Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, 9112001, Israel.
Sci Rep. 2018 Jun 22;8(1):9564. doi: 10.1038/s41598-018-27747-w.
The ability to directly monitor in vivo brain metabolism in real time in a matter of seconds using the dissolution dynamic nuclear polarization technology holds promise to aid the understanding of brain physiology in health and disease. However, translating the hyperpolarized signal observed in the brain to cerebral metabolic rates is not straightforward, as the observed in vivo signals reflect also the influx of metabolites produced in the body, the cerebral blood volume, and the rate of transport across the blood brain barrier. We introduce a method to study rapid metabolism of hyperpolarized substrates in the viable rat brain slices preparation, an established ex vivo model of the brain. By retrospective evaluation of tissue motion and settling from analysis of the signal of the hyperpolarized [1-C]pyruvate precursor, the Ts of the metabolites and their rates of production can be determined. The enzymatic rates determined here are in the range of those determined previously with classical biochemical assays and are in agreement with hyperpolarized metabolite relative signal intensities observed in the rodent brain in vivo.
利用溶解动态核极化技术，能够在几秒钟内实时直接监测体内大脑代谢，这有望帮助理解健康和疾病状态下的大脑生理学。然而，将在大脑中观察到的超极化信号转化为脑代谢率并不简单，因为观察到的体内信号也反映了体内产生的代谢物的流入、脑血容量和穿过血脑屏障的转运速率。我们介绍了一种在活体大鼠脑切片制备中研究超极化底物快速代谢的方法，这是大脑的一种成熟的离体模型。通过对超极化[1-C]丙酮酸前体信号的组织运动和沉降进行回顾性评估，可以确定代谢物的 Ts 和它们的产生速率。这里确定的酶反应速率与先前用经典生化测定法确定的酶反应速率范围一致，并且与在活体啮齿动物大脑中观察到的超极化代谢物相对信号强度一致。
