MRI of Mobile Protein and Immobile Metabolite via Magnetization Rotation Transfer

项目摘要 该提案的目标是开发和评估一种新的磁共振成像（MRI）技术， 磁化旋转转移（MRT），可以提供有关两种类型的分子变化的信息， 组织，并且其可用于定量组织表征。捷运可以映射 组织内移动的蛋白和特定的非移动的代谢物的变化。反映MRT的图像可以 用于各种病理的诊断和评估，并将具有直接的翻译能力。 用于实体瘤的评估。溶质之间的常规磁化传递（MT） 分子和水以前曾被广泛利用，以报告非共振的影响， 在水中制备射频脉冲，但在生物中识别特定的分子MT效应 由于脂质的存在、不对称的背景线形和 重叠共振。本提案旨在通过开发MT的变体来解决这些缺陷 成像，MRT，这是一个更强大的方法相比，传统的MT成像，因为它是可行的， 隔离更具体的MT效应，并且不太容易出现伪影和实验变量的影响。 MRT包括在不同的照射翻转下用脉冲MT序列获得的两个信号的相减 但平均功率相同。通过这种策略，来自具有极短T2的自旋的贡献（例如， 大分子）、与水的相对快的交换速率（例如胺质子）和直接水饱和 将消除非共振辐射的影响。因此，MRT图像仅对以下自旋敏感： 与水的交换速率相对较慢（例如酰胺质子或核奥弗豪泽增强）。在我们 在以前的研究中，我们发现了两个特殊的对比（相对于水，MRT效应在3.5和-1.6 ppm 共振）是特别感兴趣的。我们假设：（1）MRT（3.5）反映了移动的蛋白质含量， MT（-1.6）反映了不动的代谢产物 主要对应于受限制的含胆碱化合物。移动的的非侵入性测量 蛋白质含量和含胆碱的代谢物为组织表征提供了独特的方法， 以及监测癌症的状况。在目标1中，我们将进一步开发和优化实用的MRT成像 方法.目的2和3将建立MRT（3.5）对肿瘤中移动的蛋白的特异性，并研究 通过生物化学和蛋白质组学测定，MRT（-1.6）来自不动代谢物。总体看 拟议中的研究将扩展无处不在的成像技术MRI的能力， 以新的方式定量表征组织的特定分子含量， 转化为临床实践。

PROJECT SUMMARY The goal of this proposal is to develop and evaluate a novel Magnetic Resonance Imaging (MRI) technique, Magnetization Rotation Transfer (MRT), that can provide information on two types of molecular changes within tissues simultaneously, and which may be used for quantitative tissue characterization. MRT can map variations within tissue of both mobile proteins and specific immobile metabolites. Images that reflect MRT can be used for the diagnosis and assessment of various pathologies and will have immediate translational application for the assessment of solid tumors. Conventional Magnetization Transfer (MT) between solute molecules and water has previously been extensively exploited to report the effects of off-resonance preparation radio-frequency pulses on water, but discriminating specific molecular MT effects in biological tissue has been challenging because of the presence of lipids, asymmetric background lineshapes and overlapping resonances. This proposal aims to address these deficiencies by developing a variation of MT imaging, MRT, which is a more robust method compared to conventional MT imaging because it is feasible to isolate more specific MT effects and it is less prone to artifacts and the influence of experimental variables. MRT involves the subtraction of two signals acquired with pulsed-MT sequences at different irradiation flip angles but the same average power. By this strategy, contributions from spins with extremely short T2 (e.g. macromolecules), relatively fast exchange rates with water (e.g. amine protons), and direct water saturation effects of off-resonance irradiation will be removed. MRT images are therefore sensitive only to spins with relatively slow exchange rates with water (e.g. amide protons or Nuclear Overhauser Enhancements). In our previous studies, we have found two particular contrasts (the MRT effect at 3.5 and -1.6 ppm relative to water resonance) are of special interest. We hypothesize that: (1) MRT(3.5) reflects the mobile protein content of tissues and is more specific than the conventional APT; (2) MT(-1.6) reflects immobile metabolites corresponding mainly to restricted choline-containing compounds. Non-invasive measurements of the mobile protein content and choline-containing metabolites provide a unique approach for tissue characterization, as well as monitoring the status of cancer. In Aim 1, we will further develop and optimize practical MRT imaging methods. Aims 2 and 3 will establish the specificity of MRT(3.5) to mobile proteins in tumors, and investigate the origin of MRT(-1.6) from immobile metabolites, by biochemical and proteomic assays. Overall, the proposed research will extend the capabilities of a ubiquitous imaging technology, MRI, to provide a means for quantitatively characterizing specific molecular contents of tissues in new ways that can immediately be translated into clinical practice.