Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Department of Education Science and Psychology, FU Berlin, Berlin, Germany.
Sci Rep. 2020 Nov 27;10(1):20785. doi: 10.1038/s41598-020-77624-8.
To investigate the imaging performance of an elastin-specific molecular magnetic resonance imaging (MRI) probe with respect to the extracellular matrix (ECM) in an experimental hepatic cancer model. Twelve rabbits with hepatic VX2 tumors were examined using 3 T MRI 14, 21, and 28 days after tumor implantation for two subsequent days (gadobutrol, day 1; elastin-specific probe, day 2). The relative enhancement (RE) of segmented tumor regions (central and margin) and the peritumoral matrix was calculated using pre-contrast and delayed-phase T1w sequences. MRI measurements were correlated to histopathology and element-specific and spatially resolved mass spectrometry (MS). Mixed-model analysis was performed to assess the performance of the elastin-specific probe. In comparison to gadobutrol, the elastin probe showed significantly stronger RE, which was pronounced in the tumor margin (day 14-28: P ≤ 0.007). In addition, the elastin probe was superior in discriminating between tumor regions (χ(4) = 65.87; P < 0.001). MRI-based measurements of the elastin probe significantly correlated with the ex vivo elastinstain (R = .84; P <0 .001) and absolute gadolinium concentrations (ICP-MS: R = .73, P <0 .01). LA-ICP-MS imaging confirmed the colocalization of the elastin-specific probe with elastic fibers. Elastin-specific molecular MRI is superior to non-specific gadolinium-based contrast agents in imaging the ECM of hepatic tumors and the peritumoral tissue.
研究一种针对细胞外基质(ECM)的弹性蛋白特异性分子磁共振成像(MRI)探针在实验性肝癌模型中的成像性能。
12 只兔VX2 肝癌模型,分别在肿瘤种植后第 14、21 和 28 天进行 3T MRI 检查(第 1 天使用钆布醇,第 2 天使用弹性蛋白特异性探针),共检查 2 天。使用对比前和延迟 T1w 序列计算分割肿瘤区域(中心和边缘)和肿瘤周围基质的相对增强(RE)。将 MRI 测量值与组织病理学以及元素特异性和空间分辨质谱(MS)进行相关性分析。采用混合模型分析评估弹性蛋白特异性探针的性能。
与钆布醇相比,弹性蛋白探针显示出更强的 RE,在肿瘤边缘更为明显(第 14-28 天:P≤0.007)。此外,弹性蛋白探针在区分肿瘤区域方面更具优势(χ(4) = 65.87;P < 0.001)。基于 MRI 的弹性蛋白探针测量值与离体弹性蛋白染色(R = .84;P <0 .001)和绝对钆浓度(ICP-MS:R = .73,P <0 .01)显著相关。LA-ICP-MS 成像证实了弹性蛋白特异性探针与弹性纤维的共定位。
与非特异性基于钆的造影剂相比,弹性蛋白特异性 MRI 在成像肝肿瘤 ECM 和肿瘤周围组织方面具有优越性。