Robust and highly selective proton MRSI on a clinical 3 T system using a second order gradient insert, for application in schizophrenia

项目总结- 精神分裂症的谷氨酸假说引起了人们对磁共振应用的浓厚兴趣 光谱和光谱成像(MRS/MRSI)近年来在精神分裂症病理生理学研究中的应用 泰晤士报。谷氨酸假说为公认的多巴胺能提供了补充视角。 假说，表明谷氨酸能系统功能障碍在精神分裂症的病因学中发挥了作用。 以前进行的MRS/MRSI研究报告了谷氨酸(Glu)和谷氨酰胺(Gln)的变化以及 GLX(Glu+Gln)存在于不同的大脑区域，与疾病慢性阶段的神经元功能障碍相一致。 然而，颅外脂肪污染阻碍了磁共振成像数据的可靠获取。多数 迄今为止报道的颅外脂肪抑制方法提供了不充分的脂质信号抑制，以允许 颅骨近端皮质灰质的无伪影光谱学评价。因此，MRSI在 到目前为止，在3T进行的精神分裂症有两个主要限制：1)排除近端皮质组织 颅外血脂，以及2)与Glu/Gln分离相关的不确定性，因此主要报告Glx 改变。因为谷氨酸能活性是从Glu/Gln比率推断出来的，所以开发准确和 分开测定谷氨酸和谷氨酰胺，以进一步验证谷氨酸假说的价值。 这项工作涉及发展一种高分辨率(~5x5x10mm3)3D质子磁共振成像方法 ECLIPSE是一种二阶渐变插件，用于在轴向平面上进行高度选择性的椭圆定位。高 选择性和无与伦比的颅外脂肪抑制以前在ECLIPSE中被证明，它 允许对头骨附近的皮质组织进行无伪影的讯问。将延长对MRSI的收购 利用优化的多回波时间(TE)采集和大分子靶向反转 回收组件，以使大分子基线无效。结合起来，所提出的MRSI方法是 预计将允许可靠地量化谷氨酸/谷氨酰胺。随着MRSI序列的发展，稳健性， 重复性指标和Glu/Gln量化性能将在模体和健康状态下进行评估 志愿者队列，然后是在异种队列上评估的方法的耐受性和可译性 首发精神病或新近发病的精神分裂症谱系障碍的患者。 所提出的方法的成功完成将允许可靠的谷氨酸和谷氨酰胺的MRS图像， 在其他常见检测到的代谢物中，在包括额叶皮质灰质近端的轴向平板上 射到头骨上。鉴于额叶区域受精神分裂症的影响最大，提供的能力 对于对谷氨酸能活动变化敏感的可靠代谢图像，预计会产生很大影响 通过提供可靠的代谢成像工具来表征疾病的严重性、异质性和治疗 对患者的影响。3T磁共振成像可靠的Glu/Gln定量方法的建立具有进一步的临床意义 由于3T场强是临床上最易使用的高场磁共振成像系统，因此具有重要意义。

PROJECT SUMMARY – The glutamate hypothesis of schizophrenia has generated significant interest in the utility of Magnetic Resonance Spectroscopy and Spectroscopic Imaging (MRS/MRSI) to study the pathophysiology of schizophrenia in recent times. The glutamate hypothesis provides a complementary perspective to the well-established dopaminergic hypothesis, suggesting that dysfunction of the glutamatergic system plays a role in the etiology of schizophrenia. Previous MRS/MRSI studies conducted have reported alterations of glutamate (Glu) and glutamine (Gln) and Glx (Glu + Gln) in various brain regions, consistent with neuronal dysfunction in chronic stages of the disease. The robust and reliable acquisition of MRSI data is however hindered by extracranial lipid contaminants. Most extracranial lipid suppression methods reported to-date provide inadequate lipid signal suppression, to allow artifact-free spectroscopic evaluation of cortical grey matter proximal to the skull. As a result, MRSI studies in schizophrenia conducted to-date at 3 T have two major limitations: 1) exclusion of cortical tissue proximal to extracranial lipids, and 2) uncertainties associated with Glu/Gln separation, thus predominantly reporting Glx changes. Because glutamatergic activity is inferred from the Glu/Gln ratio, it is critical to develop accurate and separate quantitation of Glu and Gln to further the value of testing the glutamate hypothesis. This work involves the development of a high resolution (~ 5 x 5 x 10 mm3) 3D proton MRSI method using ECLIPSE, a second order gradient insert, for highly selective elliptical localization over an axial plane. High selectivity and unparalleled extracranial lipid suppression was previously demonstrated with ECLIPSE, which allows artifact-free interrogation of cortical tissue adjacent to the skull. The MRSI acquisition will be extended with an optimized multiple-echo time (TE) acquisition combined with a macromolecule targeted inversion recovery component to nullify the macromolecular baseline. In combination the proposed MRSI method is expected to allow reliable quantification of Glu/Gln. Following development of the MRSI sequence, robustness, reproducibility metrics, and Glu/Gln quantification performance will be evaluated in phantom and on a healthy cohort of volunteers, followed by tolerance and translatability of the methods evaluated on a heterogenous cohort of first episode psychosis or patients with recent onset schizophrenia spectrum disorders. The successful completion of the proposed methods will allow reliable quantitative MRS images of Glu and Gln, among other commonly detected metabolites, over an axial slab including frontal cortical gray matter proximal to the skull. Given that the frontal region is the most significantly impacted by schizophrenia, the ability provided for reliable metabolic images that are sensitive to altered glutamatergic activity is expected to have a high impact by providing a reliable metabolic imaging tool for characterizing disease severity, heterogeneity, and treatment effects in patients. The development of reliable Glu/Gln quantification with MRSI at 3 T has further clinical significance, since the 3 T field strength is the most accessible high field MRI system in the clinical setting.