Three-dimensional Dynamic Contrast-enhanced US Imaging for Early Antiangiogenic Treatment Assessment in a Mouse Colon Cancer Model

Abstract

q RSNA, 2015 Purpose:To evaluate feasibility and reproducibility of three-dimensional (3D) dynamic contrast material-enhanced (DCE) ultrasonographic (US) imaging by using a clinical matrix array transducer to assess early antiangiogenic treatment effects in human colon cancer xenografts in mice. Materials and Methods:Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care at Stanford University. Three-dimensional DCE US imaging with two techniques (bolus and destruction-replenishment) was performed in human colon cancer xenografts (n = 38) by using a clinical US system and transducer. Twenty-one mice were imaged twice to assess reproducibility. Seventeen mice were scanned before and 24 hours after either antiangiogenic (n = 9) or saline-only (n = 8) treatment. Results:Reproducibility of both 3D DCE US imaging techniques was good to excellent (intraclass correlation coefficient, 0.73-0.86). PE, AUC, rBV, and rBF significantly decreased (P  .04) in antiangiogenic versus saline-treated tumors. rBV (r = 0.74; P = .06) and rBF (r = 0.85; P = .02) correlated with ex vivo percent area of blood vessels, although the statistical significance of rBV was not reached, likely because of small sample size. Overall, 2D DCE-US overestimated and underestimated treatment effects from up to 125-fold to170-fold compared with 3D DCE US imaging. If the central tumor plane was assessed, treatment response was underestimated up to threefold or overestimated up to 57-fold on 2D versus 3D DCE US images. Conclusion:Three-dimensional DCE US imaging with a clinical matrix array transducer is feasible and reproducible to assess tumor perfusion in human colon cancer xenografts in mice and allows for assessment of early treatment response after antiangiogenic therapy.q RSNA, 2015

Early prediction of tumor response to bevacizumab treatment in murine colon cancer models using three-dimensional dynamic contrast-enhanced ultrasound imaging

“…The recent availability of 3D matrix array transducers with volumetric contrast-mode imaging has potentiated 3D DCE-US as a robust technique for assessment of tumor perfusion without sampling errors [10]. A recent study demonstrated that 3D DCE-US allows quantification of early treatment effects [10] and that substantial decreases in tumor perfusion following antiangiogenic treatment can be detected with perfusion parameters [10,11].…”

“…A recent study demonstrated that 3D DCE-US allows quantification of early treatment effects [10] and that substantial decreases in tumor perfusion following antiangiogenic treatment can be detected with perfusion parameters [10,11]. In addition, quantified perfusion parameters were found to correlate well with ex vivo quantification of vascular densities in histological specimens [10,11]. However, whether these early changes of tissue perfusion parameters from 3D DCE-US could also predict treatment response remained unknown.…”

Intra-Animal Comparison between Three-dimensional Molecularly Targeted US and Three-dimensional Dynamic Contrast-enhanced US for Early Antiangiogenic Treatment Assessment in Colon Cancer

“…However, DCE US with current two-dimensional imaging capabilities is suboptimal because it fails to demonstrate the spatial heterogeneity of tumor perfusion, and it is challenging to position the two-dimensional US transducer at the exact same location for longitudinal assessment of tumor response (4–8). This limitation has been addressed by the introduction of three-dimensional (3D) DCE US techniques (9–11). Three-dimensional DCE US enables the assessment of tumor perfusion in a volumetric manner, thereby making this technique more reproducible than two-dimensional DCE US imaging techniques, in particular for the longitudinal assessment of tumor perfusion (11).…”

“…This limitation has been addressed by the introduction of three-dimensional (3D) DCE US techniques (9–11). Three-dimensional DCE US enables the assessment of tumor perfusion in a volumetric manner, thereby making this technique more reproducible than two-dimensional DCE US imaging techniques, in particular for the longitudinal assessment of tumor perfusion (11). …”

In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles

“…Although most US molecular imaging studies have acquired images in a single plane, 3D US is desirable to map the concentration of agent throughout a tumor [47–49]. Matrix arrays, capable of acquiring 3D data sets, are now available, and therefore 3D protocols are of interest.…”