Antiangiogenic tumor treatment: noninvasive monitoring with contrast pulse sequence imaging for contrast-enhanced grayscale ultrasound.
OBJECTIVE
This study was designed to test the feasibility of contrast pulse sequencing imaging for contrast-enhanced grayscale ultrasound in assessing the effects of antiangiogenic therapy.


METHODS
Mice with subcutaneously implanted H22 mouse hepatoma were treated with thalidomide or placebo by oral gavage over 7 days, starting at 24 hours after implantation. Contrast pulse sequencing ultrasound imaging was performed on day 8 to evaluate maximal cross-sectional area and nonenhanced area. Immediately after imaging, mice were euthanized, and tumor tissue was removed for fixation in a 10% formalin solution. The section equivalent to the ultrasound imaging plane was stained with hematoxylin and eosin to allow for the assessment of the largest cross-sectional area and necrotic area.


RESULTS
There was no significant difference in tumor volume between the two groups. The difference of largest cross-sectional area determined by the two methods was not significant between control and treated tumors (P > .05). The nonenhanced area and its percentage evaluated by ultrasound were significantly larger in treated tumors than in control tumors (P < .05). The necrotic area and its percentage estimated by pathology slice were also significantly larger in treated tumors than in control tumors (P < .05). The largest cross-sectional area determined by the two methods was well correlated (r = 0.815, P < .001). There was good correlation between the nonenhanced area on ultrasound and the necrotic area on pathology slides (r = 0.909, P < .001). The percentage of nonenhanced area was well correlated with the percentage of necrotic area (r = 0.910, P < .001).


CONCLUSIONS
Contrast-enhanced grayscale ultrasound with contrast pulse sequencing imaging provides a tool for early monitoring of antiangiogenic treatment of tumors, before apparent change in tumor size.
Zhou
Jianhua
J
Department of Ultrasound, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
Zheng
Wei
W
Cao
Longhui
L
Liu
Min
M
Han
Feng
F
Li
Anhua
A
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D016247:Information Storage and Retrieval / Q000379:methods*; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D051379:Mice; D010743:Phospholipids; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D013459:Sulfur Hexafluoride; D013792:Thalidomide / Q000008:administration & dosage*; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods*
D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013792:Thalidomide; D013459:Sulfur Hexafluoride