Stefanie Kuntz-Hehner

Feasibility of the flash-replenishment concept in renal tissue : Which parameters affect the assessment of the contrast replenishment?

The purpose of the study was to evaluate whether power pulse inversion (PPI) and pulse inversion (PI) techniques allow the measurement of indices of microcirculatory flow in real-time at low emission power using contrast microbubbles. PPI and PI imaging were performed in a kidney perfusion model during continuous infusion of Definity (0.12 mL/min). At steady state of tissue enhancement, contrast was destroyed by emission of echo bursts at high emission power (MI = 1.3). Consecutively, contrast replenishment was assessed at low emission power (MI = 0.09) in real-time imaging modes (PPI: 12 Hz; PI: 25 Hz). Regions-of-interest (ROI) of variable sizes were placed in the renal cortex and bigger arteries to compare replenishment of macro- and microcirculation. Nonlinear curve fitting was performed using the mathematical model y=s+A(1-e(-betat)), with A as the parameter describing blood volume and beta as a parameter describing the speed of microbubble contrast replenishment. Replenishment curves could be visually appreciated and quantitatively analyzed in all renal segments. A was significantly higher in bigger arteries compared to renal cortex (p < 0.001). beta was found to be significantly higher in the arteries as compared to the cortex (p < 0.001). The SD of beta diminishes with increasing size of the ROI. The acquisition of replenishment curves following ultrasound (US)-induced destruction of contrast microbubbles is feasible at low power using PPI and PI. Assessment of replenishment kinetics allows the differentiation between macro- and microcirculation. Size and position of the ROI have an important impact on the generation of replenishment curves in both imaging modalities, which has to be taken into account.

Blood flow assessment by ultrasound-induced destruction of echocontrast agents using harmonic power Doppler imaging: which parameters determine contrast replenishment curves?

Objective: To evaluate the feasibility of flow determinations by contrast replenishment using harmonic power Doppler imaging (H‐PDI). Background: The application of indicator dilution principles on contrast echocardiography is limited by numerous methodical problems. Recently, a new method was introduced that relies on ultrasound‐mediated microbubble destruction and evaluation of the contrast replenishment. Methods: Definity, a perfluorocarbon‐derived contrast agent under development, was continuously infused into a steady flow phantom and H‐PDI registrations were performed within a silicone tube (d = 8 mm). Replenishment interval between destruction and imaging frame was varied from 0.04–2 seconds. Nonlinear curve fitting was performed using an exponential mathematical model. Results: Strong linear correlation between contrast dose and maximum signal intensity as well as between flow and the slope variable β of the replenishment curve was found for all settings (r > 0.96). Maximum signal intensity and contrast replenishment rate were found to be a function of emission power and were significantly influenced by depth and focus position. Conclusion: The feasibility of flow assessment using replenishment curves obtained by H‐PDI was demonstrated. However, in experimental conditions, flow analysis was severely influenced by ultrasound system settings and imaging conditions such as emission power, sound field geometry, and investigation depth. For a clinical use of this promising approach, algorithms that take specific system settings and imaging conditions into account have to be found. Imaging modalities that enable a most homogeneous scan field are best suited for the assessment of contrast replenishment.

Myocardial Contrast Echocardiography Enhances Long-Term Prognostic Value of Supine Bicycle Stress Two-Dimensional Echocardiography

BACKGROUND The aim of this study was to determine the incremental prognostic value of myocardial contrast echocardiography (MCE) over two-dimensional echocardiography (2DE) in patients undergoing supine bicycle stress. METHODS Eighty-four patients with known or suspected coronary artery disease who underwent supine bicycle stress with 2DE and MCE (mean age, 58.5 +/- 9.7 years; 68 men) were followed up for 48.3 +/- 8.9 months for cardiac death (n = 1), nonfatal myocardial infarction (n = 9), and revascularization (n = 20). RESULTS In sequential Cox models, the predictive power of the clinical model was strengthened by 2DE (chi(2) = 7.73 vs 12.92, P = .02) and further improved by MCE (chi(2) = 19.04, P = .01). On multivariate analysis, the only independent follow-up event predictor was ischemia on MCE (hazard ratio, 6.79; 95% confidence interval, 2.02-22.82; P = .001). Among patients with normal results on 2DE, those with normal results on MCE had greater 4.5-year event-free survival than those with abnormal results on MCE (93% vs 69%, P = .01). CONCLUSIONS MCE enhances the predictive power of supine bicycle stress 2DE and allows the risk stratification of patients with normal results on 2DE.

Real time myocardial contrast echocardiography during supine bicycle stress and continuous infusion of contrast agent. Cutoff values for myocardial contrast replenishment discriminating abnormal myocardial perfusion.

Background: Myocardial contrast echocardiography (MCE) is a new imaging modality for diagnosing coronary artery disease (CAD). Objective: The aim of our study was to evaluate feasibility of qualitative myocardial contrast replenishment (RP) assessment during supine bicycle stress MCE and find out cutoff values for such analysis, which could allow accurate detection of CAD. Methods: Forty‐four consecutive patients, scheduled for coronary angiography (CA) underwent supine bicycle stress two‐dimensional echocardiography (2DE). During the same session, MCE was performed at peak stress and post stress. Ultrasound contrast agent (SonoVue) was administered in continuous mode using an infusion pump (BR‐INF 100, Bracco Research). Seventeen‐segment model of left ventricle was used in analysis. MCE was assessed off‐line in terms of myocardial contrast opacification and RP. RP was evaluated on the basis of the number of cardiac cycles required to refill the segment with contrast after its prior destruction with high‐power frames. Determination of cutoff values for RP assessment was performed by means of reference intervals and receiver operating characteristic analysis. Quantitative CA was carried out using CAAS system. Results: MCE could be assessed in 42 patients. CA revealed CAD in 25 patients. Calculated cutoff values for RP‐analysis (peak‐stress RP >3 cardiac cycles and difference between peak stress and post stress RP >0 cardiac cycles) provided sensitive (88%) and accurate (88%) detection of CAD. Sensitivity and accuracy of 2DE were 76% and 79%, respectively. Conclusions: Qualitative RP‐analysis based on the number of cardiac cycles required to refill myocardium with contrast is feasible during supine bicycle stress MCE and enables accurate detection of CAD.

Echoscintigraphy: a new imaging modality for the reduction of color blooming and acoustic shadowing in contrast sonography

The purpose of this study was to develop and evaluate a new imaging modality (echoscintigraphy) to reduce color blooming and acoustic shadowing in contrast sonography. After injection of various amounts (700 to 40,000 bubbles/mL) of the echo contrast agent SH-U 563A into a flow phantom, artificial vessels were insonated in the intermittent harmonic-power Doppler imaging (H-PDI) mode. The receive gain was varied from 50% to 75%. The cross-sectional area (CSA) of the tube was assessed using a new summation algorithm (echoscintigraphy) and a conventional single-frame analysis (S-FA) of the H-PDI-signals. Echoscintigraphy is based on the recording and summation of low-intensity signals that are emitted during the ultrasound (US)-induced destruction of microbubbles. Application of the summation algorithm at low-contrast concentration allowed a gain-independent automatic calculation of the CSA at medium and high gain settings. Using the S-FA method, the assessment of the vessel diameter and the CSA was gain-dependent and allowed correct measurements only from 60% to 65% gain. At a high receive-gain and high contrast concentration, S-FA resulted in an overestimation of the CSA up to 35.5%. Echoscintigraphy allows correct display of contrast-filled vessels over a wide range of gain settings at low contrast concentrations, where S-FA does not adequately display echo contrast. Thus, echoscintigraphy minimizes artefacts resulting from color blooming and acoustic shadowing.

Impact of previous myocardial infarction on the incremental value of myocardial contrast to two-dimensional supine bicycle stress echocardiography in evaluation of coronary artery disease

BACKGROUND If compared to two-dimensional echocardiography (2DE), myocardial contrast echocardiography (MCE) improves detection of coronary artery disease (CAD) during pharmacological stress, but data on MCE vs. 2DE during supine bicycle stress is limited. Although previous myocardial infarction (MI) influences sensitivity of 2DE, its effect on MCE has not been evaluated. OBJECTIVES The study sought to determine the incremental benefit of MCE over 2DE for evaluation of CAD during supine bicycle stress and to assess the impact of previous MI on diagnostic values of both methods. METHODS We studied 103 consecutive patients scheduled for coronary angiography. Prior to coronary angiography, all patients underwent supine bicycle stress. 2DE and MCE were performed during this stress test. The diagnosis of obstructive CAD (> or =50% stenosis) was based on the presence of inducible wall motion and perfusion abnormalities. RESULTS Quantitative coronary angiography revealed > or =50% stenosis in 53 of 77 patients without previous MI and in 21 of 26 patients with previous MI. If compared to 2DE, MCE was more sensitive (68% vs. 86%; p<0.001) and more accurate (73% vs. 86%; p < 0.001) to detect > or =50% stenosis. In patients without previous MI, 2DE and MCE yielded sensitivity of 65% and 85% (p < 0.01) and accuracy of 71% and 85% (p < 0.01), whereas in patients with previous MI sensitivity was 79% and 90% (p=NS) and accuracy 79% and 88% (p = NS), respectively. CONCLUSIONS MCE enhances sensitivity and accuracy of 2DE in detection of obstructive CAD during supine bicycle stress. The incremental benefit of MCE is especially present in patients without previous MI.