From the Departments of Radiology (M.I., P.R., H.E.D.L., M.W., K.W.Y.) and Pathology (P.S., H.V.), Stanford University Medical Center, 300 Pasteur Dr, Grant Building, Room S031E, Stanford, CA 94305; Richard M. Lucas Center for Imaging (S.H., M.M.) and Departments of Medicine (Biomedical Informatics Research) (A.G.), Neurosurgery (G.H., G.L., S.C.), and Neurology (Neuro-Oncology) (R.T.), Stanford University, Stanford, Calif.
Radiology. 2019 Jan;290(1):198-206. doi: 10.1148/radiol.2018181204. Epub 2018 Nov 6.
Purpose To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 400× magnification high-power fields with iron-containing macrophages. Results Ten adults (four male participants [mean age, 65 years ± 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years ± 12 years; age range, 32-65 years]; mean age of all participants, 58 years ± 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P < .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163-positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion MRI measurements of susceptibility, R2*, and R2' (R2* - R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas. © RSNA, 2018 Online supplemental material is available for this article.
目的 旨在探究超顺磁性氧化铁对比剂增强 MRI 作为一种无创性影像学生物标志物，用于检测成人高级别脑胶质瘤中的巨噬细胞。
材料与方法 本前瞻性研究纳入了 2015 年 7 月至 2017 年 7 月间的高级别脑胶质瘤成人患者。每位参与者均接受静脉注射超顺磁性氧化铁（5mg/kg），24 小时后进行 3.0T MRI 扫描。基于超顺磁性氧化铁诱导的信号变化程度，在每个肿瘤中选择 2 个部位进行术中取样。通过使用各自的后处理图谱进行感兴趣区分析，获得磁化率和弛豫率 R2*（1/T2*）和 R2（1/T2）。对每个样本进行普鲁士蓝、CD68、CD163 和胶质纤维酸性蛋白染色。通过 Pearson 相关分析和线性混合模型评估成像测量值与含有铁巨噬细胞的 400×高倍视野数量之间的关系。
结果 10 名成人（4 名男性参与者[平均年龄 65 岁±9 岁（标准差）；年龄范围 57-74 岁]和 6 名女性参与者[平均年龄 53 岁±12 岁；年龄范围 32-65 岁]；所有参与者的平均年龄 58 岁±12 岁[年龄范围 32-74 岁]）纳入高级别脑胶质瘤患者。磁化率、R2*和 R2'与 CD163 阳性（r 范围，0.64-0.71；P <.01）和 CD68 阳性（r 范围，0.55-0.57；P 值范围，.01-.02）含铁巨噬细胞的高倍视野数量呈显著正相关。R2 与 CD163 阳性（r = 0.33；P =.16）和 CD68 阳性（r = 0.24；P =.32）含铁巨噬细胞之间无显著相关性。线性混合模型也得到了相似的显著结果。在组织病理学分析中，仅在巨噬细胞中发现铁颗粒；胶质纤维酸性蛋白阳性肿瘤细胞中未见铁颗粒。
结论 铁对比剂给药后获得的 MRI 测量磁化率、R2和 R2'（R2-R2）与含铁巨噬细胞浓度相关，这表明它们可能成为恶性胶质瘤中巨噬细胞的定量成像标志物。
© 2018 RSNA，在线补充材料可用于本文。
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