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Biomedical subjects

Thomas R Porter

Publications and source records attributed to Thomas R Porter.

43 records · Page 3Linked to original sources

Correlation between myocardial perfusion abnormalities detected with intermittent imaging using intravenous perfluorocarbon microbubbles and radioisotope imaging during high-dose dipyridamole stress echo.

BACKGROUND: The clinical accuracy of myocardial contrast echocardiography (MCE) using intermittent harmonic imaging and intravenous perfluorocarbon containing microbubbles during dipyridamole stress has not been evaluated in a multicenter setting. HYPOTHESIS: The accuracy of dipyridamole stress contrast echo in the detection of coronary artery disease (CAD) using myocardial perfusion images is high in comparison with technetium-99 (99Tc) sestamibi single-photon emission computed tomography (MIBI SPECT) and increases the accuracy of wall motion data. METHODS: In 68 consecutive nonselected patients (46 men; mean age 66 years) from three different institutions in two countries. dipyridamole stress echo and SPECT with 99mTc MIBI were compared. Continuous intravenous (IV) infusion of perfluorocarbon exposed sonicated dextrose albumin (PESDA) (2-5 cc/min) was administered for baseline myocardial perfusion using triggered harmonic end systolic frames. Real-time digitized images were used for wall motion analysis. Dipyridamole was then injected in two steps: (1) 0.56 mg/kg for 3 min, (2) 0.28 mg/kg for 1 min, if the first step was negative for an inducible wall motion abnormality. After dipyridamole injection, myocardial contrast enhancement and wall motion were analyzed again by the same methodology. RESULTS: There were 35 patients with perfusion defects by SPECT. Wall motion was abnormal in 22, while MCE was abnormal in 32. Wall motion and MCE each had one false positive. The proportion of correctly assigned patients was significantly better with MCE than with wall motion (p = 0.03; chi square test). CONCLUSIONS: Myocardial contrast echocardiography, using intermittent harmonic imaging and intravenous perfluorocarbon containing microbubbles, is a very effective method for detecting coronary artery disease during dipyridamole stress echo.

Adult↗

Endocardial border delineation during dobutamine infusion using contrast echocardiography.

BACKGROUND: A significant percentage of pharmacologic stress echocardiograms produce suboptimal images despite the use of second harmonic imaging. Intravenous continuous infusion of myocardial ultrasound contrast may enhance endocardial border delineation during dobutamine-atropine stress echocardiography (DASE), improving wall-motion analysis. PATIENTS AND METHODS: We prospectively studied 68 patients (41 males and 27 females), mean age 58 years, with DASE during intravenous infusion of contrast using second harmonic imaging. Dobutamine was infused in scalar doses of 5 microg/kg/min to 40 microg/kg/min, and atropine was administered in doses of up to 1 mg. We diluted 0.1 mL of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles into 80 mL of saline solution, which was used for continuous intravenous infusion. Blinded reviewers used a 16-segment model at rest and peak DASE to analyze segmental wall delineation in two sets of images for each patient, with and without contrast. An endocardial delineation score of 0-3 (nondelineated to excellent delineation) was given to each segment. An endocardial delineation score index (EDSI), the number of endocardial delineation scores for each set of images divided by 16, was created. RESULTS: The analysis of the mean EDSI for the 2176 segments was 1.46 (+/- 0.43) at rest and 1.30 (+/- 0.48) at peak for noncontrast images and 2.22 (+/- 0.52) and 2.29 (+/- 0.52) for contrast images. Complete left ventricle opacification was obtained in all patients, with a mean dose of 4 mL/min, although in 15 (22%) patients, signs of apical bubble destruction occurred. There were 1768 (81%) of 2176 segments delineated without contrast enhancement and 2057 (95%) of 2176 with enhancement (P < 0.05). CONCLUSION: Continuous infusion of myocardial ultrasound contrast improves endocardial border delineation using second harmonic imaging in patients undergoing DASE.

Adult↗

Clinical experience in the detection of coronary artery disease with myocardial contrast echocardiography.

Myocardial contrast enhancement following intravenous infusions or injections of perfluorocarbon-containing microbubbles has now been observed consistently in humans. Currently, the major challenge facing us is interpreting accurately what we see. The myocardial contrast patterns we observe have, thus far, been shown to detect myocardial perfusion abnormalities during dipyridamole, adenosine, and dobutamine stress echocardiography. They also have been shown to detect zones of no reflow following coronary revascularization in patients with acute myocardial infarction. These preliminary data will require validation in larger multicenter clinical studies.

Animals↗

Left atrial volume determination by three-dimensional echocardiography reconstruction: validation and application of a simplified technique.

Left atrial (LA) size assessment by anteroposterior dimension is limited in accuracy. Conventional 3-dimensional (3D) reconstruction has been validated, but the process is time-consuming and the 3D system is not widely available. We developed an algorithm to simplify 3D reconstruction of LA on the basis of 3 standard apical views, tested it in 44 hemodynamic stages of 8 open-chest dogs, and compared it with LA volumes assessed by conventional 3D reconstruction. Simplified 3D reconstruction provided an accurate LA volume measurement (y = 0.93x + 0.7, r = 0.95, standard error of the estimate [SEE] = 3.6) with more than 60% of time saved. Cubic equation of anteroposterior dimension and biplane modified Simpson's method were less accurate (for biplane modified Simpson's method, y = 0.8x + 2.6, r = 0.88, SEE = 5.0; for cubic equation of anteroposterior dimension, y = 0.65x + 2.6, r = 0.76, SEE = 8.2). Without the need for a 3D-imaging acquisition tool, simplified 3D reconstruction can be applied in the clinical setting for LA size quantitation with significant time saved.

Algorithms↗

Targeted vascular delivery of antisense molecules using intravenous microbubbles.

OBJECTIVE: Perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles bind the antisense to the c-myc protooncogene (anti-c-myc) which prevents neointimal hyperplasia following vascular endothelial injury. The microbubbles also adhere to sites of damaged vascular endothelium and thus may be a method of systemically targeting delivery of anti-c-myc. METHODS: Laser scanning microscopy was performed on the aorta of 10 mice (five which were complement depleted) that received intravenous FITC-PESDA following aortic endothelial injury. C-myc expression was quantified following selective intracoronary injury in nine pigs that received intravenous (IV) anti-c-myc bound to PESDA. Finally, neointimal formation was measured following intracoronary stent deployment in 30 pigs that received either IV anti-c-myc alone or the same dose bound to PESDA. RESULTS: Fluorescent microscopy confirmed selective PESDA microbubble adherence to aortic endothelium in all mice with aortic injury. This binding was nearly abolished when serum complement was depleted prior to injury. C-myc expression at the site of coronary endothelial injury was significantly lower in pigs treated with systemic anti-c-myc bound to PESDA. There was a 33% reduction in % stenosis and a 28% reduction in intimal area at 45 days post-stent deployment in pigs that received IV antisense plus PESDA. The stent margins also had reduced neointimal formation. CONCLUSION: Systemic administration of anti-c-myc bound to PESDA microbubbles may be a good method for preventing coronary neointimal formation within and around implanted stents.

Analysis of Variance↗

Assessment of myocardial perfusion with real-time myocardial contrast echocardiography: methodology and clinical applications.

Real-time myocardial contrast perfusion imaging (RTMCI) with echocardiography is a promising technique for evaluation of patients with known or suspected coronary artery disease. The technique is based on the utilization of small (<10 mum) microbubbles, which are capable of crossing the pulmonary circulation after intravenous injection. Unlike radioactive isotopes, which are taken actively or diffuse passively in the myocytes, myocardial contrast agents remain extracellularly in the capillaries and present a measure of the myocardial capillary blood volume and microvascular integrity. RTMCI has been shown to be a safe and feasible method for the assessment of myocardial perfusion at rest and with pharmacologic stress. Recent studies have shown the value of RTMCI with dobutamine stress in improving overall and regional detection of coronary artery disease and detecting of abnormalities at submaximal stress, therefore improving sensitivity in patients who are unable to achieve the target heart rate. The advantages of the technique include the ability to assess perfusion at bedside in one setting, simultaneous assessment of myocardial function, shorter imaging time, no need for ionizing irradiation, immediate availability of the results, and the ability to determine the ischemic threshold. Recent studies have shown that RTMCI improves the prognostic utility of standard dobutamine stress in addition to wall motion analysis. Patients with normal perfusion had a better outcome than those with normal wall motion. The combination of abnormal wall motion and perfusion identified patients at greatest risk of death and nonfatal myocardial infarction. Perfusion abnormalities were also shown to predict short-term cardiac events in patients presenting to the emergency department with chest pain and no ST-segment elevation. Refinement of imaging techniques is expected to improve the specificity of RTMCI, particularly in differentiating true perfusion defects from artifacts. This review will discuss the physiologic basis, methodology, clinical utility, and limitations of RTMCI in the assessment of patients with known or suspected coronary artery disease.

Computer Systems↗

Systemic targeted delivery of antisense with perflourobutane gas microbubble carrier reduced neointimal formation in the porcine coronary restenosis model.

HYPOTHESIS: The antisense phosphorodiamidate morpholino oligomer (PMO), AVI-4126, has been effective in reducing neointimal formation in animal models following delivery by pluronic gels, local delivery catheters and coated stents. Greater flexibility of repeated-dosage regimens and reduced procedure complexity may be provided by systemic injection of AVI-4126 bound to perfluorobutane gas microbubble carriers. The purpose of this study was to investigate the effects of perfluorocarbon gas microbubble carrier (PGMC)-based systemic delivery of AVI-4126 on expression of the c-myc in vascular tissue and restenosis after stent implantation. METHODS: Seven pigs underwent stent implantation (3 stents/animal). Five pigs received IV injection of PGMC and 2 mg of AVI-4126 (AVI BioPharma). Two served as control. Four hours postprocedure, 3 pigs were sacrificed and stented segments analyzed by high-performance liquid chromatography (HPLC) and Western blot. In chronic experiments, 4 pigs (12 stent sites) were sacrificed at 28 days. RESULTS: HPLC analysis of plasma samples of treated animals showed minimal presence of AVI-4126. HPLC of the treated arteries demonstrated easily detected concentrations of AVI-4126. Western blot analysis of the stented vessels demonstrated modest inhibition of c-myc. Morphometry showed that the neointimal area was significantly reduced in the AVI-4126/PGMC group compared with control (2.63+/-1.99 vs. 4.77+/-.1.71 mm2, respectively, P<.05). CONCLUSION: In the porcine coronary stent model, systemic targeted delivery of AVI-4126 using PGMC carrier significantly inhibited neointimal formation.

Animals↗