Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI
Protein aggregation linked to Alzheimer's disease revealed by saturation transfer MRI
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DOI：
10.1016/j.neuroimage.2018.12.018
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发表时间：
2019-03-01
期刊：
影响因子：
5.7
通讯作者：
Xu, Jiadi
中科院分区：
文献类型：
--
作者：
Chen, Lin;Wei, Zhiliang;Xu, Jiadi
本研究的目的是开发一种分子生物标志物，用于检测蛋白质聚集参与阿尔茨海默病（AD）的水饱和转移光谱（Z-谱），其中的CEST信号是敏感的蛋白质的分子构型的特点。采用基于径向采样稳态序列的超短回波时间（UTE）读出对小鼠脑中的Z谱进行成像，特别是在复合蛋白酰胺质子（+3.6 ppm）和脂肪族质子（-3.6 ppm）信号的频率偏移处来自移动的蛋白的贡献。使用一个相对较弱的射频（RF）饱和振幅，由于强磁化传递对比度（MTC）从固体状大分子和直接水饱和度（DS）的贡献最小化。为了实际测量移动的蛋白质构型的变化，我们通过从8 ppm的对照信号中减去+3.6 ppm的Z-光谱信号来定义饱和转移差（Δ ST）。谷氨酸盐溶液，蛋白质（鸡蛋白色）和护发素的幻影研究表明，所提出的计划，以尽量减少胺质子，DS和MTC的贡献，分别的能力。在交联牛血清白蛋白（BSA）溶液的+/-3.6 ppm处的ST信号表明Δ ST信号可用于监测移动的蛋白质的聚集过程。AD小鼠脑在小鼠脑的+/-3.6ppm处的高分辨率Δ ST图像显示与年龄匹配的野生型（WT）小鼠相比显著降低的Δ ST（-3.6）信号。因此，该信号具有作为监测AD中蛋白质聚集的分子生物标志物的潜力。
The goal of this study was to develop a molecular biomarker for the detection of protein aggregation involved in Alzheimer's disease (AD) by exploiting the features of the water saturation transfer spectrum (Z-spectrum), the CEST signal of which is sensitive to the molecular configuration of proteins. A radial-sampling steady-state sequence based ultrashort echo time (UTE) readout was implemented to image the Z-spectrum in the mouse brain, especially the contributions from mobile proteins at the frequency offsets for the composite protein amide proton (+3.6 ppm) and aliphatic proton (-3.6 ppm) signals. Using a relatively weak radiofrequency (RF) saturation amplitude, contributions due to strong magnetization transfer contrast (MTC) from solid-like macromolecules and direct water saturation (DS) were minimized. For practical measure of the changes in the mobile protein configuration, we defined a saturation transfer difference (Delta ST) by subtracting the Z-spectral signals at +3.6 ppm from a control signal at 8 ppm. Phantom studies of glutamate solution, protein (egg white) and hair conditioner show the capability of the proposed scheme to minimize the contributions from amine protons, DS, and MTC, respectively. The ST signal at +/- 3.6 ppm of the cross-linked bovine serum albumin (BSA) solutions demonstrated that the Delta ST signal can be used to monitor the aggregation process of the mobile proteins. High-resolution Delta ST images of AD mouse brains at +/- 3.6 ppm of mouse brains showed significantly reduced Delta ST (-3.6) signal compared to the age-matched wild-type (WT) mice. Thus, this signal has potential to serve as a molecular biomarker for monitoring protein aggregation in AD.