Harald Becher

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.

Prevalence of left atrial chamber and appendage thrombi in patients with atrial flutter and its clinical significance.

OBJECTIVESnThe study was done to assess the prevalence of left atrial (LA) chamber and appendage thrombi in patients with atrial flutter (AFl) scheduled for electrophysiologic study (EPS), to evaluate the prevalence of thromboembolic complications after transesophageal echocardiographic (TEE)-guided restoration of sinus rhythm and to evaluate clinical risk factors for a thrombogenic milieu.nnnBACKGROUNDnRecent studies showed controversial results on the prevalence of atrial thrombi and the risk of thromboembolism after restoring sinus rhythm in patients with AFl.nnnMETHODSnBetween 1995 and 1999, patients with AFl who were scheduled for EPS were included in the study. After transesophageal assessment of the left atrial appendage and exclusion of thrombi, an effective anticoagulation was initiated and patients underwent EPS within 24 h.nnnRESULTSnWe performed 202 EPSs (radiofrequency catheter ablation, n = 122; overdrive stimulation, n = 64; electrical cardioversion, n = 16) in 139 consecutive patients with AFl. Fifteen patients with a thrombogenic milieu were identified. All of them had paroxysmal atrial fibrillation (AF). Transesophageal echocardiography revealed LA thrombi in two cases (1%). After EPS no thromboembolic complications were observed. Diabetes mellitus, arterial hypertension and a decreased left ventricular ejection fraction were found to be independent risk factors associated with a thrombogenic milieu.nnnCONCLUSIONSnThe findings of a low prevalence of LA appendage thrombi (1%) in patients with AFl and a close correlation between a history of previous embolism and paroxysmal AF support the current guidelines that patients with pure AFl do not require anticoagulation therapy, whereas patients with AFl and paroxysmal AF should receive anticoagulation therapy. In addition, the presence of clinical risk factors should alert the physician to an increased likelihood for a thrombogenic milieu.

Right atrial appendage thrombosis in atrial fibrillation: its frequency and its clinical predictors

This study assesses the incidence of right atrial (RA) chamber and appendage thrombosis in patients with atrial fibrillation (AF) in relation to RA appendage morphology and function. Transthoracic and multiplane transesophageal echocardiography were performed in 102 patients with AF to assess the incidence of RA and left atrial (LA) thrombi and spontaneous echo contrast. Both right and left ventricular sizes, atrial chamber and appendage sizes and function were measured. Twenty-two patients in sinus rhythm served as the control group (SR). Complete visualization of the RA appendage was feasible in 90 patients with AF. Patients with AF had lower tricuspid annular excursion (p = 0.008) and larger RA chamber area (p = 0.0001) than patients in SR. In addition, RA appendage areas were larger (p <0.05) and RA ejection fraction and peak emptying velocities (both p <0.0001) were lower in patients with AF patients than in those in SR. Equivalent differences were found for the LA appendage. Six thrombi were found in the RA appendage and 11 thrombi in the LA appendage in AF patients. Spontaneous echo contrast was found in 57% and 66% in the right atrium and in the left atrium, respectively. AF patients with RA appendage thrombi had a larger RA area (p = 0.0001), and lower RA appendage ejection fraction and emptying velocities (both p = 0.0001) than patients without thrombi. Spontaneous echo contrast was detected in all patients with thrombi. Spontaneous echo contrast was the only independent predictor of RA (p = 0.03) and LA appendage thrombosis (p = 0.036). In conclusion, multiplane transesophageal echocardiography allows the assessment of RA appendage morphology and function. RA spontaneous echo contrast is the only independent predictor of RA appendage thrombosis.

Stimulated acoustic emission: pseudo-Doppler shifts seen during the destruction of nonmoving microbubbles.

The purpose of this study was to evaluate the appearance and the characteristics of stimulated acoustic emission (SAE) as an echo contrast-specific color Doppler phenomenon with impact on myocardial contrast echocardiography (MCE). Stationary microbubbles of the new contrast agent SH-U 563A (Schering AG) were embedded within a tissue-mimicking gel material. Harmonic power Doppler imaging (H-PDI), color Doppler and pulse-wave Doppler data were acquired using an HDI-5000 equipped with a phased-array transducer (1.67/3.3 MHz). In color Doppler mode, bubble destruction resulted in random noise like Doppler signals. PW-Doppler revealed short pseudo-Doppler shifts with a broadband frequency spectrum. Quantification of SAE events by H-PDI demonstrated an exponential decay of signal intensities over successive frames. A strong linear relationship was found between bubble concentration and the square root of the linearized H-PDI signal for a range of concentrations of more than two orders of magnitude (R = 0.993, p < 0.0001). Intensity of the H-PDI signals correlated well with emission power (R = 0.96, p = 0.0014). SAE results from disintegration of microbubbles and can be demonstrated by all Doppler imaging modalities, including H-PDI. Intensity of SAE signals is influenced by the applied acoustic power and correlates highly with the concentration of microbubbles. Because intensity of SAE signals correlates highly with echo contrast concentrations, analysis of SAE signals might be used for quantitative MCE.

Stimulated Acoustic Emission Detected by Transcranial Color Doppler Ultrasound A Contrast-Specific Phenomenon Useful for the Detection of Cerebral Tissue Perfusion

BACKGROUND AND PURPOSEnExperimental and clinical data suggest that insonation of echo-contrast agents with high acoustical power produces disintegration of microbubbles, resulting in a pseudo-Doppler phenomenon called stimulated acoustic emission (SAE). The purpose of this study was to investigate whether SAE might be detected by transcranial color Doppler imaging and whether these signals might be used for cerebral tissue perfusion measurements.nnnMETHODSnNonmoving microbubbles (SHU 563 A) were insonated in vitro through the temporal parts of a human cadaver skull, and contrast signals were detected by velocity-coded color Doppler and power Doppler recordings. Transcranial color as well as power Doppler investigations were performed in 10 healthy volunteers with the echo-contrast agent Levovist (SHU 508 A).nnnRESULTSnColor Doppler signals indicating SAE were observed in vitro and in transcranial human investigations. These signals were characterized by a mosaic of color Doppler pixels ranging over the full color scale. Apparent velocity information and spatial distribution of SAE signals changed from image frame to image frame. In the experimental model, the intensity of SAE signals decreased exponentially over time. With an increase of acoustic power, there was a significant increase of the maximum signal intensity (P<0.01) and a significantly shortened signal duration (P<0.01), consistent with stronger and more rapid disintegration. In humans, SAE signals were clearly detected in cerebral tissue regions. The intensity of SAE signals in those regions (eg, temporal cortex, 3.7+/-1.2 dB) was approximately 8 times lower than the signal enhancement in the major cerebral arteries (eg, in the MCA, 29.5+/-5.6).nnnCONCLUSIONSnEcho-contrast specific color Doppler signals known as SAE are detectable by transcranial color and power Doppler sonography. Signals due to SAE might represent tissue perfusion, thereby providing a method for imaging flow with transcranial ultrasound.

On the design of a capillary flow phantom for the evaluation of ultrasound contrast agents at very low flow velocities.

Recently, a new imaging technology has become available that allows the evaluation of tissue perfusion using echo-contrast agents in real-time imaging: power pulse inversion imaging (PPI). Although numerous in vitro phantoms have been designed for different imaging modalities in ultrasound (US), there is a need for a phantom that mimics microcirculation and allows, in particular, the assessment of contrast replenishment kinetics following US-induced destruction of microbubbles using the new method. We, therefore, designed a new capillary flow phantom that takes the requirements of the new US imaging techniques and the physical properties of microbubbles into account and serves flow velocities in the range of microcirculation (1 to 10 mm/s). PPI studies were performed in the newly designed phantom. The contrast agent used was AF0150. We studied homogeneity of contrast distribution within the capillary phantom, constancy of contrast infusion, the dose-effect relationship and, finally, the feasibility of flow assessment using the method of contrast replenishment following US-induced microbubble destruction in a flow velocity range of 2.1 to 9.45 mm/s. Analysis of the replenishment kinetics was performed using the mathematical model f(t) = A(1 - e(-beta t)), with A representing the blood volume and beta the microbubble velocity. The new capillary phantom allowed homogeneous contrast opacification within the perfused capillaries independently of the flow. Constancy of signal intensity was achieved over a time period of almost 2 h, indicating constant contrast delivery. A strong linear correlation between the PPI signal and the contrast dose was found (r = 0.998). Analysis of the replenishment parameters revealed a strong linear relationship between parameter beta and flow (r = 0.994) as well as A * beta and flow (r = 0.984) in the observed flow range. The newly designed perfusion phantom for the evaluation of echo-contrast replenishment kinetics fulfills, at very low flow velocities, important prerequisites such as constancy of contrast delivery, homogeneity of contrast signals, linear dose-effect relation and minimal attenuation. Thus, the new phantom allows standardized analysis of contrast replenishment kinetics using real-time perfusion imaging techniques at flow velocities comparable to those of the microcirculation.

Enhancement of mitral regurgitation and normal left atrial color Doppler flow signals with peripheral venous injection of a saccharide-based contrast agent

OBJECTIVESnThe saccharide ultrasound contrast agent SHU 508 A was used to test the hypothesis that an intravenous, transpulmonary contrast method can enhance color Doppler flow signals in the left atrium in a clinically useful manner.nnnBACKGROUNDnColor Doppler display of mitral regurgitation may be unreliable because of variable signal to noise ratios that are at times poor. Traditional contrast agents enhance color Doppler flow signals in the right heart chambers. This study describes our observation of a recently developed contrast agent, SHU 508 A, capable of pulmonary transit after peripheral venous injection.nnnMETHODSnControl subjects (n = 10) and patients with suspected mitral regurgitation (n = 23) were studied by color Doppler flow imaging before and after 3-g intravenous doses of SHU 508 A. Reference grading of mitral regurgitation (0 to 3) was formulated from left ventricular angiography. In the four-chamber view of the left atrium, we selected for analysis the systolic frame with the maximal retrograde jet of mitral regurgitation (aliased/blue) and the diastolic frame with the maximal color coding from anterograde pulmonary venous flow (red) for planimetry and for grading the intensity of the color Doppler signal (0 to 5).nnnRESULTSnThe score of the color Doppler signal intensity increased by > or = 2.5 after 3 g of SHU 508 A (p < 0.001). Flow detection improved, as shown by the increased jet area of mitral regurgitation (> or = 170%), after 3 g of SHU 508 A (3 +/- 3 vs. 12 +/- 8 cm2, p < 0.001) and by a > or = 200% increase in normal anterograde flow area (p < 0.001) in both the mitral regurgitation group and the control group. After contrast enhancement, the correlation between angiographic grading and the relation of jet area to the left atrial area increased from r = 0.79 to r = 0.91.nnnCONCLUSIONSnContrast-mediated increased echogenicity of the left atrial blood pool improves the signal to noise ratio of Doppler images of mitral regurgitation and anterograde atrial flow. The technique is safe and simple and seems to minimize variability due to instrument design and anatomic signal attenuation.

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.

The impact of emission power on the destruction of echo contrast agents and on the origin of tissue harmonic signals using power pulse-inversion imaging.

The purpose of this study was to determine the impact of emission power on ultrasound (US)-induced destruction of echocontrast microbubbles during real-time power pulse inversion imaging (PPI) in myocardial contrast echocardiography (MCE) and to evaluate the magnitude of noncontrast PPI signals arising from myocardial tissue at variable emission power to define the cut-off emission power for optimal MCE using low power technologies. In vitro studies were performed in a flow phantom using Optison, Definity and AFO 150. PPI signal intensity during real-time imaging at 27 Hz was compared with intermittent imaging at 0.1 Hz to evaluate bubble destruction at variable emission power (MI: 0.09 to 1.3). In healthy volunteers, PPI signal intensities during constant infusion of Optison(R) was studied in real-time PPI 22 HZ and during intermittent imaging triggered end-systolic frames every, every 3rd and every 5th cardiac cycle. In addition, the impact of emission power on nonlinear PPI signals from myocardial structures was studied. In vitro, there was a 40% decrease of real-time PPI signal intensity for Optison and AFO 150 at lowest emission power (0.09), whereas no signal loss was observed for Definity. Increase of emission power resulted in a faster decay for Optison(R) and AFO 150 as compared to Definity. In vivo, real-time PPI during continuous infusion of Optison(R) resulted in a 40% decrease of myocardial signal intensity as compared to intermittent imaging every 5th cardiac cycle, even at lowest possible emission power (mechanical index = 0.09). There was a strong positive relationship between MI and noncontrast myocardial PPI signals in all myocardial segments. PPI signal intensity was found to be lower than 1 dB only for extremely low emission power (MI < 0.2). Destruction of microbubbles during real-time imaging by use of PPI at low emission power varies considerably for different echo contrast agents. However, bubble destruction and the onset of tissue harmonic signals focus the use of real-time perfusion imaging to very low emission power.

In vitro, animal, and human characterization of OPTISON infusions for myocardial contrast echocardiography.

UNLABELLEDnTraditionally, performing myocardial contrast echocardiography with OPTISON required maximal bolus dosing. However, sustained and consistent opacification of the myocardium would be preferable for perfusion imaging.nnnMETHODSnImages of 5 anesthetized dogs and 6 human volunteers were obtained with a second harmonic ultrasound system during bolus administration of OPTISON and 2 infusion techniques. One infusion technique used diluted OPTISON, and the other used the buoyant properties of OPTISON microspheres by placing the contrast agent between an infusion source and the intravenous site in a vertically oriented extension line (ELT). Myocardial intensities and in vitro microsphere characteristics were analyzed to assess the consistency of microsphere delivery over time.nnnRESULTSnIn addition to providing higher myocardial opacification intensity than diluted infusions, ELT infusions provided consistent microsphere concentration, phantom enhancement, and near-peak bolus-level myocardial opacification for 7 to 15 minutes. The myocardial intensity at 3 and 5 minutes in human subjects during ELT infusions (30 mL/h; 2.5 mL) was lower (220 arbitrary units [au] and 165 au, respectively) but not significantly different (P =.3 and.1, respectively) than the peak myocardial intensity (265 au) after bolus administration.nnnCONCLUSIONnThis new ELT infusion method provides an acceptable alternative to bolus administration of OPTISON for prolonged myocardial opacification.