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

先进分子成像探针和磁共振成像对比的开发

• 批准号: 402811-2012
• 负责人: Scholl, Timothy
• 金额: $ 1.46万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=573368
• 关键词: Development; Advanced; Molecular; Imaging; Probes

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.

分子成像是一种非侵入性的工具，用于可视化活体中的细胞功能。对于磁共振成像(MRI)，细胞功能是通过向生物体内注射造影剂来成像的，该造影剂在图像中产生可量化的变化，反映代谢功能的变化。这些化合物可能被设计成优先与特定的蛋白质结合，或者直接由细胞代谢，这样它们的生物分布的影响就可以用磁共振成像来成像。与其他成像方式相比，MRI的内在敏感性较低，挑战是生产出在较低浓度下有效的新造影剂。影响灵敏度的主要属性是造影剂“松弛”--通过增加附近组织的磁弛豫，使信号增强的试剂的有效性。当靶向造影剂处于结合状态时，其弛豫度大大增强，并且其弛豫度高度依赖于磁场。这一特征被利用在一种新型的MRI对比剂中，我们开发的这种对比剂称为dreMR，它通过产生与仅结合试剂的浓度成正比的对比剂来极大地提高有效的靶点特异性。我们还在研究一种基于超极化富含13C的内源化合物的新型试剂的松弛。这些缓释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进行光谱成像。代谢物的空间分布提供了关于体内细胞过程的有价值的信息。Discovery Grant的目标有三个：1)测量由合作化学小组生产的新型造影剂的弛豫曲线；2)改进DreMR方法并将其扩展到动物模型的活体成像；3)确定富13C化合物的超极化状态的“衰减时间”以及添加顺磁性化合物以增强超极化的效果。这笔资金将在研究计划的每一年为一名医学物理学本科生和两名研究生提供核磁共振科学方面的培训。