pH-weighted molecular imaging of gliomas using amine chemical exchange saturation transfer MRI
pH-weighted molecular imaging of gliomas using amine chemical exchange saturation transfer MRI
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DOI：
10.1093/neuonc/nov106
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发表时间：
2015-11-01
期刊：
影响因子：
15.9
通讯作者：
Ellingson, Benjamin M.
中科院分区：
文献类型：
--
作者：
Harris, Robert J.;Cloughesy, Timothy F.;Ellingson, Benjamin M.
由异常灌注和代谢引起的间质组织酸中毒是癌症的标志。目前的研究表明，化学交换饱和转移（CEST）MRI可以作为一种非侵入性的pH加权的分子成像技术，通过靶向胺质子和质子之间的化学交换在细胞外散装water.First，胺CEST的灵敏度进行了验证，在各种条件下，包括不同的磁场强度，氨基酸浓度，和pH值的phantelum。在7 T下的临床前GL 261颅内胶质瘤模型和3 T下的人类患者中，将胺CEST与组织学进行比较。探讨了生理和pH加权MRI之间的相关性，沿着预测20例胶质母细胞瘤患者进展至放化疗的时间的能力。在CEST MRI上，随着3 T和7 T扫描仪在肿瘤中观察到的范围内pH降低，3 ppm（胺范围）时z-光谱不对称性增加。具有酸性特征的病变在组织学上显示活动性肿瘤和假扁平化肿瘤，并且在MR波谱上显示FDOPA PET摄取升高、乳酸升高和灌注异常。术后酸性病变或稳定/生长的酸性病变患者在放化疗后的进展时间较低酸度病变患者短（P <0.001）。结果表明，pH加权MRI可能提供超越传统成像技术的脑肿瘤生理学的新见解。
Interstitial tissue acidosis resulting from abnormal perfusion and metabolism is a hallmark of cancer. The current study demonstrates that chemical exchange saturation transfer (CEST) MRI can be used as a noninvasive pH-weighted molecular imaging technique by targeting the chemical exchange between amine protons and protons in extracellular bulk water.First, the sensitivity of amine CEST was validated in phantoms under a variety of conditions, including different magnetic field strengths, amino acid concentrations, and pH values. Amine CEST was compared with histology in both a preclinical GL261 intracranial glioma model at 7T and human patients at 3T. The association between physiologic and pH-weighted MRI was explored, along with the ability to predict time to progression to radiochemotherapy in 20 glioblastoma patients.z-Spectral asymmetry increased at 3 ppm (amine range) on CEST MRI with decreasing pH within the range observed in tumors for both 3T and 7T scanners. Lesions with acidic signatures showed active tumor and pseudopalisading tumor on histology and showed elevated FDOPA PET uptake, lactate on MR spectroscopy, and perfusion abnormalities. Patients with acidic lesions after surgery or stable/growing acidic lesions had a shorter time to progression following radiochemotherapy compared with patients with lesions demonstrating relatively low acidity (P < .001).Results suggest pH-weighted MRI may provide new insight into brain tumor physiology beyond traditional imaging technologies.