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At least 235 records · Page 13Linked to original sources

PubMed2003

Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhesion molecule-1.

BACKGROUND: Noninvasive techniques for detecting acute cardiac transplant rejection are limited. We hypothesized that ultrasound contrast microbubbles targeted to the endothelial cell (EC) inflammatory marker intercellular adhesion molecule-1 (ICAM-1) would selectively bind to rejecting versus nonrejecting myocardium and that myocardial contrast echocardiography can therefore detect acute rejection. METHODS AND RESULTS: Lipid-based microbubbles were conjugated to anti-rat ICAM-1 (MBICAM) or isotype control antibody (MBControl). In vitro MBICAM adhesion to cultured rat ECs, as assessed in a parallel plate flow apparatus, was greater to inflammatory versus normal ECs (11+/-3 versus 3+/-2 microbubbles/EC, P<0.005). In vivo abdominal heterotopic heart transplantation was performed in rats (rejection group: Brown Norway to Lewis strain; control group: Lewis to Lewis or Brown Norway to Brown Norway). Triggered myocardial contrast echocardiography was performed during intravenous MBICAM or MBControl (2.5x10(6)) injection on postoperative day 5. Myocardial videointensity from adhered MBICAM was significantly higher in rejecting (n=8) versus control (n=7) rats (10+/-4 versus 1+/-4 U, P=0.01). Postmortem histology showed normal myocardium in control rats, whereas allograft myocardium demonstrated grade III to IV rejection and strong immunohistochemical ICAM-1 staining. CONCLUSIONS: Preferential adherence of ICAM-1-targeted microbubbles to rejecting versus nonrejecting rat cardiac transplant myocardium can be detected ultrasonically. Targeted microbubbles may thus offer a noninvasive ultrasound imaging technique for the detection of acute cardiac transplant rejection and other processes characterized by endothelial dysfunction.

Acute Disease↗

PubMed2002

Vascular gene transfer of phosphomimetic endothelial nitric oxide synthase (S1177D) using ultrasound-enhanced destruction of plasmid-loaded microbubbles improves vasoreactivity.

BACKGROUND: Local gene therapy has enormous potential for the treatment of vascular disease. We determined whether diagnostic ultrasound-mediated destruction of plasmid-loaded albumin microbubbles is a feasible and efficient technique for local vascular gene delivery. For gene transfer, we used a phosphomimetic, active endothelial nitric oxide synthase (eNOS) construct in which Ser1177 was replaced by aspartic acid (S1177D) and exhibits a 2-fold higher basal activity than the wild-type enzyme. METHODS AND RESULTS: Gas-filled microbubbles (3.0 +/- 1.2 microm) were created by sonication of 5% human albumin in the presence of plasmid DNA encoding for LacZ or eNOS S1177D. Porcine coronary arteries were perfused with DNA-loaded albumin microbubbles in vitro, exposed to diagnostic ultrasound (5 seconds), and incubated for a further 24 hours. Detection of the beta-galactosidase in LacZ-transfected vessels revealed a predominant staining of endothelial cells without any functional impairment of vasoreactivity. Western blotting demonstrated the expression of the eNOS S1177D construct in extracts from the transfected segments. Vascular responsiveness was tested with prostaglandin F(2alpha) and the NOS inhibitor N(omega)nitro-L-arginine. Compared with segments treated with the expression plasmid alone, the contractile response to prostaglandin F(2alpha) was impaired in segments transfected with eNOS S1177D, whereas the contractile response to the administration of N(omega)nitro-L-arginine was markedly enhanced. CONCLUSIONS: Ultrasound-mediated destruction of eNOS S1177D DNA-loaded albumin microbubbles is a feasible and efficient method for vascular gene transfection. Transfection resulted in significant protein expression and enhanced NO-mediated relaxation of bradykinin-stimulated porcine coronary arteries.

Amino Acid Substitution↗

PubMed2002

Improved methods for measurement of gaseous microbubbles during extracorporeal circulation.

The detection and quantification of gaseous microbubbles in the arterial line of the extracorporeal circuit (ECC) are very important aims for quality assurance of perfusion. A system that allows a continuous measurement of microbubble distribution in the range of 10 and 120 microm was tested. The two-channel ultrasonic bubble counter (UBC) was based on a 2-MHz ultrasound Doppler system with propriety ultrasound probes. The bubble size was determined using the backscattered Doppler signal and was corrected by means of a reference signal based on measurement conditions. Our studies have shown that the quality of this signal can be negatively affected in the clinical environment. Different influences are involved, such as electrocoagulation or electromagnetic disturbances. Various algorithms were tested and new ones were developed in order to minimize the effect of such interferences on the accuracy of the bubble detection. The on-line data were recorded during the entire surgical time to allow an off-line evaluation with different algorithms. This allowed us to obtain more exact results. Two clinical studies with 91 patients were performed with microbubbles measured in the arterial line during coronary artery bypass grafting (CABG) and valve replacement. The results confirmed the expected occurrence of microbubbles during various phases of surgery. The measurement itself proved to be resistant to different external disturbances.

Algorithms↗

PubMed2001

Effectiveness of transcranial and transthoracic ultrasound and microbubbles in dissolving intravascular thrombi.

OBJECTIVE: To examine the effectiveness of 1 -MHz and 40-kHz ultrasound with and without microbubbles in fragmenting thrombi in attenuated conditions. METHODS: First, an vitro transcranial model was used to examine the ability of these frequencies to fragment thrombi in the presence or absence of perfluorocarbon-exposed sonicated dextrose albumin microbubbles. Second, an in vivo transthoracic model was used to test the effectiveness of these same frequencies with intravenous perfluorocarbon-exposed sonicated dextrose albumin in fragmenting left circumflex coronary thrombotic occlusions. RESULTS: In the in vitro model, both transcranial 1-MHz and 40-kHz ultrasonic frequencies were effective at fragmenting thrombi only in the presence of microbubbles. In the in vivo model, 1-MHz ultrasound with intravenous perfluorocarbon-exposed sonicated dextrose albumin angiographically recanalized only 4 of 14 occlusions but was consistently effective at improving myocardial blood flow to the risk area even in the absence of angiographic recanalization. Both 40-kHz and 1-MHz ultrasound with perfluorocarbon-exposed sonicated dextrose albumin improved regional wall-thickening and electrocardiographic abnormalities (P < .05 compared with control or ultrasound alone). CONCLUSIONS: Transcranial and transthoracic ultrasound in the presence of intravenous microbubbles can improve flow to ischemic regions and should be considered as a supplement to current pharmacologic therapy.

Adult↗

PubMed2003

[Thrombolysis accelerated by ultrasound and microbubbles].

Therapeutic applications of ultrasound are currently limited to dental plaque removal, physiotherapy and lithotripsy. However, several in vitro and experimental studies have shown the ability of ultrasound to accelerate clot dissolution. This effect is mainly influenced by the intensity and frequency of the beam. High ultrasound energies, although effective, can induce early reocclusion, while moderate intensities and low ultrasound frequencies are better tolerated and equally effective. So far, few patients with acute myocardial infarction have been treated by ultrasound catheters. In patients with ischemic stroke, transcranial Doppler was monitored during the venous administration of recombinant tissue-type plasminogen activator (rt-PA) and the occluded vessel was recanalyzed earlier than in other studies by rt-PA alone (without Doppler monitoring). Ultrasound-accelerated thrombolysis is caused by a strengthening of the enzymatic action, favored by acoustic cavitation. As the microbubbles of echocontrast agents lower the cavitation threshold, they can further enhance the thrombolytic process. New generation microbubbles, able to bind to the thrombus surface, could facilitate thrombus-microbubbles interaction. The combination of ultrasound, microbubbles and fibrinolytic agents could benefit the treatment of a variety of cardiovascular diseases.

Gases↗

PubMed1986

Effects of platelet antagonists on the reduction in platelet density caused by microbubbles in vitro.

Platelet-rich plasma (PRP) was stirred and incubated at 37 degrees C with N2 microbubbles in vitro in the presence and absence of platelet antagonists. The N2 microbubbles acted as a platelet agonist, like "classical" agonists such as ADP, collagen, and thrombin, causing an agonist-induced aggregation requiring extracellular Ca2+. This aggregation is abolished by 2-ethylamineglycolether (N',N',N',N') tetraacetate (chelator of extracellular Ca2+), and 2-deoxy-D-glucose plus antimycin A (inhibitors of glycolysis and electron transport, and thereby of ATP production). Furthermore, this aggregation could be depressed pharmacologically by several antagonists of the aggregation induced by "classical" platelet agonists. The greatest inhibition of microbubble-induced aggregation was obtained by substances that increase the intracellular levels of cyclic AMP. Medications that are in common clinical use, such as theophylline, seem promising in this respect. The prostaglandin-thromboxane pathway did not seem to be involved in the N2 microbubble-induced platelet aggregation in vitro, since acetylsalicylic acid and indomethacin were without effect, nor did the 3',5'-cyclic guanosine monophosphate pathway seem to be linked to this aggregation mechanism.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1988

[A newly developed instrument of microbubble test for evaluation of fetal lung maturity].

A new instrument for Pattle's microbubble test was devised in order to improve the diagnosis of fetal lung maturity. This instrument consists of 4 needles fixed at 8mm intervals and an air pump. Microbubbles were produced in 175 microliter of amniotic fluid placed on a slide glass by injecting 10 ml of air at 400 ml/h with an air pump through 22 gage needles. After 4 minutes, the number of stable microbubbles less than 15 um in diameter were counted in 5 microscope fields. When over 6 microbubbles were observed, fetal lung maturity was diagnosed as positive. 72 samples of amniotic fluids were tested by our method as well as the other 5 methods. The percentage of accurate diagnostic results was 97.2% with our method, 93.1% with the L/S ratio, 83.3% with the DSPC method, 86.1% with the PG method, 93.1% with the shake method, and 94.4% with the Pattle's original method. It is concluded that ours is a reliable, rapid and simple method for evaluating fetal lung maturity.

Female↗

PubMed1987

Transmission and scanning electron microscopy of N2 microbubble-activated human platelets in vitro.

When N2 microbubbles are stirred in platelet-rich plasma, they cause a fall in the number of free platelets. Changes in the platelets ultrastructure during this interaction between gas bubbles and platelets have been studied by transmission and scanning electron microscopy. Platelets, and aggregates of platelets, adhere to the surface of the N2 microbubbles. This adhesion induces ultrastructural changes (shape change, pseudopod formation, granule centralization, fusion, and disappearance) that are similar to "classical" agonists like ADP, collagen, and thrombin. These ultrastructural studies further strengthen our previous contention that N2 microbubbles activate platelets in a way similar to these physiologic agonists, and show that the previously reported fall in the number of free platelets is due to platelet aggregation. Platelet aggregates are also present in the interstices between gas bubbles. Fixed N2 microbubbles have been demonstrated, and these can be broken like cracked eggs by means of the electron beam in the electron microscope. Possible mechanisms for activation of the platelets by the gas bubbles are: through ADP released from some few platelets; by diffusion of gas after bubble-platelet interaction; and through certain fractions of the plasma proteins and lipids in the bubble surface that may act as binding sites for the platelets and promote adhesion and spreading of the platelets over the surface.

Blood Platelets↗

PubMed2006

Microbubbles assist goat liver ablation by high intensity focused ultrasound.

High intensity focused ultrasound (HIFU) has been introduced to treat cancers. However, this therapy is a time-consuming procedure; destructing a deeper volume is also difficult as ultrasonic energy attenuates exponentially with increasing depth in tissues. The aim of the present study was to investigate the effects of introducing microbubbles on liver HIFU ablation. Seventeen goats were divided into groups A (n=8) and B (n=9). The livers in both groups were ablated using HIFU (1.0 MHz, 22,593 W/cm2) performed in the manner of a clinical regime using a clinical device. A microbubble agent was bolus-injected intravenously before HIFU exposure in group B. All animals in group A and seven goats in group B were euthanased to evaluate the ablation efficiency 24 h after HIFU. The necrosis rate (mm3/s), which was the volume of necrosis tissue per second of HIFU exposure, was used to judge the ablation efficiency. Pathological examinations were performed to determine whether there were residual intact tissues within the exposed volume. The other two goats in group B were used to determine the delayed pathological changes 7 days after ultrasonic ablation. The necrosis rate (mm3/s) was increased in group B (14.4647+/-4.1960 versus 33.5302+/-12.4484, P=0.0059). Pathological examinations confirmed that there were no residual unaffected tissue focuses within the exposed volume. Two remarkable changes occurred in the other two goats in group B 7 days after HIFU: there were ghost-cell islands at the periphery of the ablated tissues, and surrounding adjacent tissues outside the reactive zone necrotized. These findings showed that microbubbles could be used to assist liver HIFU ablation.

Animals↗

PubMed2004

Evaluation of surfactant function at birth determined by the stable microbubble test in term and near term infants with respiratory distress.

UNLABELLED: Surfactant function using the stable microbubble test (SMT) was investigated in term or near term infants with respiratory distress. Newborn infants > or = 34 weeks gestation with an initial clinical hypothesis of transient tachypnoea of the newborn (TTN) needing supplemental oxygen and controls were included. Gastric aspirates were collected immediately after birth for SMT. The first chest X-ray films were examined by three independent radiologists and according to their interpretation the babies were divided into a TTN, a respiratory distress syndrome of the newborn (RDS), or a poorly-defined X-ray group. A total of 32 infants with respiratory distress and 32 controls with similar gestational age and birth weight were studied. The median and interquartile range (IQR) of the stable microbubble (SMB) count was significantly lower (P < 0.001) for the respiratory distress group than for the control group (17; range 6-33 versus 120; range 79-275). The proportion of babies with less than 35 stable microbubbles/mm2 (SMB/mm2) was significantly different for the whole respiratory distress group (24/32-75%) and for the TTN (9/13-69%), the RDS (5/5-100%), and the poorly-defined (10/12-83%) groups as compared with the controls (2/32-6%; P < 0.05). A total of 24/26 babies (92%) who needed oxygen for > or = 24 h but only 1/6 (17%) of them who needed < 24 h had a bubble count of less than 35 SMB/mm2 (P < 0.05). CONCLUSION: the results suggest that deficiency or dysfunction of the surfactant system is involved in the majority of cases of respiratory distress in near term and possibly term babies. The stable microbubble test can enable clinicians to take an earlier decision to give surfactant to term or near term infants with more severe and progressive respiratory distress.

Case-Control Studies↗

PubMedDate not supplied

Ultrasound-mediated microbubble destruction enhances VEGF gene delivery to the infarcted myocardium in rats.

OBJECTIVE: To investigate the possibility of improving the delivery of vascular endothelial growth factor (VEGF) gene to the myocardium in rats by using ultrasound-mediated microbubble destruction (UMMD). METHODS: Fifteen male Wistar rats underwent left anterior descending coronary artery ligation in this study. The rats were divided into three groups 3 days after ligation. Ultrasound microbubble vectors (UMVs) attaching to pcD2VEGF121 gene were injected into the tail vein of rats with or without simultaneous echocardiographic microbubble destruction in two groups. The third group was used as control group. VEGF protein expression and formation of new blood vessels were evaluated by immunohistochemical technique during autopsy on 15 rats at 2 weeks after gene transformation. Microvascular density (MVD) in the area with myocardial infarction was counted under a microscope. RESULTS: VEGF protein expression and MVD in the ischemic myocardium were higher in the rats receiving UMMD than in the group that did not receive UMMD. CONCLUSION: UMMD is a noninvasive method to effectively improve the delivery of targeted genes to the heart.

Analysis of Variance↗

PubMed2006

Spinal gene transfer using ultrasound and microbubbles.

Spinal gene therapy is a promising option for treating various spinal-related disorders. Several previous studies using viral vectors reported successful transfer of therapeutic genes into the spinal nerve system. However, because of the considerable immunogenicity related to the use of viruses, non-viral gene transfer still needs to be developed. One possible approach is the combined use of ultrasound and echo-contrast microbubbles. The present study shows that this method can be applied for targeted intrathecal gene delivery. We intrathecally injected a mixture of plasmid-DNA encoded with luciferase and commercially available albumin microbubbles by needle puncture at the lower lumbar intervertebral space in mice. Subsequent percutaneous ultrasonication on the lumbar vertebrae significantly enhanced the luciferase expression, analyzed by imaging luciferin bioluminescence, in the dorsal meningeal cells at the insonated region. No apparent neurological damages were induced by the present spinal interventions. In addition to the general benefits of the combined use of ultrasound and microbubbles, our approach can offer some advantages specific to spinal gene transfection including minimal invasiveness of simple percutaneous dural puncture, targetability due to the limited access of ultrasound waves through anatomical apertures of the vertebrae, and possible paracrine delivery of therapeutic molecules to the spinal nerve system.

Animals↗

PubMed2006

Ultrasound, microbubbles and the blood-brain barrier.

The blood-brain barrier (BBB) is a specialized system of capillary endothelial cells that protects the brain from harmful substances in the blood stream, while supplying the brain with the required nutrients for proper function. The BBB controls transport through both tight junctions and metabolic barriers and is often a rate-limiting factor in determining permeation of therapeutic drugs into the brain. It is a significant obstacle for delivery of both small molecules and macromolecular agents. Although many drugs could be potentially used to treat brain disease, there has been no method that allows non-invasive-targeted delivery through the BBB. Recently, promising studies indicate that ultrasound can be used to locally deliver a drug or gene to a specific region of interest in the brain. If microbubbles are combined with ultrasound exposure, the effects of ultrasound can be focused upon the vasculature to reduce the acoustic intensity needed to produce BBB opening. Several avenues of transcapillary passage after ultrasound sonication have been identified including transcytosis, passage through endothelial cell cytoplasmic openings, opening of tight junctions and free passage through injured endothelium. This article reviews the topic of transient disruption of the BBB with ultrasound and microbubbles and addresses related safety issues. It also discusses possible roles of the BBB in brain disease and potential interactions with ultrasound and microbubbles in such disease states.

Animals↗

PubMed2004

Numerical modeling of microbubble backscatter to optimize ultrasound particle image velocimetry imaging: initial studies.

We have developed a promising non-invasive ultrasound-based method for performing particle image velocimetry (PIV) in vivo. This method, termed echo PIV, provides multi-component blood velocity data with good ( approximately 2 ms) temporal resolution. The method takes advantage of the non-linear ultrasound backscatter characteristics of small gas-filled microbubbles (ultrasound contrast) that are seeded into the blood stream. In this study, we use a numerical model to explore potential areas to focus future work in echo PIV. Ultrasound backscatter from encapsulated microbubbles was modeled using a modified Rayleigh-Plesset equation (Church model, 1995), taking into account the protein/lipid shell layer as a thick, mass-conserving incompressible fluid surrounded by incompressible blood-like fluid. The equation of motion was solved numerically to characterize the fundamental and second harmonic components of the backscattered pressure. Results show a significant advantage in using the second harmonic component for echo PIV, especially for small bubble sizes less than 3 microm in diameter at 2.2 MHz frequency. The effect of the shell thickness ranging from 10 to 500 nm on the vibration amplitude of the bubble was examined and it is shown that the presence of the shell requires mechanical index (MI) > 0.2 of incident pressure amplitude to improve bubble detectability. Analysis of the effect of pulse length shows a tradeoff between axial resolution (short pulse length) and bubble detectability (longer pulse length) will most likely be required. The effect of varying MI between 0.1 and 0.6 was also studied at a center frequency of 2.2 MHz and the results indicate that the resonance of the second harmonic is maximized for bubbles with diameter of approximately 2.75 microm. Bubble non-linearities at MI > 0.2 induced a resonant frequency shift away from the integer multiple of the incident frequency in the second harmonic backscatter. For a given bubble size, there is a combination of optimal incident frequency and mechanical index range that maximizes the ratio of the second harmonic compared to the fundamental. This resonant frequency decreases with increasing bubble radius. Further, a narrow bandwidth pulse is shown to increase signal strength. Both of these effects may cause conflict with factors governing spatial resolution. Optimization of the incident frequency, microbubble size and mechanical index to enhance bubble detectability will depend on the particular clinical application. These theoretical predictions provide further understanding of the physics behind our echo PIV technique, and should be useful for guiding the design of echo PIV systems.

Blood Flow Velocity↗

PubMed2006

Thermal response of contrast agent microbubbles: preliminary results from physico-chemical and US-imaging characterization.

Hyperthermia (HT) is a therapeutic strategy based on the selective damaging of tumoral cells when heated at temperatures in the range 41-45 degrees C. We are currently investigating the feasibility of Ultrasound (US) imaging to perform a non-invasive, efficient and cost effective temperature monitoring of heated tissues. Commercial US contrast agents (Sonovue, Bracco), consisting in microbubbles of SF(6) coated with a phospholipidic shell, greatly improve the US echo signal from tissues. Further investigations have been performed, consisting in physico-chemical and US-imaging characterization. In conclusion, we demonstrate that Sonovue microbubbles reach their maximal diameter at 40 degrees C, and then a sharp decrease is observed, possible due to the occurrence of gel-sol transition of the phospholipidic shell. At the same temperature the maximal backscattering intensity is predicted and actually experimentally observed. Sonovue, as well as other contrast agents based only on phospholipids, are, therefore, not suitable for use as non-invasive temperature monitoring medium since it is sensitive to temperatures below the hyperthermic range. Although microbubbles are in principle thermally effective, other coating materials should be investigated in order to increase their operative thermal range.

Contrast Media↗

PubMed2005

Optimising phase and amplitude modulation schemes for imaging microbubble contrast agents at low acoustic power.

A series of in vitro experiments were performed to determine the efficacy of generalised phase- and amplitude-modulated sequences for low-power nonlinear microbubble contrast imaging. The microbubble agent Definity (Dupont, Boston, MA) was exposed to sequences in which the phase and amplitude were changed from one pulse to the next. Echoes from these pulses were combined to suppress or enhance particular linear or nonlinear components. The results show that established two-pulse pulse-inversion and amplitude-modulation approaches perform similarly, providing 14 +/- 1 dB of enhancement, compared with the echoes from the linear scatterer. A two-pulse combined phase and amplitude sequence achieved an additional 4 +/- 1 dB of enhancement. This improvement is due to improved preservation of second and third order harmonic signals, while maintaining the suppression of the linear signals. These results were obtained at low power, below the threshold of microbubble destruction, and are applicable to real-time perfusion imaging.

Contrast Media↗

PubMed2005

Vascular effects induced by combined 1-MHz ultrasound and microbubble contrast agent treatments in vivo.

Previous in vivo studies have demonstrated that microvessel hemorrhages and alterations of endothelial permeability can be produced in tissues containing microbubble-based ultrasound contrast agents when those tissues are exposed to MHz-frequency pulsed ultrasound of sufficient pressure amplitudes. The general hypothesis guiding this research was that acoustic (viz., inertial) cavitation, rather than thermal insult, is the dominant mechanism by which such effects arise. We report the results of testing five specific hypotheses in an in vivo rabbit auricular blood vessel model: (1) acoustic cavitation nucleated by microbubble contrast agent can damage the endothelia of veins at relatively low spatial-peak temporal-average intensities, (2) such damage will be proportional to the peak negative pressure amplitude of the insonifying pulses, (3) damage will be confined largely to the intimal surface, with sparing of perivascular tissues, (4) greater damage will occur to the endothelial cells on the side of the vessel distal to the source transducer than on the proximal side and (5) ultrasound/contrast agent-induced endothelial damage can be inherently thrombogenic, or can aid sclerotherapeutic thrombogenesis through the application of otherwise subtherapeutic doses of thrombogenic drugs. Auricular vessels were exposed to 1-MHz focused ultrasound of variable peak pressure amplitude using low duty factor, fixed pulse parameters, with or without infusion of a shelled microbubble contrast agent. Extravasation of Evans blue dye and erythrocytes was assessed at the macroscopic level. Endothelial damage was assessed via scanning electron microscopy (SEM) image analysis. The hypotheses were supported by the data. We discuss potential therapeutic applications of vessel occlusion, e.g., occlusion of at-risk gastric varices.

Animals↗

PubMed2005

Absolute measurement of ultrasonic backscatter from single microbubbles.

Good quality acoustical experiments are needed to measure microbubble behavior. An absolute calibration of the transmitted ultrasound field is possible using a calibrated hydrophone, but characterization of the received ultrasound beam is a more elaborate process and is not described in the literature. A new system based on a hydrodynamically focused flow has been used to measure echoes from single microbubbles at well specified positions in the ultrasonic field. An experimental set-up was built around a commercial scanner (Sonos 5500, Philips Medical Systems) to measure the scatter from solid spheres with radii between 30 to 60 microm. The behavior of these linear scatterers is accurately predicted by theory and software was produced to incorporate a simulation of the experimental conditions. The calibration of a phased array transducer was achieved by quantifying the receiver's spectral sensitivity for the range of receive frequencies (1.2 to 4.5 MHz). Examples of echoes from the microbubble agent Definity are used to illustrate the implementation of the calibration technique.

Algorithms↗