From the Departments of Radiology (F.Z., J.T.G., J.K., F.R., R.W., A.B.G., S.D., C.J.D., S.U., M.C.L., M.L., A.F., S.H., J.H.G., T.M., M.J.G., F.A.G.), Clinical Neurosciences (R.M., C.W., S.J.P., T.S.), and Medicine (I.W.), University of Cambridge School of Clinical Medicine, Cambridge, England; Cancer Research UK Cambridge Institute (M.A.M., S.U., K.M.B.), Medical Research Council Biostatistics Unit (J.W.), and Department of Biochemistry (K.M.B.), University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, England; Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria (R.W.); GE Healthcare, Munich, Germany (R.F.S.); Department of Pathology (K.A.), Cambridge Cancer Trials Centre (A.C.), Department of Radiology (I.P., B.D.C., R.S.), and Department of Oncology (B.B., S.J.), Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, England; and Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, England (J.W.).
Radiol Imaging Cancer. 2022 Jul;4(4):e210076. doi: 10.1148/rycan.210076.
Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (C) MRI to monitor the exchange of the hyperpolarized C label between injected [1-C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned C-hydrogen 1 head coil. Hyperpolarized [1-C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP ( < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP ( = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers ( < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, < .001, and ρ = 0.66, < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, = .04). Conclusion Hyperpolarized C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Hyperpolarized C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Published under a CC BY 4.0 license.
目的 通过检测注射的 [1-C]丙酮酸与肿瘤内乳酸盐和碳酸氢盐之间的 13C 超极化标记物的交换，利用 13C 磁共振波谱成像（MRS）评估脑胶质瘤（GBM）的代谢。
材料与方法 本前瞻性研究纳入 7 名初治的 GBM 患者（年龄[均值 ± 标准差]，60 岁 ± 11 岁；5 名男性），在 3.0T 磁共振扫描仪上使用双调谐氢-1 碳头部线圈进行检查。注射超极化 [1-C]丙酮酸后，使用动态 MRI 螺旋序列采集信号。在肿瘤内、对侧正常脑实质（NABP）和健康志愿者中通过配对或非配对 t 检验和 Wilcoxon 符号秩检验评估代谢情况。使用 Spearman ρ 相关系数来评估代谢物标记物与乳酸脱氢酶 A（LDH-A）表达和一些免疫组化标志物之间的相关性。使用 Benjamini-Hochberg 程序对多重比较进行校正。
结果 肿瘤中的碳酸氢盐与丙酮酸（BP）比值低于对侧 NABP（ <.01）。肿瘤内的乳酸盐与丙酮酸（LP）比值与 NABP 内的比值无差异（ =.38）。NABP 内的 LP 和 BP 比值高于先前在健康志愿者中观察到的比值（ <.05）。肿瘤内乳酸盐和碳酸氢盐的信号强度与丙酮酸信号强度密切相关（ρ = 0.92， <.001 和 ρ = 0.66， <.001），LP 比值与活检样本中的 LDH-A 表达呈弱相关（ρ = 0.43， =.04）。
结论 13C 磁共振波谱成像显示了 GBM 内和肿瘤之间乳酸盐标记的变化。相比之下，肿瘤内的碳酸氢盐标记物始终低于 NABP。
