Ge Xia, Song Kyu-Ho, Engelbach John A, Yuan Liya, Gao Feng, Dahiya Sonika, Rich Keith M, Ackerman Joseph J H, Garbow Joel R
Department of Radiology, Washington University, Saint Louis, MO, United States.
Department of Neurosurgery, Washington University, Saint Louis, MO, United States.
Front Oncol. 2022 May 30;12:885480. doi: 10.3389/fonc.2022.885480. eCollection 2022.
Distinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen (H) and deuterium (H) magnetic resonance methods for distinguishing RN vs. tumor. Furthermore, proof-of-principle, range-finding deuterium (H) metabolic magnetic resonance is employed to assess glycolytic signatures distinguishing RN vs. tumor.
A pipeline of common quantitative H MRI contrasts, including an improved magnetization transfer ratio (MTR) sequence, and H magnetic resonance spectroscopy (MRS) following administration of H-labeled glucose, was applied to C57BL/6 mouse models of the following: (i) late time-to-onset RN, occurring 4-5 weeks post focal 50-Gy (50% isodose) Gamma Knife irradiation to the left cerebral hemisphere, (ii) glioblastoma, growing ~18-24 days post implantation of 50,000 mouse GL261 tumor cells into the left cerebral hemisphere, and (iii) mixed model, with GL261 tumor growing within a region of radiation necrosis (H MRI only). Control C57BL/6 mice were also examined by H metabolic magnetic resonance.
Differences in quantitative H MRI parametric values of R1, R2, ADC, and MTR comparing pure tumor vs. pure RN were all highly statistically significant. Differences in these parameter values and DCE for tumor vs. RN in the mixed model (tumor growing in an RN background) are also all significant, demonstrating that these contrasts-in particular, MTR-can effectively distinguish tumor vs. RN. Additionally, quantitative H MRS showed a highly statistically significant dominance of aerobic glycolysis (glucose ➔ lactate; fermentation, Warburg effect) in the tumor vs. oxidative respiration (glucose ➔ TCA cycle) in the RN and control brain.
These findings, employing a pipeline of quantitative H MRI contrasts and H MRS following administration of H-labeled glucose, suggest a pathway for substantially improving the discrimination of tumor vs. RN in the clinic.
区分放射性坏死（RN）与肿瘤复发仍是一个棘手的临床问题，对神经肿瘤患者的医疗保健有着重要影响。在此，采用纯肿瘤、纯RN以及RN/肿瘤混合的小鼠模型来评估氢（H）和氘（H）磁共振方法，以区分RN与肿瘤。此外，还运用原理验证性、范围探索性的氘（H）代谢磁共振来评估区分RN与肿瘤的糖酵解特征。
将一系列常见的定量H MRI对比方法，包括改进的磁化传递率（MTR）序列，以及给予H标记葡萄糖后的H磁共振波谱（MRS），应用于以下C57BL/6小鼠模型：（i）迟发性RN，在左侧大脑半球接受50 Gy（50%等剂量）伽玛刀聚焦照射后4 - 5周出现；（ii）胶质母细胞瘤，在将50,000个小鼠GL261肿瘤细胞植入左侧大脑半球后约18 - 24天生长；（iii）混合模型，GL261肿瘤在放射性坏死区域内生长（仅进行H MRI）。对照C57BL/6小鼠也通过H代谢磁共振进行检查。
比较纯肿瘤与纯RN时，R1、R2、ADC和MTR的定量H MRI参数值差异均具有高度统计学意义。在混合模型（肿瘤在RN背景中生长）中，肿瘤与RN的这些参数值及动态对比增强（DCE）差异也均显著，表明这些对比——尤其是MTR——能够有效区分肿瘤与RN。此外，定量H MRS显示，与RN和对照脑内的氧化呼吸（葡萄糖➔三羧酸循环）相比，肿瘤中糖酵解（葡萄糖➔乳酸；发酵，瓦伯格效应）具有高度统计学意义的优势。
这些采用一系列定量H MRI对比以及给予H标记葡萄糖后的H MRS的研究结果，为在临床上大幅提高肿瘤与RN的鉴别能力提供了一条途径。
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