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Biomedical subjects

Patrick Rafter

Publications and source records attributed to Patrick Rafter.

7 recordsLinked to original sources

Myocardial delivery of colloid nanoparticles using ultrasound-targeted microbubble destruction.

AIMS: Ultrasound (US)-targeted microbubble destruction (UTMD) is a promising method for delivering genetic material to the heart. The aim of this study was: (i) to test whether colloid nanoparticles can be delivered to the rat myocardium using UTMD; and (ii) to determine whether tissue damage and contractile dysfunction occurs in hearts exposed to UTMD in vivo. METHODS AND RESULTS: Hearts from anaesthetized rats were exposed to perfluorocarbon-enhanced sonicated dextrose albumin (PESDA) (at two different microbubble concentrations) and US at peak pressures of 0.6, 1.2, or 1.8 MPa for 1, 3, or 9 min. During US, pairs of 30 and 100 nm fluorescent nanospheres were infused intravenously. Left ventricular function was assessed before and immediately after US, as well as at 24 h and 7 days. At the end of the experiments, the number of ruptured microvessels and the amount of nanospheres deposited were quantified. Rats exposed to PESDA alone or US alone showed no functional abnormalities, no capillary ruptures, and no nanosphere delivery. In contrast, rats exposed to both PESDA and US exhibited microvascular ruptures and nanosphere deposits. They also showed transient contractile dysfunction and premature ventricular contractions. All these changes were time-, US peak pressure-, and PESDA concentration-dependent. CONCLUSION: UTMD allows colloid nanoparticles to be delivered to the rat myocardium through microvessel rupture sites. The efficacy of delivery depends on the peak pressure applied, the duration of US exposure, and contrast concentration. UTMD also causes time- and peak pressure-dependent contractile dysfunction, and tissue alterations that are spontaneously reversible over time.

Animals↗

Detection of coronary stenoses at rest with myocardial contrast echocardiography.

BACKGROUND: We hypothesized that autoregulatory changes in arteriolar blood volume (aBV) that develop distal to a stenosis can be measured with myocardial contrast echocardiography, allowing coronary stenosis detection at rest without recourse to stress. METHODS AND RESULTS: Patients with varying degrees of coronary artery stenosis on quantitative angiography underwent high-mechanical-index myocardial contrast echocardiography at 15 Hz to allow measurement of phasic changes in aBV in large intramyocardial vessels using either Definity (group 1; n=22) or Imagent (group 2; n=22). Progressive increases in the BACKGROUND: <0.001) and group 2 (0.10+/-0.05, 0.27+/-0.18, 0.39+/-0.28, and 0.74+/-0.37; P<0.0001) patients. A systolic/diastolic aBV signal ratio of >0.34 provided a sensitivity and specificity of 80% and 71%, respectively, for the detection of >75% coronary stenosis in group 1 patients, whereas a ratio of >0.43 provided a sensitivity and specificity of 89% and 74%, respectively, for the detection of >75% stenosis in group 2 patients. CONCLUSIONS: Both the presence and severity of a physiologically significant coronary stenosis can be detected at rest by measuring the increase in aBV on myocardial contrast echocardiography that occurs distally to the stenosis without recourse to any form of stress.

Adult↗

Microbubble contrast agents for echocardiography: rationale, composition, ultrasound interactions, and safety.

Imaging the small blood vessels within the myocardium, which contains only a small fraction of the total coronary blood volume, is a significant challenge for ultrasound imaging. Recent advances in microbubble design and ultrasound technology have improved our ability to image the microcirculation. It is essential to understand the fundamentals of microbubble behavior in an ultrasound field and how it impacts technology and safety.

Coronary Vessels↗

Imaging technologies and techniques.

Equipment manufacturers provide contrast-specific detection techniques that have excellent sensitivity and excellent agent-to-tissue specificity along with helpful tools that improve workflow efficiency dramatically. Excellent contrast agents have been approved for LV opacification and are available worldwide. Techniques designed for low-MI imaging offer real-time acquisition capabilities and lead to faster examinations. Techniques designed for medium-MI imaging offer better sensitivity than low-MI techniques while maintaining the benefit of rapid image acquisition. Techniques designed for high-MI imaging offer the best sensitivity with longer acquisition times. These techniques are viable means for imaging contrast agents tailored to clinical needs. Progress by contrast agent manufacturers, equipment manufacturers, and physicians will continue to drive improvements in the areas of detection and clinical workflow for improved patient care.

Coronary Circulation↗

Microbubble responses to a similar mechanical index with different real-time perfusion imaging techniques.

The purpose of this study was to determine differences in contrast enhancement and microbubble destruction rates with current commercially available low-mechanical index (MI) real-time perfusion imaging modalities. A tissue-mimicking phantom was developed that had vessels at 3 cm (near field) and 9 cm (far field) from a real-time transducer. Perfluorocarbon-exposed sonicated dextrose albumin microbubbles (PESDA) were injected proximal to a mixing chamber, and then passed through these vessels while the region was insonified with either pulses of alternating polarity with pulse inversion Doppler (PID) or pulses of alternating amplitude by power modulation (PM) at MIs of 0.1, 0.2 and 0.3. Effluent microbubble concentration, contrast intensity and the slope of digital contrast intensity vs. time were measured. Our results demonstrated that microbubble destruction already occurs with PID at an MI of 0.1. Contrast intensity seen with PID was less than with PM. Therefore, differences in contrast enhancement and microbubble destruction rates occur at a similar MI setting when using different real-time pulse sequence schemes.

Acoustics↗

Quantification of myocardial blood flow and assessment of its transmural distribution with real-time power modulation myocardial contrast echocardiography.

BACKGROUND: The purpose of this study was to examine the ability of real-time myocardial contrast echocardiography (MCE) with power modulation to quantitate myocardial blood flow (MBF) and to assess its transmural distribution in open-chest dogs undergoing partial or total coronary stenoses. METHODS AND RESULTS: MBF was measured in 12 dogs instrumented with a cuff occluder around the left anterior descending coronary artery at rest, during partial coronary stenosis (during infusion of adenosine), and during coronary occlusion. The MCE-derived rate of microbubble velocity, beta, and myocardial blood volume, A, were obtained by curve fitting of videointensity versus time plots, after the transient destruction of microbubbles by high-energy ultrasound. The data were compared with MBF measured with radiolabeled microspheres. Significant correlations were found between radiolabeled microsphere-derived MBF and both beta (r = 0.93) and the product of A x beta (r = 0.91). MCE beta reserve also correlated well with microsphere-derived flow reserve. Comparing endocardial/epicardial MCE ratios and microsphere-derived MBF ratios, significant correlation was also found between endomicropsheres/epimicrospheres MBF ratio and both endo/epi beta (r = 0.90) and endo/epi A x beta (r = 0.88). CONCLUSIONS: Real-time power modulation MCE allows for an accurate quantification of MBF and of its transmural distribution in open-chest dogs undergoing partial or total coronary stenoses.

Animals↗

Measurement of myocardial blood flow velocity reserve with myocardial contrast echocardiography in patients with suspected coronary artery disease: comparison with quantitative gated Technetium 99m sestamibi single photon emission computed tomography.

BACKGROUND: The ability of high and low mechanical index (MI) imaging methods during myocardial contrast echocardiography (MCE) to assess the physiologic significance of coronary stenoses were compared with technetium 99m sestamibi single photon emission computed tomography (SPECT) in patients. METHODS: Intermittent ultraharmonic imaging (high MI) and power modulation angio (low MI) were performed during continuous infusions of the echo-enhancing contrast agent, Optison, at rest and after dipyridamole stress in 39 patients. Technetium 99m sestamibi SPECT was performed simultaneously. Images from the 3 apical windows were divided into 6 walls. Myocardial blood flow (MBF) velocity and MBF velocity reserve were quantified from pulsing interval versus acoustic intensity MCE curves in each wall using postprocessed images. RESULTS: Approximately 25% of the myocardial walls could not be analyzed from MCE because of artifacts. MBF velocity and MBF derived from both MCE methods increased significantly after dipyridamole in healthy patients (n = 143 and 129 walls for high and low MI, respectively), compared with those with either reversible (n = 11 and 10 walls for high and low MI, respectively) or fixed defects (n = 18 and 14 walls for high and low MI, respectively) on SPECT. Consequently, MBF velocity and MBF reserve were significantly greater for patients with normal perfusion. Receiver operator characteristic curves obtained for MBF velocity reserve provided a sensitivity and specificity of 82% and 87%, respectively, for high MI; versus 64% and 96%, respectively, for low MI imaging after uninterpretable images were excluded from analysis. CONCLUSIONS: Both high and low MI MCE imaging techniques can be used to determine the presence of perfusion defects as identified by technetium 99m sestamibi SPECT. Low MI imaging methods have a number of drawbacks that limit its sensitivity compared with high MI techniques.

Aged↗