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

使用二阶梯度插入的临床 3 T 系统上的鲁棒性和高选择性质子 MRSI，用于精神分裂症的应用

• 批准号: 10741355
• 负责人: CHATHURA KUMARAGAMAGE
• 金额: $ 46.06万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2025-09-20
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10741355
• 关键词: 3-Dimensional; Assessment tool; Biological Markers; Brain; Brain Diseases; Brain imaging; Brain region; Cephalic; Choline; Chronic; Clinic; Clinical; Clinical Research; Data; Development; Disease; Engineering; Environment; Etiology; Evaluation; Exclusion; Functional disorder; Glutamates; Glutamine; Goals; Head; Heterogeneity; Image; Imaging Device; Lipids; Literature; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measurement; Metabolic; Methods; Modality; Morphologic artifacts; Neurologic; Neuronal Dysfunction; Pathogenesis; Patients; Performance; Physiologic pulse; Play; Recovery; Reporting; Reproducibility; Research; Resolution; Role; Scanning; Schedule; Schizophrenia; Severity of illness; Shapes; Signal Transduction; Slice; System; Technology; Testing; Time; Tissues; Translating; Translations; Uncertainty; Work; clinical application; clinically significant; cohort; cranium; design; first episode psychosis; frontal lobe; gray matter; healthy volunteer; imaging capabilities; imaging modality; imaging study; improved; in vivo; interest; macromolecule; magnetic resonance spectroscopic imaging; metabolic imaging; metabolic profile; new therapeutic target; novel; personalized medicine; prevent; schizophrenia spectrum disorder; simulation; spectroscopic imaging; treatment effect; volunteer

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.

项目摘要 - 精神分裂症的谷氨酸假说对磁共振的效用引起了重大兴趣 光谱和光谱成像（MRS/MRSI）研究精神分裂症的病理生理学 时代。谷氨酸假说为良好的多巴胺能提供了完整的观点 假设，表明谷氨酸能系统的功能障碍在精神分裂症的病因中起作用。 先前进行的MRS/MRSI研究报告了谷氨酸（GLU）和谷氨酰胺（GLN）和 在各个大脑区域的GLX（GLU + GLN），与疾病慢性阶段的神经元功能障碍一致。 但是，颅外脂质污染物阻碍了MRSI数据的强大而可靠的获取。最多 颅外脂质抑制方法报告了待办事项，以提供脂质信号抑制不足，以允许 无伪影的光谱评估颅骨近端的皮质灰质。结果，MRSI研究 在3 t下进行迄今为止的精神分裂症具有两个主要局限性：1）排除皮质组织近端 颅外脂质和2）与GLU/GLN分离相关的不确定性，因此主要报告GLX 更改。由于谷氨酸能活性是根据GLU/GLN比率推断出的，因此发展准确和 分开对GLU和GLN的定量，以进一步测试谷氨酸假设的价值。 这项工作涉及使用高分辨率（〜5 x 5 x 10 mm3）3D质子MRSI方法的发展 Eclipse是二阶梯度插入物，用于在轴向平面上高度选择性椭圆形定位。高的 先前用日食证明了选择性和无与伦比的颅外脂质抑制作用， 允许对与颅骨相邻的皮质组织进行无伪影询问。 MRSI收购将延长 通过优化的多回声时间（TE）采集结合了大分子的目标反演 恢复成分，以使大分子基线无效。结合使用的MRSI方法是 预计允许对GLU/GLN的可靠量化。随着MRSI序列的发展，鲁棒性， 可重复性指标和GLU/GLN定量性能将在幻影和健康中评估 志愿者的队列，然后是在异源队列上评估的方法的耐受性和转换性 第一事件精神病或最近发作精神分裂症谱系障碍的患者。 提出的方法的成功完成将允许GLU和GLN的可靠定量MRS图像， 在其他常见的代谢物中，在包括额叶灰质（近端）的轴向平板上 到头骨。鉴于额叶区域受到精神分裂症的影响最大，所提供的能力 对于对改变谷氨酸能活动敏感的可靠代谢图像，预计将具有很高的影响 通过提供可靠的代谢成像工具来表征疾病的严重程度，异质性和治疗 对患者的影响。使用MRSI在3 t的MRSI定量的可靠GLU/GLN的开发具有进一步的临床 显着性，因为3吨场强度是临床环境中最容易获得的高场MRI系统。