Assignment of molecular origins of NOE signal at -3.5 ppm in the brain.

Assignment of molecular origins of NOE signal at -3.5 ppm in the brain.
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DOI:
10.1002/mrm.29643
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发表时间:
2023-08
影响因子:
3.3
通讯作者:
Zu, Zhongliang
Zu, Zhongliang
中科院分区:
医学3区
文献类型:
--
作者:
Zhao, Yu;Sun, Casey;Zu, Zhongliang

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核磁共振增强介导的饱和转移效应,称为NOE(−3.5ppm),是化学交换饱和转移的主要来源,而脑部的核磁共振对比度为3.5ppm。先前的模体实验已经证明,蛋白质和脂类是组织中的两个主要成分,对NOE(−3.5ppm)信号有实质性的贡献。它们在组织中的相对贡献为解释NOE(−3.5ppm)对比提供了信息,这可能为相关疾病提供潜在的成像生物标记物,这些疾病仍未完全了解。用健康大鼠脑组织匀浆和上清液分离蛋白质和脂类,以评价脂类对NOE(−3.5ppm)信号的相对贡献。另一方面,在不同pH的鬼膜和不同化学组成的重组磷脂上进行了实验,研究了NOE(−3.5ppm)对生理条件的依赖关系。此外,还对荷瘤大鼠和健康大鼠脑进行了CEST成像,分析了肿瘤与正常组织、灰质与白质之间NOE(−3.5ppm)对比度差异的原因。我们的实验表明,脂质对NOE(−3.5ppm)信号具有主导作用。进一步的分析表明,肿瘤中NOE信号的减少(−3.5ppm)和白质中NOE(−3.5ppm)信号的增加主要是由于膜脂的变化,而不是蛋白质的变化。NOE(−3.5ppm)可作为脑膜脂成像的高灵敏度磁共振成像对比剂。
Nuclear Overhauser Enhancement mediated saturation transfer effect, termed NOE(−3.5 ppm), is a major source of chemical exchange saturation transfer (CEST) MRI contrasts at 3.5 ppm in the brain. Previous phantom experiments have demonstrated that both proteins and lipids, two major components in tissues, have substantial contributions to NOE(−3.5 ppm) signals. Their relative contributions in tissues are informative for the interpretation of NOE(−3.5 ppm) contrasts that could provide potential imaging biomarkers for relevant diseases, which remain incompletely understood. Experiments on homogenates and supernatants of brain tissues collected from healthy rats, that could isolate proteins from lipids, were performed to evaluate the relative contribution of lipids to NOE(−3.5 ppm) signals. On the other hand, experiments on ghost membranes with varied pH, and reconstituted phospholipids with different chemical compositions were conducted to study the dependence of NOE(−3.5 ppm) on physiological conditions. Besides, CEST imaging on rat brains bearing 9L tumors and healthy rat brains was performed to analyze the causes of the NOE(−3.5 ppm) contrast variations between tumors and normal tissues, and between gray matter and white matter. Our experiments reveal that lipids have dominant contributions to the NOE (−3.5 ppm) signals. Further analysis suggests that decreased NOE(−3.5 ppm) signals in tumors and higher NOE(−3.5 ppm) signals in white matter than in gray matter are mainly explained by changes in membrane lipids, rather than proteins. NOE(−3.5 ppm) could be exploited as a highly sensitive MRI contrast for imaging membrane lipids in the brain.
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