Department of Physics & Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Chemphyschem. 2021 Jun 16;22(12):1219-1228. doi: 10.1002/cphc.202100183. Epub 2021 May 19.
Gas microbubbles are an established clinical ultrasound contrast agent. They could also become a powerful magnetic resonance (MR) intravascular contrast agent, but their low susceptibility-induced contrast requires high circulating concentrations or the addition of exogenous paramagnetic nanoparticles for MR detection. In order to detect clinical in vivo concentrations of raw microbubbles via MR, an alternative detection scheme must be used. HyperCEST is an NMR technique capable of indirectly detecting signals from very dilute molecules (concentrations well below the NMR detection threshold) that exchange hyperpolarized Xe. Here, we use quantitative hyperCEST to show that microbubbles are very efficient hyperCEST agents. They can accommodate and saturate millions of Xe atoms at a time, allowing for their indirect detection at concentrations as low as 10 femtomolar. The increased MR sensitivity to microbubbles achieved via hyperCEST can bridge the gap for microbubbles to become a dual modality contrast agent.
气体微泡是一种成熟的临床超声造影剂。它们也可能成为一种强大的磁共振(MR)血管内造影剂,但它们的低顺磁性诱导对比度需要高循环浓度或添加外源性顺磁纳米粒子来进行 MR 检测。为了通过 MR 检测临床体内的原始微泡浓度,必须使用替代的检测方案。HyperCEST 是一种能够间接检测来自非常稀释的分子(浓度远低于 NMR 检测阈值)的信号的 NMR 技术,这些分子可以交换超极化氙气。在这里,我们使用定量 HyperCEST 表明微泡是非常有效的 HyperCEST 试剂。它们可以一次容纳和饱和数百万个氙原子,从而可以在低至 10 飞摩尔的浓度下对其进行间接检测。通过 HyperCEST 实现的对微泡的增强的 MR 灵敏度可以弥合微泡成为双重模式造影剂的差距。