Isolating CEST from MT Asymmetry in MRI

描述（申请人提供）：化学交换饱和转移（CEST） MRI是一项相对较新的技术，已经成为一个蓬勃发展的研究领域，新的对比机制不断被开发出来。该技术的例子包括体内代谢物、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对比有望通过大体积水池测量小浓度分子，因此大大提高了灵敏度。CEST MRI广泛应用的主要障碍仍然是(1)磁化转移（MT）不对称性的出现，(2)对B0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不对称是由不可移动的大分子结构和大量水之间的质子交换或通过空间磁化转移过程引起的，在包括软骨、肌肉和大脑在内的许多组织中都有很强的影响。该提案旨在通过实施一种新策略，完全直接地将MT不对称从CEST中“解耦”：研究人员最近发现，组织中的广泛共振可以通过适当放置的同时双频照射有效饱和，并且MT不对称可以在CEST中有效且均匀地饱和（2frequCEST）。MT饱和过程不依赖于减法或MT效应的线性。此外，问题(2)将通过使用与此新方法相适应的B0校正协议来解决。这种方法的主要试验场将是软骨中的糖胺聚糖（GAG）评估。这一策略本身对于骨关节炎早期标志物的开发非常重要。研究人员在这一领域获得了相当多的专业知识，包括gagCEST和钠核磁共振方法学。总体假设是双频CEST比常规CEST提供更好的诊断能力，因为有效地消除了MT不对称性。相关性将通过磁共振光谱（GAG的n -乙酰基信号）和钠核磁共振来评估。该策略分为三个具体目标：(1)在体外开发、量化和模拟2frequCEST，(2)通过体外微成像验证2frequCEST的钠含量（钠MR已被证明是体内GAG浓度的有效标记）。(3)在体内3T/7T扫描仪上用流体抑制23Na MRI验证2freucest。该项目的成功完成将为设计有效的骨关节炎监测策略提供一个强大的基于质子的诊断工具，但也可能用于许多其他疾病，如肌肉功能障碍，2型糖尿病，以及体内代谢监测和其他需要从MT不对称中分离CEST的诊断任务。

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.