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效用的浓厚兴趣 光谱学和光谱成像（MRS/MRSI）近年来研究精神分裂症的病理生理学 谷氨酸假说为公认的多巴胺能提供了一个补充视角。 假设，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着作用。 之前进行的 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) 存在于各个脑区，与疾病慢性阶段的神经元功能障碍一致。 然而，颅外脂质污染物阻碍了 MRSI 数据的稳健和可靠采集。 迄今为止报道的颅外脂质抑制方法提供了不充分的脂质信号抑制，以允许 因此，MRSI 研究对颅骨附近的皮质灰质进行了无伪影光谱评估。 迄今为止在 3 T 上进行的精神分裂症有两个主要局限性：1）排除了近端皮质组织 颅外脂质，2) 与 Glu/Gln 分离相关的不确定性，因此主要报告 Glx 由于谷氨酸活性是根据 Glu/Gln 比率推断的，因此开发准确且可靠的数据至关重要。 单独定量 Glu 和 Gln，以进一步验证谷氨酸假说的价值。 这项工作涉及开发高分辨率 (~ 5 x 5 x 10 mm3) 3D 质子 MRSI 方法，使用 ECLIPSE，二阶梯度插入，用于在轴向平面上进行高选择性椭圆定位。 先前通过 ECLIPSE 证明了选择性和无与伦比的颅外脂质抑制， 允许对颅骨附近的皮质组织进行无伪影询问。MRSI 采集将得到扩展。 优化的多回波时间 (TE) 采集与大分子靶向反演相结合 结合起来，所提出的 MRSI 方法是无效的大分子基线。 MRSI 序列开发后，预计可实现 Glu/Gln 的可靠定量。 再现性指标和 Glu/Gln 定量性能将在体模和健康环境中进行评估 志愿者队列，然后是在异质队列上评估方法的耐受性和可翻译性 首发精神病或近期发病的精神分裂症谱系障碍患者。 所提出方法的成功完成将提供可靠的 Glu 和 Gln 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 鉴于额叶区域受精神分裂症影响最严重，因此提供了这种能力。 对于谷氨酸活性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程度、异质性和治疗 使用 MRSI 在 3 T 下进行可靠的 Glu/Gln 定量的开发具有进一步的临床意义。 意义重大，因为 3 T 场强是临床环境中最容易使用的高场 MRI 系统。