Estimation of intra-operator variability in perfusion parameter measurements using DCE-US

Abstract

AIM:To investigate intra-operator variability of semiquantitative perfusion parameters using dynamic contrast-enhanced ultrasonography (DCE-US), following bolus injections of SonoVue ® . METHODS:The in vitro experiments were conducted using three in-house sets up based on pumping a fluid through a phantom placed in a water tank. In the in vivo experiments, B16F10 melanoma cells were xenografted to five nude mice. Both in vitro and in vivo , images were acquired following bolus injections of the ultrasound contrast agent SonoVue ® (Bracco, Milan, Italy) and using a Toshiba Aplio ® ultrasound scanner connected to a 2.9-5.8 MHz linear transducer (PZT, PLT 604AT probe) (Toshiba, Japan) allowing harmonic imaging ("Vascular Recognition Imaging") involving linear raw data. A mathematical model based on the dye-dilution theory was developed by the Gustave Roussy Institute, Villejuif, France and used to evaluate seven perfusion parameters from time-intensity curves. Intra-operator variability analyses were based on determining perfusion parameter coefficients of variation (CV). RESULTS:In vitro , different volumes of SonoVue ® were tested with the three phantoms: intra-operator variability was found to range from 2.33% to 23.72%.In vivo , experiments were performed on tumor tissues and perfusion parameters exhibited values ranging from 1.48% to 29.97%. In addition, the area under the curve (AUC) and the area under the wash-out (AUWO) were two of the parameters of great interest since throughout in vitro and in vivo experiments their variability was lower than 15.79%. CONCLUSION:AUC and AUWO appear to be the most reliable parameters for assessing tumor perfusion using DCE-US as they exhibited the lowest CV values.

Impact of the arterial input function on microvascularization parameter measurements using dynamic contrast-enhanced ultrasonography

“…Following bolus injections of SonoVue ® , several harmonic images were acquired. Image analysis followed a protocol described in previous studies [27,28] using dedicated software called CHIQ ® (Toshiba). Thus, the current method allowed one to graphically extract semi-quantitative microvascularization parameters following the fitting of the tumor TIC based on minimizing the differences between the parameters of the raw curve and the coefficients of the IGR equation (Patent: WO/2008/053268 entitled "Method and system for quantification of tumoral vascularization"): I(t) describes the variation in the intensity of contrast uptake as a function of time.…”

“…Semi-quantitative microvascularization parameters have already been described in previous studies [27,28] . These are PI, the time to peak intensity (TPI), the area under the curve (AUC), the wash-in (AUWI), the wash-out (AUWO) and the full width at half maximum (FWHM) (Figure 1 [12] ).…”

“…The deconvolution method developed in our lab and dedicated to the DCE-US imaging is based on the Tikhonov regularization and was previously described by Gauthier et al [12] . Three quantitative microvascularization parameters are thus graphically extracted from the residue function: the BF, the tissue blood volume (BV) and the mean transit time (MTT) (Figure 2 [27] ).…”

“…To minimize potential errors due to SonoVue ® residues, all of the injection materials were changed before each injection: the circuit was entirely emptied, rinsed and reset with water. Thus no contrast agent residues were present in the circuit, allowing the initial conditions to be exactly the same throughout all of the experiments [27] . Before the series of acquisitions, a Doppler image was acquired to help the operator image the same setup through all the experiments.…”

“…Variations in flow rates were controlled using the peristaltic pump. [12,27] ) of five mice through a subcutaneous injection of 2 × 10 6 melanoma cells in 0.2 mL of phosphate buffered saline. DCE-US exams were performed following three 0.1 mL injections of SonoVue ® according to the methodology used in our lab.…”