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利用基因敲除小鼠模型研究脑中总肌酸对 CEST Z 谱的贡献。

Investigation of the contribution of total creatine to the CEST Z-spectrum of brain using a knockout mouse model.

机构信息

Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, China.

Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

出版信息

NMR Biomed. 2017 Dec;30(12). doi: 10.1002/nbm.3834. Epub 2017 Sep 29.

DOI:10.1002/nbm.3834
PMID:28961344
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5685917/
Abstract

The current study aims to assign and estimate the total creatine (tCr) signal contribution to the Z-spectrum in mouse brain at 11.7 T. Creatine (Cr), phosphocreatine (PCr) and protein phantoms were used to confirm the presence of a guanidinium resonance at this field strength. Wild-type (WT) and knockout mice with guanidinoacetate N-methyltransferase deficiency (GAMT-/-), which have low Cr and PCr concentrations in the brain, were used to assign the tCr contribution to the Z-spectrum. To estimate the total guanidinium concentrations, two pools for the Z-spectrum around 2 ppm were assumed: (i) a Lorentzian function representing the guanidinium chemical exchange saturation transfer (CEST) at 1.95 ppm in the 11.7-T Z-spectrum; and (ii) a background signal that can be fitted by a polynomial function. Comparison between the WT and GAMT-/- mice provided strong evidence for three types of contribution to the peak in the Z-spectrum at 1.95 ppm, namely proteins, Cr and PCr, the latter fitted as tCr. A ratio of 20 ± 7% (protein) and 80 ± 7% tCr was found in brain at 2 μT and 2 s saturation. Based on phantom experiments, the tCr peak was estimated to consist of about 83 ± 5% Cr and 17 ± 5% PCr. Maps for tCr of mouse brain were generated based on the peak at 1.95 ppm after concentration calibration with in vivo magnetic resonance spectroscopy.

摘要

本研究旨在分配并估计 11.7T 下小鼠脑内 Z 谱中总肌酸(tCr)信号的贡献。使用肌酸(Cr)、磷酸肌酸(PCr)和蛋白质仿体来确认在该场强下是否存在胍基共振。野生型(WT)和胍基乙酸 N-甲基转移酶缺乏型(GAMT-/-)的敲除小鼠被用于分配 tCr 对 Z 谱的贡献。为了估计总胍基浓度,假定 Z 谱中围绕 2ppm 的两个池:(i)代表在 11.7-T Z 谱中 1.95ppm 处的胍基化学交换饱和转移(CEST)的洛伦兹函数;(ii)可拟合多项式函数的背景信号。WT 和 GAMT-/- 小鼠之间的比较为 Z 谱中 1.95ppm 处的峰提供了三种类型的贡献的有力证据,即蛋白质、Cr 和 PCr,后者拟合为 tCr。在 2μT 和 2s 饱和时,在脑中发现蛋白质的比例为 20±7%,tCr 为 80±7%。基于仿体实验,tCr 峰被估计由约 83±5% Cr 和 17±5% PCr 组成。基于体内磁共振波谱的浓度校准后,在 1.95ppm 处生成了小鼠脑 tCr 的图谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/716c3ec2cf92/nihms916533f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/fdd8bdee3001/nihms916533f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/b31e6c749077/nihms916533f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/1f354cedd689/nihms916533f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/1927fdc79023/nihms916533f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/2e8b3337259a/nihms916533f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/716c3ec2cf92/nihms916533f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/fdd8bdee3001/nihms916533f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/b31e6c749077/nihms916533f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/1f354cedd689/nihms916533f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/1927fdc79023/nihms916533f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/2e8b3337259a/nihms916533f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9542/5685917/716c3ec2cf92/nihms916533f6.jpg

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