Purpose

This prospective clinical trial investigated sodium (²³Na) MRI at 7 Tesla (T) field strength as biomarker for tumor extent, isocitrate dehydrogenase (IDH) mutation and O6-methylguanine DNA methyltransferase (MGMT) promotor methylation in glioma patients.

Methods

28 glioma patients underwent ²³Na MRI on a 7T scanner (Siemens Healthcare, Erlangen, Germany) parallel to standard 3T MRI before chemoradiation. Areas of Gadolinium-contrast enhancement (gdce), non-enhancing T2-hyperintensity (regarded as edema), necrosis, and normal-appearing white matter (nawm) were segmented on 3T MRI imaging and were co-registered with the ²³Na images. The median total ²³Na concentrations of all areas were compared by pairwise t-tests. Furthermore, areas of gdce and edema were merged to yield the whole tumor area without necrosis. Subsequently, the difference in median of the ²³Na concentration of this whole tumor area was compared between IDH-mutated and IDH wild-type gliomas as well as MGMT methylated and MGMT not-methylated glioblastomas using Whitney-Mann U-tests. All p-values were corrected after the Bonferroni-Holm procedure.

Results

The ²³Na concentration increased successively from nawm to necrotic areas (mean ± sd: nawm = 37.84 ± 5.87 mM, edema = 54.69 ± 10.64 mM, gdce = 61.72 ± 12.95 mM, necrosis = 81.88 ± 17.53 mM) and the concentrations differed statistically significantly between all regarded areas (adjusted p-values for all pairwise comparisons < 0.05). Furthermore, IDH-mutated gliomas showed significantly higher ²³Na concentrations than IDH wild-type gliomas (median [interquartile range]: IDH wild-type = 52.37 mM [45.98 – 58.56 mM], IDH mutated = 65.02 mM [58.87–67.05 mM], p = 0.039). Among the glioblastomas, there was a trend towards increased ²³Na concentration in MGMT methylated tumors that did not reach statistical significance (median [interquartile range]: MGMT methylated = 57.59 mM [50.70 – 59.17 mM], MGMT not methylated = 48.78 mM [45.88 – 53.91 mM], p = 1.0).

Conclusions

²³Na MRI correlates with the IDH mutation status and could therefore enhance image guidance towards biopsy sites as wells as image-guided surgery and radiotherapy. Furthermore, the successive decrease of ²³Na concentration from central necrosis to normal-appearing white matter suggests a correlation with tumor infiltration.

中文翻译：

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超高场钠 MRI 作为神经胶质瘤患者肿瘤范围、分级和 IDH 突变状态的生物标志物

 目的

这项前瞻性临床试验研究了 7 特斯拉 (T) 场强的钠 ( ²³ Na) MRI 作为神经胶质瘤患者肿瘤范围、异柠檬酸脱氢酶 (IDH) 突变和 O6-甲基鸟嘌呤 DNA 甲基转移酶 (MGMT) 启动子甲基化的生物标志物。

 方法

28 名神经胶质瘤患者在放化疗前接受了与标准 3T MRI 平行的 7T 扫描仪（德国埃尔兰根西门子医疗保健公司）上的²³ Na MRI。在 3T MRI 成像上对钆对比增强 (gdce)、非增强 T2 高信号（视为水肿）、坏死和正常白质 (nawm) 区域进行分割，并与²³ Na 图像共同配准。通过成对 t 检验比较所有区域的中位总²³ Na 浓度。此外，合并gdce和水肿区域以产生没有坏死的整个肿瘤区域。随后，使用 Whitney-Mann U 检验比较 IDH 突变和 IDH 野生型胶质瘤以及 MGMT 甲基化和 MGMT 非甲基化胶质母细胞瘤之间整个肿瘤区域²³ Na 浓度中位数的差异。所有 p 值均在 Bonferroni-Holm 程序后进行了校正。

 结果

²³ Na浓度从nawm到坏死区域依次增加（平均值±sd：nawm = 37.84 ± 5.87 mM，水肿= 54.69 ± 10.64 mM，gdce = 61.72 ± 12.95 mM，坏死= 81.88 ± 17.53 mM），并且浓度差异具有统计学意义所有关注区域之间（所有成对比较的调整 p 值 < 0.05）。此外，IDH 突变神经胶质瘤的²³ Na 浓度显着高于 IDH 野生型神经胶质瘤（中位数[四分位数范围]：IDH 野生型 = 52.37 mM [45.98 – 58.56 mM]，IDH 突变 = 65.02 mM [58.87–67.05 mM] ，p = 0.039）。在胶质母细胞瘤中，MGMT 甲基化肿瘤中²³ Na 浓度有增加的趋势，但未达到统计显着性（中位数[四分位数范围]：MGMT 甲基化 = 57.59 mM [50.70 – 59.17 mM]，MGMT 未甲基化 = 48.78 mM [45.88 – 53.91 mM]，p = 1.0）。

 结论

²³ Na MRI 与 IDH 突变状态相关，因此可以增强对活检部位的图像引导以及图像引导手术和放疗。此外， ²³ Na浓度从中央坏死到正常白质的连续降低表明与肿瘤浸润相关。