Study of the reliability of quantification methods of dynamic contrast-enhanced ultrasonography: numerical modeling of blood flow in tumor microvascularization.

Dynamic contrast-enhanced ultrasonography is a recent functional dynamic imaging technique that allows evaluation of the efficacy of anti-angiogenic treatments by quantifying changes in specific parameters of the tumor vasculature. Preclinical and clinical experimental studies now reveal the existence of sources of variability in the quantitative methods. In order to study the reliability of quantification methods (both semi-quantitative and quantitative), we have developed the first numerical model of blood flow and contrast agents in vascular networks with computational fluid dynamics Fluent software version 15.0 (ANSYS, France). We studied four vascular networks (1.84 × 10-3, 2.28 × 10-3, 2.4 × 10-3 and 2.54 × 10-3 ml) and four blood velocities (0.01, 0.02, 0.03 and 0.05 m s-1). For variations in tumor vascular volume the quantitative method is more sensitive, with variations of parameter perfusion of 25.7%, in contrast to variations of the semi-quantitative parameters between 14.9 and 19.5%. For changes in blood velocity the semi-quantitative method is more sensitive, with variation of the area under the enhancement curve (64%), the maximum of the enhancement curve (60%), and the slope of the enhancement curve (73%). The transit time parameters from the two quantitative methods were weakly sensitive to both blood volume and blood flow variations. This study is hopeful and may be extended to the treatment of more complex vascular networks, to approach clinical conditions, and to the evaluation of quantification methods in contrast imaging.

A Novel Microflow Phantom Dedicated to Ultrasound Microvascular Measurements.

Tumor microvascularization is a biomarker of response to antiangiogenic treatments and is accurately assessed by ultrasound imaging. Imaging modes used to visualize slow flows include Power Doppler imaging, dynamic contrast-enhanced ultrasonography, and more recently, microvascular Doppler. Flow phantoms are used to evaluate the performance of Doppler imaging techniques, but they do not have a steady flow and sufficiently small channels. We report a novel device for robust and stable microflow measurements and the study of the microvascularization. Based on microfluidics technology, the prototype features wall-less cylindrical channels of diameters ranging from as small as 147 up to 436 µm, cast in a soft silicone polymer and perfused via a microfluidic flow pressure controller. The device was assessed using flow rates from 49 to 146 µL/min, with less than 1% coefficient of variation over three minutes, corresponding to velocities of 6 to 142 mm/s. This enabled us to evaluate and confirm the reliability of the Superb Microvascular Imaging Doppler mode compared with the Power Doppler mode at these flow rates in the presence of vibrations mimicking physiological motion.