Whole-brain spectroscopic MRI biomarkers identify infiltrating margins in glioblastoma patients
Whole-brain spectroscopic MRI biomarkers identify infiltrating margins in glioblastoma patients
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DOI：
10.1093/neuonc/now036
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发表时间：
2016-08-01
期刊：
影响因子：
15.9
通讯作者：
Shim, Hyunsuk
中科院分区：
文献类型：
--
作者：
Cordova, James S.;Shu, Hui-Kuo G.;Shim, Hyunsuk
胶质母细胞瘤(GBM)的治疗标准是最大限度地安全切除，然后进行放射治疗和化疗。目前，对比度增强MRI用于确定外科手术和放射治疗的初级治疗量。然而，增强扫描并不能完全识别肿瘤，导致局部控制有限。质子光谱磁共振成像(SMRI)是一种报告内源性代谢的方法，可以更好地确定肿瘤边缘。在这里，我们开发了一个全脑sMRI流水线，并用肿瘤浸润性的定量测量来验证sMRI指标。全脑sMRI代谢物图与手术计划MRI共同配准，并导入神经导航系统，以指导接受5-氨基乙酰丙酸荧光引导手术的GBM患者的组织采样。样本是从代谢异常的区域采集的，在大块切除之前以活组织检查的方式进行。使用手持光谱仪在体外测量组织荧光。组织样本进行Sox2免疫组织化学染色，并使用一种新的数字病理图像分析工具进行分析，以定量染色细胞的密度。对sMRI标志物、SOX2密度和体外荧光之间的相关性进行了评估。光谱MRI生物标志物与SOX2阳性细胞密度和体外荧光显著相关。胆碱/N-乙酰天冬氨酸比值与各定量指标均有显著相关性(Pearson‘s Rho分别为0.82和0.36，P均<0.0001)。临床上，sMRI代谢异常先于肿瘤复发部位的增强增强，并与无进展生存期呈负相关。由于sMRI可以识别肿瘤的浸润和复发的高危区域，sMRI可以补充常规MRI来改善GBM患者的局部控制。
The standard of care for glioblastoma (GBM) is maximal safe resection followed by radiation therapy with chemotherapy. Currently, contrast-enhanced MRI is used to define primary treatment volumes for surgery and radiation therapy. However, enhancement does not identify the tumor entirely, resulting in limited local control. Proton spectroscopic MRI (sMRI), a method reporting endogenous metabolism, may better define the tumor margin. Here, we develop a whole-brain sMRI pipeline and validate sMRI metrics with quantitative measures of tumor infiltration.Whole-brain sMRI metabolite maps were coregistered with surgical planning MRI and imported into a neuronavigation system to guide tissue sampling in GBM patients receiving 5-aminolevulinic acid fluorescence-guided surgery. Samples were collected from regions with metabolic abnormalities in a biopsy-like fashion before bulk resection. Tissue fluorescence was measured ex vivo using a hand-held spectrometer. Tissue samples were immunostained for Sox2 and analyzed to quantify the density of staining cells using a novel digital pathology image analysis tool. Correlations among sMRI markers, Sox2 density, and ex vivo fluorescence were evaluated.Spectroscopic MRI biomarkers exhibit significant correlations with Sox2-positive cell density and ex vivo fluorescence. The choline to N-acetylaspartate ratio showed significant associations with each quantitative marker (Pearson's rho = 0.82, P < .001 and rho = 0.36, P < .0001, respectively). Clinically, sMRI metabolic abnormalities predated contrast enhancement at sites of tumor recurrence and exhibited an inverse relationship with progression-free survival.As it identifies tumor infiltration and regions at high risk for recurrence, sMRI could complement conventional MRI to improve local control in GBM patients.