Jütten Kerstin, Mainz Verena, Gauggel Siegfried, Patel Harshal Jayeshkumar, Binkofski Ferdinand, Wiesmann Martin, Clusmann Hans, Na Chuh-Hyoun
Department of Neurosurgery, RWTH Aachen University, Aachen, Germany.
Faculty of Medicine, Institute of Medical Psychology and Medical Sociology, RWTH Aachen University, Aachen, Germany.
Front Oncol. 2019 Jun 26;9:536. doi: 10.3389/fonc.2019.00536. eCollection 2019.
Immunohistochemical data based on isocitrate-dehydrogenase (IDH) mutation status have redefined glioma as a whole-brain disease, while occult tumor cell invasion along white matter fibers is inapparent in conventional magnetic resonance imaging (MRI). The functional and prognostic impact of focal glioma may however relate to the extent of white matter involvement. We used diffusion tensor imaging (DTI) to investigate microstructural characteristics of whole-brain normal-appearing white matter (NAWM) in relation to cognitive functions as potential surrogates for occult white matter involvement in glioma. Twenty patients (12 IDH-mutated) and 20 individually matched controls were preoperatively examined using DTI combined with a standardized neuropsychological examination. Tumor lesions including perifocal edema were masked, and fractional anisotropy (FA) as well as mean, radial, and axial diffusivity (MD, RD, and AD, respectively) of the remaining whole-brain NAWM were determined by using Tract-Based Spatial Statistics and histogram analyses. The relationship between extratumoral white matter integrity and cognitive performance was examined using partial correlation analyses controlling for age, education, and lesion volumes. In patients, mean FA and AD were decreased as compared to controls, which agrees with the notion of microstructural impairment of NAWM in glioma patients. Patients performed worse in all cognitive domains tested, and higher anisotropy and lower MD and RD values of NAWM were associated with better cognitive performance. In additional analyses, IDH-mutated and IDH-wildtype patients were compared. Patients with IDH-mutation showed higher FA, but lower MD, AD, and RD values as compared to IDH-wildtype patients, suggesting a better preserved microstructural integrity of NAWM, which may relate to a less infiltrative nature of IDH-mutated gliomas. Diffusion-based phenotyping and monitoring microstructural integrity of extratumoral whole-brain NAWM may aid in estimating occult white matter involvement and should be considered as a complementary biomarker in glioma.
基于异柠檬酸脱氢酶（IDH）突变状态的免疫组织化学数据已将胶质瘤重新定义为一种全脑疾病，而在传统磁共振成像（MRI）中，沿白质纤维的隐匿性肿瘤细胞浸润并不明显。然而，局灶性胶质瘤的功能和预后影响可能与白质受累程度有关。我们使用扩散张量成像（DTI）来研究全脑正常外观白质（NAWM）的微观结构特征与认知功能的关系，将其作为胶质瘤隐匿性白质受累的潜在替代指标。对20例患者（12例IDH突变型）和20例个体匹配的对照者在术前进行DTI检查，并结合标准化神经心理学检查。对包括瘤周水肿在内的肿瘤病变进行屏蔽，使用基于纤维束的空间统计学和直方图分析确定剩余全脑NAWM的分数各向异性（FA）以及平均、径向和轴向扩散率（分别为MD、RD和AD）。使用偏相关分析控制年龄、教育程度和病变体积，研究瘤外白质完整性与认知表现之间的关系。与对照组相比，患者的平均FA和AD降低，这与胶质瘤患者NAWM微观结构受损的观点一致。患者在所有测试的认知领域表现较差，NAWM较高的各向异性以及较低的MD和RD值与较好的认知表现相关。在额外的分析中，对IDH突变型和IDH野生型患者进行了比较。与IDH野生型患者相比，IDH突变型患者显示出更高的FA，但MD、AD和RD值更低，这表明NAWM的微观结构完整性保存更好，这可能与IDH突变型胶质瘤浸润性较小的性质有关。基于扩散的表型分析和监测瘤外全脑NAWM的微观结构完整性可能有助于评估隐匿性白质受累情况，应被视为胶质瘤的一种补充生物标志物。
