研究动态
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pH加权氨基化学交换饱和转移回波成像(CEST-EPI)可可视化浸润性胶质母细胞瘤细胞。

pH-Weighted Amine Chemical Exchange Saturation Transfer Echo Planar Imaging (CEST-EPI) Visualizes Infiltrating Glioblastoma Cells.

发表日期:2023 Aug 18
作者: Kunal S Patel, Jingwen Yao, Nicholas S Cho, Francesco Sanvito, Kaleab Tessema, Alvaro Alvarado, Lindsey Dudley, Fausto Rodriguez, Richard Everson, Timothy F Cloughesy, Noriko Salamon, Linda Liau, Harley Kornblum, Benjamin M Ellingson
来源: NEURO-ONCOLOGY

摘要:

鉴于胶质母细胞瘤的侵袭性特质,在治疗过程中,肿瘤细胞存在于超过对比增强(CE)区域的范围内。然而,非增强(NE)肿瘤区域与水肿组织之间很难可视化和区分。氨基化学交换饱和转移回波成像(CEST-EPI)是一种pH敏感的分子磁共振成像技术,通过评估其识别浸润性非增强肿瘤及预测生存的能力予以研究。在这项前瞻性研究中,对30名患者进行CEST-EPI,对NE区域内的CEST对比度升高区域(根据3ppm处磁化率转移比的不对称性定义为"CEST+")进行定量分析。并且,将3ppm处的中位数MTRasym和CEST+ NE区域的体积与无进展生存期(PFS)进行相关性分析。在14名患者的20个样本中,通过图像引导活检获取这些区域的MTRasym与肿瘤和非肿瘤细胞负荷之间的相关性,使用免疫组织化学进行分析。 在15例新诊断和15例复发性胶质母细胞瘤中,CEST+ NE区域内较高的中位数3ppm处MTRasym [p=0.007; p=0.0326] 和CEST+ NE肿瘤较大的体积 [p=0.020; p<0.001] 与PFS减少相关。CE复发在手术前的CEST+ NE区域中的发生率达到95.4%。3ppm处MTRasym与肿瘤存在、细胞密度、Ki-67阳性率和CD31阳性率相关 [p=0.001; p<0.001; p<0.001; p=0.001]。 pH加权的氨基CEST-EPI可以可视化NE肿瘤,可能是通过其周围肿瘤微环境的酸化作用。CEST+ NE肿瘤的幅度和体积与肿瘤细胞密度、增殖程度或“活跃”肿瘤以及PFS有相关性。© 2023年,作者发表于牛津大学出版社代表神经肿瘤学会。保留所有权利。有关权限,请发送电子邮件至:journals.permissions@oup.com。
Given the invasive nature of glioblastoma, tumor cells exist beyond the contrast enhancing (CE) region targeted during treatment. However, areas of non-enhancing (NE) tumor are difficult to visualize and delineate from edematous tissue. Amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) is a pH-sensitive molecular MRI technique that was evaluated in its ability to identify infiltrating non-enhancing tumor and prognosticate survival.In this prospective study, CEST-EPI was obtained in 30 patients and areas with elevated CEST contrast ("CEST+" based on the asymmetry in magnetization transfer ratio: MTRasym at 3ppm) within NE regions were quantitated. Median MTRasym at 3ppm and volume of CEST+ NE regions were correlated with progression-free survival (PFS). In 20 samples from 14 patients, image guided biopsies of these areas were obtained to correlate MTRasym at 3ppm to tumor and non-tumor cell burden using immunohistochemistry.In 15 newly diagnosed and 15 recurrent glioblastoma, higher median MTRasym at 3ppm within CEST+ NE regions [p=0.007;p=0.0326] and higher volumes of CEST+ NE tumor [p=0.020;p<0.001] were associated with decreased PFS. CE recurrence occurred in areas of pre-operative CEST+ NE regions in 95.4% of patients. MTRasym at 3ppm was correlated with presence of tumor, cell density, %Ki-67 positivity, and %CD31 positivity [p=0.001;p<0.001;p<0.001;p=0.001].pH-weighted amine CEST-EPI allows for visualization of NE tumor, likely through surrounding acidification of the tumor microenvironment. The magnitude and volume of CEST+NE tumor correlates with tumor cell density, degree of proliferating or "active" tumor, and PFS.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.