While the intracellular–extracellular distribution of lactate has been suggested to play a critical role in the healthy and diseased brain, tools are lacking to noninvasively probe lactate in intracellular and extracellular spaces. Here, we show that, by measuring the diffusion of lactate with diffusion-weighted magnetic resonance (MR) spectroscopy in vivo and comparing it to the diffusion of purely intracellular metabolites, noninvasive quantification of extracellular and intracellular lactate fractions becomes possible. More specifically, we detect alterations of lactate diffusion in the APP/PS1 mouse model of Alzheimer’s disease. Data modeling allows quantifying decreased extracellular lactate fraction in APP/PS1 mice as compared to controls, which is quantitatively confirmed with implanted enzyme-microelectrodes. The capability of diffusion-weighted MR spectroscopy to quantify extracellular–intracellular lactate fractions opens a window into brain metabolism, including in Alzheimer’s disease.

中文翻译：

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使用体内扩散加权磁共振波谱捕获大脑中细胞内-细胞外乳酸分布的变化


虽然乳酸的细胞内-细胞外分布被认为在健康和患病的大脑中发挥着关键作用，但缺乏无创地探测细胞内和细胞外空间中乳酸的工具。在这里，我们表明，通过使用扩散加权磁共振（MR）光谱测量体内乳酸的扩散并将其与纯细胞内代谢物的扩散进行比较，细胞外和细胞内乳酸部分的无创定量成为可能。更具体地说，我们检测了阿尔茨海默病 APP/PS1 小鼠模型中乳酸扩散的变化。数据建模可以量化 APP/PS1 小鼠与对照组相比细胞外乳酸分数的减少，这通过植入的酶微电极进行了定量证实。扩散加权磁共振波谱能够量化细胞外-细胞内乳酸分数，这为了解大脑代谢（包括阿尔茨海默病）打开了一个窗口。