Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
J Magn Reson Imaging. 2018 Jun;47(6):1589-1600. doi: 10.1002/jmri.25898. Epub 2017 Dec 4.
Steady state susceptibility contrast (SSC)-MRI provides information on vascular morphology but is a rarely used method.
To investigate the utility of the ultrasmall superparamagnetic iron oxide particles (USPIOs) GEH121333 for measuring tumor response to bevacizumab and compare this with gadolinium-based DCE-MRI.
Prospective preclinical animal model study.
Mice bearing subcutaneous TOV-21G human ovarian cancer xenografts treated with bevacizumab (n = 9) or saline (n = 9).
FIELD STRENGTH/SEQUENCE: Imaging was performed on a 7T Bruker Biospec. For SSC-MRI with GEH121333 we acquired R -maps (RARE-sequence with variable TR), R -maps (multi-spin echo), and R2*-maps (multi-gradient echo). Additionally, R and R maps were measured on the days after USPIO injection. For DCE-MRI with gadodiamide we acquired 200 T -weighted images (RARE-sequence).
ΔR , ΔR , and ΔR2* maps were computed from SSC-MRI. DCE-MRI was analysed using the extended Tofts model.
Results from pre- and 3 days posttreatment SSC-MRI were compared using paired-sample t-tests. Treatment and control groups were compared using independent sample t-tests. Performance of SSC- and DCE-MRI was compared using multivariate partial least squares discriminant analysis.
Already one day after treatment and USPIO injection, R and R values were lower in treated (R = 0.49 ± 0.03s , R = 23.07 ± 1.49s ) compared with control tumors (R = 0.52 ± 0.02s , R = 24.98 ± 1.01s ), indicating lower USPIO accumulation. Posttreatment SSC-MRI displayed significantly decreased tumor blood volume (change in ΔR = -0.43 ± 0.26s , P = 0.001) and vessel density (change in Q = -0.032 ± 0.020s , P = 0.002). DCE-MRI showed among others lower K in treated tumors (control = 0.064 ± 0.011min , tx = 0.046 ± 0.008min , P = 0.002). Multivariate analysis suggests that SSC-MRI was slightly inferior to DCE-MRI in distinguishing treated from control tumors (accuracy = 75%, P = 0.058 versus 80%, P = 0.028), but a combination of both was best (accuracy = 85%; P = 0.003).
SSC-MRI with GEH121333 is sensitive to early (<24 h) and late changes in tumor vasculature. SSC-MRI and DCE-MRI provide complementary information and can be used to assess different aspects of vascular responses to anti-angiogenic therapies.
1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1589-1600.
稳态顺磁性对比(SSC)-MRI 可提供血管形态学信息,但应用较少。
研究超小超顺磁性氧化铁颗粒(USPIO)GEH121333 用于测量贝伐珠单抗治疗肿瘤的疗效,并与基于钆的 DCE-MRI 进行比较。
前瞻性临床前动物模型研究。
皮下接种 TOV-21G 人卵巢癌异种移植瘤的小鼠,给予贝伐珠单抗(n=9)或生理盐水(n=9)治疗。
磁场强度/序列:在 7T Bruker Biospec 上进行成像。对于 SSC-MRI 用 GEH121333,我们采集 R-图(具有可变 TR 的 RARE 序列)、R-图(多自旋回波)和 R2*-图(多梯度回波)。此外,在 USPIO 注射后的几天内测量 R 和 R 图。对于 DCE-MRI 用钆喷酸葡胺,我们采集 200T 加权图像(RARE 序列)。
从 SSC-MRI 计算 ΔR、ΔR 和 ΔR2*图。使用扩展 Tofts 模型分析 DCE-MRI。
使用配对样本 t 检验比较治疗前和治疗后 3 天 SSC-MRI 的结果。使用独立样本 t 检验比较治疗组和对照组。使用多元偏最小二乘判别分析比较 SSC 和 DCE-MRI 的性能。
在治疗和 USPIO 注射后 1 天,治疗肿瘤的 R 和 R 值就已经较低(R=0.49±0.03s,R=23.07±1.49s),低于对照肿瘤(R=0.52±0.02s,R=24.98±1.01s),表明 USPIO 积累减少。治疗后 SSC-MRI 显示肿瘤血容量显著降低(ΔR=-0.43±0.26s,P=0.001)和血管密度降低(Q=-0.032±0.020s,P=0.002)。DCE-MRI 还显示治疗肿瘤的 K 值较低(对照=0.064±0.011min,tx=0.046±0.008min,P=0.002)。多元分析表明,SSC-MRI 在区分治疗和对照肿瘤方面略逊于 DCE-MRI(准确性=75%,P=0.058 与 80%,P=0.028),但两者结合效果最佳(准确性=85%;P=0.003)。
GEH121333 的 SSC-MRI 对肿瘤血管早期(<24h)和晚期变化敏感。SSC-MRI 和 DCE-MRI 提供互补信息,可用于评估抗血管生成治疗的不同血管反应方面。
1 技术功效:第 2 阶段 J. Magn. Reson. Imaging 2018;47:1589-1600.