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，用于可视化的细胞功能在活的有机体。对于磁共振成像（MRI），通过向生物体注射造影剂来成像细胞功能，从而在图像中产生反映代谢功能变化的可量化变化。这些化合物可以被设计成优先结合特定的蛋白质或被细胞直接代谢，这样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，其挑战在于生产出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“弛豫性”——造影剂通过增强附近组织的磁弛豫来增强信号的有效性。当造影剂处于束缚态时，其弛豫度大大增强，并且其弛豫度高度依赖于磁场。这一特点在一种新型的MRI造影剂中得到了利用，我们已经开发了一种称为dreMR的新型MRI造影剂，通过产生与仅结合剂浓度成正比的造影剂，大大增加了有效的目标特异性。我们也在研究一种基于超极化13c富集内源性化合物的新型药剂的弛豫。这些缓慢放松剂在体外被高度磁化（超极化），然后注射到动物模型中，并与它们的代谢产物一起进行光谱成像。代谢物的空间分布为体内细胞过程提供了有价值的信息。该发现基金的目标有三个方面：1)测量由合作化学小组生产的新型造影剂的弛豫谱；2)改进dreMR方法并将其扩展到动物模型的体内成像；3)确定富含13c的化合物的超极化状态的“衰减时间”以及添加顺磁性化合物增强超极化的效果。这项资助将在每年的研究项目中为一名医学物理学本科生和两名医学物理学研究生提供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.