Shouping Li

Detection of Myocardial Perfusion in Multiple Echocardiographic Windows With One Intravenous Injection of Microbubbles Using Transient Response Second Harmonic Imaging

OBJECTIVESnThe purpose of this study was to prove that transient response harmonic imaging could detect normal and abnormal myocardial perfusion in multiple echocardiographic windows with one intravenous injection of microbubbles in humans.nnnBACKGROUNDnMyocardial ultrasound contrast can be produced from intravenous perfluorocarbon-exposed sonicated dextrose albumin, and ultrasound can be significantly improved by briefly suspending the interval between frame rates. Whether this contrast can noninvasively quantify myocardial perfusion in humans is unknown.nnnMETHODSnIn 28 patients, harmonic transient response imaging was used to image the heart in multiple different imaging planes after one intravenous injection of ultrasound contrast agent. Twenty-five of these 28 patients had a repeat injection during dipyridamole stress. In the primary view, the ultrasound transmission rate was one frame per cardiac cycle; in secondary and tertiary views, the transmission rate was once every multiple cardiac cycles. Regional myocardial contrast was visually assessed and quantified off-line. Quantitative rest thallium and dipyridamole stress sestamibi imaging was also performed.nnnRESULTSnPerfusion abnormalities were evident in the secondary and tertiary views only with one frame every multiple cardiac cycles. Regional peak myocardial videointensity (PMVI) correlated closely with regional tracer uptake in individual patients both at rest (r = 0.84) and during stress (r = 0.88). A PMVI ratio (abnormal region divided by the region with highest nuclear uptake) < 0.6 in any view had a 92% sensitivity and a 84% specificity in identifying a regional nuclear perfusion abnormality.nnnCONCLUSIONSnTransient response imaging produces myocardial contrast in multiple views with one intravenous injection of contrast agent and can accurately identify regional myocardial perfusion abnormalities.

Noninvasive In Vivo Clot Dissolution Without a Thrombolytic Drug Recanalization of Thrombosed Iliofemoral Arteries by Transcutaneous Ultrasound Combined With Intravenous Infusion of Microbubbles

BACKGROUNDnPrevious in vivo studies have shown that microbubbles not only enhance the effectiveness of thrombolytic agents in the presence of ultrasound but may also augment clot dissolution without thrombolytic drugs.nnnMETHODS AND RESULTSnThe objective of this study was to examine the efficacy of arterial clot disruption by a noninvasive, nonlytic approach with intravenous administration of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) and transcutaneous delivery of ultrasound alone. Pairs of iliofemoral arteries in 10 rabbits were randomized to receive transcutaneous ultrasound treatment or no ultrasound treatment after an acute artery thrombotic occlusion and intravenous PESDA infusion. Five arteries from 3 additional rabbits served as controls (ultrasound alone). All 10 iliofemoral arteries treated with PESDA + ultrasound were recanalized by angiography after ultrasound treatment. None of the 10 contralateral arteries treated with PESDA alone and none of the 5 arteries treated with ultrasound alone were patent after 1 hour. D-Dimer levels did not change after intravenous PESDA + ultrasound-mediated reperfusion.nnnCONCLUSIONSnIn vivo arterial clot dissolution can be achieved with intravenous microbubbles and transcutaneous ultrasound delivery alone. This technique has potential for clinical application in patients with acute arterial and venous thrombotic occlusions.

The clinical implications of no reflow demonstrated with intravenous perfluorocarbon containing microbubbles following restoration of Thrombolysis in Myocardial Infarction (TIMI) 3 flow in patients with acute myocardial infarction

Intravenous injections or infusions of perfluorocarbon-exposed sonicated dextrose albumin microbubbles were given 2.4 +/- 1.6 days following acute myocardial infarction to 45 consecutive patients. Patients were divided into 3 groups: patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 angiographic flow but persistent myocardial contrast defects by echocardiography (no reflow), patients with TIMI 3 flow and myocardial contrast enhancement (reflow), and patients with TIMI grade 0 to 2 flow in the infarct vessel. Thirty-five patients had TIMI 3 flow at the time of contrast study. Of these, 25 had evidence of reflow with intravenous contrast, whereas 10 (29%) still had contrast defects. At follow-up, end-systolic volume index decreased significantly in patients who exhibited reflow (21 +/- 8 ml/m2 at baseline to 18 +/- 8 ml/m2 at follow-up; p = 0.04), whereas those with no reflow had a significant increase (26 +/- 9 ml/m2 at baseline to 32 +/- 9 ml/m2 at follow-up; p = 0.006). A persistent contrast defect in the infarct zone demonstrated with intravenous ultrasound contrast following restoration of TIMI grade 3 flow in the infarct vessel identified patients likely to have deterioration in both regional and global systolic function.

Interaction of diagnostic ultrasound with synthetic oligonucleotide-labeled perfluorocarbon-exposed sonicated dextrose albumin microbubbles.

The purpose of this study was to determine, first, whether the albumin on perfluorocarbon‐exposed sonicated dextrose albumin microbubbles has retained its known ability to bind antisense oligonucleotides (DNA utilized to inhibit viral replication and intimal hyperplasia). The binding kinetics of synthetic antisense oligonucleotides to perfluorocarbon‐exposed sonicated dextrose albumin microbubbles as well as to room air‐containing sonicated dextrose albumin microbubbles were compared. Second, the effect of diagnostic ultrasound on this binding is unknown. The ability of diagnostic ultrasound to release synthetic antisense oligonucleotides from perfluorocarbon‐exposed sonicated dextrose albumin microbubbles also was tested in vitro and in vivo in three dogs. Synthetic antisense oligonucleotides exhibited binding to perfluorocarbon‐exposed sonicated dextrose albumin microbubbles much like that of native albumin but did not bind uniformly with room air‐containing sonicated dextrose albumin microbubbles. Diagnostic ultrasound resulted in significant partitioning of synthetic antisense oligonucleotides into non‐bubble containing regions after insonation in vitro as well as deposition of greater amounts of synthetic antisense oligonucleotides in the insonated kidney after intravenous injections of synthetic anti‐sense oligonucleotide‐labeled perfluorocarbon‐exposed sonicated dextrose albumin microbubbles. We conclude that perfluorocarbon‐exposed sonicated dextrose albumin microbubbles, unlike room air‐containing sonicated dextrose albumin microbubbles, have bioactive albumin on their surface that can bind synthetic antisense oligonucleotides and then release them in the presence of diagnostic ultrasound.

Increased Ultrasound Contrast and Decreased Microbubble Destruction Rates With Triggered Ultrasound Imaging

Although transient myocardial contrast imaging has been able to produce visually evident myocardial contrast in animals and humans with very low intravenous doses of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles, the mechanism for improved contrast remains unclear. In this study we devised a flow chamber that measured the concentration of PESDA microbubbles that remained after exposure to diagnostic ultrasound pressures of 0.9 to 1.9 MPa and frequencies of 2.0, 2.5, and 3.5 MHz (first and second harmonic for 2.0 MHz), which were delivered at either 30 Hz (frames per second), 0.5 to 1.0 Hz, or without any ultrasound transmission. The videointensity within the flow chamber was also measured at 0, 20, 40, and 100 ml/min flow rates with the flow loop closed (i.e., constant microbubble concentration) with both triggered (0.5 to 1.0 Hz) and conventional (30 Hz) frame rates. The effluent microbubble concentration was significantly larger when PESDA was exposed to either no ultrasound or 0.5 to 1.0 Hz ultrasound. Furthermore, the videointensity of a constant number of microbubbles was significantly greater with 0.5 to 1.0 Hz (triggered) compared with 30 Hz (conventional) frame rates at each transmit frequency. The greatest difference was noted with the lower 2.0 MHz transmit frequency and the 20 ml/min flow rate, especially when a second harmonic receiving frequency was used. We conclude that the mechanism for improved contrast with triggered ultrasound imaging is because of both less microbubble destruction and increased videointensity from a constant number of microbubbles. Lower transducer frequencies and lower flow rates result in the greatest improvement in videointensity with triggered ultrasound transmission.

The effect of ultrasound frame rate on perfluorocarbon-exposed sonicated dextrose albumin microbubble size and concentration when insonifying at different flow rates, transducer frequencies, and acoustic outputs

The purpose of this article was to compare the effects of 1 and 30 Hz frame rates on perfluorocarbon-exposed sonicated dextrose albumin microbubble size and concentration in a flow cell containing either saline or blood at 37 degrees C. Microbubble size and concentration of perfluorocarbon-exposed sonicated dextrose albumin were measured after insonation at different acoustic outputs, transducer frequencies, and flow rates with the use of the two different frame rates and compared with no ultrasound exposure. At 2.0 MHz insonation frequency, microbubble concentration was significantly reduced with the use of a 30 Hz frame rate and peak negative pressures of 1.1 megaPascal (mPa). This destruction did not occur when using a lower acoustic output, a 1 Hz frame rate, or when flow rate was increased to 100 cc/min. One-hertz frame rates at 2.0 MHz resulted in a significantly larger mean microbubble size than 30 Hz or no ultrasound in both saline and blood, which was in part due to selective destruction of smaller microbubbles. These findings indicate that 30 Hz frame rates destroy perfluorocarbon-exposed sonicated dextrose albumin microbubbles only at higher diagnostic acoustic outputs. A 1 Hz frame rate prevents this destruction, especially destruction of larger (> 5.0 microns) microbubbles.

Effect of Significant Two-Vessel Versus One-Vessel Coronary Artery Stenosis on Myocardial Contrast Defects Observed With Intermittent Harmonic Imaging After Intravenous Contrast Injection During Dobutamine Stress Echocardiography

OBJECTIVESnWe sought to determine the effect of multivessel as opposed to single-vessel coronary artery stenosis on myocardial contrast defects observed with intermittent harmonic imaging and intravenous perfluorocarbon-exposed sonicated dextrose albumin contrast injection.nnnBACKGROUNDnIntermittent harmonic imaging has permitted the detection of myocardial perfusion abnormalities with an intravenous ultrasound contrast agent. The effect of multivessel disease on inducibility of these perfusion abnormalities is unknown.nnnMETHODSnIn 10 dogs, intravenous injections of contrast agent were given at rest and during dobutamine stress echocardiography when a single coronary artery stenosis was present (> or = 50% diameter by quantitative angiography) and again when a second stenosis (range 44% to 92% diameter) was present in the vessel supplying the adjacent perfusion bed. The peak myocardial contrast was visually and quantitatively assessed in the mid and lateral regions of the perfusion bed of the first stenosis (original stenosis zone) in the presence of one- and two-vessel stenosis.nnnRESULTSnPeak myocardial contrast defects in both the mid and lateral segments of the original stenosis zone during dobutamine stress echocardiography was significantly lower when two-vessel stenosis was present (p = 0.015), especially in the lateral segment. The spatial extent of the perfusion defect in the original stenosis zone risk area increased significantly when two-vessel stenosis was present, and correlated closely with actual risk area (r = 0.99). Previous total occlusion followed by reperfusion of the vessel supplying the original stenosis zone significantly increased the amount of collateral activity between perfusion beds.nnnCONCLUSIONSnCollateral flow limits the spatial extent of inducible ischemia within the risk area of single-vessel stenosis. Restoring blood flow to one perfusion bed reduces the extent of a perfusion abnormality that can be induced in an adjacent stenosed bed.

Smaller intravenous perfluorocarbon-containing microbubbles produce greater myocardial contrast with intermittent harmonic imaging and better delineation of risk area during acute myocardial ischemia

The purpose of this article was to determine whether applying negative or positive pressure to perfluorocarbon-containing microbubbles before intravenous injection would improve the myocardial contrast when using newer imaging techniques such as harmonic and intermittent imaging. Perfluorocarbon-containing microbubbles were exposed to sustained negative or positive pressure before intravenous injection in 10 dogs. Microbubble size distribution and concentration were measured after each exposure. Peak myocardial videointensity with intermittent harmonic imaging with each sample was compared. Microbubbles exposed to -200 mm Hg pressure before intravenous injection produced both the highest concentration of microbubbles and greater numbers of microbubbles less than 4 microns. Peak myocardial videointensity did not correlate with microbubble concentration or size but did correlate with the absolute number of microbubbles < 4 microns (mean r value 0.76, range 0.61 to 0.90). Risk area was best visualized with perfluorocarbon-containing microbubble samples containing the smallest microbubbles. We conclude that the myocardial contrast observed with perfluorocarbon-containing microbubbles can be enhanced by applying negative pressure before injection. The mechanism for this improved contrast appears to be related to creation of smaller microbubbles.

Effect of Transducer Standoff on the Detection, Spatial Extent, and Quantification of Myocardial Contrast Defects Caused by Coronary Stenoses

Intermittent harmonic imaging during a continuous infusion of microbubbles may be able to quantify myocardial perfusion abnormalities. Measurements of the spatial extent of these perfusion abnormalities depends on homogenous destruction of the microbubbles in the elevation plane of the transducer. We hypothesized that uneven microbubble destruction caused by attenuation of beam intensity could alter quantitative measurements of perfusion abnormalities during stress. To test this hypothesis, we measured the spatial extent of perfusion defects at peak dobutamine stress with a continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin and intermittent harmonic imaging in dogs with nonflow-limiting coronary stenoses in the left anterior descending artery. The spatial extent of perfusion defects was also measured during total occlusion of the artery. Measurements were made at standoffs of 2- to 3-cm and 4- to 5-cm distance from transducer surface to myocardium. These spatial extents were correlated with risk area determined after death. The risk area during left anterior descending occlusion at a standoff of 2 to 3 cm was significantly larger at a 1500-ms pulsing interval (6.5 +/- 2.6 cm(2) for 2- to 3-cm standoff versus 3.7 +/- 1.4 cm(2) for 4- to 5-cm standoff; P =.01). The spatial extent at the 2- to 3-cm standoff more closely approximated risk area measured with Monastral Blue (7.8 +/- 2.7 cm(2)). Myocardial perfusion abnormalities during peak dobutamine stress were significantly smaller with the 4- to 5-cm standoff and undetectable in 4 of the 5 dogs. We conclude that ultrasound beam attenuation can reduce the size of a myocardial perfusion abnormality observed with intermittent harmonic imaging during a continuous infusion of microbubbles. This may reduce the sensitivity of this technique when transthoracic imaging is used.

Effect of blood and microbubble oxygen and nitrogen content on perfluorocarbon-filled dextrose albumin microbubble size and efficacy: In vitro and in vivo studies

We hypothesized, on the basis of in vitro observations, that a higher oxygen partial pressure within perfluorocarbon-containing microbubbles (PCMB) would enhance inward nitrogen diffusion after venous injection, leading to improved myocardial contrast. The in vitro studies measured PCMB size and concentration after injection into arterial blood that was obtained during inhalation of either room air or 100% oxygen. We then compared the myocardial contrast produced from PCMB sonicated in the presence of either a nitrogen-free environment (100% oxygen) or room air in three closed chest dogs. PCMB exposed to oxygenated blood in vitro were significantly smaller after insonation than PCMB exposed to arterial blood obtained during room air inhalation, confirming the important role of dissolved nitrogen in stabilizing PCMB size. In vivo studies demonstrated that intravenous PCMB sonicated with 100% oxygen produced significantly greater anterior and posterior myocardial contrast than PCMB sonicated in the presence of room air.