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.

项目概要- 精神分裂症的谷氨酸假说引起了人们对磁共振成像的极大兴趣。 波谱和波谱成像（MRS/MRSI）在精神分裂症病理生理研究中的应用 次谷氨酸假说提供了一个补充的观点，以完善的多巴胺能 这一假说，表明神经系统功能障碍在精神分裂症的病因中起作用。 先前进行的MRS/MRSI研究已经报道了谷氨酸（Glu）和谷氨酰胺（Gln）的改变， Glx（Glu + Gln）在不同的大脑区域，符合神经元功能障碍的慢性阶段的疾病。 然而，颅外脂质污染物阻碍了MRSI数据的稳健和可靠采集。最 迄今为止报道的颅外脂质抑制方法提供的脂质信号抑制不足， 颅骨近端皮质灰质的无伪影光谱评估。因此，MRSI研究在 迄今为止在3 T下进行精神分裂症治疗有两个主要局限性：1）排除了邻近 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 变化由于谷氨酸能活性是从Glu/Gln比率推断的，因此开发准确且 单独定量Glu和Gln以进一步检验谷氨酸假设的价值。 这项工作涉及开发高分辨率（~ 5 x 5 x 10 mm 3）3D质子MRSI方法， ECLIPSE，二阶梯度插入，用于轴向平面上的高度选择性椭圆定位。高 ECLIPSE先前已证明具有选择性和无与伦比的颅外脂质抑制作用， 允许无伪影地询问邻近颅骨的皮质组织。MRSI收购将延长 采用优化的多回波时间（TE）采集与大分子靶向反转相结合 回收组分以使大分子基线无效。结合所提出的MRSI方法， 预计可以可靠地定量Glu/Gln。在开发MRSI序列后，稳健性， 再现性指标和Glu/Gln定量性能将在体模和健康 志愿者队列，然后在异质性队列中评价方法的耐受性和可翻译性 首次发作的精神病患者或近期发作的精神分裂症谱系障碍患者。 所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，在包括额叶皮质灰质近端的轴向板上， 头骨上鉴于额叶区域是精神分裂症最显著的影响， 对于可靠的代谢图像，对改变的代谢能活动敏感， 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。在3 T MRSI上可靠的Glu/Gln定量的发展具有进一步的临床意义。 这是非常重要的，因为3 T场强是临床环境中最容易使用的高场MRI系统。