VERY LOW FREQUENCY EPR IMAGING FOR IN VIVO PHYSIOLOGY

一种新型的成像技术可以对动物和人类活组织的生理特征和有毒自由基进行成像。到目前为止，还没有这方面的资料。尽管在如此低的频率下获得良好EPR信号的可能性存在广泛的误解，但该技术在世界各地的许多实验室中一直在缓慢发展。然而，近年来光谱技术和自旋探针的发展，以及对可以提供的信息的理解，使这项技术处于突破的边缘。该技术使用甚低频电子顺磁共振成像（VLF-EPRI）。非常低的频率（100到300兆赫）是必要的，以允许电磁能量，刺激共振吸收，深入渗透到动物的组织。在许多应用中，光谱来源于无毒的自旋探针，类似于或完全相同的磁共振成像造影剂，注入动物组织。旋转探针，类似或相同的磁共振成像对比材料，这是注入到动物组织。自旋探针可定位于组织内的各种液体腔室。自旋探针光谱的变化准确地反映了局部氧浓度。作为氧测量的副产品，光谱还可以报告微粘度，这可能对细胞增殖很重要。药物的自旋标记可以获得其药效学的体内图像。最近用VLF-EPRI报道了动物组织深处的这些图像。VLF-EPRI可以在体内检测到信号和有毒自由基。在动物组织中检测到一氧化氮和羟基自由基。这些早期的测量结果相对粗糙。然而，在生理敏感性和空间分辨率上有明显的改善途径。为了提高灵敏度和分辨率，我们建议在中心设施中安装一组VLF-EPRI光谱成像仪。它将存在于一个大型医疗中心内。这将提供相邻的，协调的动物护理，获得MRI/螺旋CT扫描和先进的图像相关能力。VLF-EPRI设施还将与自旋探针和自旋陷阱合成研究人员协调，以改进一般技术，并根据个人研究人员的需要进行调整。我们设想发展一个独特的中心，为研究人员提供从VLF-EPRI产生新的生理信息的能力。

A novel technician has been developed which will image physiologic characteristics and toxic radicals in living tissues of animals and humans. This information has, heretofore, been unavailable. The technique has been slowly developing in a number of laboratories throughout the world despite widespread misconceptions about the possibility of obtaining good EPR signals at such low frequencies. However, recent advances in spectroscopic technique and spin probe development, as well as the understanding of the information that can be provided, poise this technique on the verge of breakthrough. The technique uses very low frequency electron paramagnetic resonance imaging, VLF-EPRI. Very low frequency (100 to 300 MHZ) is necessary to allow the electromagnetic energy, which stimulates resonant absorption, to penetrate deep into the tissue of animals. In many applications, the spectra are derived from a non-toxic spin probe, similar or identical to magnetic resonance imaging contrast material, which is infused into animal tissues. The spin probe, similar or identical to magnetic resonance imaging contrast material, which is infused into animal tissues. The spin probe can target various fluid compartment in tissues. Changes in the spectrum of the spin probe report local oxygen concentration with high accuracy. As a byproduct of the oxygen measurement, the spectrum can also report microviscosity, which may be important for cellular proliferation. Spin labeling of medicinal agents may allow in vivo images of their pharmacodynamics. These images deep in animal tissues have been recently reported with VLF-EPRI. Both signaling and toxic free radicals can be detected with VLF-EPRI in vivo. Nitric oxide and hydroxyl radical have been detected in animal tissues with VLF-EPRI. These early measurements have been relatively crude. However, there are clear paths to improvements in physiologic sensitivity and spatial resolution by orders of magnitude. We propose the development of center facilities with an array of VLF-EPRI spectroscopic imagers to achieve this improvement in sensitivity and resolution. It would exist within a major medical center. This would offer adjacent, coordinated animal care, access to MRI/Spiral CT scanning and advanced image correlation capability. The VLF-EPRI facilities would also coordinate with spin probe and spin trap synthesis investigators to improve the general technique and tailor it to the needs of an individual researcher. We envision the development of a unique center offering researchers the capability of generating new physiologic information from VLF-EPRI.