Development of Advanced Molecular Imaging Probes and Contrasts for Magnetic Resonance Imaging

分子成像是一种非侵入性的工具，用于可视化活生物体中的细胞功能。 对于磁共振成像（MRI），通过将造影剂注射到生物体中来对细胞功能进行成像，所述造影剂在反映代谢功能的变化的图像中产生可量化的变化。 这些化合物可以被设计为优先结合特定的蛋白质或直接被细胞代谢，使得它们的生物分布的影响可以使用MRI成像。 与其他成像方式相比，MRI的固有灵敏度较低，挑战在于生产在较低浓度下有效的新型造影剂。 影响灵敏度的主要特性是造影剂的“弛豫率”--造影剂通过增加附近组织的磁弛豫而引起信号增强的有效性。 当靶向造影剂处于其结合状态时，其弛豫率大大增强，并且其弛豫率高度依赖于磁场。 这一特性在一种新形式的MRI造影剂中得到利用，我们开发了称为dreMR的MRI造影剂，通过产生与仅结合试剂的浓度成比例的造影剂，大大增加了有效的靶特异性。 我们还在研究一种基于超极化13 C富集内源性化合物的新型药物的弛豫作用。 这些缓慢松弛剂在体外被高度磁化（超极化），然后被注射到动物模型中，并与它们的代谢产物一起沿着光谱成像。 代谢物的空间分布产生关于体内细胞过程的有价值的信息。 该发现资助的目标有三个方面：1）测量合作化学小组生产的新型造影剂的弛豫率曲线，2）改进dreMR方法并将其扩展到动物模型的体内成像，3）确定13 C富集化合物超极化状态的“衰减时间”以及添加顺磁性化合物以增强超极化的效果。 该补助金将在研究计划的每一年为医学物理学的一名本科生和两名研究生提供MRI科学培训。

Molecular imaging is a non-invasive tool for visualization of cellular function in living organisms. For magnetic resonance imaging (MRI), cellular function is imaged by injecting a contrast agent into an organism that produces quantifiable changes in the image reflecting variations in metabolic function. These compounds may be designed to bind preferentially to a specific protein or be metabolized directly by cells so that the effects of their biodistribution can be imaged using MRI. Compared with other imaging modalities, the intrinsic sensitivity of MRI is low and the challenge is to produce newer contrast agents that can be effective at lower concentrations. The chief property affecting sensitivity is the contrast agent "relaxivity" - the effectiveness of an agent to cause signal enhancement through increased magnetic relaxation of nearby tissue. The relaxivity of targeted contrast agents is greatly enhanced when the agent is in its bound state and its relaxivity is highly dependent on the magnetic field. This characteristic is exploited in a novel form of MRI contrast, which we have developed called dreMR that greatly increases the effective target specificity by producing a contrast that is proportional to the concentration of only bound agent. We are also studying the relaxation of a new type of agent based on hyperpolarized 13C-enriched endogenous compounds. These slowly relaxing agents are highly magnetized (hyperpolarized) in vitro and then are injected into an animal model and spectroscopically imaged along with their metabolic products. The spatial distributions of the metabolites yield valuable information about in vivo cellular processes. The objectives of this Discovery Grant are three-fold: 1) measure relaxivity profiles of novel contrast agents produced by collaborating chemistry groups, 2) improve the dreMR method and extend it to in vivo imaging with animal models, and 3) determine the "decay time" of the hyperpolarization state for 13C-enriched compounds and the effects of adding paramagnetic compounds to enhance hyperpolarization. This grant will provide training in MRI science for one undergraduate and two graduate students in medical physics during each year of the research program.