非侵入性三维1H-磁共振波谱成像的人脑葡萄糖和神经递质代谢,利用3T的氘标记:可行性和扫描仪再现性。
Noninvasive 3-Dimensional 1H-Magnetic Resonance Spectroscopic Imaging of Human Brain Glucose and Neurotransmitter Metabolism Using Deuterium Labeling at 3T: Feasibility and Interscanner Reproducibility.
发表日期:2023 Feb 03
作者:
Fabian Niess, Lukas Hingerl, Bernhard Strasser, Petr Bednarik, Dario Goranovic, Eva Niess, Gilbert Hangel, Martin Krššák, Benjamin Spurny-Dworak, Thomas Scherer, Rupert Lanzenberger, Wolfgang Bogner
来源:
INVESTIGATIVE RADIOLOGY
摘要:
非侵入性、经济实惠、可靠的大脑葡萄糖代谢图谱映射对于临床研究和例行应用至关重要,因为代谢障碍与许多病理变化相关,例如癌症、痴呆和抑郁症。最近在超高场磁共振(MR)扫描仪(≥7T)上提出了一种新方法,利用氘标记葡萄糖和下游代谢物,如谷氨酸、谷氨酰胺和乳酸的间接检测,在人脑中非侵入性地绘制葡萄糖代谢图谱。本研究的目的是展示通过在临床3T MR扫描仪上进行三维(3D)质子(1H)MR光谱成像,在人脑中间接非侵入性地检测氘标记下游葡萄糖代谢物的可行性,而无需额外的硬件。
在获得书面知情同意后,我们在7名健康志愿者(平均年龄31岁±4岁,男5女2)中进行了这项前瞻性、机构审查委员会批准的研究。进行过夜禁食和口服氘标记葡萄糖后,使用实时运动、shim和频率校正的无回声3D 1H-MR光谱成像,在临床常规3T MR系统上每约4分钟获取3D代谢图。同时以∼0.24 mL等向空间分辨率采集数据。为了测试方法的MRI仪器可重复性,测量对象在类似的3T MR系统上重新测量。时间序列使用线性回归和非参数统计检验进行分析。通过标记和未标记分子交换的动态1H MR谱中的信号下降间接检测到了氘标记的葡萄糖和下游代谢物。
在口服氘标记葡萄糖后65分钟,灰质/白质(GM/WM)中的谷氨酸+谷氨酰胺(Glx)信号强度分别下降了-1.63±0.3/-1.0±0.3 mM(-13%±3%,P = 0.02/-11%±3%,P = 0.02)。在GM/WM中观察到Glx和时间之间的中到强的负相关关系(r = -0.64,P <0.001/r = -0.54,P <0.001),其中GM比WM坡度陡峭60%±18%(P = 0.02),表明代谢活动更快。其他未标记的代谢物没有显著变化。静态结果在测量开始时在扫描仪之间表现出优异的被测对象内部可重复性(变差系数4%±4%),而在个体Glx动态方面观察到了差异,可能是由于葡萄糖代谢的生理变化造成的。
我们的方法将氘代谢成像技术应用到广泛使用的临床常规MR扫描仪中,而无需专门硬件,提供了一种安全、经济实惠、多功能(诸如非葡萄糖物质也可以标记)的非侵入性大脑葡萄糖和神经递质代谢成像方法。
版权所有 ©2023作者。 Wolters Kluwer Health, Inc.出版。
Noninvasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies, for example, cancer, dementia, and depression. A novel approach to map glucose metabolism noninvasively in the human brain has been presented recently on ultrahigh-field magnetic resonance (MR) scanners (≥7T) using indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine, and lactate. The aim of this study was to demonstrate the feasibility to noninvasively detect deuterium-labeled downstream glucose metabolites indirectly in the human brain via 3-dimensional (3D) proton (1H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware.This prospective, institutional review board-approved study was performed in 7 healthy volunteers (mean age, 31 ± 4 years, 5 men/2 women) after obtaining written informed consent. After overnight fasting and oral deuterium-labeled glucose administration, 3D metabolic maps were acquired every ∼4 minutes with ∼0.24 mL isotropic spatial resolution using real-time motion-, shim-, and frequency-corrected echo-less 3D 1H-MR spectroscopic Imaging on a clinical routine 3T MR system. To test the interscanner reproducibility of the method, subjects were remeasured on a similar 3T MR system. Time courses were analyzed using linear regression and nonparametric statistical tests. Deuterium-labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic 1H MR spectra due to exchange of labeled and unlabeled molecules.Sixty-five minutes after deuterium-labeled glucose administration, glutamate + glutamine (Glx) signal intensities decreased in gray/white matter (GM/WM) by -1.63 ± 0.3/-1.0 ± 0.3 mM (-13% ± 3%, P = 0.02/-11% ± 3%, P = 0.02), respectively. A moderate to strong negative correlation between Glx and time was observed in GM/WM (r = -0.64, P < 0.001/r = -0.54, P < 0.001), with 60% ± 18% (P = 0.02) steeper slopes in GM versus WM, indicating faster metabolic activity. Other nonlabeled metabolites showed no significant changes. Excellent intrasubject repeatability was observed across scanners for static results at the beginning of the measurement (coefficient of variation 4% ± 4%), whereas differences were observed in individual Glx dynamics, presumably owing to physiological variation of glucose metabolism.Our approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware, offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for noninvasive imaging of glucose and neurotransmitter metabolism in the human brain.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.