NMR Microscopy of Single Neural Cells and Brain Slices

超出所提供的空间。核磁共振成像（MRI）现在是一种主要的诊断工具。然而，它仍然主要以定性的方式使用。我们认为，对临床MRI中观察到的信号变化的彻底和潜在的定量理解需要了解组织的基本构建块（即单细胞）的行为。了解MR信号的生物物理起源是实现MR全部潜力的公认需求。核磁共振（NMR）显微成像已经能够直接检查大的单细胞。在上一个资助周期中，我们一直在确定单个神经元、血细胞鬼和脑切片中的水T1、T2和多组分表观扩散系数（ADC），以努力利用这些数据开发一个现实的组织数学模型。此外，我们开始了初步研究，检查各种扰动对单细胞，血细胞鬼和脑切片的影响。在这次更新中，我们实现了新开发的模型，这将使确定的MR信号的温度依赖性;为此，我们已经开发了培养的脑切片，开发的方法来exmaine组织异质性的MR信号的依赖性，和一种技术来检查单个神经元在较低的温度。有了这些方法，我们原来的目的就能完全实现。我们相信，对单细胞和脑切片的信号特征的透彻理解将导致对MRI中观察到的信号变化的更好理解，这反过来可能有助于开发临床MRI的更定量方法。这一点尤其重要，因为已经在人体中测量了使用长扩散时间的多组分ADC，从而迫切需要本提案中的研究。新的认识将最终提高MRI的诊断灵敏度和特异性。公共卫生：中风仍然是世界上发病的主要原因。本研究的目的是了解脑卒中MRI信号改变的根本原因，从而提高脑卒中的诊断和治疗水平。这些方法也将对其他脑部疾病和其他疾病如癌症和心脏缺血有更广泛的应用。性能现场=

EXCEED THE SPACE PROVIDED. Nuclear magnetic resonance imaging (MRI) is now a major diagnostic tool. However it is still used primarily in a qualitative fashion. We believe that a thorough and potentially quantitative understanding of signal changes observed in clinical MRI requires knowledge of how the basic building blocks of tissues behave, i.e. single cells. An understanding of the biophysical origins of MR signals is a recognised need for the full potential of MR to be realised. Nuclear magnetic resonance (NMR) microimaging has enabled the direct examination of large single cells. In the last funding cycle, we have been determining the water T1, T2 and multicomponent apparent diffusion coefficient (ADC) in single neurons, blood cell ghosts and brain slices in an effort to use the data to develop a realistic mathematical model of tissues. Additionally we began preliminary studies examining the effects of a variety of perturbations on single cells, blood cell ghosts and brain slices. In this renewal we implement newly developed models that will enable the determination of the temperature dependance of the MR signals; for this purpose we have developed the cultured brain slice, developed methods to exmaine the dependance of MR signals on tissue heterogeneity, and a technique to examine single neurons at lower temperatures. With these methods our original aims can be fully realised. We believe that a thorough understanding of the signal characteristics of single cells and brain slices will lead to an improved understanding of the signal changes observed in MRI, which in turn may help develop a more quantitative approach to clinical MRI. This is especially important now that multicomponent ADCs, using long diffusion times, have been measured in humans, providing a compelling need for the studies in this proposal. The new understanding will ultimately improve the diagnostic sensitivity and specificity of MRI. Public Health: Stroke remains a major cause of morbidity in the world. The goal of this study is to understand the fundemental origin of signal changes seen in MRI of stroke, so that diagnosis and treatment of stroke may be improved. The methods will also have a broader application to other brain disorders and other diseases such as cancer and cardiac ischemia. PERFORMANCE SITE ========================================Section End===========================================