Persigehl Thorsten, Bieker Ralf, Matuszewski Lars, Wall Alexander, Kessler Torsten, Kooijman Hendrik, Meier Norbert, Ebert Wolfgang, Berdel Wolfgang E, Heindel Walter, Mesters Rolf M, Bremer Christoph
Department of Clinical Radiology, University Hospital Muenster, Albert-Schweitzer-Str 33, D-48129 Muenster, Germany.
Radiology. 2007 Aug;244(2):449-56. doi: 10.1148/radiol.2442060371. Epub 2007 Jun 11.
To prospectively investigate steady-state blood volume measurements for early quantitative monitoring of antiangiogenic treatment with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging.
The institutional animal care committee approved all experiments. HT-1080 fibrosarcoma-bearing nude mice were injected with a thrombogenic vascular targeting agent (VTA) (11 nude mice, 20 tumors) or saline (12 nude mice, 20 tumors). USPIO-enhanced (SH U 555C) MR imaging was performed after the VTA was administered. USPIO-induced changes in tissue R2* (DeltaR2*) were measured with a T2-weighted dual-echo echo-planar imaging sequence, and the vascular volume fraction (VVF) was calculated. Parametric DeltaR2* maps were analyzed with respect to tumor perfusion patterns. Correlative histologic analysis was performed for grading of tissue thrombosis, and tissue perfusion was quantified with fluorescent microbeads. Unpaired Student t test and Spearman nonparametric correlation coefficient were used for statistical analysis.
The DeltaR2* values were significantly (P < .001) reduced shortly after treatment initiation (mean DeltaR2*, 0.017 msec(-1) +/- 0.0014 [standard error] in control animals vs 0.005 msec(-1) +/- 0.0007 in animals that received VTA), which was also reflected by a decrease in the VVF (2.47% +/- 0.18 vs 0.41% +/- 0.48, P < .001). Histologic analysis revealed various degrees of tumor thrombosis after VTA treatment that correlated inversely with the DeltaR2* values (r = -0.83). Moreover, tumor perfusion measurements corroborated the MR results, indicating a significant reduction in tissue perfusion after VTA treatment (mean tissue fluorescence, 570.4 arbitrary units [au] per gram +/- 27 vs 161.7 au/g +/- 17; P < .05).
USPIO-enhanced MR imaging enables early monitoring of antiangiogenic treatment of tumors.
前瞻性研究使用超小超顺磁性氧化铁（USPIO）增强磁共振（MR）成像进行稳态血容量测量，以早期定量监测抗血管生成治疗。
机构动物护理委员会批准了所有实验。给荷HT - 1080纤维肉瘤的裸鼠注射促血栓形成血管靶向剂（VTA）（11只裸鼠，20个肿瘤）或生理盐水（12只裸鼠，20个肿瘤）。在给予VTA后进行USPIO增强（SH U 555C）MR成像。使用T2加权双回波平面回波成像序列测量USPIO诱导的组织R2变化（ΔR2），并计算血管体积分数（VVF）。针对肿瘤灌注模式分析参数化ΔR2*图。进行相关组织学分析以对组织血栓形成进行分级，并用荧光微珠对组织灌注进行定量。采用非配对学生t检验和Spearman非参数相关系数进行统计分析。
治疗开始后不久，ΔR2值显著降低（P <.001）（对照动物的平均ΔR2为0.017 msec⁻¹±0.0014 [标准误差]，接受VTA的动物为0.005 msec⁻¹±0.0007），这也反映在VVF的降低上（2.47%±0.18对0.41%±0.48，P <.001）。组织学分析显示VTA治疗后肿瘤血栓形成程度各异，且与ΔR2*值呈负相关（r = - 0.83）。此外，肿瘤灌注测量结果证实了MR结果，表明VTA治疗后组织灌注显著降低（平均组织荧光，每克570.4任意单位[au]±27对161.7 au/g±17；P <.05）。
USPIO增强MR成像能够早期监测肿瘤的抗血管生成治疗。
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