Brain metabolism across anatomic regions and cellular compartments plays an integral role in many aspects of neuronal function. Changes in key metabolic pathway fluxes, including oxidative and reductive energy metabolism, have been implicated in a wide range of brain diseases. Given the complex nature of the brain and the need for understanding compartmentalized metabolism noninvasively in vivo, new tools are required. Herein, using hyperpolarized (HP) magnetic resonance imaging coupled with in vivo isotope tracing, we develop a platform to simultaneously probe redox and energy metabolism in the murine brain. By combining HP dehydroascorbate and pyruvate, we are able to visualize increased lactate production in the white matter and increased redox capacity in the deep gray matter. Leveraging positional labeling, we show differences in compartmentalized tricarboxylic acid cycle entry versus downstream flux to glutamate. These findings lay the foundation for clinical translation of the proposed approach to probe brain metabolism.

中文翻译：

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同时无创定量氧化还原和下游糖酵解通量揭示了区室化的脑代谢


跨解剖区域和细胞区室的大脑代谢在神经元功能的许多方面起着不可或缺的作用。关键代谢途径通量的变化，包括氧化和还原能量代谢，与多种脑部疾病有关。鉴于大脑的复杂性以及在体内无创地了解区室化代谢的需求，需要新的工具。在此，使用超极化 （HP） 磁共振成像与体内同位素示踪相结合，我们开发了一个平台来同时探测小鼠大脑中的氧化还原和能量代谢。通过结合 HP 脱氢抗坏血酸和丙酮酸，我们能够可视化白质中乳酸产生的增加和深灰质中氧化还原能力的增加。利用位置标记，我们显示了区室化三羧酸循环进入与下游谷氨酸通量的差异。这些发现为所提出的探测脑代谢的方法的临床转化奠定了基础。