Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina, USA; Medical Physics Graduate Program, Duke University, Durham, North Carolina, USA.
Magn Reson Med. 2013 Nov;70(5):1192-9. doi: 10.1002/mrm.24915. Epub 2013 Sep 4.
Hyperpolarized (HP) (129) Xe gas in the alveoli can be detected separately from (129) Xe dissolved in pulmonary barrier tissues (blood plasma and parenchyma) and red blood cells (RBCs) of humans, allowing this isotope to probe impaired gas uptake. Unfortunately, mice, which are favored as lung disease models, do not display a unique RBC resonance, thus limiting the preclinical utility of (129) Xe MR. Here we overcome this limitation using a commercially available strain of transgenic mice that exclusively expresses human hemoglobin.
Dynamic HP (129) Xe MR spectroscopy, and three-dimensional radial MRI of gaseous and dissolved (129) Xe were performed in both wild-type (C57BL/6) and transgenic mice.
Unlike wild-type animals, transgenic mice displayed two dissolved (129) Xe NMR peaks at 198 and 217 ppm, corresponding to (129) Xe dissolved in barrier tissues and RBCs, respectively. Moreover, signal from these resonances could be imaged separately, using a 1-point variant of the Dixon technique.
It is now possible to examine the dynamics and spatial distribution of pulmonary gas uptake by the RBCs of mice using HP (129) Xe MR spectroscopy and imaging. When combined with ventilation imaging, this ability will enable translational "mouse-to-human" studies of impaired gas exchange in a variety of pulmonary diseases.
肺泡中的超极化（HP）（129）Xe 气体可以与（129）Xe 溶解在肺屏障组织（血浆和实质）和红细胞（RBC）中区分开来，允许该同位素探测气体摄取受损。不幸的是，作为肺部疾病模型而受到青睐的小鼠不显示独特的 RBC 共振，从而限制了（129）Xe MR 的临床前应用。在这里，我们使用商业上可获得的转染小鼠品系克服了这一限制，该品系专门表达人血红蛋白。
在野生型（C57BL/6）和转基因小鼠中进行了动态 HP（129）Xe MR 光谱和气态和溶解（129）Xe 的三维径向 MRI。
与野生型动物不同，转基因小鼠在 198 和 217 ppm 处显示出两个溶解（129）Xe NMR 峰，分别对应于溶解在屏障组织和 RBC 中的（129）Xe。此外，可以使用 Dixon 技术的 1 点变体分别对这些共振的信号进行成像。
现在可以使用 HP（129）Xe MR 光谱和成像来检查 RBC 摄取肺部气体的动力学和空间分布。当与通气成像结合使用时，这种能力将能够在各种肺部疾病中进行受损气体交换的转化“小鼠到人类”研究。
