Brain Tumor Enhancement in Magnetic Resonance Imaging at 3 Tesla Intraindividual Comparison of Two High Relaxivity Macromolecular Contrast Media With a Standard Extracellular Gd-Chelate in a Rat Brain Tumor Model
Brain Tumor Enhancement in Magnetic Resonance Imaging at 3 Tesla Intraindividual Comparison of Two High Relaxivity Macromolecular Contrast Media With a Standard Extracellular Gd-Chelate in a Rat Brain Tumor Model
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DOI：
10.1097/rli.0b013e31819817ff
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发表时间：
2009-04-01
影响因子：
6.7
通讯作者：
Schneider, Guenther
中科院分区：
文献类型：
--
作者：
Fries, Peter;Runge, Val M.;Schneider, Guenther
目的：本研究的目的是评估P846（一种新型中等尺寸、高弛豫率的基于Gd的造影剂）在3特斯拉下在大鼠脑胶质瘤模型中的病变增强（LE）和对比噪声比（CNR）特性，并将该造影剂与高弛豫率、大分子化合物（P792）和标准细胞外Gd螯合物（Gd-DOTA）进行比较。材料和方法：使用3种不同的造影剂对7只实验性诱导脑胶质瘤大鼠进行评价，每次MR检查间隔至少24小时。注射之间的时间保证了在下一次检查之前，药物从肿瘤中充分清除。P792（Gadomelitol，Guerbet，法国）和P846（Guerbet Research的一种新化合物）是不与蛋白质结合的大分子高驰豫造影剂，并与细胞外试剂Gd-DOTA（多它灵，Guerbet，法国）进行了比较。T1 w梯度回波序列TR/TE 200毫秒/7.38毫秒，翻转角。= 90度，采集时间：1：42分：秒，体素尺寸：0.2 x 0.2 x 2.0 mm（3），FOV = 40 mm，采集矩阵：256 X 256），在每次静脉注射造影剂之前和之后的5个连续时间点，以相同的切片方向，使用专用的4通道头部阵列动物线圈采集。造影剂注射的顺序是随机的，然而Gd-DOTA用作第一或第二造影剂。调整造影剂剂量以补偿3种造影剂的不同T1弛豫率。使用感兴趣区域分析评价信噪比、CNR和LE。兽医组织病理学家证实存在的胶质瘤在每个科目，完成后的成像study.Results：P792显示显着较低的LE相比，Gd-DOTA造影剂注射后的第一个7分钟内（P < 0.05），然而，达到相当的LE值在注射后9分钟（P = 0.07）。但P792在各检测时间点的CNR均显著低于Gd-DOTA（P < 0.05）。与Gd-DOTA相比，P846提供了相当但持久的LE（P < 0.05），并且与P792相比，P846显示出显著更大的LE和CNR（P < 0.05）。在所有检查时间点，Gd-DOTA和P846的CNR值之间没有统计学显著差异（P < 0.05），与Gd-DOTA相比，P846以四分之一的剂量施用。血管内造影剂P792与Gd-DOTA和P846相比显示出显著更少的LE和CNR，这表明在该大鼠神经胶质瘤模型中，它没有显示出从肿瘤新血管的显著外渗，并且没有显著地穿过破坏的血脑屏障。与之不同的是，P846在3特斯拉的场强下提供了与细胞外造影剂Gd-DOTA相当的增强特性，使用调整后的剂量，这表明它穿过破坏的血脑屏障和肿瘤毛细血管，最有可能是基于与P792相比降低的分子量。同时，该化合物的高弛豫率允许将注射的钆剂量降低4倍，而当与0.1 mmol/kg体重剂量的标准细胞外Gd-螯合物（Gd-DOTA）相比时，提供相当的增强特性。
Objectives: The aim of this study was to evaluate lesion enhancement (LE) and contrast-to-noise ratio (CNR) properties of P846, a new intermediate sized, high relaxivity Gd-based contrast agent at 3 Tesla in a rat brain glioma model, and to compare this contrast agent with a high relaxivity, macromolecular compound (P792), and a standard extracellular Gd-chelate (Gd-DOTA).Materials and Methods: Seven rats with experimental induced brain glioma were evaluated using 3 different contrast agents, with each MR examination separated by at least 24 hours. The time between injections assured sufficient clearance of the agent from the tumor, before the next examination. P792 (Gadomelitol, Guerbet, France) and P846 (a new compound front Guerbet Research) are macromolecular and high relaxivity contrast agents with no protein binding, and were compared with the extracellular agent Gd-DOTA (Dotarem, Guerbet, France). T1w gradient echo sequences TR/TE 200 milliseconds/7.38 milliseconds, flip angle. = 90 degrees, acquisition time: 1:42 minutes:sec, voxel size: 0.2 x 0.2 x 2.0 mm(3), FOV = 40 mm, acquisition matrix: 256 X 256) were acquired before and at 5 consecutive time points after each intravenous contrast injection in the identical slice orientation, using a dedicated 4-channel head array animal coil. The order of contrast media injection was randomized, with however Gd-DOTA used either as the first or second contrast agent. Contrast agent dose was adjusted to compensate for the different T1 relaxivities of the 3 agents. Signal-to-noise ratio, CNR, and LE were evaluated using region-of-interest analysis. A veterinary histopathologist confirmed the presence of a glioma in each subject, after completion of the imaging study.Results: P792 showed significantly less LE as compared with Gd-DOTA within the first 7 minutes after contrast agent injection (P < 0.05) with, however, reaching comparable LE values at 9 minutes after injection (P = 0.07). However, P792 provided significantly less CNR as compared with Gd-DOTA (P < 0.05) for all examination time points. P846 provided comparable but persistent LE as compared with Gd-DOTA (P < 0.05) and demonstrated significantly greater LE and CNR when compared with P792 (P < 0.05). No statistically significant differences between CNR values for Gd-DOTA and P846 were noted for all examination time points (P < 0.05), with P846 administered at one-fourth the dose as compared with Gd-DOTA.Conclusion: The intravascular contrast medium P792 showed significantly less LE and CNR in comparison to Gd-DOTA and P846, suggesting that it does not show marked extravasation from tumor neocapillaries and does not significantly cross the disrupted blood brain-barrier in this rat glioma model. In distinction, P846 provides comparable enhancement properties at a field strength of 3 Tesla to the extracellular contrast agent Gd-DOTA, using the adjusted dose, suggesting that it crosses the disrupted blood-brain-barrier and tumor capillaries, most likely based on the decreased molecular weight as compared with P792. At the same time, the high relaxivity of this compound allows for decreasing the injected gadolinium dose by a factor of 4 whereas providing comparable enhancement properties when compared with a standard extracellular Gd-chelate (Gd-DOTA) at a dose of 0.1 mmol/kg body weight.