Ischemia/Reperfusion Injury Enhances Accumulation of Perfluoropropane Droplets.

Objective: Perfluoropropane droplets (PD) are nanometer-sized particles that can be formulated from commercially available contrast agents. The preferential retention of PDs in diseased microvascular beds can be detected by ultrasound imaging techniques after acoustic activation and offers an opportunity for the detection of such processes as scar formation or inflammation. We hypothesized that in the presence of ischemia/reperfusion (I/R) injury, retention of intravenously injected PDs would be enhanced.

Acoustic Activation Imaging With Intravenous Perfluoropropane Nanodroplets Results in Selective Bioactivation of the Risk Area.

Background: Acoustically activatable perfluoropropane droplets (PD) can be formulated from commercially available microbubble preparations. Diagnostic transthoracic ultrasound frequencies have resulted in acoustic activation (AA) predominately within myocardial infarct zones (IZ).

Objective: We hypothesized that the AA area following acute coronary ischemia/reperfusion (I/R) would selectively enhance the developing scar zone, and target bioeffects specifically to this region.

Acoustic Detection of Retained Perfluoropropane Droplets Within the Developing Myocardial Infarct Zone.

Perfluoropropane droplets (PDs) cross endothelial barriers and can be acoustically activated for selective myocardial extravascular enhancement following intravenous injection (IVI). Our objective was to determine how to optimally activate extravascular PDs for transthoracic ultrasound-enhanced delineation of a developing scar zone (DSZ). Ultrafast-frame-rate microscopy was conducted to determine the effect of pulse sequence on the threshold of bubble formation from PDs.

Efficacy of Sonothrombolysis Using Acoustically Activated Perflutren Nanodroplets versus Perflutren Microbubbles.

Nanoscale-diameter liquid droplets from commercially available microbubbles may optimize thrombus permeation and subsequent thrombus dissolution (TD). Thrombi were made using fresh porcine arterial whole blood and placed in an in vitro vascular simulation. A diagnostic ultrasound probe in contact with a tissue-mimicking phantom tested intermittent high-mechanical-index (HMI) fundamental multipulse (focused ultrasound [FUS], 1.

Diagnostic Ultrasound High Mechanical Index Impulses Restore Microvascular Flow in Peripheral Arterial Thromboembolism.

We sought to explore mechanistically how intermittent high-mechanical-index (MI) diagnostic ultrasound impulses restore microvascular flow. Thrombotic microvascular obstruction was created in the rat hindlimb muscle of 36 rats. A diagnostic transducer confirmed occlusion with low-MI imaging during an intravenous microbubble infusion.

Improved sonothrombolysis from a modified diagnostic transducer delivering impulses containing a longer pulse duration.

Although guided high-mechanical-index (MI) impulses from a diagnostic ultrasound transducer have been used in preclinical studies to dissolve coronary arterial and microvascular thrombi in the presence of intravenously infused microbubbles, it is possible that pulse durations (PDs) longer than that used for diagnostic imaging may further improve the effectiveness of this approach. By use of an established in vitro model flow system, a total of 90 occlusive porcine arterial thrombi (thrombus age: 3-4 h) within a vascular mimicking system were randomized to 10-min treatments with two different PDs (5 and 20 μs) using a Philips S5-1 transducer (1.6-MHz center frequency) at a range of MIs (from 0.

Diagnostic ultrasound induced inertial cavitation to non-invasively restore coronary and microvascular flow in acute myocardial infarction.

Ultrasound induced cavitation has been explored as a method of dissolving intravascular and microvascular thrombi in acute myocardial infarction. The purpose of this study was to determine the type of cavitation required for success, and whether longer pulse duration therapeutic impulses (sustaining the duration of cavitation) could restore both microvascular and epicardial flow with this technique. Accordingly, in 36 hyperlipidemic atherosclerotic pigs, thrombotic occlusions were induced in the mid-left anterior descending artery.

Microbubble cavitation imaging.

Ultrasound cavitation of microbubble contrast agents has a potential for therapeutic applications such as sonothrombolysis (STL) in acute ischemic stroke. For safety, efficacy, and reproducibility of treatment, it is critical to evaluate the cavitation state (moderate oscillations, stable cavitation, and inertial cavitation) and activity level in and around a treatment area. Acoustic passive cavitation detectors (PCDs) have been used to this end but do not provide spatial information.

Effects of attenuation and thrombus age on the success of ultrasound and microbubble-mediated thrombus dissolution.

The purpose of this study was to examine the effects of applied mechanical index, incident angle, attenuation and thrombus age on the ability of 2-D vs. 3-D diagnostic ultrasound and microbubbles to dissolve thrombi. A total of 180 occlusive porcine arterial thrombi of varying age (3 or 6 h) were examined in a flow system.

Treatment of acute intravascular thrombi with diagnostic ultrasound and intravenous microbubbles.

The purpose of this study was to determine whether high mechanical index (MI) impulses from diagnostic ultrasound (DUS) could dissolve intravascular thrombi using intravenous microbubbles. Using a canine model, DUS was applied during a continuous intravenous infusion of microbubbles. Completely thrombosed grafts were assigned to 2 treatment regimens: low-MI (<0.

Bioeffects considerations for diagnostic ultrasound contrast agents.

Diagnostic ultrasound contrast agents have been developed for enhancing the echogenicity of blood and for delineating other structures of the body. Approved agents are suspensions of gas bodies (stabilized microbubbles), which have been designed for persistence in the circulation and strong echo return for imaging. The interaction of ultrasound pulses with these gas bodies is a form of acoustic cavitation, and they also may act as inertial cavitation nuclei.

Differences in definity and optison microbubble destruction rates at a similar mechanical index with different real-time perfusion systems.

The purpose of this study was to determine microbubble responses to different pulse sequence schemes that exist on low mechanical index (MI) real-time perfusion imaging systems using either intravenous albumin-coated (Optison) or lipid-encapsulated (Definity) microbubbles. A tissue-mimicking phantom was created that permitted insonation of microbubbles at 3 cm (near field) and 9 cm (far field) from the diagnostic transducer face. Differences in effluent microbubble concentration were measured after they passed through vessels being insonified with pulse sequence schemes that transmitted alternating polarity (pulse inversion Doppler), alternating amplitude (power modulation), or both (contrast pulse sequencing) at a similar MI, frame rate, and transmit frequency.

Enhanced retention in the passive-avoidance task by 5-HT(1A) receptor blockade is not associated with increased activity of the central nucleus of the amygdala.

The effect of blockade of 5-HT1A receptors was investigated on (1). retention in a mildly aversive passive-avoidance task, and (2). spontaneous single-unit activity of central nucleus of the amygdala (CeA) neurons, a brain site implicated in modulation of retention.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: 2. Medium dissolved gas (pO2) content.

The data collected in this project supported the a priori hypothesis that the concentration of dissolved oxygen in whole human blood in vitro affected the extent of ultrasound (US)-induced hemolysis under conditions conducive to the occurrence of inertial cavitation. Aliquots of whole human blood in vitro with a relatively high O(2) level had statistically significantly more 1-MHz US-induced hemolysis than aliquots with a relatively low O(2) level in the presence of controlled gas nucleation (Albunex or ALX, supplementation), with US-induced hemolytic yields being substantially less at 2.2- and 3.

Biological and environmental factors affecting ultrasound-induced hemolysis in vitro: 1. HIV macrocytosis (cell size).

This paper reports the results of a further test of the hypothesis that the extent of ultrasound (US)-induced cell lysis in the presence of a US contrast agent to enhance cavitational effects is a function of cell size. The present data support the hypothesis. Human adult erythrocytes in vitro derived from patients with HIV (n = 15) and apparently healthy individuals (n = 15) were compared for US-induced hemolysis in vitro.