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Biomedical subjects

C M Moran

Publications and source records attributed to C M Moran.

At least 19 recordsLinked to original sources
PubMed2006

Manufacture and acoustical characterisation of a high-frequency contrast agent for targeting applications.

The aim of this study was to develop and acoustically to optimise an ultrasonic contrast agent for research imaging applications at 40 MHz. A range of liposomal dispersions were manufactured and the mean backscatter power was measured using a Boston Scientific ClearView Ultra intravascular scanner with a 40 MHz, 2.5 Fr Atlantis SR Plus catheter. The scanner had been modified to allow access to the unprocessed ultrasound data, which were digitised, and the mean backscatter power was calculated over a region-of-interest centred at 2 mm from the transducer. Mean backscatter power was normalised to the data collected from a water-air interface. The effects of sonication and rapid shaking on six liposomal samples were also studied and this indicated that both techniques significantly reduced the size of the liposomes within the dispersions. Maximum mean backscatter power was measured for sonicated liposomal dispersions with 60% by weight of phosphatidylethanolamine. Moreover, this dispersion had greater mean backscatter power than sheep blood at 40 MHz.

Contrast Media↗
PubMed2006

Nanointerrogation of ultrasonic contrast agent microbubbles using atomic force microscopy.

Predicting the acoustic response of an encapsulated microbubble to ultrasound requires an accurate assessment of the mechanical properties of the microbubble shell. Atomic force microscopy (AFM) provides an unprecedented spatial and force resolution of the order of Angstroms and subnanonewtons, respectively. It is introduced here as a means to interrogate microbubbles manufactured for ultrasonic imaging. The advantage of AFM over scanning electron microscopy (SEM) is that the microbubbles need not be subjected to a low temperature or low-pressure environment. The microbubbles were interrogated in a liquid environment, which could potentially be a simulated physiological environment. AFM was used in tapping mode imaging to reveal topographical detail of biSphere microbubbles. Because microbubbles are large objects compared with the overall size of usual AFM tips, a convolution between the AFM tip and the microbubble was typical of the acquired topographies. However, a part of the top half of the bubble was imaged with nanometer resolution, and roughness measurements are reported. Force-distance curves were captured using contact mode AFM. The range of stiffness or effective spring constant of biSphere was found to be between 1 and 6 N m(-1). In conclusion, the AFM is proposed here for the first time as a tool to image the surface of bubbles at the nanometer range in liquid and to perform reproducible measurements on the mechanical properties of individual microbubbles.

Biomechanical Phenomena↗
PubMed2004

An in vitro study of a microbubble contrast agent using a clinical ultrasound imaging system.

Optimal insonation settings for contrast imaging are yet to be specified, mainly due to the lack of good understanding of the behaviour of the microbubbles. A satisfactory model that explains the behaviour of individual contrast agent scatterers has not yet been reported in the literature. An in vitro system based on a commercial scanner (ATL HDI3000) has been developed to investigate the backscatter of such agents. Suspensions of Definity were introduced in an anechoic tank. The frequency of transmitted ultrasound varied from 1 to 5 MHz, pulse period from 2 to 10 periods and peak negative acoustic pressure from 0.08 to 1.7 MPa. The backscatter at the fundamental and second harmonic frequency windows from the agent was normalized in terms of the corresponding components of backscatter from a blood mimicking fluid suspension. The agent provided a dominant resonance effect at 1.6 MHz transmit frequency. Second harmonic normalized backscatter averaged around 9 dB higher than the fundamental. The normalized fundamental backscatter intensity was linear with peak negative pressure. The second harmonic at resonance peaked at 0.5 MPa suggestive of bubble disruption above such pressure. The system proved capable of illustrating the ultrasonic behaviour of Definity in vitro, and the investigation suggested particular insonation conditions for optimal image enhancement using Definity.

Acoustics↗
PubMed2003

The behaviour of individual contrast agent microbubbles.

In recent years, our knowledge of the behaviour of ultrasonic microbubble contrast agents has improved substantially through in vitro experiments. However, there has been a tendency to use high concentrations of contrast agents in suspension, so that ultrasonic backscatter data are generated by a cloud of microbubbles. Such experiments involve a variety of assumptions with validity that is open to question. In addition, high concentrations of microbubbles cannot be used to understand the behaviour of individual microbubble scatterers. This paper proposes a technique that minimises the number of assumptions that need to be made to interpret in vitro experimental data. The basis of the technique is a dilute suspension of microbubbles that makes single scattering events distinguishable. A commercial scanner was used to collect radio frequency (RF) data from suspensions of two different contrast agents, Quantison and Definity. Backscatter data were collected over a range of acoustic pressures. It was found that Definity provided a constant number of scattering events per unit volume of suspension for almost all applied acoustic pressures. Quantison demonstrated an increasing number of scattering events per unit volume with increasing acoustic pressure. Below 0.6 MPa, Quantison scatterers were not individually detectable and provided levels of backscatter similar to those of a blood-mimicking fluid, which suggests that Quantison microbubbles had almost linear scattering behaviour. At acoustic pressures greater than 0.6 MPa, both agents appeared to provide echoes from free bubbles. The change in the number of scatterers per unit volume with acoustic pressure cannot be demonstrated using high concentrations of contrast agent.

Acoustics↗
PubMed2002

Understanding the limitations of ultrasonic backscatter measurements from microbubble populations.

Despite over ten years of in vitro investigations of ultrasound contrast agents, the level of understanding of their behaviour in ultrasound fields is limited. Several problems associated with these investigations, particular to the nature of contrast agents, are discussed. Using a commercial scanner the RF normalized backscatter of two different contrast agents (Definity and Quantison) was measured at different suspension concentrations and acoustic pressures. Both contrast agents scattered ultrasound nonlinearly and the backscatter showed a dependence on acoustic pressure. In order to assess the average behaviour of the agents across the range of acoustic pressures and microbubble concentrations the experimental data were fitted to a theoretically acceptable model using nonlinear regression analysis. The analysis showed that both the backscatter and the attenuation of the Quantison suspensions displayed a higher order of dependence on acoustic pressure than the Definity suspensions. It was also discovered that Quantison microbubbles did not demonstrate uniform behaviour across the acoustic pressure range. At lower acoustic pressures the behaviour could not follow a model similar to that which predicted the behaviour at higher acoustic pressures, which was mainly due to the fact that free bubbles were released in a fashion dependent on acoustic pressure. The fact that two different populations of scatterers exist in the same suspensions makes the assessment of the behaviour of the particular agent impossible with the high concentrations that are commonly used. Very low concentration suspensions whereby single scattering events can be monitored should be more useful. In conclusion, the approach of using high microbubble concentrations in order to investigate the properties of ultrasonic contrast agents is limited in that the results of such studies cannot be used to understand the behaviour of single microbubbles.

Acoustics↗
PubMed2002

The dependence of ultrasound contrast agents backscatter on acoustic pressure: theory versus experiment.

Experimental investigations have not fully explored the interaction between ultrasound beams and microbubble contrast agents. Moreover theoretical investigations have not solved the problem of the microbubble oscillation. A simple in-vitro system based on a commercial scanner (ATL UM9) was used to insonate (3 MHz transmission) diluted contrast suspensions of Definity and Quantison at different acoustic pressures (0.27-1.52 MPa). The experimental data were referred to a blood mimicking fluid in order to extract an estimate of their scattering cross-section. The results were compared with the solutions of the three main bubble oscillatidn models, Rayleigh-Plesset, Herring and Gilmore. Non-linear solutions of the above models were produced numerically using the Mathematica Package Software. The experiments showed that both agents provided a linear increase in scattering cross-section with increasing acoustic pressure. The thick shelled Quantison provided an increasing number of scatterers with increasing acoustic pressure, which proved that free bubbles leaked out of the shell. At high acoustic pressures both Quantison and Definity scattering cross-sections were almost identical, and were probably that of a free bubble. The Rayleigh-Plesset model provided a scattering cross-section almost independent of acoustic pressure. On the contrary the scattering cross-sections calculated by the Herring and Gilmore models solutions displayed a definite dependence on acoustic pressure of an order higher than one, which is slightly higher than the order of dependence exhibited by the experimental data. However, the increase of the experimentally measured scattering cross-section with acoustic pressure was sharper than the calculated one by the above two models. This is most probably due to the fact that the models simulated damped and not free bubble oscillations. In conclusion the Rayleigh-Plesset model was inadequate in describing the bubble oscillations even at small diagnostic acoustic pressures. The Herring and Gilmore models could simulate the dependence of the scattering cross-section of encapsulated microbubbles on acoustic pressure. However the contribution of free bubble oscillations has still to be modelled.

Journal Article↗
PubMed2002

In vitro acoustic characterisation of four intravenous ultrasonic contrast agents at 30 MHz.

The acoustic properties of four ultrasonic contrast agents (Optison, Definity, SonoVue and Sonazoid) were studied at 30 MHz using a Boston Scientific ClearView Ultra intravascular ultrasound (US) scanner modified to allow access to the unprocessed US data. A range of contrast agent concentrations were studied using either saline or glucose as the diluent of choice. Mean backscatter power was measured over regions-of-interest (ROI) at distances of 1, 1.5, 2, 3, 4 and 5 mm from the centre of the intravascular probe and normalised to the US data collected from a standard glass reflector. For all of the agents, the mean backscatter power at 30 MHz varied in a linear manner with concentration between 0.01 million microbubbles/mL and 1 million microbubbles/mL. Furthermore, for two of the agents, mean backscatter enhancement was detectable at concentrations as low as 2 microbubbles/sample volume.

Albumins↗
PubMed2001

Contrast agent stability: a continuous B-mode imaging approach.

The stability of contrast agents in suspensions with various dissolved gas levels has not been reported in the literature. An in vitro investigation has been carried out that studied the combined effect of varying the acoustic pressure along with degassing the suspension environment. In this study, the contrast agents were introduced into suspensions with different oxygen concentration levels, and their relative performance was assessed in terms of decay rate of their backscatter echoes. The partial pressures of oxygen in those solutions ranged between 1.5 and 26 kPa. Two IV and one arterial contrast agents were used: Definity, Quantison, and Myomap. It was found that Quantison and Myomap released free bubbles at high acoustic pressure that also dissolved faster in degassed suspensions. The backscatter decay for Definity did not depend on the air content of the suspensions. The destruction of bubbles was dependent on acoustic pressure. Different backscatter performance was observed by different populations of bubbles of the last two agents. The physical quantity of "overall backscatter" (OB) was defined as the integral of the decay rate over time of the backscatter of the contrast suspensions, and improved significantly the understanding of the behaviour of the agents. A quantitative analysis of the backscatter properties of contrast agents using a continuous imaging approach was difficult to achieve. This is due to the fact that the backscatter in the field of view is representative of a bubble population affected by the ultrasound (US) field, but this bubble population is not representative of the contrast suspension in the whole tank. Single frame insonation is suggested to avoid the effects of decay due to the ultrasonic field, and to measure a tank-representative backscatter. The definition of OB was useful, however, in understanding the behaviour of the agents.

Acoustics↗
PubMed2001

An in vitro system for the study of ultrasound contrast agents using a commercial imaging system.

An in vitro system for the investigation of the behaviour of contrast microbubbles in an ultrasound field, that provides a full diagnostic range of settings, is yet to be presented in the literature. The evaluation of a good compromise of such a system is presented in this paper. It is based on (a) an HD13000 ATL scanner (Bothell, WA, USA) externally controlled by a PC and (b) on the use of well-defined reference materials. The suspensions of the reference ultrasonic scattering material are placed in an anechoic tank. The pulse length ranges from 2 to 10 cycles, the acoustic pressure from 0.08 to 1.8 MPa, the transmit frequency from 1 to 4.3 MHz, and the receive frequency from 1 to 8 MHz. The collection of 256 samples of RF data, at an offset distance from the transducer face, was performed at 20 MHz digitization rate, which corresponds to approximately 1 cm depth in water. Two particle suspensions are also presented for use as reference scatterers for contrast studies: (a) a suspension of Orgasol (ELF Atochem, Paris, France) particles (approximately 5 microm mean diameter) and (b) a suspension of Eccosphere (New Metals & Chemicals Ltd, Essex, UK) particles (approximately 50 microm mean diameter). A preliminary experiment with the contrast agent Definity (DuPont Pharmaceutical Co, Waltham, MA) showed that the above two materials are suitable for use as a reference for contrast backscatter.

Contrast Media↗
PubMed2000

Quantification of microbubble destruction of three fluorocarbon-filled ultrasonic contrast agents.

The assessment of myocardial blood velocity using ultrasonic contrast agents is based on the premise that the vast majority of contrast microbubbles within a myocardial region can be destroyed by an acoustic pulse of sufficient magnitude. Determination of the period of time after destruction that a region of myocardium needs to reperfuse may be used to assess myocardial blood velocity. In this study, we investigated the acoustic pressure sensitivity of three solutions of intravenous fluorocarbon-filled contrast agents and the magnitude of acoustic pulse required to destroy the contrast agent microbubbles. A novel tissue-mimicking phantom was designed and manufactured to investigate the relationships between mean integrated backscatter, incident acoustic pressure and number of frames of insonation for three fluorocarbon-filled contrast agents (Definity(R), Optison(R), and Sonazoid(R), formerly NC100100). Using a routine clinical ultrasound (US) scanner (Acuson XP-10), modified to allow access to the unprocessed US data, the contrast agents were scanned at the four acoustic output powers. All three agents initially demonstrated a linear relationship between mean integrated backscatter and number of frames of insonation. For all three agents, mean integrated backscatter decreased more rapidly at higher acoustic pressures, suggesting a more rapid destruction of the microbubbles. In spite of the fact that there was no movement of microbubbles into or out of the beam, only the results from Definity(R) suggested that a complete destruction of the contrast agent microbubbles had occurred within the total duration of insonation in this study.

Albumins↗
PubMed2000

An in vitro comparison of ultrasonic contrast agents in solutions with varying air levels.

The performance, in particular, the stability of ultrasound (US) contrast agents has yet to be assessed. An in vitro system has been set up to investigate the properties of ultrasonic contrast agents under different suspension conditions. This is designed to contribute to the optimal use of agents in clinical practice. In this study, the contrast agents were introduced into solutions of different oxygen concentration levels, as might be encountered in blood, and their relative performance was assessed in terms of decay in the solution environment. The partial pressures of oxygen in those solutions ranged between 1.5 and 26 kPa. Three IV and one arterial contrast agents were used: Levovist, DMP115, Quantison and Myomap. Levovist showed the highest sensitivity to oxygen concentration in the solution, and the other three proved tolerant for the above values of oxygen concentrations.

Capsules↗
PubMed2000

Evaluation of an experimental system for the in vitro assessment of ultrasonic contrast agents.

The ultrasonic properties of microbubble contrast agents need to be fully understood if reproducible images and quantitative results are to be produced. Additional aspects of the physical and chemical environment into which the contrast agents are introduced also need to be taken into account, and their effect on contrast agent performance evaluated. A setup that provides an accurate and reproducible data-acquisition system is presented and evaluated in this paper. The linear range of this system is assessed, as well as its accuracy and precision. A new approach to the investigation of contrast agents, based on normalised backscatter, is discussed. Also, a common technique of degassing, widely used in other areas, is described and evaluated to determine its appropriateness to contrast agent studies.

Contrast Media↗
PubMed1998

Developments in cardiovascular ultrasound. Part 3: Cardiac applications.

Echocardiography is still the principal, non-invasive method of investigation for the evaluation of cardiac disorders. Using Doppler ultrasound, indices such as coronary flow reserve and cardiac output can be determined. The severity of valvular stenosis can be determined by the area of the valve, either directly from 2D echo, from pressure half-time calculations, from continuity equations or from the proximal isovelocity surface area method. Alternatively, the severity of regurgitation can be estimated by colour or pulsed ultrasound detection of the back-projection of the high-velocity jet into the chamber. Myocardial wall abnormalities can be assessed using 2D ultrasound, M-mode or analysis from the radio-frequency-ultrasound signal. Doppler tissue imaging can be used to quantify intra-myocardial wall velocities, and 3D reconstruction of cardiac images can provide visualisation of the complete cardiac anatomy from any orientation. The development of myocardial contrast agents and associated imaging techniques to enhance visualisation of these agents within the myocardium has aided qualitative assessment of myocardial perfusion abnormalities. However, quantitative myocardial perfusion has still to be realised.

Cardiac Output↗
PubMed1998

Quantification of the enhanced backscatter phenomenon from an intravenous and an intra-arterial contrast agent.

The phenomenon of enhanced backscatter from myocardial contrast agents was studied using two examples, a robust thicker-walled, intra-arterial agent (AIP 201) and a smaller thinner-walled, intravenous agent (Quantison). Both agents are composed of albumin-encapsulated microbubbles. Samples of the agents were inserted into an in vitro phantom and insonated under different scanning regimes. Upon insonation, Quantison exhibited a pronounced increase in mean backscatter at medium and low concentrations, which decreased dramatically with increasing number of frames of insonation. At high concentrations, no dramatic decrease or increase in mean backscatter was observed over the period of the experiment. AIP 201 exhibited an overall decrease in mean backscatter with increasing number of frames of insonation. These results suggest that the difference in size and wall thickness of the contrast microcapsules can significantly affect the behaviour of the contrast agents in an ultrasound field.

Contrast Media↗
PubMed1997

Measurement of cyclic variation in ultrasonic integrated backscatter in conscious, unsedated, clinically normal dogs.

OBJECTIVE: To assess the feasibility and repeatability of measuring ultrasonic integrated backscatter in unsedated conscious dogs, using a protocol previously validated in pigs with open thorax. ANIMALS: 11 clinically normal conscious unsedated German Shorthair Pointers. PROCEDURE: A modified commercially available echocardiography system was used to record long-axis views of the heart. The radiofrequency data from 15 consecutive frames were digitized and analyzed. Regions of interest were chosen within the myocardium, and the ultrasonic integrated backscatter within each region was calculated in the time domain for each frame. RESULTS: Cyclic variation in integrated backscatter values was observed, with maximal values at end-diastole and minimal values at end-systole. Mean +/-SD amplitude of cyclic variation was 5.81 +/- 3.86 dB over all the regions chosen. CONCLUSIONS: Results agreed with those obtained by other investigators working with dogs with open thorax and those with closed thorax while under general anesthesia. The analysis of the components of variance indicates that this is a consistent, reliable technique in conscious unsedated dogs. CLINICAL RELEVANCE: Integrated ultrasonic backscatter measurement provides a noninvasive means of tissue characterization. Use of this protocol reliably yields cyclic variation in integrated backscatter and could be applied clinically to dogs with myocardial disease.

Anesthesia, General↗
PubMed1996

Regional variations of ultrasonic integrated backscatter in normal and myopathic left ventricles. A new multi-view approach.

The purpose of the present study was to determine whether the cyclic variation of integrated backscatter is measurable and quantifiable in all left ventricular walls and whether the information obtained using both parasternal and apical transducer positions can be used to identify changes in myocardial structure and contractility. The cyclic variation of integrated backscatter was measured from the parasternal long-axis, apical four-chamber and two-chamber views in 26 patients with idiopathic dilated cardiomyopathy (mean age 58 +/- 9 years; ejection fraction 29 +/- 10%) and compared with information obtained from 30 aged-matched healthy volunteers. For each subject, the cyclic variation of integrated backscatter was calculated from 16 predetermined regions-of-interest located within the myocardium of the basal and mid-segments of the left ventricle imaged from the long-axis view and also the basal mid and apical left ventricular segments imaged from the two apical views. The cyclic variation of integrated backscatter was found to be present in 100% of the analysed regions-of-interest in healthy volunteers and in 87.5% of the analysed regions-of-interest in patients with idiopathic dilated cardiomyopathy. The mean value of cyclic variation of integrated backscatter, averaged from all regions-of-interest in the idiopathic dilated cardiomyopathy group, was significantly reduced compared to that in the healthy volunteers group (3.2 +/- 2.5 dB [mean +/- SD] vs 4.8 +/- 2.9 dB, P < 0.0001). Additionally, the healthy volunteers group demonstrated marked regional variability in the magnitude of cyclic variation of integrated backscatter which closely followed the regional changes in the contractile function of the normal heart. These regional differences in the magnitude of the cyclic variation of integrated backscatter were only partially retained in the idiopathic dilated cardiomyopathy group, and suggest that a multi-view approach of the recording of cyclic variation of integrated backscatter can be of value to differentiate normal from myopathic myocardium and to quantify regional differences in myocardial contractile performance throughout the left ventricular walls.

Adult↗