Isolating CEST from MT Asymmetry in MRI

描述（由申请人提供）：化学交换饱和转移（CEST）MRI是一种相对较新的技术，并且已成为一个充满活力的研究领域，其中不断开发新的对比机制。该技术的实例包括体内代谢物、神经递质和造影剂浓度的测量，体内pH值的测量，以及诸如神经胶质瘤、骨关节炎、肌肉功能障碍和2型糖尿病等疾病的生物标志物的开发。CEST对比度保证了通过大体积水池测量小浓度分子的能力，因此具有大大增强的灵敏度。CEST MRI广泛实施的主要障碍仍然是（1）磁化传递（MT）不对称的外观，以及（2）对B 0场不均匀性的敏感性，这两者都可能导致假阳性和假阴性。MT不对称性源于固定大分子结构和大量水之间的可交换质子或通过空间磁化转移过程，并且在许多组织（包括软骨、肌肉和大脑）中具有强烈的影响。该建议旨在通过实施一种新的策略，将MT不对称性完全直接与CEST“解耦”：研究人员最近发现，通过适当放置的同时双频照射，组织中的宽共振可以有效地饱和，并且MT不对称性可以在CEST（2frequencCEST）中有效且均匀地饱和。MT饱和过程不依赖于减法或MT效应的线性。此外，问题（2）将通过使用具有这种新方法的适应的B 0校正协议来解决。这种方法的主要测试基础将是软骨中的糖胺聚糖（GAG）评估。这种策略本身对于骨关节炎早期标志物的发展非常重要。研究者在这一领域获得了相当多的专业知识，包括gagCEST和钠MRI方法。总的假设是，双频CEST提供了更好的诊断能力比传统CEST由于有效地消除MT不对称。将通过MR光谱（GAG的N-乙酰基信号）和钠MRI评估相关性。该策略分为三个具体目标：（1）体外开发、定量和模拟2frequencCEST，（2）通过体外显微成像检测2frequencCEST中的钠含量（钠MR已被证明是体内GAG浓度的有效标志物）。(3)在体内3 T/7 T扫描仪上使用液体抑制23 Na MRI进行202频率CEST。该项目的成功完成将提供一个强大的基于质子的诊断工具，用于为骨关节炎设计有效的监测策略，但也可能用于许多其他疾病，如肌肉功能障碍，2型糖尿病，以及体内监测代谢和其他诊断任务，其中需要将CEST与MT不对称性隔离。

DESCRIPTION (provided by applicant): Chemical exchange saturation transfer (CEST) MRI is a relatively new technology, and has become a vigorous research field where new contrast mechanisms are constantly being developed. Examples of this technology include the measurement of in vivo metabolite, neurotransmitter, and contrast agent concentrations, the measurement of in vivo pH, and the development of biomarkers for disorders such as glioma, osteoarthritis, muscle dysfunction, and type 2 diabetes. CEST contrast promises the ability to measure small concentrations of molecules via the large bulk water pool, hence with largely enhanced sensitivity. The major obstacles to widespread implementation of CEST MRI remain (1) the appearance of magnetization transfer (MT) asymmetry, and (2) the susceptibility to B0 field inhomogeneities, both of which can lead to false positives and false negatives. MT asymmetry arises from exchangeable protons or through-space magnetization transfer processes between immobile macromolecular structures and bulk water, and is a strong effect in many tissues including cartilage, muscle, and the brain. This proposal aims at 'decoupling' MT asymmetry from CEST entirely and directly, via the implementation of a new strategy: the investigators have recently discovered that broad resonances in tissues can be efficiently saturated via properly-placed simultaneous two-frequency irradiation and that MT asymmetry can be saturated efficiently and uniformly in CEST (2frequCEST). The MT saturation process does not rely on subtraction or the linearity of the MT effect. In addition, problem (2) will be addressed by using adapted B0 correction protocols with this new methodology. The primary testing ground of this approach will be the glycosaminoglycan (GAG) assessment in cartilage. This strategy is in itself very important for the development of early markers for osteoarthritis. The investigators have acquired considerable expertise in this field, both with gagCEST and sodium MRI methodology. The overall hypothesis is that two-frequency CEST provides better diagnostic ability than conventional CEST due to efficient elimination of MT asymmetry. The correlation will be assessed via MR spectroscopy (N-acetyl signal of GAG) and sodium MRI. The strategy is broken down into three specific aims: (1) Develop, quantify, and simulate 2frequCEST ex vivo, (2) Validate 2frequCEST with sodium content via microimaging ex vivo (sodium MR has been shown to be an efficient marker for GAG concentration in vivo). (3) Validate 2frequCEST with fluid-suppressed 23Na MRI on 3T/7T scanners in vivo. Successful completion of this project will provide a powerful proton-based diagnostic tool for devising effective monitoring strategies for osteoarthritis, but also potentially for many other disorders, such as muscle dysfunction, type 2 diabetes, as well as for the in vivo monitoring of metabolism and other diagnostic tasks where isolation of CEST from MT asymmetry is required.