Size Of Emboli Research Articles

Emboli detection using a new transducer design

We have presented, in a previous study, a new approach to detect, characterize and estimate the size of gaseous emboli, based on the nonlinear behavior of gaseous bubbles. In this study, a specific transducer design has been developed to be used for such a purpose. It is composed of two separate transmitting and receiving capabilities. The transmit part, consisting of a lead zirconate-titanate (PZT) material, emits at a frequency of 500 kHz and could generate pressures up to 410 kPa. On the top of the transmit surface, a thin polyvinylidene difluoride (PVDF) layer is glued and used for receiving frequencies from 250 kHz ( f 0/2) up to 2.5 MHz (5 f 0). To evaluate this new design, ultrasonic measurements were carried out with gas bubbles with diameters ranging from 10 μm up to 90 μm and solid particles between 350 μm and 550 μm. The experimental results confirmed our previous findings: gaseous emboli with a diameter close to the resonance size scatter significantly at higher harmonic components (from the second harmonic up to the fifth), and bubbles with a diameter around twice the resonance size produce a subharmonic and/or an ultraharmonic component. Meanwhile, solid particles and other bubble sizes behave only linearly and their scattered spectrum appeared without any harmonics. The study demonstrates the utility of this approach in using a single transducer to detect and characterize selective gaseous emboli from other particles using their nonlinear behavior. (E-mail: p.palanchon@erasmusmc.nl)

Carotid angioplasty in a pulsatile flow model: Factors affecting embolic potential

Ojectives: carotid endoluminal intervention is an alternative to urgery but carries a risk of embolic stroke even with distal rotection devices. We investigated the clinical features and degree of stenosis related to number and size of emboli during carotid angioplasty. Design: an experimental ex vivo study. Materials: an ex vivo pulsatile flow model was used in which temperature, velocity, flow, pressure and viscosity characteristics were designed to simulate the carotid circulation. Methods: carotid endarterectomy specimens excised as intact cylinders (n = 28) were subjected to a standardised angioplasty procedure using radiological guidance. Emboli collected in filters placed distally were counted and sized using microscopy. Results: median number of emboli during angioplasty was 133 (range 15-1331). Median size of the largest embolus was 700 microns (range 75-2400). Severity of stenosis correlated with increased maximum size (r = 0.55, p = 0.012). Statin therapy >4 weeks pre-operatively was associated with reduced emboli number and size (54 (range 15-748) vs 247 (range 37-1331) [p = 0.023] and 400 μm (range 75-2400) vs 1300 μm (range 600-2200) [p = 0.022]). Conclusions: in this model a wide range of emboli number and size were produced. Number and size of embolic particles were highest in patients with high-grade stenoses not receiving statin therapy.Eur J Vasc Endovasc Surg 26, 22-31 (2003)

Cerebral protection devices for treatment of carotid stenoses: Where do we stand today?

The carotid bifurcation is currently a subject of controversial discussion within the vascular territory. These controversies are obvious for diagnostic imaging but the more so for therapy. Performing stenting as a treatment tool, controversies exist also as to whether angioplasty is performed without or obligatory with cerebral protection. Théron and colleagues first described the concept of cerebral protection during carotid angioplasty and stent placement. Currently, there are three temporary cerebral protection systems, i. e. balloon occlusion, filtration baskets, and systems for flow reversal in the internal carotid artery. While these systems provide a considerable degree of protection, as has been shown in in vitro and preliminary clinical studies, embolization might still occur, even under protection. In addition, it is still not clear what the minimum size of emboli is that need to be stopped to prevent a stroke, and what the relevance of cerebral microemboli is. Clinical evidence suggests that the usage of protection systems favours a good outcome of the intervention; however, whether or not such systems should be used routinely remains a matter of discussion and should thus be verified in further clinical studies.

Retinal embolization during carotid angioplasty and stenting: mechanisms and role of cerebral protection systems.

Carotid stenting has become an accepted alternative to endarterectomy, but fear of embolic stroke has impeded its generalized application. The retina provides a unique observatory for the study of emboli, which may occur either directly or indirectly via collaterals to the ophthalmic artery. Systems under development for cerebral protection differ in their capacity to trap small emboli and in their protection of the collateral circulation. We evaluated 118 sequential patients undergoing carotid stenting using fundoscopy, fluorescein retinal angiography, and visual field examination. The site and size of emboli was assessed, and degree of edema estimated. All patients were treated using distal protection during carotid stent implantation: 38 patients with the Théron system (using routine flushing toward the external carotid) and 80 patients with the Percusurge system (aspiration only). Retinal embolization occurred in 6 of the 118 patients (4%), of whom 2 were symptomatic (1.7%). Using the Théron system, 5 of 38 patients (13.2%) had emboli while 1 of 80 (1.25%) had emboli using the Percusurge system (P = 0.019). Symptoms occurred only with emboli >20 microm. Symptomatic retinal embolization is uncommon during carotid stenting, but is more likely when external to internal carotid collaterals are not protected. Cerebral protection system designs should take into consideration the existence of collaterals and the need to protect against smaller sized emboli, which may cause blindness in the retinal circulation.

Combined MR proton lung perfusion/angiography and helium ventilation: Potential for detecting pulmonary emboli and ventilation defects

Three-dimensional (3D) perfusion imaging allows the assessment of pulmonary blood flow in parenchyma and main pulmonary arteries simultaneously. MRI using laser-polarized (3)He gas clearly shows the ventilation distribution with high signal-to-noise ratio (SNR). In this report, the feasibility of combined lung MR angiography, perfusion, and ventilation imaging is demonstrated in a porcine model. Ultrafast gradient-echo sequences have been used for 3D perfusion and angiographic imaging, in conjunction with the use of contrast agent injections. 2D multiple-section (3)He imaging was performed subsequently by inhalation of 450 ml of hyperpolarized (3)He gas. The MR techniques were examined in a series of porcine models with externally delivered pulmonary emboli and/or airway occlusions. With emboli, perfusion deficits without ventilation defects were observed; airway occlusion resulted in matched deficits in perfusion and ventilation. High-resolution MR angiography can unambiguously reveal the location and size of the blood emboli. The combination of the three imaging methods may provide complementary information on abnormal lung anatomy and function.

Pulmonary Embolism: Comparison of Gadolinium-Enhanced MR Angiography with Contrast-Enhanced Spiral CT in a Porcine Model

Rationale and Objectives The purpose of this study was to compare gadolinium-enhanced magnetic resonance (MR) angiography with contrast material–enhanced computed tomography (CT) for the detection of small (4–5-mm) pulmonary emboli (PE), with a methacrylate cast of the porcine pulmonary vasculature used as the diagnostic standard. Materials and Methods In 15 anesthetized juvenile pigs, colored methacrylate beads (5.2 and 3.8 mm diameter—the size of segmental and subsegmental emboli in humans) were injected via the left external jugular vein. After embolization, MR angiographic and CT images were obtained. The pigs were killed, and the pulmonary arterial tree was cast in clear methacrylate, allowing direct visualization of emboli. Three readers reviewed CT and MR angiographic images independently and in random order. Results Forty-nine separate embolic sites were included in the statistical analysis. The mean sensitivity (and 95% confidence intervals) for CT and MR angiography, respectively, were 76% (68%–82%) and 82% (75%–88%) ( P > .05); the mean positive predictive values, 92% (85%–96%) and 94% (88%–97%) ( P > .05). In this porcine model, PE were usually seen as parenchymal perfusion defects (98%) with MR angiography and as occlusive emboli (100%) with CT. Conclusion MR angiography is as sensitive as CT for the detection of small PE in a porcine model.

Early complete recanalization in internal carotid artery embolism treated with high-dose t-PA. A sequential angiographic study in a novel model of embolism in rats

Complete early recanalization rate of human internal carotid artery embolic occlusion treated with thrombolytic drugs is low. To study factors related with this difficulty to recanalize we have developed a novel model of rat ica embolism using a fragment of human embolus. In 50 male Wistar rats the ica was embolized through the external carotid artery with a fragment of an embolus obtained from a human embolectomy passed through a catheter of 0.8 mm diameter. Recanalization was assessed by sequential angiograms from 15 to 120 min after embolization. Reperfusion was classified according to TIMI grades. Emboli of either 1 (group 1) or 2 mm (group 2) in length were cut. In group 1, four groups of nine animals each were treated, 15 min after embolization, with i.v. t-PA at doses of 1 mg/kg, 10 mg/kg and 20 mg/kg or saline. In group 2 there was one control group of seven animals treated with saline and another of seven animals treated with 10 mg/kg t-PA. Complete recanalization (TIMI grade 3) within the first 30 min was present in two animals treated with 10 and 20 mg/kg. Complete recanalization within the first 60 min was present in 0% of controls and animals treated with 1 mg/kg and in 44% of the 10 and 20 mg/kg groups ( P<0.05 in chi-square test). Incomplete recanalization (TIMI grades 0,1 and 2) occurred in 33%. In group 2 total recanalization occurred in 1/7 controls and in 3/7 animals receiving 10 mg/kg of t-PA. Early (60 min) complete i.v. t-PA induced internal carotid artery embolic recanalization is low with standard doses and increases moderately when high doses are used. Further increases in the dose do not improve recanalization rate, which is not clearly influenced by embolus size. Complete recanalization within 30 min, the period after which infarction develops in the rat, is uncommon in our model.

Atheroembolic occlusion of the left axillary artery after percutaneous transluminal coronary angioplasty

Atheromatous embolism may occur in two forms, according to the size of embolus [1]. Atheroemboli occlude major arteries such as coronary, renal, and peripheral arteries, and are easy to recognize clinically. On the other hand, cholesterol emboli involve multiple vessels of 150 to 200 μm in diameter and may go unrecognized, or present with nonspecific manifestations that mimic other systemic diseases. Simultaneous atheroembolization and cholesterol embolization has been seldom reported [2].

Determination of size of aortic emboli and embolic load during coronary artery bypass grafting

Embolic signals have been detected within both the aortic lumen and the intracranial vasculature during coronary artery bypass grafting. Total numbers of these emboli have been reported. The present study examined the size of individual emboli and the total volume of embolization. Using transesophageal echocardiography, we continuously monitored the aortic lumen of 10 patients undergoing isolated coronary artery bypass grafting. We manually analyzed 720,000 individual echo frames over a 4-minute period after the release of aortic clamps to track and to calculate the volume of 657 individual particles. The embolic load for the entire procedure was calculated from mean volume based on analysis of 1,508 particles. We simultaneously monitored the middle cerebral artery using transcranial Doppler ultrasonography and compared numbers of emboli detected by the two techniques. Particle diameter ranged from 0.3 to 2.9 mm (mean, 0.8 mm), and particle volume from 0.01 to 12.5 mm3 (mean, 0.8 mm3). Twenty-eight percent of particles measured 1 mm or more, 44% measured 0.6 to 1.0 mm, and only 27% measured 0.6 mm or less in diameter. Aortic embolic load for the procedure ranged from 0.6 cm3 to 11.2 cm3 (mean, 3.7 cm3). Estimated cerebral embolic load for the procedure ranged from 60 to 510 mm3 (mean, 276 mm3). The fraction of aortic emboli entering the cerebral circulation was very variable (3.9% to 18.1%). Seventy-six percent of the embolic volume after the release of clamps occurred over a 20-second period. Only 1 patient was encephalopathic perioperatively. This patient had the largest estimated cerebral embolic load (510 mm3) and the second largest aortic embolic load (8.4 cm3). We determined the size of individual intraaortic embolic particles and the total volume of embolization during coronary artery bypass grafting, and found the proportion entering the cerebral circulation to be very variable. The constitution of these particles and the neurologic impairment resulting from such embolization remains to be determined.

Microembolus Sizing in a Blood-Mimicking Fluid Using a Novel Dual-Frequency Pulsed Doppler.

Sizing of emboli in a blood-mimicking fluid is explored with the application of a theoretical description of emboli to embolic signatures obtained in a phantom flow loop. The theoretical predictions for the backscattered power versus embolus size are based on the embolus to blood power ratio (EBR) model. The experimental setup utilizes a customized ultrasound pulsed Doppler that is capable of interrogating a sample volume with two different frequencies concurrently. Polystyrene "emboli" having nominal diameters of 161 &mgr;m are placed in a specially constructed flow loop and scattering signatures are recorded. These signatures are investigated and the effect of beam refraction is discussed, which, combined with the EBR theory, yields a method to determine embolus size from an embolic signal. Embolus size determined experimentally is in close agreement with manufacturer's reported size. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

Sizing emboli in blood using pulse Doppler ultrasound--I: Verification of the EBR model.

An experiment to verify a theory describing ultrasound backscattering from emboli in flowing blood is presented. The theoretical predictions for the backscattered power versus embolus size are based on the measurement of the embolus to blood ratio (EBR) of backscattered acoustic power. This tool is necessary for in vivo clinical application because it removes the need to characterize attenuation and reflection loss in heterogeneous tissue. The experiment presented utilizes a customized ultrasound pulse Doppler that is capable of interrogating a sample volume with two different frequencies concurrently. A flow circuit including a 3.6-mm-diameter conduit in polyacrylamide gel in which emboli are observed with the dual frequency Doppler is described. The flow within the circuit has acoustic backscatter coefficient similar to blood due to a calibrated concentration of 31.1-mu diameter polystyrene microspheres. Polystyrene microsphere "emboli" having nominal diameters of 161 and 239 mu are placed in this flow loop and time series Doppler shift signatures are recorded. These signatures are investigated and a refraction artifact hypothesis is proposed to explain systematic deviation of the signatures away from theoretically expected results. Results show that gross discrimination of embolus size is feasible.

Venous thromboembolism: Detection by duplex scanning

The usefulness of transcranial Doppler monitoring in identifying emboli in the arterial circulation has been established. We attempted to extend this technique to identify embolism in the venous circulation and to note any changes in embolism rate with anticoagulation. From March to July 1993, 218 patients were evaluated by duplex scan for deep venous thrombosis. Sixty patients had positive study results; 26 scans (43%) demonstrated embolism. In five patients (19%) the emboli were also seen on a B-mode image, enabling us to estimate embolus size, which ranged from 200 to 5000 micrometer. Embolus counts varied from 5 to 800 per minute. Deep venous thrombosis was located in the iliofemoral vein in 2 patients, superficial femoral/profunda vein in 8, saphenofemoraal junction in 1, popliteal vein in 1, and the calf in 10. Concomitantly, studies in 158 patients were negative for deep venous thrombosis; embolism was detected in 4 patients (3%) in this group. In patients taking heparin, the embolus counts decreased 50% or more within 24 hours, and all embolism was abolished within 72 hours. Two patients died of pulmonary embolus. Patients with duplex scans that are positive for deep venous thrombosis have a high incidence of ongoing embolism. Heparin appears effective in eliminating the microemboli detected. The relationship among microembolism, deep venous thrombosis, and clinically significant pulmonary embolism remains to be elucidated.

Multiple Emboli and Filter Function: An in Vitro Comparison of Three Vena Cava Filters

To establish the influence of number of emboli on the trapping ability of vena cava filters in vitro. Three filters, the titanium Greenfield, Vena Tech-LGM, and Günther Tulip retrievable, were studied with use of 20- or 26-mm-diameter tubes to simulate the inferior vena cava. In the first protocol, five small (4 x 20-mm) or medium (6 x 10-mm) emboli were delivered in sequence, and the fate of each was recorded. In the second protocol, medium or large (6 x 30-mm) clots were sequentially introduced until filter occlusion occurred or 50 clots had been delivered. For the first protocol, 82% of first small clots and 60% of second clots were trapped in 20-mm tubes (P = .001) and 63% and 45%, respectively, were trapped in 26-mm tubes (P - .02). With medium clots, the proportion trapped also dropped significantly with ascending clot rank. In the second protocol the proportion of clots captured was invariably higher for the first 10 clots (P < .001 for all combinations of covariables). Filter function deteriorates with number of emboli delivered, irrespective of embolus size and simulated vein caliber.

In vitro evaluation of a new temporary venous filter: The spring filter

To evaluate in vitro the function efficacy of a new variable-sized, temporary venous filter, the Spring filter (SF). The SF was tested in a flow phantom, using flexible, thin-walled polyethylene tubes 12, 14, and 16 mm in diameter to simulate veins. Clots of three sizes were used: 6 x 10 mm, 6 x 20 mm, 9 x 20 mm. Filter deployment was performed, ensuring that its functional diameter after placement was a predetermined multiple of the radius 'r' of the tube: 3.0r, 2.8r, 2.6r, 2.4r. The terminal coil was visually examined for changes in configuration. Clot retention by the filter for a period of 3 min was recorded as a success. The baseline intraluminal pressure and the maximum pressure reached after clot introduction were recorded. The trapping ability was calculated from the results for 10 clots. The effect of the following parameters on filter function were studied: size of embolus, caliber of simulated vein, and functional diameter of filter. The filter configuration was stable. Not a single instance of axial tilting occurred on deployment. Functional diameter was the major determinant of filter function. One hundred percent of clots were trapped irrespective of clot size and tube caliber when the functional diameter was 3.0r. Only 73% (95% confidence interval (CI): 57% - 88%) and 77% (95% CI: 61% - 92%) of small emboli were held up by the filter when the functional diameters were 2.6r and 2.4r, respectively (p = 0.0001). A significant reduction in clot trapping was encountered even with medium clots when the functional diameter was 2.4r (p = 0.02). Against the background of available data on retrievable vena caval filters, the current model of SF warrants further investigation.

Experimental aspects of high-intensity transient signals in the detection of emboli.

Experimental studies in the 1960s and 1970s demonstrated the high sensitivity of Doppler ultrasound in detecting gaseous bubbles. More recent studies have shown that microscopic air bubbles, as well as glass microspheres as small as 5 mu to 20 mu, cause characteristic high-intensity signals. Recently it has been demonstrated that less echogenic embolic materials such as thrombus, platelet aggregates, and atheroma can also be detected with a high sensitivity. Such "solid," or formed-element, emboli as small as 200 mu to 400 mu can be detected; the lower size limit of detection was due to an inability to make smaller embolic particles rather than to the sensitivity of the detection process itself. Analysis of the Doppler signals provides some information about embolus size and composition, but accurate characterization in clinical practice is not possible using current technology. Studies in experimental models have allowed the detailed description of embolic signals; they appear as a short-duration, frequency-focused increase in intensity, predominantly unidirectional in the direction of flow, and usually contained within the spectral envelope. In contrast, artifacts appear as a bidirectional, high-intensity increase with maximum intensity at low frequencies. These differences have been exploited to develop automatic embolus detection programs, and an off-line version has been successfully validated in an experimental model.

The effect of velocity on the appearance of embolic signals studied in transcranial Doppler models.

Transcranial Doppler ultrasound can be used to detect circulating cerebral emboli. Recent studies have demonstrated that embolus size is significantly related to both the relative intensity increase and duration of an embolic signal. This may allow information about embolus size to be obtained by analysis of Doppler embolic signals. However, theoretically duration will be inversely related to velocity, and therefore velocity may need to be accounted for if information on embolus size is to be derived from the duration of Doppler embolic signals. The relation between velocity and both relative intensity increase and duration of embolic signal was investigated in an in vitro flow model, a sheep carotid artery model, and in patients with prosthetic heart valves. The same standard transcranial Doppler ultrasound machine was used for all studies. Embolic signals resulting from 99 glass microspheres (size, 210 to 250 microns) were studied in the in vitro model, as were those from 64 glass microspheres (size, 105 to 150 microns) in the sheep model. Embolic signals recorded from the six middle cerebral arteries of three patients with prosthetic cardiac valves were also studied. There was a significant (P < .001) inverse relation between velocity and duration of high-intensity signal (in vitro model, r = -.82; sheep model, r = -.43); the exact relations were described using best-fit equations. Correlation coefficients for this relation in patients varied between -.30 and -.55. There was also an unexpected significant positive relation between velocity and intensity in the sheep model (r = .44, P < .001) but not in the in vitro model (P > .05). This relation was also seen in some, but not all, patients. When the duration of embolic signals is used to provide information about the relative size of an embolus, the velocity of the embolic signal should be taken into account. A relation between velocity and relative intensity increase was found in the sheep model and in some patient recordings. It is suggested this relation may result from greater power being supplied to emboli traveling at higher velocities in the center of the vessel; this may occur under certain recording conditions.

Detection of circulating cerebral emboli using Doppler ultrasound in a sheep model

We describe a validation study of a new technique for detecting circulating pathological cerebral emboli. Theoretically one would expect solid emboli to be detectable as high intensity signals on the Doppler waveform, and such signals have been reported in humans with potential embolic sources. Pathological cerebral emboli (thrombi, platelet aggregates and atheroma) were introduced into the proximal carotid artery of an in vivo sheep model, and their passage detected in the cerebral circulation using Doppler ultrasound. All of 74 emboli, with a maximum dimension as small as 0.24 mm, were detected as short duration high intensity signals. Smaller pathological emboli could not be made but glass microspheres as small as 5–20 micron resulted in high intensity signals. A significant positive correlation was found between embolus size and relative intensity increase of the embolic signal. A significant positive correlation was also found between embolus size and duration of embolic signal. This study demonstrates that detection of circulating cerebral emboli is possible in vivo. This technique may allow selection of patients at particularly high risk of cerebral embolisation so that they can be given specific prophylactic treatment. Analysis of the Doppler signal may give information on the size of the embolus, although using current signal analysis it is impossible to distinguish between the signals produced by say a larger platelet embolus or a smaller thrombus embolus.

Venous Air Embolism During Cesarean Section: More Common Than Previously Thought

To confirm the incidence of venous air embolism (VAE), we simultaneously monitored expired nitrogen concentration (FEN2) and precordial Doppler in 30 patients undergoing cesarean delivery during general anesthesia. Patients were randomized into two groups and the effect of a 10 degrees reverse Trendelenburg tilt versus the horizontal position was evaluated. Forty-two episodes of VAE, defined by an increase in FEN2 of 0.1%, were detected in 97% (29/30) of patients. Doppler ultrasound failed to detect 9 of the episodes and 23 (41%) changes in Doppler tones were not associated with an increase in FEN2. These spurious Doppler signals were synchronous with compression of retroperitoneal structures, suggesting turbulent venous return to be the cause. The reverse Trendelenburg position did not reduce the incidence of VAE. Compared with the preinduction baseline, mean arterial blood pressure decreased by 31.5 +/- 10.1 mm Hg in this position and 22.6 +/- 13.4 mm Hg in the supine position after hysterotomy. We conclude that VAE in cesarean delivery during general anesthesia occurs very frequently, and that changes in Doppler tones may not be reliable indicators of this complication. Measures to reduce the size and effect of air emboli therefore should be applied routinely in all patients.

The Effect of Different Settings of Ultrasound Pulse Amplitude, Gain and Sample Volume on the Appearance of Emboli Studied in a Transcranial Doppler Model

Circulating cerebral emboli can be detected by transcranial Doppler (TCD) sonography. However, there has been little systematic study of parameters necessary for optimal embolus detection. Both the intensity increase associated with an embolic signal, compared to the background, and the duration of an embolic signal have been suggested as indicators of embolus size and material. We investigated the effect of different TCD machine settings on the appearance of 145 embolic signals associated with microspheres of known size in a tube model of the middle cerebral artery. The results demonstrated that optimal separation of emboli from the background signal will occur if recordings utilise the lower part of the dynamic range. This is due to the fact that the dynamic range of the displayed intensity is logarithmically compressed. The intensity of the embolic signal relative to the intraspectral background was inversely related to both gain (p < 0.0001) and sample volume (p < 0.0001). There was only a weak relationship between relative intensity increase and emitted ultrasound pulse amplitude. These findings will also need to be taken into consideration if signal analysis is used to derive information on the size of emboli.

Pulse Doppler ultrasound detection, characterization and size estimation of emboli in flowing blood

A theory describing pulse Doppler ultrasound signals due to backscattering due to emboli in flowing blood is presented. From this theory, the minimum detectable size of a formed-element embolus can be established as a function of carrier frequency and vessel size. Emboli can be sized and characterized, based on the ratio of the amplitude of the Doppler signal during embolus passage through the sample volume to background bloodflow Doppler signal when no embolus is present. This ratio is defined as the "embolus to blood ratio" (EBR). Size estimation of emboli can be done by insonating an embolus with a single frequency and measuring the EBR, only if the embolus does not exceed a certain size, and if the vessel diameter and per cent hematocrit are known. Using two different frequencies, the vessel geometry (diameter and sample volume length) and per cent hematocrit can be eliminated from calculation of embolus size. Sources of uncertainty in the EBR and their effect on embolus size estimation are discussed. Discrimination between gas and formed-element emboli is described, given a detector with sufficient dynamic range, and use of three carrier frequencies. The theory presented here is in agreement with experimental findings of other investigators.