Development of MR Microscopy at the Cellular Level

描述（由申请人提供）：在过去的二十年中，MR显微镜已经发展成为MR成像的一个子集，具有广泛的应用，其最大的好处仍然是能够对活体组织进行无创成像。尽管如此，与其他显微镜相比，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不可能实现。此外，组织中MR信号的细胞起源仍然未知，试图阐明这一问题的数学模型是争论的主题。最近，利用高场微表面线圈，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绘制了具有直接组织学相关性的纤维束图。不过，这些研究是针对固定组织的，数据需要几个小时才能获得。该提案将证明，较小的微表面线圈，更高的磁场和较小，更快和更强的平面梯度线圈的组合可以保守地将信噪比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亚细胞分辨率MR显微镜。此外，新的微体积线圈将开发准确的定量研究。目标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，在更高的磁场强度（14.1、17.6和21特斯拉）下进行MR显微镜，并测试系统的定量稳定性和准确性。我们将主要探索这些进展在神经组织（单个海兔神经元和大鼠脑切片，分别在固定组织和活体灌注组织上）和心脏组织中的应用。一旦成功，广泛的组织将有可能被研究。通过定量细胞内和细胞外信号以及它们如何随生理扰动（例如缺血）而变化，我们将能够开发组织中MR信号的工作现实数学模型。此外，我们将能够在细胞水平上准确验证纤维跟踪技术。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镜技术。相关性：能够在生理上可接受的成像时间内在亚细胞水平上对活体哺乳动物组织进行成像的磁共振显微镜的发展将首次促进对MRI信号起源的定量理解。这反过来又会影响MRI的敏感性和特异性，提高其临床潜力。例如，对脑和心脏缺血信号变化的定量理解可能能够解决卒中和心脏病发作中可逆性和不可逆性损伤之间的差异，并对提高MRI在各种组织和疾病中的应用具有重要影响。

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.