Division of Neurosurgical Research, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Department of Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
MAGMA. 2023 Feb;36(1):107-118. doi: 10.1007/s10334-022-01040-4. Epub 2022 Sep 2.
It is well known that the use of shift reagents (SRs) in nuclear magnetic resonance (NMR) studies is substantially limited by an intact blood-brain barrier (BBB). The current study aims to develop a method enabling chemical shift imaging in the living rat brain under physiological conditions using an SR, Tm[DOTP].
Hyperosmotic mannitol bolus injection followed by 60 min infusion of a Tm[DOTP] containing solution was administered via a catheter inserted into an internal carotid artery. We monitored the homeostasis of physiological parameters, and we measured the thulium content in brain tissue post mortem using total reflection fluorescence spectroscopy (T-XRF). The alterations of the Na resonance spectrum were followed in a 9.4T small animal scanner.
Based on the T-XRF measurements, the thulium concentration was estimated at 2.3 ± 1.8 mM in the brain interstitial space. Spectroscopic imaging showed a split of the Na resonance peak which became visible 20 min after starting the infusion. Chemical shift imaging revealed a significant decrease of the initial intensity level to 0.915 ± 0.058 at the end of infusion.
Our novel protocol showed bulk accumulation of Tm[DOTP] thus enabling separation of the extra-/intracellular Na signal components in the living rat brain while maintaining physiological homeostasis.
众所周知，在核磁共振（NMR）研究中使用位移试剂（SRs）受到血脑屏障（BBB）完整的极大限制。本研究旨在开发一种方法，在生理条件下使用 SR Tm[DOTP]对活体大鼠大脑进行化学位移成像。
通过插入颈内动脉的导管给予高渗甘露醇推注，随后 60 分钟输注含 Tm[DOTP]的溶液。我们监测生理参数的动态平衡，并使用全反射荧光光谱法（T-XRF）测量死后脑组织中的铥含量。在 9.4T 小动物扫描仪中跟踪 Na 共振光谱的变化。
根据 T-XRF 测量结果，脑间质中的铥浓度估计为 2.3±1.8mM。光谱成像显示 Na 共振峰的分裂在开始输注 20 分钟后变得可见。化学位移成像显示初始强度水平显著降低，在输注结束时降至 0.915±0.058。
我们的新方案显示 Tm[DOTP]的大量积累，从而能够在保持生理动态平衡的情况下分离活体大鼠大脑中的细胞外/细胞内 Na 信号成分。
