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PubMed1988

Occurrence of transient cavitation in pulsed sawtooth ultrasonic fields.

Thus far, studies conducted to assess the safety of diagnostic ultrasound have employed sinusoidal sound fields. To evaluate the influence of nonlinearly distorted acoustic fields, this article compares the responses of microbubbles of variable size, exposed to (1) a sinusoidal pulse and (2) a sawtooth pulse. The nonlinear oscillations of a spherical bubble in a viscous compressible liquid stimulated into motion by an ultrasonic pulse are predicted, using a theoretical model for bubble dynamics. The maximum gas pressures inside the bubble when it collapses under the influence of a sinusoid or a sawtooth are deduced. Experimental work on Drosophila larvae exposed to sinusoidal and to sawtooth fields is consistent with the theoretical analysis.

Acoustics↗

PubMed1989

A theoretical study of cavitation generated by an extracorporeal shock wave lithotripter.

The intense acoustic wave generated at the focus of an extracorporeal shock wave lithotripter is modeled as the impulse response of a parallel RLC circuit. The shock wave consists of a zero rise time positive spike that falls to 0 at 1 microsecond followed by a negative pressure component 6 microseconds long with amplitudes scaled to +1000 and -160 bars, P+ and P-, respectively. This pressure wave drives the Gilmore-Akulichev formulation for bubble dynamics; the zero-order effect of gas diffusion on bubble response is included. The negative pressure component of a 1000-bar shock wave will cause a preexisting bubble in the 1- to 10-microns range to expand to over 100 times its initial size, R0, for 250 microseconds, with a peak radius of approximately 1400 microns, then collapse very violently, emitting far UV or soft x-ray photons (black body). Gas diffusion does not appreciably mitigate the amplitude of the pressure wave radiated at the primary collapse, but does significantly reduce the collapse temperature. Diffusion also increases the bubble radius from R0 up to 40 microns and extends the duration of ringing following the primary collapse, assuming that the bubble does not break up or shed microbubbles. Results are sensitive to P+/P- and to the duration of the negative pressure cycle but not to rise time.

Lithotripsy↗

PubMed1990

An acoustic backscattering technique for the detection of transient cavitation produced by microsecond pulses of ultrasound.

An acoustic backscattering technique for detecting transient cavitation produced by 10-microseconds-long pulses of 757-kHz ultrasound is described. The system employs 10-microseconds-long, 30-MHz center frequency tone bursts that scatter from cavitation microbubbles. Experiments were performed with suspensions of hydrophobic polystyrene spheres in ultraclean water. Transient cavitation threshold pressures measured with the active cavitation detector (ACD) were always less than or equal to those measured using a passive acoustic detection scheme. The measured cavitation thresholds decreased with increasing dissolved gas content and increasing suspended particle concentration. Results also show that ultrasonic irradiation of the polystyrene sphere suspensions by the ACD lowered the threshold pressure measured with the passive detector. A possible mechanism through which suspensions of hydrophobic particles might nucleate bubbles is presented.

Acoustic Stimulation↗

PubMed1990

Collapse and rebound of a gas-filled spherical bubble immersed in a diagnostic ultrasonic field.

This work is concerned with the influence of the finite-amplitude distortion of a driving diagnostic ultrasonic field on the collapse and rebound of a gas-filled spherical microbubble, present in the exposed compressible liquid. Such an analysis is especially important since one of the mechanisms for cavitation damage comes from the very large gas pressures generated at bubble collapse and in the subsequent pressure wave formed by bubble rebound. Gilmore's model [F.R. Gilmore, "The growth or collapse of a spherical bubble in a viscous compressible liquid," Hydrodynamics Lab. Rep. No. 26-4, California Institute of Technology, Pasadena, CA (1952)] for bubble dynamics is used to obtain the motion of the bubble interface when subjected to a pulsed diagnostic ultrasonic field of large amplitude. Knowledge of the bubble motion allows one to derive the pressure distribution around the bubble. Numerical results over a range of initial bubble sizes, acoustic pressures, and frequencies relevant to medical use show that the strength of the pressure spikes radiated by the rebounding bubble depends upon (i) the acoustic frequency (f), (ii) the initial bubble size (R0), and (iii) the magnitude of the pressure amplitude of the fundamental (PF) in a Fourier series description of the distorted pulse. As the pressure spikes propagate outward from the bubble wall, their strength is attenuated as the reciprocal of the distance from the center of collapse.

Air Pressure↗

PubMed1990

Thresholds for transient cavitation produced by pulsed ultrasound in a controlled nuclei environment.

Transient cavitation is a discrete phenomenon that relies on the existence of stabilized nuclei, or pockets of gas within a host fluid, for its genesis. A convenient descriptor for assessing the likelihood of transient cavitation is the threshold pressure, or the minimum acoustic pressure necessary to initiate bubble growth and subsequent collapse. An automated experimental apparatus has been developed to determine thresholds for cavitation produced in a fluid by short tone bursts of ultrasound at 0.76, 0.99, and 2.30 MHz. A fluid jet was used to convect potential cavitation nuclei through the focal region of the insonifying transducer. Potential nuclei tested include 1-microns polystyrene spheres, microbubbles in the 1- to 10-microns range that are stabilized with human serum albumin, and whole blood constituents. Cavitation was detected by a passive acoustical technique that is sensitive to sound scattered from cavitation bubbles. Measurements of the transient cavitation threshold in water, in a fluid of higher viscosity, and in diluted whole blood are presented. These experimental measurements of cavitation thresholds elucidate the importance of ultrasound, host fluid, and nuclei parameters in determining these thresholds. These results are interpreted in the context of an approximate analytical theory for the prediction of the onset of cavitation.

Acoustics↗

PubMed1995

A test of the hypothesis that cavitation at the focal area of an extracorporeal shock wave lithotripter produces far ultraviolet and soft x-ray emissions.

Church hypothesized that the violent collapse of microbubbles in water in the focal area of an extra-corporeal shock wave lithotripter (ESWL) can generate biologically damaging far uv and soft x-ray photons. Two techniques were used to test this hypothesis. Gassy water (10 ml) was exposed to ten piezoelectric lithotripter shocks (P+ = 43 MPa, P- = 9 MPa). The resultant sonoluminescence was filtered by optical band-pass filters and measured using a photomultiplier tube (PMT). Next, a commercially available scintillation cocktail (Ecoscint A), which is formulated to convert high energy photons to visible light, was exposed to varying numbers of lithotripter shocks and the relative luminescence intensity measured and compared to background and distilled water luminescence readings. Results showed support for the hypothesized presence of near uv emissions (approximately 250 nm) and marginal support for the production of higher energy photons, possibly including far uv and soft x-ray emissions.

Equipment Design↗

PubMed1999

Subharmonic backscattering from ultrasound contrast agents.

The ultrasonic contrast of blood in tissue, which is needed for ultrasonic estimation of tissue perfusion, can be increased by injecting the blood with bubbles or hollow microspheres. It has been shown that an even greater improvement in contrast can be obtained by using the subharmonic generated by irradiated microspheres. By obtaining analytical solutions to the modified RPNNP equation for a coated microbubble, the relationship between the physical parameters of the encapsulated bubble and the threshold pressure is established. The observed increase in the resonance frequency of a coated microsphere is explained by introducing the concept of "acoustic radius" of the encapsulated bubble. It is predicted that subharmonic generation in contrast agents requires a threshold insonifying pressure, and should be a minimum when microspheres are insonated at twice their resonance frequency. Experiments confirm the existence of this optimum incident frequency and of a reasonably low threshold pressure for the generation of the subharmonic. The existence of the low threshold pressures for subharmonic generation in contrast agents may prove to be very valuable in ultrasonic contrast imaging.

Contrast Media↗

PubMed2000

Decay of large underwater bubble oscillations

Pressure-time series from breathing-mode oscillation of large (centimeter scale or larger) underwater bubbles reveal much higher decay rates than can be explained using viscous, thermal, or radiative mechanisms which apply to microbubbles. It is shown that if one assumes energy transfer to shape oscillations (surface capillary waves) of large amplitude in subharmonic resonance with the breathing mode [M. S. Longuet-Higgins, J. Acoust. Soc. Am. 91, 1414 (1992)], then the shape oscillations can drive fluid motions outside the bubble capable of exciting turbulent instabilities. Application of an appropriate eddy viscosity from mixing-length theory to the viscous decay mechanism appears to offer a credible explanation for the observed large decay rates. An analysis is given to show that energy is transferred from the breathing mode to surface capillaries fast enough to make the proposed decay mechanism viable.

Journal Article↗

PubMed1996

Characterizing replication intermediates in the amplified CHO dihydrofolate reductase domain by two novel gel electrophoretic techniques.

Using neutral/neutral and neutral/alkaline two-dimensional (2-D) gel techniques, we previously obtained evidence that initiation can occur at any of a large number of sites distributed throughout a broad initiation zone in the dihydrofolate reductase (DHFR) domain of Chinese hamster ovary (CHO) cells. However, other techniques have suggested a much more circumscribed mode of initiation in this locus. This dichotomy has raised the issue whether the patterns of replicating DNA on 2-D gels have been misinterpreted and, in some cases, may represent such noncanonical replication intermediates as broken bubbles or microbubbles. In an accompanying study (R. F. Kalejta and J. L. Hamlin, Mol. Cell. Biol. 16:4915-4922, 1996), we have shown that broken bubbles migrate to unique positions in three different gel systems and therefore are not likely to be confused with classic replication intermediates. Here, we have applied a broken bubble assay developed from that study to an analysis of the amplified DHFR locus in CHO cells. This assay gives information about the number and positions of initiation sites within a fragment. In addition, we have analyzed the DHFR locus by a novel stop-and-go-alkaline gel technique that measures the size of nascent strands at all positions along each arc in a neutral/neutral 2-D gel. Results of these analyses support the view that the 2-D gel patterns previously assigned to classic, intact replication bubbles and single-forked structures indeed correspond to these entities. Furthermore, potential nascent-strand start sites appear to be distributed at very frequent intervals along the template in the intergenic region in the DHFR domain.

Animals↗

PubMed2002

Power Doppler sonography in the assessment of synovial tissue of the knee joint in rheumatoid arthritis: a preliminary experience.

OBJECTIVE: To investigate the intra-articular vascularisation of the synovial pannus in the knee of patients with rheumatoid arthritis (RA) with power Doppler ultrasonography (PDS) and an echo contrast agent and correlate the area under the time-intensity curves with the clinical findings and laboratory measures of disease activity. METHOD: Forty two patients with RA (31 women, 11 men) with history and signs of knee arthritis, classified according to a modified index of synovitis activity (active, moderately active, and inactive), were studied. Clinical and functional assessment (number of swollen joints, intensity of pain, general health-visual analogue scale, disability index-Health Assessment Questionnaire, Ritchie articular index) and a laboratory evaluation were made on all patients. Disease activity was evaluated using the disease activity score (DAS) and the chronic arthritis systemic index (CASI) for each patient. All patients were examined with conventional ultrasonography and PDS before injection of intravenous ultrasound contrast agent (Levovist). The quantitative estimation of the vascularisation of the synovial membrane was performed with time-intensity curves and calculation of the area under the curves. RESULTS: The mean (SD) value of the area underlying time-intensity curves was 216.2 (33.4) in patients with active synovitis, 186.8 (25.8) in patients with moderately active synovitis, and 169.6 (20.6) in those with inactive synovitis. The mean value of the areas differed significantly between the patients with active and those with inactive synovitis (p<0.01). The mean value of the area under the curve of the entire group was weakly correlated with the number of swollen joints (p=0.038), but a strong correlation was found with composite indexes of disease activity such as the DAS (p=0.006) and CASI (p=0.01). No correlation was found with age, disease duration, and other laboratory and clinical variables. CONCLUSION: PDS may be a valuable tool to detect fractional vascular volume and to assist clinicians in distinguishing between inflammatory and non-inflammatory pannus. The transit of microbubbles of ultrasound contrast across a tissue can be used to estimate haemodynamic alterations and may have a role in assessing synovial activity and the therapeutic response to treatment of synovitis of the knee joint.

Adult↗

PubMed1994

First experience with a new echographic contrast agent.

The intravenous injection of an ultrasound contrast agent can enhance signals from blood flow. Broad toxicological and pharmaceutical studies in animals confirmed the safety and efficacy of an ultrasound contrast agent made of microparticles of galactose with stabilised microbubbles in watery suspension (SH U 508 A). In this paper 10 patients with different malignant orbital and ocular tumours have been evaluated with an echo colour Doppler machine before and after the injection of SH U 508 A. An enhancement of the Doppler signals in the lesions in different degrees has been detected. This echographic contrast agent seems to be very important not only in the evaluation of vascular lesions, but also in evaluating the effectiveness of radiotherapy in malignant tumours and could spread the echographic indications in several other ophthalmic fields.

Adult↗

PubMed2006

Cerebral emboli as a potential cause of Alzheimer's disease and vascular dementia: case-control study.

OBJECTIVE: To compare the occurrence of spontaneous cerebral emboli and venous to arterial circulation shunts in patients with Alzheimer's disease or vascular dementia and controls without dementia. DESIGN: Cross sectional case-control study. SETTING: Secondary care old age psychiatry services, Manchester. PARTICIPANTS: 170 patients with dementia (85 with Alzheimer's disease, 85 with vascular dementia) and 150 age and sex matched controls. Patients on anticoagulant treatment, patients with severe dementia, and controls with marked cognitive impairment were excluded. MAIN OUTCOME MEASURES: Frequencies of detection of spontaneous cerebral emboli during one hour monitoring of the middle cerebral arteries with transcranial Doppler and venous to arterial circulation shunts by a transcranial Doppler technique using intravenous microbubbles as an ultrasound contrast. RESULTS: Spontaneous cerebral emboli were detected in 32 (40%) of patients with Alzheimer's disease and 31 (37%) of those with vascular dementia compared with just 12 each (15% and 14%) of their controls, giving significant odds ratios adjusted for vascular risk factors of 2.70 (95% confidence interval 1.18 to 6.21) for Alzheimer's disease and 5.36 (1.24 to 23.18) for vascular dementia. These spontaneous cerebral emboli were not caused by carotid disease, which was equally frequent in dementia patients and their controls. A venous to arterial circulation shunt indicative of patent foramen ovale was found in 27 (32%) Alzheimer's disease patients and 25 (29%) vascular dementia patients compared with 19 (22%) and 17 (20%) controls, giving non-significant odds ratios of 1.57 (0.80 to 3.07) and 1.67 (0.81 to 3.41). CONCLUSION: Spontaneous cerebral emboli were significantly associated with both Alzheimer's disease and vascular dementia. They may represent a potentially preventable or treatable cause of dementia.

Aged↗

PubMed2004

Dynamic imaging of pancreatic diseases by contrast enhanced coded phase inversion harmonic ultrasonography.

BACKGROUND: Coded phase inversion harmonic ultrasonography, a newly available sonographic technique, enables visualisation of slow flow in minute vessels in a real time fashion with the use of a sonographic contrast agent containing monosaccharide. Our purpose was to employ this novel technique to observe microvessels in pancreatic tumours. SUBJECTS AND METHODS: Sixty five patients with suspicious pancreatic tumours received contrast enhanced coded phase inversion harmonic ultrasonography, contrast enhanced computed tomography, and endosonography. Final diagnoses based on histological findings were pancreatic ductal carcinomas in 49 patients, inflammatory pseudotumours with chronic pancreatitis in seven, and endocrine tumours in nine. For contrast enhanced coded harmonic ultrasonography, Levovist, a contrast agent, was injected intravenously as a bolus. When the first microbubble signal appeared in the pancreas, images of the ideal scanning plane were displayed in a real time continuous fashion (vessel images). Subsequently, interval delay scanning (perfusion images) was taken to demonstrate parenchymal flow. Tumour vascularity was evaluated by using the two types of imaging. Sensitivities for depicting pancreatic tumours were compared between three examinations. RESULTS: Contrast enhanced ultrasonography demonstrated tumour vessels in 67% of pancreatic ductal carcinomas, although most were relatively hypovascular compared with the surrounding pancreatic tissue. The vascular patterns of tumours obtained by contrast enhanced ultrasonography were closely correlated with those obtained by contrast enhanced computed tomography. Values for sensitivity in depicting pancreatic tumours of 2 cm or less in size were 68% for contrast enhanced computed tomography, 95% for endosonography, and 95% for contrast enhanced ultrasonography. CONCLUSION: Contrast enhanced coded phase inversion harmonic ultrasonography successfully visualised fine vessels in pancreatic tumours and may play a pivotal role in the depiction and differential diagnosis of pancreatic tumours.

Adult↗

PubMed2000

Comparison of myocardial contrast echocardiography with NC100100 and (99m)Tc sestamibi SPECT for detection of resting myocardial perfusion abnormalities in patients with previous myocardial infarction.

OBJECTIVE: To determine whether myocardial contrast echocardiography (MCE) following intravenous injection of perfluorocarbon microbubbles permits identification of resting myocardial perfusion abnormalities in patients who have had a previous myocardial infarction. PATIENTS AND INTERVENTIONS: 22 patients (mean (SD) age 66 (11) years) underwent MCE after intravenous injection of NC100100, a novel perfluorocarbon containing contrast agent, and resting (99m)Tc sestamibi single photon emission computed tomography (SPECT). With both methods, myocardial perfusion was graded semiquantitatively as 1 = normal, 0.5 = mild defect, and 0 = severe defect. RESULTS: Among the 203 normally contracting segments, 151 (74%) were normally perfused by SPECT and 145 (71%) by MCE. With SPECT, abnormal tracer uptake was mainly found among normally contracting segments from the inferior wall. By contrast, with MCE poor myocardial opacification was noted essentially among the normally contracting segments from the anterior and lateral walls. Of the 142 dysfunctional segments, 87 (61%) showed perfusion defects by SPECT, and 94 (66%) by MCE. With both methods, perfusion abnormalities were seen more frequently among akinetic than hypokinetic segments. MCE correctly identified 81/139 segments that exhibited a perfusion defect by SPECT (58%), and 135/206 segments that were normally perfused by SPECT (66%). Exclusion of segments with attenuation artefacts (defined as abnormal myocardial opacification or sestamibi uptake but normal contraction) by either MCE or SPECT improved both the sensitivity (76%) and the specificity (83%) of the detection of SPECT perfusion defects by MCE. CONCLUSIONS: The data suggest that MCE allows identification of myocardial perfusion abnormalities in patients who have had a previous myocardial infarction, provided that regional wall motion is simultaneously taken into account.

Aged↗

PubMed2000

Ultrasonic evaluation of pathological brain perfusion in acute stroke using second harmonic imaging.

OBJECTIVE: To evaluate the use of transient response second harmonic imaging (HI) by means of ultrasound to assess abnormalities of cerebral echo contrast agent enhancement in patients with acute stroke. METHODS: The study comprised 25 patients with acute onset of hemispheric stroke (<24 h) with sufficient insonation conditions and 14 control subjects without cerebrovascular disease. All stroke patients had HI, extracranial and transcranial colour coded duplex examinations of the arteries supplying the brain, and clinical examinations (European stroke scale) performed in the acute phase, on day 2, and within 1 week. Acute CT was repeated within 1 week and facultatively accompanied by angiography. Examinations using HI were performed in an axial diencephalic plane of section using the transtemporal acoustic bone window. After bolus application of galactose based microbubbles, 61 ultrasound images with a cardiac cycling triggering frequency of once every 2 seconds were recorded and evaluated off line. Focal perfusion deficit was identified if no contrast enhancement was visualised in a circumscribed region of interest and insufficient temporal bone window was excluded. In cases of reappearance of contrast enhancement reperfusion was assessed. RESULTS: Adequate cerebral contrast enhancement could be seen in 21 subjects. In seven, a large hemispheric deficit of contrast enhancement affecting the entire middle cerebral artery (MCA) territory was detectable; the lentiform nucleus was affected in three subjects. Assessment of cerebral contrast abnormalities was possible in two patients with superficial MCA infarctions but in none of the patients with lacunar ischaemias. None of the control persons had focal deficits of cerebral echo contrast enhancement. In all patients with complete MCA infarction and striatocapsular infarction, presumed ischaemic areas in HI examinations correlated with final CT findings. Overall sensitivity and specifity of HI examinations for predicting size and localisation of the infarction were 75 and 100%, respectively. During follow up, reappearance of contrast enhancement was determined in three patients, in two patients circulatory arrest due to malignant brain oedema with missing contrast enhancement in the entire cerebral hemisphere could be seen. Extent of contrast enhancement deficits significantly correlated with the clinical status on admission and after 1 week (p<0.01). CONCLUSIONS: Second harmonic imaging is the first ultrasonic technique that enables visualisation of pathological cerebral echo contrast enhancement. Because this method identifies deficits of focal contrast enhancement in patients with acute stroke and allows estimation of the final infarct size and clinical prognosis, it may help to select and monitor patients for invasive therapies.

Acute Disease↗

PubMed1978

An ultrasonic analysis of the comparative efficiency of various cardiotomy reservoirs and micropore blood filters.

The ability of 12 commercially available cardiotomy reservoirs to remove bubbles from aspirated blood was investigated by means of a simulated cardiopulmonary bypass circuit and an ultrasonic microbubble detector. Performance varied considerably. The number of gaseous microemboli remaining after passage of blood through the reservoir was reduced by (a) holding the blood in the reservoir, (b) reducing the volume of air mixed with the aspirated blood, and (c) using a reservoir that did not induce turbulence and that contained integral micropore filtration material. Further micropore filtration of the blood after passage through the cardiotomy reservoir was beneficial, and significantly more bubbles were extracted when the microfilter was sited below the reservoir than when it was placed in the arterial line.

Cardiopulmonary Bypass↗

PubMed2001

Benign and malignant breast masses and axillary nodes: evaluation with echo-enhanced color power Doppler US.

PURPOSE: To evaluate microbubble contrast enhancement in distinguishing malignant from benign breast masses and malignant from benign axillary nodes in patients with breast cancer. MATERIALS AND METHODS: Eighty-six patients with 86 breast masses and 32 patients with breast cancer (subgroup of 86 patients) with 32 axillary nodes underwent color power Doppler ultrasonography with and without contrast material. Vascular features and contrast material transit times were recorded. Nodal enhancement was compared with corresponding primary breast cancer enhancement in the subset of 32 patients. RESULTS: Pathologic analysis revealed 58 breast carcinomas and 28 benign breast lesions and 20 malignant and 12 benign axillary nodes in the 32 patients with breast cancer. Breast cancers had a greater total number and greater number of peripheral vessels than did benign lesions before and after contrast material administration (P <.001). Malignant nodes had a greater total number and greater number of peripheral vessels at baseline and after contrast enhancement (P <.05), and a longer enhancement duration (P =.004) compared with benign nodes. Malignant nodes enhanced more than did corresponding primary breast cancers. Postcontrast number of peripheral vessels was an independent predictor of primary breast cancer (P <.05), and increased number of peripheral vessels after contrast enhancement and enhancement duration were independent predictors of nodal malignancy (P <.05). CONCLUSION: Primary breast cancers and malignant axillary nodes had a greater total number and greater number of peripheral vessels compared with benign breast masses and axillary nodes, respectively.

Adult↗

PubMed2002

Contrast-enhanced US of the prostate with Sonazoid: comparison with whole-mount prostatectomy specimens in 12 patients.

PURPOSE: To compare areas of contrast material enhancement in the prostate at ultrasonography (US) with whole-mount radical prostatectomy specimens to determine if the use of contrast material improves the detection rate of prostate cancer. MATERIALS AND METHODS: Transrectal US was performed in 12 subjects with cancer of the prostate prior to radical prostatectomy. Each gland was evaluated with conventional gray-scale and wide-band harmonic US at baseline and again during intravenous infusion of a microbubble contrast agent. Focal areas of contrast enhancement were identified prospectively in the transverse plane at the base, midgland, and apex of the prostate. US findings were then compared with whole-mount prostatectomy specimens. Baseline and contrast-enhanced findings were compared by using the Wilcoxon signed rank test. RESULTS: Thirty-one foci of prostate cancer were present at pathologic evaluation, with multiple foci of cancer in 11 of the 12 glands. Three of 10 inner-gland cancers and five of 21 outer-gland cancers were detected at baseline imaging. Diffuse inner-gland enhancement was identified in all subjects during contrast agent infusion. Contrast-enhanced imaging demonstrated an additional five cancer foci in the outer gland (P =.025), for an overall sensitivity of 42% (13 of 31 foci). Seven additional sites of focal contrast enhancement were identified. Five of these sites corresponded to foci of hyperplasia. Two sites were false-positive with no pathologic abnormality. Increased flow was not demonstrated posteriorly in the midline, even when a tumor was present. CONCLUSION: Contrast-enhanced US of the prostate with Sonazoid can improve sensitivity for the detection of cancers in the outer gland, but it can also demonstrate focal enhancement in areas of benign hyperplasia.

Aged↗