Department of Radiology, University of Cambridge, Box 218, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Cambridge University Hospitals, Addenbrooke's Hospital, Cambridge, UK; Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, UK.
Department of Radiology, University of Cambridge, Box 218, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK; Cambridge University Hospitals, Addenbrooke's Hospital, Cambridge, UK; Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge, UK.
Neuroimage. 2022 Aug 15;257:119284. doi: 10.1016/j.neuroimage.2022.119284. Epub 2022 May 6.
Deuterium metabolic imaging (DMI) and hyperpolarized C-pyruvate MRI (C-HPMRI) are two emerging methods for non-invasive and non-ionizing imaging of tissue metabolism. Imaging cerebral metabolism has potential applications in cancer, neurodegeneration, multiple sclerosis, traumatic brain injury, stroke, and inborn errors of metabolism. Here we directly compare these two non-invasive methods at 3 T for the first time in humans and show how they simultaneously probe both oxidative and non-oxidative metabolism. DMI was undertaken 1-2 h after oral administration of [6,6'-H]glucose, and C-MRI was performed immediately following intravenous injection of hyperpolarized [1-C]pyruvate in ten and nine normal volunteers within each arm respectively. DMI was used to generate maps of deuterium-labelled water, glucose, lactate, and glutamate/glutamine (Glx) and the spectral separation demonstrated that DMI is feasible at 3 T. C-HPMRI generated maps of hyperpolarized carbon-13 labelled pyruvate, lactate, and bicarbonate. The ratio of C-lactate/C-bicarbonate (mean 3.7 ± 1.2) acquired with C-HPMRI was higher than the equivalent H-lactate/H-Glx ratio (mean 0.18 ± 0.09) acquired using DMI. These differences can be explained by the route of administering each probe, the timing of imaging after ingestion or injection, as well as the biological differences in cerebral uptake and cellular physiology between the two molecules. The results demonstrate these two metabolic imaging methods provide different yet complementary readouts of oxidative and reductive metabolism within a clinically feasible timescale. Furthermore, as DMI was undertaken at a clinical field strength within a ten-minute scan time, it demonstrates its potential as a routine clinical tool in the future.
氘代谢成像（DMI）和 13C 标记丙酮酸的极化磁共振成像（C-HPMRI）是两种新兴的非侵入性、非电离性组织代谢成像方法。脑代谢成像在癌症、神经退行性疾病、多发性硬化症、创伤性脑损伤、中风和先天性代谢缺陷等疾病的应用中有很大的潜力。在此，我们首次在人体中直接比较了这两种非侵入性方法，并展示了它们如何同时探测氧化和非氧化代谢。DMI 在口服[6,6'-H]葡萄糖后 1-2 小时进行，C-MRI 则在静脉注射极化[1-C]丙酮酸后立即进行，分别在每只手臂的 10 名和 9 名正常志愿者中进行。DMI 用于生成氘标记水、葡萄糖、乳酸和谷氨酸/谷氨酰胺（Glx）的图谱，且光谱分离表明 DMI 在 3T 下是可行的。C-HPMRI 生成了极化的 13C 标记丙酮酸、乳酸和碳酸氢盐的图谱。C-HPMRI 获得的 C-乳酸/C-碳酸氢盐比值（平均值 3.7±1.2）高于 DMI 获得的等效 H-乳酸/H-Glx 比值（平均值 0.18±0.09）。这些差异可以用两种探针的给药途径、摄入或注射后成像的时间、以及两种分子在大脑摄取和细胞生理学方面的生物学差异来解释。这些结果表明，这两种代谢成像方法提供了不同但互补的氧化和还原代谢读数，时间范围在临床可行的范围内。此外，由于 DMI 是在临床场强下进行的，扫描时间为十分钟，因此它展示了作为未来常规临床工具的潜力。
