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.

项目总结-