Vendel Kemény

Contrast transcranial doppler ultrasound in the detection of right-to- left shunts: Time window and threshold in microbubble numbers

BACKGROUND AND PURPOSE Cardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) and by transcranial Doppler ultrasound (TCD) with the use of contrast agents and a Valsalva maneuver (VM) as provocation procedure. Currently, data on the appropriate timing of the VM, the use of a diagnostic time window, and a threshold in contrast agent microbubbles detected are insufficient. METHODS Fifty-eight patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with injections of 10 mL of the commercial galactose-based contrast agent Echovist was applied in a randomized way: (1) no VM, (2) VM for 5 seconds starting 2 seconds after the beginning of contrast injection, (3) VM for 5 seconds starting 5 seconds after the beginning of contrast injection, (4) VM for 5 seconds starting 8 seconds after the beginning of contrast injection, and (5) repetitive short VMs in between 2 and 13 seconds after the beginning of contrast injection. In addition to the single tests, we also tested the sensitivity and specificity of combined results of the tests with VM. RESULTS In 21 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-one patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 16 patients were only positive on at least 1 TCD investigation but negative during TEE. Test 3 was the most appropriate test when combined with the results of 1 of the other tests with VM. The highest sensitivities were achieved with a diagnostic time window of 40 seconds and when the presence of a single microbubble was sufficient for the diagnosis of a shunt. CONCLUSIONS TCD performed twice with 2 provocation maneuvers with Echovist is a sensitive method to identify TEE-proven cardiac right-to-left shunts. The VM should be performed for 5 seconds starting at 5 seconds after the beginning of contrast injection.

Potential and Limitations of Echocontrast-Enhanced Ultrasonography in Acute Stroke Patients A Pilot Study

BACKGROUND AND PURPOSE Ultrasonography (US) is a well-established method used to assess the brain-supplying arteries in the acute stroke setting. However, several technical and anatomic limitations are known to reduce its diagnostic accuracy and confidence level. Echocontrast agents (ECA) are known to improve the signal-to-noise ratio by enhancing the intensity of the reflecting Doppler signal. We undertook this prospective study to evaluate the diagnostic value of ECA in a consecutive, nonselected cohort of acute stroke patients with insufficient native US investigations. METHODS During a 1-year period, 25 patients were examined within 48 hours of the onset of stroke. The need for ECA was due to an insufficient transtemporal (n=18), transforaminal (n=4), or extracranial (n=3) imaging of arteries potentially involved in the ischemic event. In 12 patients, a diagnostic suspicion could natively be raised, whereas in the other 13 patients, the strongly reduced image quality did not allow for any neurovascular conclusions. Four grams of Levovist was injected at a concentration of 200 mg/mL and 400 mg/mL for the extracranial and transcranial insonations, respectively. The effect of the echocontrast enhancement was assessed with respect to (1) signal enhancement, (2) image quality, (3) final diagnostic confidence, and (4) the need for additional neurovascular imaging methods. RESULTS In all but one patient (96%), a strong signal enhancement was noted, leading to a moderate (n=11) or strong improvement (n=10) of the transcranial image quality. Thus in a total of 18 patients (72%), the echoenhancement provided a neurovascular diagnosis of sufficient confidence. This led to the confirmation of the previously suspected findings and disclosed three further occlusions and four stenoses of the intracranial arteries. In contrast, for the three extracranial examinations the image quality was not sufficiently improved because of persistent color artifacts derived from adjacent neck vessels. Besides the seven patients with inconclusive examinations, five patients with conclusive echoenhanced US studies (48% in total) demanded additive neurovascular imaging studies, based on the clinical decision of the attending physicians. This led to confirmation of all high-confident sonographic diagnoses. CONCLUSIONS In summary, in approximately three fourths of our acute stroke patients with insufficient native US investigations, echocontrast enhancement enabled a reliable neurovascular diagnosis, allowing the cancellation of additive neurovascular imaging procedures in half of our cohort. Our preliminary results suggest that ECA can reasonably support the early cerebrovascular workup in the acute stroke setting.

Prevalence and frequency of microembolic signals in 105 patients with extracranial carotid artery occlusive disease

Besides the established factors “presence of symptoms” and “degree of stenosis”, plaque echolucency is considered to be associated with increased risk of stroke in patients with carotid artery disease. An evaluation was carried out as to whether the prevalence and number of microembolic signals (MES) detected by transcranial Doppler ultrasound were higher in patients with echolucent carotid plaques.  One hundred and five patients with carotid artery stenosis from 20%-99% or occlusion underwent clinical investigations, duplex ultrasound of the carotid arteries, and a 1 hour recording from the middle cerebral artery downstream to the carotid artery pathology using the four gate technique. The presence of MES was more frequent and the number greater in symptomatic patients (21 out of 64 patients (33%); mean number of MES in all 64 patients 3.1) than in asymptomatic patients (four out of 41 patients (10%); mean number of MES in all 41 patients 0.3) (p=0.007, and p=0.006, respectively). Echogenicity of the lesions did not affect either number or presence of MES. Positivity for MES and the number of MES increased with increasing degree of stenosis (both p=0.002). Four out of 12 patients with carotid artery occlusion showed MES. No MES could be detected in carotid artery stenosis below 80%. There was a decline in positivity of MES and of the number of MES with the time after the ischaemic event. After 80 days or more after the index event, only one patient showed MES.  In conclusion, increasing degree of stenosis and presence of symptoms similarly affect macroembolic and microembolic risk. Thus MES may be a surrogate parameter for risk of stroke. The presence of MES in a few asymptomatic patients suggests that clinically silent circulating microemboli may give additional information on the pending embolic potential of carotid artery stenoses. Echolucency of the plaque was not related to an increased number of MES.

Oxygen inhalation can differentiate gaseous from nongaseous microemboli detected by transcranial Doppler ultrasound.

BACKGROUND AND PURPOSE Clinically silent circulating microemboli can be detected by transcranial Doppler sonography. The composition of these emboli in different clinical conditions is unclear. METHODS We performed 1-hour transcranial Doppler sonographic recordings from the middle cerebral or posterior cerebral artery in 20 patients with mechanical prosthetic heart valves, in 78 patients with an arterial embolic source, and in 20 control subjects. During 30 minutes of this recording, the patients inspired room air and 6 L of oxygen per minute via a loosely fitting facial mask; during the remaining 30 minutes, they breathed room air only. RESULTS There was a significant decline of embolic signals (ES) under oxygen in the patients with mechanical prosthetic cardiac valves (144 ES without oxygen versus 63 ES with oxygen; P = .002) but not in the patients with arterial embolic sources (145 ES without oxygen versus 135 ES with oxygen; P = NS). In the control subjects, no ES were found. CONCLUSIONS ES in patients with mechanical prosthetic cardiac valves correspond mainly to gas bubbles. Oxygen inhibits the cavitation process of mechanical prosthetic heart valves or speeds up redissolution of gas bubbles generated by cavitation. In contrast, solid microemboli originating from thrombus or atheroma cannot be suppressed by oxygen inhalation. This simple method of oxygen inhalation should help to clarify the composition of microemboli in various clinical and experimental settings.

Controlled Contrast Transcranial Doppler and Arterial Blood Gas Analysis to Quantify Shunt Through Patent Foramen Ovale

Background and Purpose— A right-to-left shunt can be identified by contrast transcranial Doppler ultrasonography (c-TCD) at rest and/or after a Valsalva maneuver (VM) or by arterial blood gas (ABG) measurement. We assessed the influence of controlled strain pressures and durations during VM on the right-to-left passage of microbubbles, on which depends the shunt classification by c-TCD, and correlated it with the right-to-left shunt evaluation by ABG measurements in stroke patients with patent foramen ovale (PFO). Methods— We evaluated 40 stroke patients with transesophageal echocardiography–documented PFO. The microbubbles were recorded with TCD at rest and after 4 different VM conditions with controlled duration and target strain pressures (duration in seconds and pressure in cm H2O, respectively): V5-20, V10-20, V5-40, and V10-40. The ABG analysis was performed after pure oxygen breathing in 34 patients, and the shunt was calculated as percentage of cardiac output. Results— Among all VM conditions, V5-40 and V10-40 yielded the greatest median number of microbubbles (84 and 95, respectively; P <0.01). A significantly larger number of microbubbles were detected in V5-40 than in V5-20 (P <0.001) and in V10-40 than in V10-20 (P <0.01). ABG was not sensitive enough to detect a shunt in 31 patients. Conclusions— The increase of VM expiratory pressure magnifies the number of microbubbles irrespective of the strain duration. Because the right-to-left shunt classification in PFO is based on the number of microbubbles, a controlled VM pressure is advised for a reproducible shunt assessment. The ABG measurement is not sensitive enough for shunt assessment in stroke patients with PFO.

Microembolic Load in Asymptomatic Patients with Cardiac Aneurysm, Severe Ventricular Dysfunction, and Atrial Fibrillation

Transcranial Doppler sonography has become a widely used method for detecting cerebral circulating microemboli (ME) arising from the carotid arteries or the heart. Yet, studies on subgroups of patients with distinct cardiac sources of embolism are still limited. The same holds true for investigations on the relationship between microembolization and hemorheological parameters. A total of 142 patients suffering from left ventricular aneurysm (LVA, n = 52), severe left ventricular dysfunction (LVD, n = 43), or chronic atrial fibrillation (AF, n = 47) were enrolled in this study. All patients had been neurologically asymptomatic for at least 1 month. Further relevant embolic disorders of the carotid arteries and the heart had been excluded. Unilateral monitoring for ME over the middle cerebral artery was performed for 30 min. Blood was drawn after each monitoring for determination of plasmatic coagulation parameters, as well as plasma viscosity, and platelet reactivity. The overall prevalence of ME was 31%, with a slightly higher prevalence in patients with LVA (37%) compared to patients suffering from AF (30%) or LVD (26%). With single-factor analysis, a trend towards higher ME prevalences was found with (a) a history of remote embolic events, (b) ineffective anticoagulation, (c) increased platelet aggregation, or (d) increased plasma viscosity (all p > 0.1). The combination of ineffective anticoagulation in conjunction with increased platelet aggregation, however, was significantly associated with higher ME rates even after adjustment for other factors by logistic regression analysis. Our results demonstrate a low ongoing microembolic activity in asymptomatic patients suffering from LVA, LVD and AF. An activated plasmatic coagulation system together with increased platelet aggregation contributes to ME generation.

Preoperative B-mode ultrasound plaque appearance compared with carotid endarterectomy specimen histology

In carotid artery stenosis both the degree of the lesion and its plaque morphology are thought to be associated with the carriers thromboembolic risk. In this study we evaluated the diagnostic preciseness of non‐invasively B‐mode ultrasound in predicting the histopathological plaque structure. We examined 44 patients with 70% ICA stenosis by B‐mode within 6 weeks prior to carotid endarterectomy. At the affected bifurcations, up to 10 different regions of interest (ROI) per artery were investigated. Plaque appearance was classified according to 6 subtypes considering different ultrasonic plaque features. Postoperatively, plaque specimens were examined histopathologically for their relative content of calcification, fibrous tissue and different soft tissue. B‐mode ultrasound was compared with histopathological features in ROI. A total of 265 regions of interest were evaluated. In mainly echolucent types of plaques, atheromatous debris was most frequently seen, whereas fibrosis was rare. Homogeneous echolucent plaques showed a high proportion of cholesterol and/or recent haemorrhage. Thrombosis at the plaque surface was often seen in “completely echolucent” plaque type (each P<0.001). Carotid B‐mode ultrasonography is able to predict the histopathological components and the texture of carotid plaques.

Diagnostic benefit of echocontrast enhancement for the insufficient transtemporal bone window

Echocontrast agents (ECA) are known to improve transcranial color‐coded duplex (TCCD) imaging, but its diagnostic benefit in the routine clinical setting has not clearly been defined. The authors investigated the diagnostic benefit of ECA application in 54 patients with insufficient transtemporal bone window, consecutively referred to their ultrasound laboratory. According to the precontrast imaging quality, patients were assigned to three categories: A, no intracranial structures or vessel segments visible on B‐mode imaging and TCCD (n = 5); and intracranial structures visible on B‐mode imaging and vessel segments less than 5 mm in length (B, n = 21 ), or larger than 5 mm in length (C, n = 28) visible on TCCD. The effect of the echocontrast enhancement was assessed with respect to signal enhancement, imaging quality, and diagnostic confidence. In 49 out of 54 patients (91%), a significant improvement of the imaging quality was noted, enabling 43 (80%) neurovascular diagnoses of sufficient diagnostic confidence. The diagnostic ECA effect was strongly dependent on the precontrast imaging quality: upon echoenhancement, a satisfactory image quality was obtained in none of the patients of category A, as opposed to 16 (76%) and 27 (96%) patients of categories B and C, respectively. In summary, in 80% of our consecutive patient series with insufficient transtemporal bone window, application of ECA allowed for a conclusive TCCD study. Properties of the transtemporal precontrast scans are strongly predictive of the diagnostic benefit and should be taken into the decisive consideration.

Echocontrast enhanced transcranial colour-coded duplex offers improved visualization of the vertebrobasilar system

Objectives – By means of transcranial colour‐coded duplex sonography (TCCD) through the foramen magnum, the intracranial vertebral arteries (VAs) and the basilar artery (BA) can be investigated. In this study we evaluated the additional diagnostic value of echocontrast administration in patients with an insufficient pre‐contrast TCCD investigation of the vertebrobasilar system. Material and methods – In 22 patients the intracranial VAs and the proximal, middle and distal BA were evaluated before and after the application of 4 g of the echocontrast agent Levovist. The length of the different vessel segments visualized on colour mode before and after echocontrast, and the diagnostic benefit and the diagnostic confidence were assessed. Results – Echocontrast enlarged in each vessel segment the length that could be visualized. Using echocontrast, in 5/22 patients (23%) definite and probable pathological findings unnoted in the native scans were detected. In 12 additional patients (55%) the investigator and the clinician became confident with the vascular diagnosis by echocontrast to a degree that angiography could be avoided. In only 3/22 patients (14%) no gain and in 2/22 patients (9%) an insufficient diagnostic gain was noted. Conclusions – Our study demonstrates that echocontrast provides effective Doppler signal enhancement and considerably increases the diagnostic gain of TCCD in the intracranial vertebral and basilar vasculature.

Microembolus detections at follow-up in 19 patients with acute stroke. Correlation with stroke etiology and antithrombotic treatment

The present study was designed to perform follow-up transcranial Doppler investigations for microembolic signals (MES) in acute stroke patients by means of a strict protocol. The number of MES was correlated with stroke etiology and the strength of antithrombotic treatment. Concurrently, we wanted to demonstrate that MES in acute stroke patients are solid in nature and not gaseous. Nineteen patients with middle cerebral artery ischemic events, 16 with completed stroke and 3 with transient ischemic attack (TIA) were investigated within 24 h following the onset of symptoms. Six 1-hour recordings on days 1, 2, 3, 4, 7 and 14 were performed from the affected middle cerebral artery. The four-gate technique and recently established criteria for the identification of MES were used. Eight of 19 patients showed MES in at least one recording. Variability was high and showed no uniform tendency with respect to time since onset of symptoms or treatment. All 3 patients with internal carotid artery dissection showed MES. In 3 patients with lacunar stroke, no MES were detected. Two patients with MES suffered recurrent TIAs during the observation period, whereas none of the patients without MES suffered a recurrent ischemic event. In the acute phase following stroke, ongoing, emerging and vanishing embolization in some patients may reflect individual active processes of remodelling, healing and disruption or disappearance of the embolic source.