Signal amplification strategies are critical for overcoming the intrinsically poor sensitivity of nuclear magnetic resonance (NMR) reporters in noninvasive molecular detection. A mechanism widely used for signal enhancement is chemical exchange saturation transfer (CEST) of nuclei between a dilute sensing pool and an abundant detection pool. However, the dependence of CEST amplification on the relative size of these spin pools confounds quantitative molecular detection with a larger detection pool typically making saturation transfer less efficient. Here we show that a recently discovered class of genetically encoded nanoscale reporters for ¹²⁹Xe magnetic resonance overcomes this fundamental limitation through an elastic binding capacity for NMR-active nuclei. This approach pairs high signal amplification from hyperpolarized spins with ideal, self-adjusting saturation transfer behavior as the overall spin ensemble changes in size. These reporters are based on gas vesicles, i.e., microbe-derived, gas-filled protein nanostructures. We show that the xenon fraction that partitions into gas vesicles follows the ideal gas law, allowing the signal transfer under hyperpolarized xenon chemical exchange saturation transfer (Hyper-CEST) imaging to scale linearly with the total xenon ensemble. This conceptually distinct elastic response allows the production of quantitative signal contrast that is robust to variability in the concentration of xenon, enabling virtually unlimited improvement in absolute contrast with increased xenon delivery, and establishing a unique principle of operation for contrast agent development in emerging biochemical and in vivo applications of hyperpolarized NMR and magnetic resonance imaging.

中文翻译：

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蛋白质纳米结构通过物理气体分配产生自调节超极化磁共振成像对比度

信号放大策略对于克服无创分子检测中核磁共振（NMR）报告基因固有的敏感性差至关重要。广泛用于信号增强的机制是稀检测池和丰富检测池之间原子核的化学交换饱和转移（CEST）。但是，CEST扩增对这些自旋池相对大小的依赖性使定量分子检测与较大的检测池混淆，通常会使饱和转移效率降低。在这里，我们显示了最近发现的一类用于^129个基因编码的纳米级报告基因Xe磁共振通过对NMR活性核的弹性结合能力克服了这一基本限制。这种方法将超极化自旋的高信号放大与理想的，自调整的饱和转移行为结合在一起，因为整个自旋合奏的大小会发生变化。这些记者是基于囊泡，即，微生物衍生的，充满气体的蛋白质纳米结构。我们表明，分成气体囊泡的氙部分遵循理想的气体定律，从而允许信号在超极化氙化学交换饱和转移（Hyper-CEST）成像下的转移与总氙集合成线性比例关系。这种在概念上截然不同的弹性响应可产生定量信号对比度，该信号对比度对氙气浓度的变化具有鲁棒性，通过增加氙气输送量，可以使绝对对比度几乎无限地提高，并为新兴的生化试剂和显影剂中造影剂的开发建立了独特的操作原理。极化NMR和磁共振成像的体内应用。