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Ultra-high-field sodium MRI as biomarker for tumor extent, grade and IDH mutation status in glioma patients
NeuroImage: Clinical ( IF 3.4 ) Pub Date : 2020-09-12 , DOI: 10.1016/j.nicl.2020.102427
Sebastian Regnery 1 , Nicolas G R Behl 2 , Tanja Platt 3 , Nina Weinfurtner 4 , Paul Windisch 5 , Katerina Deike-Hofmann 4 , Felix Sahm 6 , Martin Bendszus 7 , Jürgen Debus 1 , Mark E Ladd 8 , Heinz-Peter Schlemmer 4 , Stefan Rieken 1 , Sebastian Adeberg 1 , Daniel Paech 4
Affiliation  

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:


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。

更新日期:2020-09-29
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