Rationale and objectives: 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.
Materials and 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).
Conclusion: 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.
Copyright 2010 AUR. Published by Elsevier Inc. All rights reserved.