Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo.
Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo.
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DOI：
10.1126/sciadv.aat7314
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发表时间：
2018-08
期刊：
影响因子：
13.6
通讯作者：
de Graaf RA
中科院分区：
文献类型：
--
作者：
De Feyter HM;Behar KL;Corbin ZA;Fulbright RK;Brown PB;McIntyre S;Nixon TW;Rothman DL;de Graaf RA
图4显示了脑和肝脏中乙酸盐和葡萄糖的代谢，并揭示了脑肿瘤患者的瓦尔堡效应。目前，临床上唯一广泛使用的代谢成像技术是放射性葡萄糖类似物2- 18 F-氟-2-脱氧-d-葡萄糖（18 FDG）的正电子发射断层扫描（PET）检测。然而，18FDG-PET不能提供葡萄糖摄取下游的代谢信息，并且通常在具有内在高葡萄糖摄取的器官（例如大脑）中提供模糊的结果。氘代谢成像（DMI）是一种新型的非侵入性方法，它将氘磁共振光谱成像与口服或静脉输注非放射性2 H标记底物相结合，以生成三维代谢图。荧光标记物可以显示葡萄糖代谢，而不仅仅是摄取，也可以与其他2 H标记的底物一起使用。我们通过使用[6，6 ′-2H2]葡萄糖或[2 H3]乙酸盐绘制动物模型和人类受试者大脑和肝脏中的代谢图来证明这一点。在大鼠神经胶质瘤模型中，高对比度代谢图显示了正常脑和肿瘤组织之间明显的代谢差异，显示了瓦尔堡效应。我们观察到类似的代谢模式和图像对比度在两个高级别的脑肿瘤患者口服摄入2 H标记的葡萄糖。此外，在大鼠和人类肝脏中使用的荧光素显示[6，6 ′-2H2]葡萄糖作为标记的糖原储存。磁共振成像是一种多功能、强大且易于实现的技术，只需对现有临床磁共振成像扫描仪进行最小的修改。在临床前研究和临床中，代谢成像有很大的潜力成为一种广泛的代谢成像方法。
DMI shows metabolism of acetate and glucose in the brain and liver and reveals the Warburg effect in patients with brain tumors. Currently, the only widely available metabolic imaging technique in the clinic is positron emission tomography (PET) detection of the radioactive glucose analog 2-18F-fluoro-2-deoxy-d-glucose (18FDG). However, 18FDG-PET does not inform on metabolism downstream of glucose uptake and often provides ambiguous results in organs with intrinsic high glucose uptake, such as the brain. Deuterium metabolic imaging (DMI) is a novel, noninvasive approach that combines deuterium magnetic resonance spectroscopic imaging with oral intake or intravenous infusion of nonradioactive 2H-labeled substrates to generate three-dimensional metabolic maps. DMI can reveal glucose metabolism beyond mere uptake and can be used with other 2H-labeled substrates as well. We demonstrate DMI by mapping metabolism in the brain and liver of animal models and human subjects using [6,6′-2H2]glucose or [2H3]acetate. In a rat glioma model, DMI revealed pronounced metabolic differences between normal brain and tumor tissue, with high-contrast metabolic maps depicting the Warburg effect. We observed similar metabolic patterns and image contrast in two patients with a high-grade brain tumor after oral intake of 2H-labeled glucose. Further, DMI used in rat and human livers showed [6,6′-2H2]glucose stored as labeled glycogen. DMI is a versatile, robust, and easy-to-implement technique that requires minimal modifications to existing clinical magnetic resonance imaging scanners. DMI has great potential to become a widespread method for metabolic imaging in both (pre)clinical research and the clinic.
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