NMR MICROSCOPY & LOCALIZED SPECTROSCOPY AT 360 & 200 MHZ

这项提案的目标是发展核磁共振技术 (NMR)360 MHz的显微镜和空间分辨光谱学 (8.5 T/8.9cm孔径）和200 MHz（4.7T/33 cm孔径）， 提取的组织，以及有或没有肿瘤的小动物， 从而评估其可行性和适用性。 细胞质 大单体的特性、细胞动力学和代谢 细胞（超过100微米），特别是青蛙卵，将被 通过体内受精前后的1H研究进行检查。 在以下条件下对透镜进行成像和分光镜研究 正常和高葡萄糖培养基条件将改善 了解糖尿病和白内障，因为影响 糖尿病对透镜的影响反映了它对其他人的影响。 组织中 将通过显微镜检查小动物的肿瘤 和局部光谱学以及肿瘤的意义 从而解决了异质性问题。 根据这些研究， 肿瘤的形态和光谱特征 将获得植入动物体内的细胞， 对癌症的诊断进行了调查。 分辨率限制 在大鼠和家兔的200 MHz仪器上定义（使用和 无植入肿瘤）将决定 显微镜到更大的系统，特别是人类。 选择这些研究中的生物系统是因为它们 目前正在研究中， 实验室，是应用这项技术的领域， 将在他们的理解和临床上有很大的潜力 应用程序. 本建议的具体目标是：（1） 获得尽可能好的分辨率，并定义空间的限制， 分辨率与NMR显微镜在两个领域上不同的大小 生物系统;（2）对单细胞进行NMR显微镜检查 并研究细胞代谢，动力学（分裂）和 （3）确定解决能力 完整活组织（晶状体）中细胞簇的结构， 小动物（有肿瘤）;（4）实施31 P和1H 空间分辨光谱学在小的成像区域上 动物、晶状体和细胞（仅1H），并定义 分辨率限制;以及（5）获得空间分辨弛豫 时间（T1和T2）和自扩散系数在选定的 问题研究

The goal of this proposal is to develop nuclear magnetic resonance (NMR) microscopy and spatially resolved spectroscopy at 360 MHz (8.5 T/8.9cm bore) and 200MHz (4.7T/33cm bore) on single cells, extracted tissues, and small animals with and without tumors and thus assess their feasibility and applicability. The cytoplasmic characteristics and cell dynamics and metabolism of large single cells (more than 100 microns), specifically frogs eggs, will be examined by 1H studies before and after fertilization in vivo. Imaging and spectrosocopic studies conducted on lenses under normal and high glucose media conditions will improve understanding of diabetes and cataractogenesis, since the effects of diabetes on the lens are reflective of its effect on other tissues. Tumors on small animals will be examined by microscopy and localized spectroscopy and the significance of tumor heterogeneity thus addressed. From these studies the morphologic and spectroscopic characteristics of tumors implanted in animals will be obtained and their implications with respect to cancer diagnosis investigated. The resolution limits defined on the 200MHz instrument on rats and rabbits (with and without implanted tumors) will determine the applicability of microscopy to larger systems, specifically humans. The biological systems in these studies are selected because they are well defined, are currently being investigated in this laboratory, and are areas in which application of this technology will have great potential in their understanding and clinical application. The specific objectives of this proposal are (1) to obtain the best possible resolution and define the limits of spatial resolution with NMR microscopy at both fields on different sized biological systems; (2) to perform NMR microscopy on single cells and study cell metabolism, dynamics (division) and compartmentalization; (3) to determine the capability of resolving the structure of cell clusters in intact living tissues (lenses) and small animals (with tumors); (4) to implement 31P and 1H spatially resolved spectroscopy on imaged regions of small animals, lenses and cells (1H only) at both fields and define the resolution limits; and (5) to obtain spatially resolved relaxation times (T1 and T2) and self-diffusion coefficients in selected studies.