Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room 3D46, 10 Center Drive, MSC 1216, Bethesda, MD, 20892-1216, USA.
Sci Rep. 2023 Jul 27;13(1):12211. doi: 10.1038/s41598-023-39375-0.
Cell pathology in neuropsychiatric disorders has mainly been accessible by analyzing postmortem tissue samples. Although molecular transverse relaxation informs local cellular microenvironment via molecule-environment interactions, precise determination of the transverse relaxation times of molecules with scalar couplings (J), such as glutamate and glutamine, has been difficult using in vivo magnetic resonance spectroscopy (MRS) technologies, whose approach to measuring transverse relaxation has not changed for decades. We introduce an in vivo MRS technique that utilizes frequency-selective editing pulses to achieve homonuclear decoupled chemical shift encoding in each column of the acquired two-dimensional dataset, freeing up the entire row dimension for transverse relaxation encoding with J-refocusing. This results in increased spectral resolution, minimized background signals, and markedly broadened dynamic range for transverse relaxation encoding. The in vivo within-subject coefficients of variation for the transverse relaxation times of glutamate and glutamine, measured using the proposed method in the human brain at 7 T, were found to be approximately 4%. Since glutamate predominantly resides in glutamatergic neurons and glutamine in glia in the brain, this noninvasive technique provides a way to probe cellular pathophysiology in neuropsychiatric disorders for characterizing disease progression and monitoring treatment response in a cell type-specific manner in vivo.
神经精神疾病的细胞病理学主要通过分析死后组织样本来研究。尽管分子横向弛豫通过分子-环境相互作用为局部细胞微环境提供信息，但使用活体磁共振波谱（MRS）技术精确确定具有标量耦合（J）的分子（如谷氨酸和谷氨酰胺）的横向弛豫时间一直很困难，因为其测量横向弛豫的方法几十年来没有改变。我们介绍了一种活体 MRS 技术，该技术利用频率选择编辑脉冲在获得的二维数据集中的每一列实现同核去耦化学位移编码，将整个行维度用于具有 J 重聚的横向弛豫编码。这导致了更高的光谱分辨率、最小化的背景信号和明显拓宽的横向弛豫编码动态范围。在 7T 下，使用该方法在人脑内测量谷氨酸和谷氨酰胺的横向弛豫时间的体内个体内变异系数约为 4%。由于谷氨酸主要存在于谷氨酸能神经元中，谷氨酰胺存在于胶质细胞中，因此这种非侵入性技术为研究神经精神疾病中的细胞病理生理学提供了一种方法，可用于以细胞类型特异性的方式在体内对疾病进展进行特征描述和监测治疗反应。
