Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors
Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors
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DOI：
10.1158/1078-0432.ccr-04-0603
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发表时间：
2004-12-15
影响因子：
11.5
通讯作者：
Black, PM
中科院分区：
文献类型：
--
作者：
Astrakas, LG;Zurakowski, D;Black, PM
儿童脑肿瘤大多数为低级别肿瘤，其诊断和治疗可能很复杂，因为它们经常邻近关键结构，这限制了诊断性活检。此外，尽管通过分子分析或 DNA 微阵列基因分析鉴定出的新的预后生物标志物很有前景，但它们也依赖于侵入性活检。在这里，我们测试了这样一个假设：结合通过质子磁共振波谱成像无创获得的生物学上重要的细胞内分子（生物标志物）的信息，将提高确定儿童脑肿瘤临床分级的诊断准确性。我们评估了 66 名患有脑肿瘤的儿童的质子磁共振波谱成像检查。在最高 Cho 区域测量含胆碱化合物 (Cho)、N-乙酰天冬氨酸、总肌酸以及脂质和/或乳酸的细胞内生物标志物，并将其标准化为周围健康组织的总肌酸。神经病理学分级按照世界卫生组织标准进行。与低级别肿瘤 (n = 43) 相比，标准化 Cho 和脂质和/或乳酸在高级别肿瘤 (n = 23) 中升高，多重逻辑回归证实这是肿瘤级别的独立预测因子（对于 Cho，优势比为 24.8，P < 0.001；对于脂质和/或乳酸，优势比为 4.4，P < 0.001）。通过最大化接受者操作特征曲线下的面积来计算标准化的Cho和脂质和/或乳酸的线性组合，其最大化诊断准确性。质子磁共振波谱成像虽然不能代表组织学，但提供了非侵入性体内生物标志物，用于预测儿科脑肿瘤的临床分级。
The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors. We evaluate the proton magnetic resonance spectroscopic imaging exams for 66 children with brain tumors. The intracellular biomarkers for choline-containing compounds (Cho), N-acetylaspartate, total creatine, and lipids and/or lactate were measured at the highest Cho region and normalized to the surrounding healthy tissue total creatine. Neuropathological grading was done with WHO criteria. Normalized Cho and lipids and/or lactate were elevated in high-grade (n = 23) versus low-grade (n = 43) tumors, which multiple logistic regression confirmed are independent predictors of tumor grade (for Cho, odds ratio 24.8, P < 0.001; and for lipids and/or lactate, odds ratio 4.4, P < 0.001). A linear combination of normalized Cho and lipids and/or lactate that maximizes diagnostic accuracy was calculated by maximizing the area under the receiver operating characteristic curve. Proton magnetic resonance spectroscopic imaging, although not a proxy for histology, provides noninvasive, in vivo biomarkers for predicting clinical grades of pediatric brain tumors.