Reproducibility of quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound.

OBJECTIVES: The aim of this clinical study was to evaluate the reproducibility of quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound. METHODS: Fifteen patients with colorectal liver metastases and 5 volunteers were studied. The hepatic artery proper and the portal vein were imaged simultaneously with dynamic contrast-enhanced ultrasound. The examination was repeated with 2 different contrast bolus volumes (1.2 and 2.4 mL), and time-intensity curves were formed from dynamic contrast-enhanced ultrasound image loops. The rise time, peak intensity, and wash-in slope were derived from hepatic artery and portal vein time-intensity curves. Inter-reader, intra-reader, and inter-scan agreement was assessed by 2 independent readers. Quantitative (intraclass correlation coefficients and coefficients of variation [CVs]) and qualitative (Landis and Koch classification) analyses were performed. RESULTS: Intra-reader and inter-reader agreement was "almost perfect" for the hepatic artery (CV, 10%-15% and 8%-9%, respectively), portal vein (CV, 5%-8% and 6%-12%), and hepatic artery/portal vein ratio (CV, 8%-14% and 10%-15%) measurements of 3 all studied parameters. In contrast, inter-scan agreement was only "slight" to "moderate" (CV, 25%-27%) and "fair" to "moderate" (CV, 19%-24%) for rise time and peak intensity measurements in the hepatic artery and portal vein, respectively. CONCLUSIONS: Quantitative assessment of altered hepatic hemodynamics with dynamic contrast-enhanced ultrasound is reproducible provided that measurements in the hepatic artery are normalized by those in the portal vein.

In vitro evaluation of the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves.

The objective of this study was to assess in vitro the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves formed from dynamic contrast-enhanced ultrasound image loops. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and two transducers (L9-3 linear and C5-1 curvilinear). The following ultrasound scanner settings were investigated, along with contrast bolus volume: contrast-specific nonlinear pulse sequence, gain, mechanical index, focal zone depth, acoustic pulse center frequency and bandwidth. Four parameters (rise time, mean transit time, peak intensity, and area under the curve) were derived from time-intensity curves which were obtained after pixel by pixel linearization of log-compressed data (also referred to as video data) included in a region of interest. Rise time was found to be the parameter least impacted by changes to ultrasound scanner settings and contrast bolus volume; the associated coefficient of variation varied between 0.7% and 6.9% while it varied between 0.8% and 19%, 12% and 71%, and 9.2% and 66%, for mean transit time, peak intensity, and area under the curve, respectively. The present study assessed the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curve analysis. One should be aware of these issues to standardize their technique in each specific organ of interest and to achieve accurate, sensitive, and reproducible data using dynamic contrast-enhanced ultrasound. One way to mitigate the impact of ultrasound scanner settings in longitudinal, multi-center quantitative dynamic contrast-enhanced ultrasound studies may be to prohibit any adjustments to those settings throughout a given study. Further clinical studies are warranted to confirm the reproducibility and diagnostic or prognostic value of time-intensity curve parameters measurements in a particular clinical scenario of interest, for example that of cancer patients undergoing vascular targeting therapies.

Assessment of global liver blood flow with quantitative dynamic contrast-enhanced ultrasound.

OBJECTIVES: This study assessed the potential of quantitative analysis of contrast bolus kinetics to reflect global liver blood flow. METHODS: A dynamic contrast-enhanced ultrasound flow phantom was developed. A peristaltic pump established constant volume flow ranging between 16.5 and 49.5 mL/min (2-mm tube) and 85.5 and 256.5 mL/min (5-mm tube). After bolus injection of 2 doses of a contrast agent, a region of interest was drawn over the cross section of the tube used for a particular acquisition; the rise time, peak intensity, and wash-in slope were derived from time-intensity curves. Twenty healthy volunteers and 25 patients with biopsy-proven colorectal liver metastases were scanned with dynamic contrast-enhanced ultrasound. The rise time, peak intensity, and wash-in slope were derived from hepatic artery and portal vein time-intensity curves. Hepatic artery/portal vein ratios of the parameters were also calculated. RESULTS: In the in vitro experiment, the rise time decreased while the peak intensity and wash-in slope increased with increasing volume flow for both tube diameters and contrast bolus volumes. In the clinical study, the rise time was lowered in the hepatic artery but elevated in the portal vein, and the peak intensity and wash-in slope were elevated in the hepatic artery but lowered in the portal vein in patients with colorectal liver metastases compared with healthy volunteers, although not in a statistically significant manner. This finding was consistent with an increase in hepatic artery blood flow, a decrease in portal vein blood flow, or both in patients with colorectal liver metastases compared with healthy volunteers. Only the 3 hepatic artery/portal vein ratios of the parameters achieved statistical significance in differentiating healthy volunteers from patients with colorectal liver metastases (P < .05). CONCLUSIONS: Surrogate measurements of liver blood flow may be derived from quantitative analysis of dynamic contrast-enhanced ultrasound studies. They may have potential for quick and easy assessment of altered hepatic hemodynamics.

Perfusion quantification using dynamic contrast-enhanced ultrasound: the impact of dynamic range and gain on time-intensity curves.

The objective of this study was to assess the impact of dynamic range and gain on perfusion quantification using linearized log-compressed data. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and a C5-1 curvilinear transducer using a contrast-specific nonlinear pulse sequence (power modulation) at 1.7MHz. Clinical dynamic contrast-enhanced ultrasound image loops of liver tumors were also collected for preliminary validation of the in vitro findings. Time-intensity curves were extracted from image loops with two different approaches: from linearized log-compressed data and from linear (uncompressed) data. The error of time-intensity curve parameters derived from linearized log-compressed data (deviation from linear data) was found to be less than 2.1% and 5.4% for all studied parameters in the in vitro experiment and in the clinical study, respectively, when a high dynamic range setting (at least 50dB on the iU22) is used. The gain must be carefully adjusted to ensure a high signal-to-noise ratio and to avoid signal saturation. From the time-intensity curve analysis it was also found that rise time of the bolus time-intensity curve is the least variable of all the studied time-intensity curve parameters.