Evaluation of high frequency ultrasound methods and contrast agents for characterising tumor response to anti-angiogenic treatment

被引:18
作者
Rix, Anne [1 ,2 ]
Lederle, Wiltrud [1 ,2 ]
Siepmann, Monica [3 ,4 ]
Fokong, Stanley [1 ,2 ]
Behrendt, Florian F. [5 ]
Bzyl, Jessica [1 ,2 ]
Grouls, Christoph [1 ,2 ]
Kiessling, Fabian [1 ,2 ]
Palmowski, Moritz [1 ,2 ,5 ]
机构
[1] Dept Expt Mol Imaging, D-52074 Aachen, Germany
[2] Rhein Westfal TH Aachen, Aachen, Germany
[3] Dept Med Engn, D-44780 Bochum, Germany
[4] Ruhr Univ Bochum, Bochum, Germany
[5] Dept Nucl Med, D-52074 Aachen, Germany
关键词
Ultrasound; Microbubbles; High frequency waves; Tumor; Treatment monitoring; Rodents imaging; ANTIANGIOGENIC THERAPY; MICROBUBBLES; XENOGRAFTS; PERFUSION;
D O I
10.1016/j.ejrad.2011.10.004
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Purpose: To compare non-enhanced and contrast-enhanced high-frequency 3D Doppler ultrasound with contrast-enhanced 2D and 3D B-mode imaging for assessing tumor vascularity during antiangiogenic treatment using soft-shell and hard-shell microbubbles. Materials and methods: Antiangiogenic therapy effects (SU11248) on vascularity of subcutaneous epidermoid-carcinoma xenografts (A431) in female CD1 nude mice were investigated longitudinally using non-enhanced and contrast-enhanced 3D Doppler at 25 MHz. Additionally, contrast-enhanced 2D and 3D B-mode scans were performed by injecting hard-shell (poly-butyl-cyanoacrylate-based) and soft-shell (phospholipid-based) microbubbles. Suitability of both contrast agents for high frequency imaging and the sensitivity of the different ultrasound methods to assess early antiangiogenic therapy effects were investigated. Ultrasound data were validated by immunohistology. Results: Hard-shell microbubbles induced higher signal intensity changes in tumors than soft-shell microbubbles in 2D B-mode measurements (424 +/- 7 vs. 169 +/- 8 A.U.; p < 0.01). In 3D measurements, signals of soft-shell microbubbles were hardly above the background (5.48 +/- 4.57 vs. 3.86 +/- 2.92 A.U.), while signals from hard-shell microbubbles were sufficiently high (30.5 +/- 8.06 A.U). Using hard-shell microbubbles 2D and 3D B-mode imaging depicted a significant decrease in tumor vascularity during antiangiogenic therapy from day 1 on. Using soft-shell microbubbles significant therapy effects were observed at day 4 after therapy in 2D B-mode imaging but could not be detected in the 3D mode. With non-enhanced and contrast-enhanced Doppler imaging significant differences between treated and untreated tumors were found from day 2 on. Conclusion: Hard-shell microbubble-enhanced 2D and 3D B-mode ultrasound achieved highest sensitivity for assessing therapy effects on tumor vascularisation and were superior to B-mode ultrasound with soft-shell microbubbles and to Doppler imaging. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:2710 / 2716
页数:7
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