Development of MR Microscopy at the Cellular Level

描述(申请人提供)：在过去的二十年里，MR显微镜已经发展成为MR成像的一个子集，有着广泛的应用，其最大的好处仍然是能够非侵入性地对活组织进行成像。尽管如此，与其他显微镜相比，这种分辨率是有限的，直到最近，哺乳动物组织的细胞和亚细胞分辨率还是不可能的。此外，磁共振信号在组织中的细胞起源尚不清楚，试图阐明这一问题的数学模型也是激烈辩论的主题。最近，利用高场下的微表面线圈，我们首次获得了哺乳动物细胞的直接磁共振图像，并进一步在细胞水平上获得了与组织学直接相关的纤维束图谱。尽管如此，这些研究是针对固定组织的，数据需要几个小时才能获得。这一建议将证明，更小的微表面线圈、更高的磁场和更小、更快、更强的平面梯度线圈的组合，可以保守地将SNR提高一个数量级或更多。然后，再加上新的微灌注室，可以在生理上可接受的成像时间内实现哺乳动物活体组织的哺乳动物亚细胞分辨率磁共振显微镜。此外，还将开发新的微体积线圈，以进行准确的定量研究。AIMS 1-5将使用新的微表面和体积微线圈、新的平面微梯度和优化的序列，在依次更高的磁场强度(14.1、17.6和21特斯拉)下进行磁共振成像，并测试系统的稳定性和定量的准确性。我们将主要探索这些发展在神经组织(单个海兔神经元和大鼠脑片，都在固定组织上，然后是活的灌流组织上)以及类似的心脏组织上的用途。一旦成功，将有可能对广泛的组织进行研究。通过量化细胞内和细胞外的信号以及它们如何随着生理扰动(例如，缺血)的变化，我们将能够开发出组织中磁共振信号的实际数学模型。此外，我们将能够在细胞水平上准确验证光纤跟踪技术。因此，磁共振显微镜将为亚细胞水平的活组织成像提供一种补充的显微技术。相关性：MR显微镜的发展能够在生理上可接受的成像时间内在亚细胞水平对活的哺乳动物组织进行成像，这将首次促进对MRI中信号来源的定量了解。这反过来将影响MRI的敏感性和特异性，提高其临床潜力。例如，对脑和心肌缺血信号变化的定量了解可能能够解决中风和心脏病发作中可逆和不可逆损害的区别，并对提高MRI在各种组织和疾病中的应用具有重要影响。 与公共健康相关：将开发一种磁共振显微镜，使用新的微线圈、微梯度和高磁场下的微灌流系统，能够在生理相关的采集时间内获得活哺乳动物组织中的细胞和亚细胞分辨率。将对活的大脑和心脏组织进行定量研究。因此，对磁共振信号来源的理解将会对临床磁共振成像的敏感性和特异性产生影响。

DESCRIPTION (provided by applicant): Over the last two decades MR microscopy has evolved into a subset of MR Imaging with a wide range of applications, with its greatest benefit still the ability to image live tissue non-invasively. Still, the resolution is limited compared to other microscopies and until recently cellular and subcellular resolutions on mammalian tissue were not possible. Additionally, the cellular origins of MR signals in tissues are still unknown, and mathematical models attempting to elucidate this issue are the subject of great debate. Recently, using microsurface coils at high fields, we have obtained the first direct MR images of mammalian cells, and further, fiber tract maps at the cellular level with direct histological correlation. Still, these studies were of fixed tissue and the data took several hours to acquire. This proposal will demonstrate that the combination of smaller microsurface coils, higher magnetic fields and smaller, faster and stronger planar gradient coils can, conservatively, improve the SNR by an order of magnitude or more. Then, coupled with new microperfusion chambers, mammalian sub-cellular resolution MR microscopy of live mammalian tissue can be achieved in physiologically acceptable imaging times. Additionally new microvolume coils will be developed for accurate quantitative studies. Aims 1-5 will implement MR microscopy at successively higher magnetic field strengths (14.1, 17.6 and 21 Tesla) using new microsurface and volume microcoils, new planar microgradients and optimized sequences, and testing the system for stability and accuracy of quantitation. We will explore the utility of these developments primarily on neural tissue (single Aplysia neurons and rat brain slices, both on fixed tissue and then live perfused tissue) and similarly in cardiac tissue. When successful, a wide range of tissues will be possible to study. Through quantitation of intra and extracellular signals and how they change with physiological perturbations (for example, ischemia), we will be able to develop working realistic mathematical models of MR signals in tissues. Additionally, we will be able to accurately validate fiber tracking techniques at the cellular level. Thus, MR microscopy will provide a complementary microscopy technique for imaging live tissue at the sub-cellular level. Relevance: The development of the MR microscope capable of imaging live mammalian tissue at the sub-cellular level in physiologically acceptable imaging times will for the first time facilitate a quantitative understanding of the signal origins in MRI. This in turn will impact the sensitivity and specificity of MRI, improving its clinical potential. For example, a quantitative understanding of the signal changes in brain and cardiac ischemia may be able to resolve the difference between reversible and irreversible damage in stroke and heart attack, and have a major impact in improving the utility of MRI in a wide variety of tissues and diseases. PUBLIC HEALTH RELEVANCE: An MR microscope will be developed capable of obtaining cellular and sub-cellular resolution in live mammalian tissue in physiologically relevant acquisition times using new microcoils, microgradients and a micro-perfusion system at high magnetic fields. Quantitative studies will be undertaken on live brain and cardiac tissue. Consequently an understanding of the origins in MR signals will be developed, impacting on the sensitivity and specificity of clinical MRI.