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Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography.

An international Consensus Meeting to determine a standard in the examination technique for the detection of right-to-left shunt (RLS) using contrast transcranial Doppler sonography (TCD) led to the following recommendations to standardize the examination procedure: The patient should be prepared with an 18-gauge needle inserted into the cubital vein and should be in the supine position. Insonation of at least one middle cerebral artery (MCA) using TCD is performed. The contrast agent is prepared using 9 ml isotonic saline solution and 1 ml air mixed with a three-way stopcock by exchange of saline/air mixture between the syringes and injected as a bolus. In case of little or no detection of microbubbles (MB) in the MCA under basal conditions, the examination will be repeated using the Valsalva maneuver (VM). Contrast agent will be injected 5 s before the start of the VM; the overall VM duration should be 10 s. The patient should start the VM on examiner's command. The strength of the VM can be controlled by peak flow velocity of the Doppler curve. The time when the first MB appears at the MCA level will be noted. A four-level categorization according to the MB count should be applied: (1) 0 MB (negative result); (2) 1-10 MB; (3) >10 MB and no curtain, and (4) curtain. ('Curtain' refers to a shower of MB, where a single bubble cannot be identified.) The results should be documented for basal condition and VM testing separately. The clinical significance of the diagnosis of a RLS in a particular patient is not fully evaluated and requires further studies. A minimum amount of MB suggestive of a clinical relevant RLS is not yet established. It probably depends on interindividual differences in hemodynamics that are currently not fully understood. Transesophageal echocardiography remains the gold standard for detection of a patent foramen ovale or an atrial septum defect. However, TCD with a contrast agent has been turned out as a potential method to diagnose a RLS in several studies which have been published during the last years, and a RLS other than at the atrial level may be detected only by this method. Furthermore, the VM can be applied more comfortably and more reliably during Doppler examination than during transesophageal echocardiography.

Cerebrovascular Circulation↗

The application of three-dimensional contrast-enhanced ultrasound to measure volume of affected tissue after HIFU treatment for localized prostate cancer.

INTRODUCTION: Adequate monitoring of volume and location of affected tissue might provide helpful information when performing localized ablative therapy for prostate cancer. We hypothesize that the change in blood flow patterns after therapy in comparison to the blood flow pattern prior to therapy can be used to locate and quantify the amount of affected tissue due to the therapy. We describe the use of three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) to determine its additive value to visualize the extent of tissue defects created by high-intensity focused ultrasound (HIFU) in correlation with the histopathology of the prostatectomy specimen. MATERIALS AND METHODS: Nine patients with biopsy-proven localized prostate cancer, who gave informed consent, were included in the protocol. HIFU treatment was performed 1 week in advance of radical retropubic prostatectomy (RRP) as part of a protocol to study the value of HIFU treatment as local ablative therapy for clinical T(1-2)N(0)M(0) prostate carcinoma. 3D-CE-PDU was performed 1 day prior to unilateral HIFU treatment of the affected lobe on biopsy indication and 1 day before RRP using 2.5 g Levovist((R)) (Schering AG, Germany) microbubble ultrasound contrast agent and a Kretz((R)) Voluson 530D ultrasound scanner (Kretztechnik AG, Austria). Ultrasound data and pathology whole-mount sections were stored digitally to allow off-line processing. Human interpretations of HIFU measurements in three-dimensional ultrasound data were based on gray-scale information (local increase in gray level) in combination with power Doppler mode (absence of blood flow). Histopathological analysis of the whole-mount section revealed a broad band of hemorrhagic necrosis in the HIFU-treated area. Using both the ultrasound data and the pathology sections, the total volume of the prostate and of the HIFU-treated area was measured, and relative volumes were obtained. RESULTS: Visual inspection of the three-dimensional reconstruction of contrast-enhanced Doppler measurements revealed the HIFU-affected prostate tissue by the absence of a blood flow pattern. Paired t tests of the relative HIFU volume indicated that Doppler results (mean 21.7%, SD +/-10.8%) differed from the pathology results (mean 32.6%, SD +/-16.0%), but a good correlation was found between the relative pathology HIFU volume (Pearson correlation r = 0.94, p<0.0015) and mean 3D-CE-PDU HIFU. Closer inspection of the pathology specimen revealed that the outer ring of the macroscopic hemorrhagic necrosis overestimated the actually dead tissue. On microscopy, the border of dead tissue appeared to be 1-2 mm inside the macroscopically identified red hemorrhagic band. 3D-CE-PDU HIFU volumes indicated by the single observers were not statistically different and correlated very well (Pearson correlation r = 0.98, p<0.001). CONCLUSION: The results illustrate that 3D-CE-PDU is a promising method to determine the size of the defect of HIFU ablative therapy for prostate carcinoma. The absence of blood flow indicated by three-dimensional power Doppler ultrasound images reflects affected tissue after HIFU treatment, and volume measurements of these areas can quantify the amount of affected tissue.

Aged↗

Right-to-left atrial shunt without pulmonary artery hypertension.

A 70-year-old woman without any history of pulmonary or cardiac disease developed breathlessness with severe arterial hypoxemia. Cardiac ultrasound examination and spirometry were normal. Cardiac catheterization and intravenous microbubble injection demonstrated an interatrial right-to-left shunt. The defect was closed surgically, and the patient recovered immediately. On surgery, the aorta was elongated, inducing an angulation of the interatrial septum and leading to the atrial septal defect just above the inferior vena cava.

Acute Disease↗

Benefit of echocontrast-enhanced transcranial arterial color-coded duplex ultrasound.

OBJECTIVES: Proper assessment of the intracranial arteries by transcranial color-coded duplex sonography (TCCD) is occasionally made difficult by an insufficient temporal bone window, an unfavorable insonation angle, or low flow velocity or volume. In these cases, echocontrast could be helpful to increase the diagnostic confidence or to make the diagnosis at all. MATERIAL AND METHODS: We investigated 67 temporal windows of 47 patients with insufficient native transtemporal insonation conditions before and after the application of the second-generation (gas-filled) microbubble contrast agent Sonovue (in 20 patients out of these 47, both temporal windows were insufficient, in the remaining 27 only one side). RESULTS: As compared to the precontrast scans, echocontrast allowed for more segments to be evaluated by pulsed Doppler sonography (p < 0.0001) and for longer lumen segments to be displayed on color mode (p < 0.0001). With the help of contrast medium, flow velocity in the middle cerebral artery could be measured through 65 windows as compared to only 26 windows before contrast was applied (p < 0.0001). CONCLUSIONS: In patients with poor precontrast visualization of intracranial arteries, echocontrast-enhanced TCCD is very helpful.

Adult↗

Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy.

BACKGROUND: Pulmonary vein (PV) stenosis is a complication of ablation for atrial fibrillation. The impact of different ablation strategies on the incidence of PV stenosis and its functional characterization has not been described. METHODS AND RESULTS: PV isolation was performed in 608 patients. An electroanatomic approach was used in 71 and circular mapping in 537 (distal isolation, 25; ostial isolation based on PV angiography, 102; guided by intracardiac echocardiography, 140; with energy delivery based on visualization of microbubbles, 270). Severe (> or =70%) narrowing was detected in 21 patients (3.4%), and moderate (50% to 69%) and mild (<50%) narrowing occurred in 27 (4.4%) and 47 (7.7%), respectively. Severe stenosis occurred in 15.5%, 20%, 2.9%, 1.4%, and 0%, respectively. Development of symptoms was correlated with involvement of >1 PV with severe narrowing (P=0.01), whereas all patients with mild and moderate narrowing were asymptomatic. In the latter group, lung perfusion (V/Q) scans were normal in all but 4 patients. All patients with severe stenosis had abnormal perfusion scans. CONCLUSIONS: V/Q scans are useful to assess the functional significance of PV stenosis. Mild and moderate degrees of PV narrowing are not associated with development of symptoms and seem to have no or minimal detrimental effect on pulmonary flow. The incidence of severe PV stenosis seems to be declining with better imaging techniques to ensure ostial isolation and to guide power titration. Mild narrowing 3 months after ablation does not preclude future development of severe stenosis and should be assessed with repeat imaging studies.

Atrial Fibrillation↗

Combined assessment of myocardial perfusion and regional left ventricular function by analysis of contrast-enhanced power modulation images.

BACKGROUND: Echocardiographic contrast media have been used to assess myocardial perfusion and to enhance endocardial definition for improved assessment of left ventricular (LV) function. These methodologies, however, have been qualitative or have required extensive offline image analysis. Power modulation is a recently developed imaging technique that provides selective enhancement of microbubble-generated reflections. Our goal was to test the feasibility of using power modulation for combined quantitative assessment of myocardial perfusion and regional LV function in an animal model of acute ischemia. METHODS AND RESULTS: Coronary balloon occlusions were performed in 18 anesthetized pigs. Transthoracic power modulation images (Agilent 5500) were obtained during continuous intravenous infusion of the contrast agent Definity (DuPont) at baseline and during brief coronary occlusion and reperfusion and were analyzed with custom software. At each phase, myocardial perfusion was assessed by calculation, in 6 myocardial regions of interest, of mean pixel intensity and the rate of contrast replenishment after high-power ultrasound impulses. LV function was assessed by calculation of regional fractional area change from semiautomatically detected endocardial borders. All ischemic episodes caused detectable and reversible changes in perfusion and function. Perfusion defects, validated with fluorescent microspheres, were visualized in real time and confirmed by a significant decrease in pixel intensity in the left anterior descending coronary artery territory after balloon inflation and reduced rate of contrast replenishment. Fractional area change decreased significantly in ischemic segments and was restored with reperfusion. CONCLUSIONS: Power modulation allows simultaneous online assessment of myocardial perfusion and regional LV wall motion, which may improve the echocardiographic diagnosis of myocardial ischemia.

Animals↗

Ventricular septal defect after myocardial infarction: diagnosis by two-dimensional contrast echocardiography.

Thirteen patients who had ventricular septal defects (VSDs) after myocardial infarction (MI) underwent two-dimensional echocardiography (2-D echo), with confirmation of the VSD by oximetry. Eight of the patients were male and five were female, ages 51-76 years. Five had anterior and eight inferior MIs. Two-dimensional echocardiography revealed akinesis or dyskinesis of the interventricular septum (IVS) in all 13 patients. In only six could a defect in the IVS be directly visualized. Two-dimensional echocardiographic left ventricular (LV) wall motion abnormalities correlated with ECG and angiographic site of infarction in all patients. Twelve patients had adequate saline contrast studies. Positive LV contrast (microbubbles entering the left ventricle through the VSD) was seen in 11 patients, and negative right ventricular (RV) contrast (washout of the RV bubbles by LV blood crossing the VSD) in five patients; at least one abnormality was present in every patient. The location of the VSD was determined by visualizing a VSD or by the site of the positive LV or negative RV contrast. Oximetry showed VSD shunts of 1.4:1 to 7:1, with no correlation between the degree of negative RV contrast and shunt size. Surgical or pathologic confirmation of VSD was obtained in 12 patients, with agreement of VSD location by 2-D echo in all. Four of the 11 patients who underwent surgical repair died, and two patients died before surgery could be attempted. We conclude tht 2-D echo is a sensitive, rapid and safe technique for diagnosing VSD after MI. Positive LV contrast, with or without negative RV contrast, is more sensitive in the diagnosis and localization of post-MI VSD than direct echocardiographic visualization of the defect.

Aged↗

Contrast ultrasonography of the kidney: a new method for evaluation of renal perfusion in vivo.

Assessment of the effects of pharmacologic agents on renal blood flow (RBF) is clinically important in many disease states, including hypertension and congestive heart failure. However, because of the complexities of RBF, quantitation in vivo has been technically difficult. This study demonstrates the utility of ultrasound imaging of the kidney combined with injection of a sonicated radiocontrast solution (Renografin-76) for the assessment of regional renal blood flow. The technique uses a suspension of uniform microbubbles (diameter 4.4 +/- 2.8 micron), which when injected directly into the descending aorta are distinctly visualized by renal ultrasound. Five dogs were studied. Catheters were placed in the descending aorta for injection of sonicated Renografin and in the renal artery for drug infusions. Data were collected before and during intrarenal artery infusions of bradykinin and norepinephrine. Total RBF was measured by electromagnetic flowmeter. Video density time curves were generated for comparable segments of the outer renal cortex and fit to a monoexponential decay curve. This allowed calculation of the mean exponential decay index (t1/2). An increase in t1/2 paralleled decreased renal perfusion (i.e., longer washout of contrast material). The opposite was true for a decrease in t1/2. Bradykinin increased RBF from 134 +/- 26 to 249 +/- 19 ml/min (p less than .01 vs control), and norepinephrine decreased RBF from 130 +/- 25 to 51 +/- 17 ml/min (p less than .01 vs control).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Functional significance of collateral blood flow in patients with recent acute myocardial infarction. A study using myocardial contrast echocardiography.

BACKGROUND: We hypothesized that myocardial contrast echocardiography (MCE) can be used to both measure collateral blood flow as well as assess the functional significance of collaterals in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: MCE was performed in 33 patients with recent AMI (12 +/- 7 days) and an occluded infarct-related artery (IRA), both before and after attempted percutaneous transluminal coronary angioplasty (PTCA). The size of the occluded bed was defined in patients with successful PTCA by injecting contrast directly into the opened IRA and expressed as a percent of the myocardium in the short-axis view. The percent of the perfusion bed supplied by collaterals before PTCA was determined. Transit rates of the microbubbles within the collateralized regions were also measured and were expressed as a percent of the transit rates in the normal adjacent beds. Regional function within the occluded bed was assessed using echocardiography and was graded as 1 (normal) to 5 (dyskinetic). Collaterals were graded on coronary angiography as 0 (none) to 3 (abundant). The perfusion bed size was larger for the left anterior descending (LAD) than for the right (RCA) and left circumflex (LCx) coronary arteries (37 +/- 6% versus 27 +/- 12% of the myocardium, p = 0.02). The percent of the occluded bed supplied by collateral flow was greater for RCA and LCx compared with the LAD (87 +/- 30% versus 72 +/- 22%, p less than 0.01). There was poor correlation between MCE-defined percent of occluded bed supplied by collaterals and angiographic collateral grade (r = 0.13). Regions supplied by collaterals were less likely to show confluent hypoperfused zones after reperfusion compared with those not supplied by collaterals. Similarly, the percent of myocardium not perfused by either anterograde or collateral flow correlated well (r = 0.67, p less than 0.01) with peak creatine kinase levels and was more likely to be associated with Q waves. Finally, although there was poor correlation between angiographic collaterals and regional function (r = 0.20), there was a significant negative correlation between MCE-defined spatial extent of collateral flow and regional function (r = -0.57, p less than 0.01). CONCLUSION: MCE can be used to measure collateral flow in patients with recent AMI and to assess the functional significance of collaterals in these patients. This technique may be ideally suited for the assessment of collateral perfusion in patients undergoing cardiac catheterization.

Angioplasty, Balloon, Coronary↗

Characterization of spatial patterns of flow within the reperfused myocardium by myocardial contrast echocardiography. Implications in determining extent of myocardial salvage.

BACKGROUND: Since myocardial blood flow changes dynamically after reperfusion and since both hyperemia and impairment in microvascular function exist within the acutely reperfused bed, we sought to investigate the role of myocardial contrast echocardiography (MCE) in (1) defining the temporal variability in perfusion patterns after reflow and relating these to microsphere-derived blood flow; (2) differentiating viable from infarcted tissue during different periods of reflow; and (3) defining spatial perfusion patterns within the infarct bed in response to exogenously induced maximal vasodilation and relating these to infarct size and extent of myocardial salvage. METHODS AND RESULTS: Twenty-one dogs with 3 hours of left anterior descending coronary artery occlusion and 2 to 3 hours of reflow were studied. MCE was performed at 15 and 45 minutes and 2 and 3 hours after reflow. It was also performed at either 2 or 3 hours after reflow in the presence of 0.56 mg/kg of dipyridamole. Radiolabeled microsphere-derived blood flow was measured at 15 minutes and 2 and 3 hours after reflow and during dipyridamole effect. Infarct size was measured at the end of the experiment by use of triphenyl tetrazolium chloride. MCE data were processed with color-coding schemes that highlighted differences in myocardial videointensities in proportion to the concentration of microbubbles within the microvasculature. There was significant variability in MCE-defined perfusion patterns after reflow, with contrast defects noted mainly within the endocardium. There were fair and significant (P < .05) correlation (r = -.73 to r = -.55) between MCE defect size and normalized endocardial blood flow. Except at 15 minutes after reflow, there was poor correlation (r = .31 to r = .51) between MCE defect and infarct sizes. Even at 15 minutes after reflow, MCE defect size underestimated infarct size by 50%. In comparison, in the presence of dipyridamole, MCE defect size correlated strongly (r = .87, P < .001) with infarct size and reasonably well with normalized transmural blood flow (r = -.62, P = .04). Moreover, the topography of the MCE perfusion defect reflected the topography of the infarct. CONCLUSIONS: MCE revealed striking temporal heterogeneity in the spatial distribution of myocardial perfusion during postischemia reflow and either significantly underestimated or did not correlate with infarct size during reperfusion. Because of abnormalities in coronary vascular reserve specific to infarcted tissue, MCE in conjunction with intravenous dipyridamole depicted, in vivo, the actual topography of the infarct with remarkable accuracy.

Animals↗

Effects of radiofrequency catheter ablation on regional myocardial blood flow. Possible mechanism for late electrophysiological outcome.

BACKGROUND: We postulated that the late electrophysiological effects of radiofrequency (RF) ablation may be related to microvascular injury extending beyond the region of acute coagulation necrosis. METHODS AND RESULTS: Eighteen RF lesions created in the left anterior descending coronary artery (LAD) perfusion bed of seven open chest anesthetized dogs were studied. The ablation electrode and surrounding myocardium were imaged using high-resolution two-dimensional echocardiography at x 4 magnification. After 60 seconds of RF delivery, sonicated albumin microbubbles (mean size, 4.3 microns) were injected into the LAD to measure regional myocardial perfusion, and time-intensity plots were generated from simultaneously acquired two-dimensional echocardiography images. The regions with persistent contrast effect on two-dimensional echocardiography were larger than the pathological lesions (mean cross-sectional area, 48.3 +/- 6.3 versus 19.3 +/- 4.7 mm2, respectively; P < .0001). The mean contrast transit rate in the area corresponding to the pathological lesion was 25 +/- 12% of that in the normal myocardium, but it was also reduced beyond the lesion, being 48 +/- 27% and 82 +/- 28% of normal, respectively, in the 3-mm and 3- to 6-mm circumferential rims surrounding the pathological lesion (P < .05). Electron microscopy performed in two additional dogs with similar lesions demonstrated the presence of ultrastructural damage to the microvascular endothelium well beyond the pathological lesion edge. CONCLUSIONS: RF catheter ablation not only results in a marked reduction in blood flow within the acute pathological lesion but also causes reduced flow beyond the borders of the acute lesion because of microvascular endothelial cell injury. The progression or resolution of tissue injury within the region beyond the border of the pathological lesion may explain the late electrophysiological effects of RF ablation.

Animals↗

Papillary muscle perfusion pattern. A hypothesis for ischemic papillary muscle dysfunction.

BACKGROUND: The pathogenesis of posterior papillary muscle dysfunction is poorly understood. We hypothesized that papillary muscle perfusion pattern may explain the higher prevalence of posterior papillary muscle dysfunction after myocardial infarction. METHODS AND RESULTS: Twenty patients were monitored by transesophageal echocardiography during coronary surgery. Superselective coronary graft injections of 0.2 to 0.5 mL of sonicated albumin microbubbles were performed to assess graft patency and papillary muscle perfusion. Thirty-five graft injections were analyzed: 13 in the right coronary artery, 15 in an obtuse marginal branch, 1 in the left anterior descending coronary artery, and 6 in the first diagonal branch. The posterior papillary muscle was opacified in 16 patients, 11 from the right coronary artery and 5 from one obtuse marginal branch. In 10 of 16 patients (63%), the papillary muscle was perfused by one vessel, while in 6 of 16 (37%), it was perfused by two vessels. The anterior papillary muscle was opacified in 14 patients. Ten patients (71%) had double-vessel and 4 (29%) had single-vessel supply. In the subgroup of 10 patients with old inferior myocardial infarction, mitral regurgitation was present only among those 6 with single rather than double blood supply (P < .05). CONCLUSIONS: Myocardial infarction may cause papillary muscle dysfunction when the blood supply is provided by one rather than two vessels, as is more frequently the case with the posterior rather than the anterior papillary muscle.

Adult↗

Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute anterior wall myocardial infarction.

BACKGROUND: Epicardial coronary flow is occasionally reduced even after coronary intervention despite the absence of vessel obstruction in patients with acute myocardial infarction. Our aim was to clarify the cause and outcomes of radiocontrast slow filling in patients with reperfused acute anterior myocardial infarction by assessing microvascular damage with the use of myocardial contrast echocardiography (MCE) and functional outcomes. METHODS AND RESULTS: We carefully reviewed the cineangiograms of 86 patients who achieved coronary revascularization within 12 hours of the onset and underwent MCE before and soon after recanalization with the intracoronary injection of sonicated microbubbles. Antegrade coronary flow after recanalization was graded by two observers based on Thrombolysis in Myocardial Infarction (TIMI) trial flow grades. Left ventricular ejection fraction was measured on the day of infarction and 1 month later. TIMI grade 2 was observed in 18 patients (21%), and the other 68 patients manifested TIMI grade 3 after recanalization. All patients with TIMI 2 showed substantial MCE no reflow, whereas only 11 patients (16%) with TIMI 3 showed MCE no reflow. Functional improvement was worse in patients with TIMI 2 than in those with TIMI 3 (TIMI 2, 38 +/- 8% versus 40 +/- 8%, P = NS [acute versus late]; TIMI 3, 44 +/- 13% versus 55 +/- 13%, P < .001). Among patients with TIMI 3, significant functional improvement was observed only in patients with MCE reflow (MCE reflow, 46 +/- 13% versus 57 +/- 12%, P < .001; MCE no reflow, 35 +/- 11% versus 45 +/- 12%, P = NS). CONCLUSIONS: Despite no obstructive lesion of the vessel, TIMI 2 is caused by advanced microvascular damage and is a highly specific, although not sensitive, predictor of poor functional outcomes in patients with acute myocardial infarction. TIMI 3 does not necessarily indicate myocardial salvage, and detection of MCE no reflow in these patients is particularly useful for the prediction of functional outcome.

Adult↗

Clinical implications of the 'no reflow' phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction.

BACKGROUND: Recent studies demonstrated that the "no reflow" phenomenon after coronary reflow implies the presence of advanced myocardial damage. In this study, we verified the prognostic value of the detection of this phenomenon by studying complications, left ventricular morphology, and in-hospital survival after acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 126 patients with a first anterior AMI. All patients received coronary reflow within 24 hours of onset of symptoms and underwent myocardial contrast echocardiography (MCE) before and shortly after coronary reflow with an intracoronary injection of sonicated microbubbles. From contrast reperfusion patterns, patients were divided into two subsets: those with MCE no reflow (47 patients, 37%) and those with MCE reflow (79 patients). There was no difference in the frequency of arrhythmia or coronary events between the two subsets. Pericardial effusion and early congestive heart failure were observed more frequently in patients with MCE no reflow than in those with MCE reflow (26% versus 4%, P < .05; 45% versus 15%, P < .05, respectively). Congestive heart failure tended to be prolonged in those with MCE no reflow, and 3 patients (7%) of this subset died of pump failure. Left ventricular end-diastolic volume progressively increased in the convalescent stage in patients with MCE no reflow (early versus late, 145 +/- 43 versus 169 +/- 60 mL, P < .001), whereas it decreased in those with MCE reflow (154 +/- 42 versus 144 +/- 44 mL, P < .01). CONCLUSIONS: The substantial size of the MCE no reflow phenomenon at coronary reflow conveys useful information about an outcome of coronary intervention and left ventricular remodeling in individual patients with anterior wall AMI, although these are suggestive results in a limited number of patients.

Adult↗

Automatic online embolus detection and artifact rejection with the first multifrequency transcranial Doppler.

BACKGROUND AND PURPOSE: The goal of this study was to assess the first multifrequency transcranial Doppler system specially developed for online automatic detection of cerebral microemboli. METHODS: The multifrequency Doppler instrumentation insonates simultaneously with 2.0- and 2.5-MHz frequencies. The detection threshold for embolus detection used in this study was a relative Doppler energy increase of >20 dB. ms, at which point the Doppler power increase was at least 5 dB and lasted >4 ms above the background energy. Four parameters were used in an optimized binary decision tree to recognize emboli: quarter Doppler shift, maximum duration limit, reference gate, and bidirectional enhancement. In in vitro studies, 200 plastic microspheres (80 micro m), 200 gas bubbles (8 to 25 micro m), and 600 artifacts were studied in a pulsatile closed-loop system. In vivo studies were carried out for 1 hour in 15 patients with mechanical heart valves and in 45 patients with carotid stenosis. This gave a total of 60 hours of online automatic monitoring in patients. RESULTS: All 400 plastic spheres and microbubbles were automatically detected and correctly classified. Of the 600 artifacts, 596 (99.3%) were correctly classified as artifacts, and 4 (0.7%) were incorrectly identified as emboli (kappa=0.992, P<0.001). The experienced observer detected a total of 554 emboli and 800 artifacts in the heart valve (521 emboli, 400 artifacts) and carotid stenosis (33 emboli, 400 artifacts) patients. With multifrequency Doppler, 546 of these emboli (98.6%) and 791 of these artifacts (98.9%) were automatically detected and correctly classified as embolus or artifact (kappa=0.953, P<0.0001). CONCLUSIONS: We found that multifrequency transcranial Doppler had a relatively high sensitivity and specificity when used to automatically detect cerebral microemboli and reject artifacts online.

Artifacts↗

Comparison between echo contrast agent-specific imaging modes and perfusion-weighted magnetic resonance imaging for the assessment of brain perfusion.

BACKGROUND AND PURPOSE: Contrast burst imaging (CBI) and time variance imaging (TVI) are new ultrasonic imaging modes enabling the visualization of intravenously injected echo contrast agents in brain parenchyma. The aim of this study was to compare the quantitative ultrasonic data with corresponding perfusion-weighted MRI data (p-MRI) with respect to the assessment of brain perfusion. METHODS: Twelve individuals with no vascular abnormalities were examined by CBI and TVI after an intravenous bolus injection of 4 g galactose-based microbubble suspension (Levovist) in a concentration of 400 mg/mL. Complementary, a dynamic susceptibility contrast MRI, ie, p-MRI, of each individual was obtained. In both ultrasound (US) methods and p-MRI, time-intensity curves were calculated offline, and absolute time to peak intensities (TPI), peak intensities (PI), and peak width (PW) of US investigations and TPI, relative cerebral blood flow (CBF) and relative cerebral blood volume (CBV) of p-MRI examinations were determined in the following regions of interest (ROIs): lentiform nucleus (LN), white matter (WM), posterior (PT), and anterior thalamus (AT). In addition, the M(2) segment of the middle cerebral artery (MCA) was evaluated in the US, and the precentral gyrus (PG) was examined in the p-MRI examinations. In relation to a reference parenchymal ROI (AT), relative TPIs were compared between the US and p-MRI methods and relative PI of US investigations with the ratio of CBF (rCBF) of p-MRI examinations in identical ROIs. RESULTS: Mean TPIs varied from 18.3+/-5.0 (AT) to 20.1+/- 5.8 (WM) to 17.2+/-4.9 (MCA) seconds in CBI examinations and from 19.4+/-5.3 (AT) to 20.4+/-4.3 (WM) to 17.3+/-4.0 (MCA) seconds in TVI examinations. Mean PIs were found to vary from 581.9+/-342.4 (WM) to 1522.9+/-574.2 (LN) to 3400.9+/- 621.7 arbitrary units (MCA) in CBI mode and from 7.5+/-4.6 (WM) to 17.5+/-4.9 (LN) to 46.3+/-7.1 (MCA) arbitrary units in TVI mode. PW ranged from 7.3+/-4.5 (AT) to 9.1+/-4.0 (LN) to 24.3+/-12.8 (MCA) seconds in CBI examinations and from 7.1+/-3.9 (AT) to 8.7+/-3.5 (LN) to 26.7+/-18.2 (MCA) seconds in TVI examinations. Mean TPI was significantly shorter and mean PI and mean PW were significantly higher in the MCA compared with all other ROIs (P<0.05). Mean TPI of the p-MRI examinations ranged from 22.0+/-6.9 (LN) to 23.0+/-6.8 (WM) seconds; mean CBF ranged from 0.0093+/- 0.0041 (LN) to 0.0043+/-0.0021 (WM). There was no significant difference in rTPI in any ROI between US and p-MRI measurements (P>0.2), whereas relative PIs were significantly higher in areas with lower insonation depth such as the LN compared with rCBF. CONCLUSIONS: In contrast to PI, TPI and rTPI in US techniques are robust parameters for the evaluation of cerebral perfusion and may help to differentiate physiological and pathological perfusion in different parenchymal regions of the brain.

Adult↗

Contrast burst depletion imaging (CODIM): a new imaging procedure and analysis method for semiquantitative ultrasonic perfusion imaging.

BACKGROUND AND PURPOSE: Established methods of ultrasonic perfusion imaging using a bolus application of echo contrast agent provide only qualitative data because of various physical phenomena. This study was intended to investigate whether a new ultrasound perfusion imaging method termed contrast burst depletion imaging (CODIM) may provide semiquantitative measures of parenchymal perfusion independent of examination depth and acoustic energy distribution. METHODS: In a system with a constant concentration of contrast agent, analyzing the decrease in image intensity that occurs with microbubble-destructive imaging modes yields parameters that are considered to correlate with tissue perfusion. This method was first evaluated with a perfusion model that showed that the main resulting parameter "perfusion coefficient" (PC) is a monotonic nonlinear function of flow velocity. Seventeen human volunteers were then scanned according to this method with the use of 2 different contrast agents. Results were correlated with those from perfusion-weighted MRI examinations. RESULTS: The PC did not show significant differences in gray matter areas (ranging from 1.466x10(-2) x s(-1) to 1.641x10(-2) x s(-1)) of the brain despite different insonation depths (eg, ipsilateral and contralateral thalamus). In contrast, white matter exhibited significantly lower perfusion values in both imaging modes (PC: 0.604x10(-2) x s(-1) to 0.745x10(-2) x s(-1); P<0.05). CONCLUSIONS: CODIM is a promising new tool of imaging parenchymal (brain) perfusion in healthy persons. The method provides semiquantitative and depth-independent perfusion parameters and in this way overcomes the limitations of the perfusion methods using a bolus kinetic. Further investigations must be done to evaluate the potential of the method in patients with perfusion deficits.

Adult↗

A comparison of transesophageal echocardiography and transcranial Doppler sonography with contrast medium for detection of patent foramen ovale.

BACKGROUND: Patent foramen ovale as a possible stroke risk factor can be diagnosed with transcranial Doppler sonography (TCD) by detecting intravenous contrast medium crossing from the right to the left atrium. The present study evaluates the reliability of this method. SUMMARY OF REPORT: We performed TCD and transesophageal echocardiography simultaneously in 50 patients using galactose microbubbles. We observed bubble signals passing the middle cerebral artery in 7 patients less than 20 seconds after injection; we found positive TCD tests in 14 patients using the Valsalva maneuver. With transesophageal echocardiography patent foramen ovale could be detected in 15 patients (sensitivity, 0.93; specificity, 1; P < .01). CONCLUSIONS: TCD with echo contrast is a reliable screening tool for patent foramen ovale. A standardized procedure including the Valsalva maneuver is essential to prevent false-negative results.

Adult↗