Background: The DCE-US (Dynamic Contrast-Enhanced Ultrasonography) imaging protocol predicts the vascular modifications compared with Response Evaluation Criteria in Solid Tumors (RECIST) based mainly on morphological changes. A quantitative biomarker has been validated through the DCE-US multi-centric study for early monitoring of the efficiency of anti-angiogenic cancer treatments. In this context, the question of transposing the use of this biomarker to other types of ultrasound scanners, probes and settings has arisen to maintain the follow-up of patients under anti-angiogenic treatments. As a consequence, radiologists encounter standardization issues between the different generations of ultrasound scanners to perform quantitative imaging protocols.
Purpose: The aim of this study was to develop a new calibration setup to transpose the DCE-US imaging protocol to the new generation of ultrasound scanners using both abdominal and linear probes.
Methods: This calibration method has been designed to be easily reproducible and optimized, reducing the time required and cost incurred. It is based on an original set-up that includes using a concentration splitter to measure the variation of the harmonic signal intensity, obtained from the Area Under the time-intensity Curve (AUC) as a function of various contrast-agent concentrations. The splitter provided four different concentrations simultaneously ranging from 12.5% to 100% of the initial concentration of the SonoVue contrast agent (Bracco Imaging S.p.A., Milan, Italy), therefore, measuring four AUCs in a single injection. The plot of the AUC as a function of the four contrast agent concentrations represents the intensity variation of the harmonic signal: the slope being the calibration parameter. The standardization through this method implied that both generations of ultrasound scanners had to have the same slopes to be considered as calibrated. This method was tested on two ultrasound scanners from the same manufacturer (Aplio500, Aplioi900, Canon Medical Systems, Tokyo, Japan). The Aplio500 used the settings defined by the initial multicenter DCE-US study. The Mechanical Index (MI) and the Color Gain (CG) of the Aplioi900 have been adjusted to match those of the Aplio500. The reliability of the new setup was evaluated in terms of measurement repeatability, and reproducibility with the agreement between the measurements obtained once the two ultrasound scanners were calibrated.
Results: The new setup provided excellent repeatability measurements with a value of 96.8%. Once the two ultrasound scanners have been calibrated for both types of probes, the reproducibility was excellent with the agreement between their respective quantitative measurement was at the lowest 95.4% and at the best 98.8%. The settings of the Aplioi900 (Canon Medical Systems) were adjusted to match those of the Aplio500 (Canon Medical Systems) and these validated settings were for the abdominal probe: MI = 0.13 and CG = 34 dB; and for the linear probe: MI = 0.10 and CG = 38 dB.
Conclusion: This new calibration setup provided reliable measurements and enabled the rapid transfer and the use of the DCE-US imaging protocol on new ultrasound scanners, thus permitting a continuation of the therapeutic evaluation of patients through quantitative imaging.
Keywords: Dynamic contrast-enhanced ultrasound (DCE-US); Methodologies of ultrasound calibration; Ultrasound contrast agent; phantom.
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