI反映了铁相关的动态退相机制(例如，局部不同磁化率中的化学交换和扩散)，显示PD组和对照组之间有统计学差异，而常规T2 MRI没有。其次，T1？测量似乎反映了神经元计数，显示帕金森病患者SN中的神经元丢失。我们在这里表明，亚毫米分辨率的T1？和T2？磁共振弛豫方法可以提供铁含量的非侵入性测量以及帕金森病患者中脑神经元丢失的证据

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