对脑胶质瘤中跨膜和跨内皮钠离子梯度的成像。
Imaging the transmembrane and transendothelial sodium gradients in gliomas.
机构信息
Department of Biomedical Engineering, Yale University, N143 TAC (MRRC), 300 Cedar Street, New Haven, CT, 06520, USA.
Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, 06520, USA.
出版信息
Sci Rep. 2021 Mar 23;11(1):6710. doi: 10.1038/s41598-021-85925-9.
Under normal conditions, high sodium (Na) in extracellular (Na) and blood (Na) compartments and low Na in intracellular milieu (Na) produce strong transmembrane (ΔNa) and weak transendothelial (ΔNa) gradients respectively, and these manifest the cell membrane potential (V) as well as blood-brain barrier (BBB) integrity. We developed a sodium (Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic polyanionic agent to measure ΔNa and ΔNa. In vitro Na-MRSI established that the Na signal is intensely shifted by the agent compared to other biological factors (e.g., pH and temperature). In vivo Na-MRSI showed Na remained unshifted and Na was more shifted than Na, and these together revealed weakened ΔNa and enhanced ΔNa in rat gliomas (vs. normal tissue). Compared to normal tissue, RG2 and U87 tumors maintained weakened ΔNa (i.e., depolarized V) implying an aggressive state for proliferation, whereas RG2 tumors displayed elevated ∆Na suggesting altered BBB integrity. We anticipate that Na-MRSI will allow biomedical explorations of perturbed Na homeostasis in vivo.
在正常情况下，细胞外（Na）和血液（Na）隔间中的高钠（Na）和细胞内环境（Na）中的低钠分别产生强跨膜（ΔNa）和弱跨内皮（ΔNa）梯度，这些分别表现为细胞膜电位（V）和血脑屏障（BBB）的完整性。我们开发了一种使用静脉内给予的顺磁性聚阴离子剂来测量ΔNa 和 ΔNa 的钠磁共振波谱成像（MRSI）方法。体外 Na-MRSI 表明，与其他生物学因素（例如 pH 和温度）相比，该试剂强烈改变了 Na 信号。体内 Na-MRSI 显示 Na 保持未移位，而 Na 比 Na 更移位，这共同揭示了大鼠神经胶质瘤（与正常组织相比）中 ΔNa 减弱和 ΔNa 增强。与正常组织相比，RG2 和 U87 肿瘤保持较弱的 ΔNa（即，去极化的 V），这暗示了增殖的侵袭性状态，而 RG2 肿瘤显示出升高的 ∆Na，提示 BBB 完整性改变。我们预计，Na-MRSI 将允许对体内紊乱的钠动态平衡进行生物医学探索。
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