Meerang Mayura, Boss Andreas, Kenkel David, Broggini-Tenzer Angela, Bérard Karima, Lauk Olivia, Arni Stephan, Weder Walter, Opitz Isabelle
Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
Department of Radiology, University Hospital Zurich, Zurich, Switzerland.
Eur J Cardiothorac Surg. 2015 Jan;47(1):e34-41. doi: 10.1093/ejcts/ezu393. Epub 2014 Oct 25.
An orthotopic rat tumour recurrence model for malignant pleural mesothelioma (MPM) provides clinical similarity to patients and is useful for drug testing combined with surgical intervention. Importantly, a reliable imaging method is required allowing for noninvasive and repetitive evaluation of the tumour load. We compared the tumour load assessed by bioluminescence and magnetic resonance imaging (MRI) to the macroscopic tumour volume as a reference standard.
A total of 500,000 syngeneic rat MPM cells transfected with luciferase were implanted underneath the parietal pleura of immunocompetent rats (n=13). From the second day after implantation, bioluminescence measurements of the tumour load expressed as the maximum bioluminescent intensity (photon/second) were performed daily after intraperitoneal injection of the luciferase substrate, d-luciferin, to observe the first occurrence of tumour. Six days after the first detection of tumour, bioluminescence, MRI and macroscopic tumour volume measurement were conducted. For MRI, a 4.7-Tesla small animal imager equipped with a 1H whole-body rat coil was employed using T2-weighted fast spin-echo sequences. Tumour burden (mm3) was quantified from magnetic resonance transverse images by two independent readers by manual segmentation. Finally, the tumour burden assessed by bioluminescence and MRI was correlated (Pearson's correlation) with the macroscopic measurement of tumour (ellipsoid) volume.
In all rats, a single tumour nodule was found at the inoculation site with a median macroscopic volume of 46 mm3 (18-377 mm3). For tumour burden quantification of MRIs, we observed good interobserver correlation (R2=0.81, P<0.0001) as well as significant association with the macroscopic tumour volume (R2=0.59, P=0.002). However, the signal intensity of bioluminescence did not correspond to the macroscopic tumour volume (R2=0.01, P=0.76).
MRI is a reliable and reproducible noninvasive in vivo imaging method for MPM tumour burden assessment for the present MPM model.
恶性胸膜间皮瘤（MPM）的原位大鼠肿瘤复发模型与患者临床情况相似，对于联合手术干预的药物测试很有用。重要的是，需要一种可靠的成像方法，以便对肿瘤负荷进行无创且重复性的评估。我们将通过生物发光和磁共振成像（MRI）评估的肿瘤负荷与作为参考标准的宏观肿瘤体积进行了比较。
将总共500,000个转染了荧光素酶的同基因大鼠MPM细胞植入具有免疫活性的大鼠（n = 13）的壁层胸膜下方。从植入后的第二天开始，在腹腔注射荧光素酶底物d - 荧光素后，每天进行以最大生物发光强度（光子/秒）表示的肿瘤负荷的生物发光测量，以观察肿瘤的首次出现。在首次检测到肿瘤六天后，进行生物发光、MRI和宏观肿瘤体积测量。对于MRI，使用配备有1H全身大鼠线圈的4.7特斯拉小动物成像仪，采用T2加权快速自旋回波序列。由两名独立的阅片者通过手动分割从磁共振横向图像中量化肿瘤负荷（mm3）。最后，将通过生物发光和MRI评估的肿瘤负荷与肿瘤（椭圆形）体积的宏观测量值进行相关性分析（Pearson相关性）。
在所有大鼠中，在接种部位发现单个肿瘤结节，宏观体积中位数为46 mm3（18 - 377 mm3）。对于MRI的肿瘤负荷量化，我们观察到观察者间具有良好的相关性（R2 = 0.81，P < 0.0001），并且与宏观肿瘤体积具有显著相关性（R2 = 0.59，P = 0.002）。然而，生物发光的信号强度与宏观肿瘤体积不对应（R2 = 0.01，P = 0.76）。
对于当前的MPM模型，MRI是一种可靠且可重复的无创体内成像方法，用于评估MPM肿瘤负荷。
