Autry Adam, Phillips Joanna J, Maleschlijski Stojan, Roy Ritu, Molinaro Annette M, Chang Susan M, Cha Soonmee, Lupo Janine M, Nelson Sarah J
Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Transl Oncol. 2017 Dec;10(6):895-903. doi: 10.1016/j.tranon.2017.08.009. Epub 2017 Sep 22.
Although the contrast-enhancing (CE) lesion on T-weighted MR images is widely used as a surrogate for glioblastoma (GBM), there are also non-enhancing regions of infiltrative tumor within the T-weighted lesion, which elude radiologic detection. Because non-enhancing GBM (Enh-) challenges clinical patient management as latent disease, this study sought to characterize ex vivo metabolic profiles from Enh- and CE GBM (Enh+) samples, alongside histological and in vivo MR parameters, to assist in defining criteria for estimating total tumor burden.
Fifty-six patients with newly diagnosed GBM received a multi-parametric pre-surgical MR examination. Targets for obtaining image-guided tissue samples were defined based on in vivo parameters that were suspicious for tumor. The actual location from where tissue samples were obtained was recorded, and half of each sample was analyzed for histopathology while the other half was scanned using HR-MAS spectroscopy.
The Enh+ and Enh- tumor samples demonstrated comparable mitotic activity, but also significant heterogeneity in microvascular morphology. Ex vivo spectroscopic parameters indicated similar levels of total choline and N-acetylaspartate between these contrast-based radiographic subtypes of GBM, and characteristic differences in the levels of myo-inositol, creatine/phosphocreatine, and phosphoethanolamine. Analysis of in vivo parameters at the sample locations were consistent with histological and ex vivo metabolic data.
The similarity between ex vivo levels of choline and NAA, and between in vivo levels of choline, NAA and nADC in Enh+ and Enh- tumor, indicate that these parameters can be used in defining non-invasive metrics of total tumor burden for patients with GBM.
尽管T加权磁共振成像（MR）上的对比增强（CE）病变被广泛用作胶质母细胞瘤（GBM）的替代指标，但在T加权病变内也存在浸润性肿瘤的非增强区域，这些区域难以通过放射学检测到。由于非增强型GBM（Enh-）作为潜在疾病对临床患者管理构成挑战，本研究旨在对Enh-和CE型GBM（Enh+）样本的离体代谢谱进行表征，并结合组织学和体内MR参数，以协助确定估计肿瘤总负荷的标准。
56例新诊断的GBM患者接受了术前多参数MR检查。根据怀疑为肿瘤的体内参数确定获取图像引导组织样本的靶点。记录获取组织样本的实际位置，每个样本的一半用于组织病理学分析，另一半使用高分辨率魔角旋转光谱法（HR-MAS）进行扫描。
Enh+和Enh-肿瘤样本显示出相当的有丝分裂活性，但微血管形态也存在显著异质性。离体光谱参数表明，在这些基于对比的GBM放射学亚型之间，总胆碱和N-乙酰天门冬氨酸水平相似，而肌醇、肌酸/磷酸肌酸和磷酸乙醇胺水平存在特征性差异。对样本位置的体内参数分析与组织学和离体代谢数据一致。
Enh+和Enh-肿瘤中胆碱和NAA的离体水平之间，以及胆碱、NAA和标准化表观扩散系数（nADC）的体内水平之间的相似性，表明这些参数可用于定义GBM患者肿瘤总负荷的非侵入性指标。
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