Background and Purpose— The CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts. Methods— As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (ps±values). For all DATs included in CARESS (n=300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator). Results— For the reference tape, the cumulative ps±value was 0.894 based on 12 of 14 observers. Two observers with very different results improved after a training procedure. Agreement between post-trial validator and central reader was ps+=0.805, indicating very good agreement. Correlation between online evaluation and off-line evaluation of DATs was very good overall (cumulative &rgr;=0.84; P<0.001). Conclusion— Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.

OBJECTIVE:Five different calliper methods for assessing the degree of carotid artery stenosis and visual estimation ("eyeballing") of postmortem carotid arteriograms were compared with the planimetric gold standard of the area reduction at the site of the stenosis.METHODS:During autopsy 53 carotid specimens were removed in toto from 31 neurological patients. Carotid arteries were ligated and redistended to a physiological degree for standardised three-plane arteriography. Afterwards, the entire specimen was filled with an embedding medium under the same conditions and sectioned. Slices at the site of stenoses were histologically processed. Computerised planimetric analysis of the lumen area reduction was performed and compared with the arteriographic findings. Arteriograms were evaluated by two independent observers by means of linear Common Carotid Artery (CC), the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET), and squared measurements (NASCET2, ECST2) after applying the pi r2 function. Further, three independent observers performed eyeballing of the degree of stenosis from the postmortem arteriographies.RESULTS:Planimetry was carried out in 29 internal carotid artery (ICA) and 17 common carotid artery (CCA) stenoses ranging from 8.5 to 100%. The smallest mean differences of the degree of stenosis in % between planimetry and arteriography were -0.5 and 0.6%. The narrowest 95 %-limits of agreement covered a range of +/-24.1 and 26.3% of stenoses, and the highest correlation coefficients were both 0.9 for the CC and ECST2 techniques, respectively. By eyeballing, the degree of stenosis was underestimated by 13.5 to 15.8% on average. The narrowest limits of agreement between two observers for eyeballing covered a range of 35%.CONCLUSION:Three-plane arteriography has only a moderate accuracy and reproducibility in detecting and measuring carotid artery stenosis independent of the technique of measurement used.

Objectives: Clinically silent microembolic signals (MES) can be detected by transcranial Doppler sonography (TCD). There is theoretical evidence that lower ultrasound emission frequencies may lead to a higher signal intensity and thus sensitivity to detect MES. We compared a 1-MHz probe with a 2-MHz probe regarding sensitivity in the detection of MES. Moreover, embolus detection by transcranial Doppler ultrasound is very time consuming and semi-automated detection is mandatory. Therefore, we studied an on-line algorithm using the bi-gate technique and the two transmission frequencies.Methods: After defining detection thresholds of >= 12 dB (1 MHz) and >= 10 dB (MHz) with eight normal subjects as MES-negative controls, taking into account natural fluctuations of the Doppler spectrum, we studied 36 patients with ischaemic events and five asymptomatic patients with incidental embolic sources. All patients subsequently underwent a 1-hour unilateral embolus detection from the middle cerebral artery (MCA) or the posterior cerebral artery (PCA), respectively, using 1 and 2 MHz for 30 minutes each in a randomized order. The software algorithm was compared with a blinded off-line analysis by an experienced observer as a gold standard.Results: The investigator detected 198 MES (range 0-41 MES) in the recordings of 29 patients out of the 41 patients using the 1-MHz probe and 101 MES (range 0-32 MES) in the recordings of 14 patients using the 2-MHz probe (p=0.0007). Sensitivity of the software to detect MES confirmed by the investigator was 31% using 1 MHz and 41% using 2 MHz. The positive predictive value was 6 and 30%, respectively.Discussion: The sensitivity and positive predictive values of the automated algorithm to detect MES were unacceptably low for clinical practice with both frequencies. The use of 1 MHz instead of 2 MHz may, however, be useful when evaluating the recordings off-line by an experienced blinded observer.

Objective: To assess the interaction of cerebral amyloid angiopathy (CAA) and arterial hypertension as cofactors for intracerebral hemorrhage (ICH). Methods: The authors investigated 129 postmortem brains of hypertensive patients with and without ICH. Sixty-four patients had had deep (n = 40) or lobar (n = 24) ICH. Sixty-five patients without ICH served as controls. Established risk factors for ICH ( age, gender, severity of hypertension, bleeding disorders, intake of anticoagulants, and chronic alcoholism) were identified from medical records. Four specimens per brain were stained with hematoxylin-eosin and Congo red. The entire ICH cohort and subgroups were compared with controls using single-factor and multiple logistic regression analyses. Results: CAA was found in 15 of 64 subjects (23%) with ICH and in five of 65 controls (8%; p = 0.026). In single-factor analysis, CAA was more prevalent in lobar ICH compared with controls (p = 0.007) but not in deep ICH. Poor control of hypertension was more prevalent in the entire ICH group (p = 0.01) and in deep ICH (p = 0.016) but not in lobar ICH. ICH was predictive of the presence of CAA ( odds ratio: 5.6, 95% CI: 1.8 to 19.5, p = 0.003), and CAA was more likely to be found in lobar ICH in multivariable-adjusted analysis. After adjustment for conventional risk factors, there was a weak association between CAA and deep ICH. Conclusion: Cerebral amyloid angiopathy plays a major role in the pathogenesis of intracerebral hemorrhage even in patients with more evident risk factors.

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.

Background and Purpose-Cerebral embolism is a common cause of stroke. Microembolic signals(MES) detected by transcranial Doppler represent ongoing embolisms, but the lack of reliable data about its clinical relevance hinders its widespread use in clinical practice.Methods-We prospectively monitored 114 consecutive acute ischemic stroke patients with middle cerebral artery (MCA) stenosis for MES. The signals on digital audio tape were analyzed by an independent observer who was blinded to all other data. All patients were followed-up for the occurrence of recurrent stroke or transient ischemic attack (TIA) in the indexed MCA territory.Results-MES was detected in 25 (22%) patients. The mean number of MES was 18 (range, 1 to 102). MES were more common in patients with severe stenosis (10/21, 48%) than in those with mild-moderate stenosis (4/26, 15%) (Pearson chi(2) P=0.02). During follow-up for a mean of 13.6 months (range, 1 to 32), 12 (12%) patients had further ischemic events (10 strokes and 2 TIAs) in the affected MCA region during follow-up. Among these, 7 (58%) had recurred within 1 month ( 1 recurred within 1 week, the other 6 patients had recurrences in week 3 or 4 after discharge), 3 within 6 months, 1 within 6 to 12 months, and the remaining 1 recurred after 1 year. The presence of MES was the only predictor of a further ischemic stroke/TIA by Cox regression (adjusted odds ratio, 8.45; 95% CI, 1.69 to 42.22; P=0.01) even after controlling for age, sex, diabetes, hypertension, previous stroke, smoking, and acute treatment.Conclusions-In acute stroke patients with MCA stenosis, MES predicts further cerebral ischemia. This procedure should be considered as part of routine investigation and might identify a group of patients who are most likely to benefit from antithrombotic treatment.

Cardiac and extracardiac right-to-left shunts can be identified by transesophageal echocardiography (TEE) as well as by transcranial Doppler ultrasound (TCD) using contrast agents that do not pass the lungs. Currently, the appropriate performance of a Valsalva manoeuvre (VM) to provoke the shunt, the use of different contrast agents and the classification of the TCD results are still under debate. In this study, we looked also at possible side effects of provoked cardiac micro-emboli in the left and right hemisphere. Seventy-one patients were investigated by both TEE and bilateral TCD of the middle cerebral arteries. The following protocol was applied in a randomized way: (1) Echovist(R)-300 without VM; (2) Echovist(R)-300, VM for 5 seconds starting 5 seconds after the beginning of contrast injection; (3) repetitive short VMs in between 2 and 13 seconds after the beginning of Echovist(R)-300 injection; and (4) repetitive short VMs in between 2 and 13 seconds after the beginning of agitated saline injection. Only if one of the tests (2-4) was negative, this particular negative test was repeated. Use of Echovist(R)-300, but not of saline yielded 100% sensitivity in the detection of TEE-proven shunts. The repetitive VM was slightly Superior to the conventional VM. Introduction of a threshold of two or even three rnicrobubbles produced less falsely positive TCD results in comparison to the TEE. There was no difference in microbubbles. TCD using Echovist(R)-300 is a sensitive method to identify TEE-proven cardiac right-to-left shunts. Repetitive VM is an alternative to conventional VM.

High-intensity transient signals (HITS) detected by transcranial Doppler (TCD) ultrasound may correspond to artifacts or to microembolic signals, the latter being either solid or gaseous emboli. The goal of this study was to assess what can be achieved with an automatic signal processing system for artifact/microembolic signals and solid/gas differentiation in different clinical situations. The authors studied 3,428 HITS in vivo in a multicenter study, i.e., 1,608 artifacts in healthy subjects, 649 solid emboli in stroke patients with a carotid stenosis, and 1,171 gaseous emboli in stroke patients with patent foramen ovale. They worked with the dual-gate TCD combined to three types of statistical classifiers: binary decision trees (BDT), artificial neural networks (ANN), and support vector machines (SVM). The sensitivity and specificity to separate artifacts from microembolic signals by BDT reached was 94% and 97%, respectively. For the discrimination between solid and gaseous emboli, the classifier achieved a sensitivity and specificity of 81% and 81% for BDT, 84% and 84% for ANN, and 86% and 86% for SVM, respectively. The current results for artifact elimination and solid/gas differentiation are already useful to extract data for future prospective clinical studies.

Background: Transesophageal echocardiography (TEE) and transcranial Doppler sonography (TCD) can identify right-to-left-shunts that predispose to paradoxical embolism. In a large cohort we compared the results of both techniques. Methods: 222 patients were investigated by both techniques using the contrast agent Echovist®-300 and performing each test once without and once with the Valsalva maneuver (VM). Results: TEE-proven right-to-left-shunts were detected by TCD with a high sensitivity of 94%. In addition, TCD revealed shunts not noted during TEE in about 20% of all patients studied. These shunts are in general smaller than those concordantly identified; however, 9% of the patients without a TEE-proven shunt presented with a shunt that allows a considerable amount of contrast medium to pass. There were 12% more microbubbles detected in the right middle cerebral artery than in the left middle cerebral artery during the TCD test performed with VM, but not during the TCD test performed without VM. Conclusions: Contrast-enhanced TEE and TCD are complementary methods in the assessment of stroke and stroke-prone patients. The side difference of microbubbles may indicate a selective streaming of cardiac emboli during VM.

BACKGROUND AND PURPOSE:The major limitation of native transcranial colour-coded duplex sonography (TCCS) in older stroke patients is the relatively frequent occurrence of an insufficient temporal window. Our goal was to investigate the relationship between the in vivo Doppler ultrasound image quality of the temporal bone, and computed tomography (CT)-determined thickness, density, and homogeneity of cadaver temporal bone.METHODS:Thirty-three moribund neurological patients who eventually died were examined by TCCS using the transtemporal approach. The sonographer categorized the quality of the TCCS image (excellent, intermediate, and poor). During autopsy, a rectangular sample of the temporal squama was removed, which corresponded to the area of the in vivo acoustic window. The thickness of the whole temporal bone, cortical, and cancellous (= diploe) bone as well as the density and homogeneity were determined by high-resolution CT.RESULTS:Thirty-seven temporal bones were obtained. The quality of the acoustic window was classified as excellent in 13, intermediate in 6 and poor in 18 cases. A significant correlation between the complete bone thickness, as well as between the absolute thickness of the diploe and the quality of the acoustic window was found: the thinner the bone/diploe, the better the colour Doppler signal. The thickness of the cortical plates and the homogeneity of the bones were identical in the three image quality categories.CONCLUSION:The transtemporal TCCS image quality depends mainly on the thickness of the cancellous component of the temporal bone.

118 critically ill patients from the Neurological Department of University Medical School of Debrecen, Hungary were prospectively examined by Dopplerand Bmode sonography of the extraand intracranial brain supplying arteries. Eighty-two of them died within a few days or weeks. Of 82 cases, carotid specimens could be obtained in 67 cases (118 carotid specimen). In the remaining cases, the carotids were severely damaged or lost during autopsy. Another 25 specimens were damaged during macropathological work-up or histologic processing so that a reliable planimetric measurement was possible on 93 carotid arteries. These arteries came from 59 patients, 37 men, 22 women, mean age 69.9 +/13.4 years; range 37-95 years.The median interval between the patients’ ultrasound examination and their deaths was 3 days (mean 10.1 days).

Objective: Neurosonological investigations of the extracranial and intracranial brain supplying arteries are helpful in the assessment of stroke and stroke-prone patients. However, the individual patient's anatomy and pathology (deep location of arteries, shadowing of the ultrasound beam, low flow, insufficient bone window) may hamper their proper visualization. Methods: The role of echocontrast agents, which are useful to overcome these limitations, is summarized in this presentation with special focus on SonoVue® (Bracco, Milan, Italy). Results: Echocontrast agents provide better delineation of normal blood flow, occlusions, pseudoocclusions, stenoses, and collaterals in the extracranial and intracranial vascular beds. They are of particular value during color-coded transcranial duplex investigations via the temporal and foraminal (nuchal) window. Future applications include the visualization of brain tissue perfusion and of tumors. SonoVue® has a strong enhancing effect and a long duration of the echo enhancing effect of several minutes enabling the sonographer to perform the investigation with a single injection or 2–4 repeated injections without the use of an injection pump and as a one-person procedure. SonoVue® is easy to prepare and has virtually no side effects. Conclusions: Echocontrast agents give additional information on the patient's vascular situation that is crucial to plan further diagnostic and therapeutic steps. They help to avoid unnecessary, expensive, and potentially harmful additional investigations such as intra-arterial DSA. SonoVue® is particularly useful in this context.

Objective: to analyse whether ultrasound contrast agent (UCA) improves the diagnostic accuracy to differentiate between benign and malignant superficial lymph node enlargement by using colour-coded duplex sonography (CCDS) and power Doppler (PD). Methods: 32 patients with suspected malignant superficial lymph node enlargement prospectively underwent standardised ultrasound examinations using B-mode sonography and native and contrast-enhanced CCDS and PD immediately before biopsy. Solbiati-Index (longitudinal-transverse diameter ratio) and intranodal flow patterns by using different vascularisation types were assessed. Histological and sonographical findings were correlated. Results: 27 malignant and 5 benign lymph nodes were found. Solbiati-Index was lower in malignant lymph nodes than in benign nodes (mean 1.5 vs. 2.4, P < 0.045). More intranodal flow patterns could be detected after UCA (53 vs. 43) but the number of correctly identified malignant nodes decreased after UCA (26 vs. 24) and the number of correctly identified benign nodes remained constant compared with native CCDS and PD. In 31% of the colour-mode studies, PD was considered to visualise more clearly intranodal vascular flow patterns than CCDS. Conclusion: despite depicting more intranodal vascular patterns, the use of an ultrasound contrast agent seems not to improve the diagnostic value of CCDS and PD compared with native colour-mode studies in superficial lymph node enlargement. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

OBJECTIVES:Arterial hypertension is, besides age, the number one risk factor for ischaemic stroke. Patients with arterial hypertension frequently present with additional coexisting vascular risk factors interacting in a complex way.MATERIAL AND METHODS:This paper reviews the benefit of antihypertensive treatment, as well as different treatment options of arterial hypertension and their side-effects.RESULTS:Patients with definite arterial hypertension, but also patients with so-called normal or high-normal blood pressure are at increased risk to develop stroke and other cardiovascular complications. Vascular remodelling of small and large vessels provoked by arterial hypertension is the initial step in the development of atherosclerosis and lipohyalinosis. Vascular remodelling can be improved or even normalized by antihypertensive treatment with angiotensin-converting-enzyme inhibitors and angiotensin-I-receptor antagonists showing the most convincing effects. Angiotensin-converting-enzyme inhibitors and angiotensin-I-receptor antagonists have the lowest rate of side-effects, however, economic restraints hinder their general application. Statins are needed to treat dyslipidaemia. They also lower blood pressure and have a synergistic effect with the above two antihypertensive components in lowering blood pressure. In hypertensive patients, risk of stroke and other cardiovascular complications is determined by the blood pressure level and the presence or absence of target organ damage and the interaction with other risk factors, such as cigarette smoking, dyslipidaemia, and diabetes. These high-risk patients should be treated even more aggressively than usual.CONCLUSIONS:In the vast majority of patients and healthy individuals, target blood pressure should be as high as or below 120/80 mmHg to minimize the occurrence of stroke and other cardiovascular complications.

BACKGROUNDChronic microembolization that can be demonstrated by pulsed Doppler ultrasound may give rise to pulmonary side-effects during haemodialysis by direct vessel obstruction, increased complement activation or platelet aggregation. The objective of the present investigation was to study whether the use of pre-filled instead of dry dialysers would help to minimize the number of microemboli.METHODSThe study cohort consisted of 23 patients undergoing maintenance haemodialysis. Using a 2 MHz pulsed ultrasound device, the subclavian vein downstream to the dialysis fistula was investigated for 10 min during the dialysis session. The ultrasound examination was performed twice during two successive dialysis sessions, using a pre-filled or a dry dialyser in randomized order.RESULTSIn all patients investigated, numerous microembolic signals (MES) could be observed in the subclavian vein. Treatment with pre-filled dialysers was associated with significantly less MES (82 +/- 94) as compared with dry dialysers (268 +/- 296; P = 0.002).CONCLUSIONSIn comparison to dry dialysers, the use of pre-filled dialysers leads to a significant reduction in microembolization, which may prevent repeated damage to the pulmonary vasculature and, thus, cause less pulmonary damage.

Fabry's disease is a sex-linked recessive storage disorder leading to cerebrovascular symptoms in many cases. Whether the primary origin of cerebrovascular symptoms in these patients is due to autochthonous thrombosis of small vessels or embolic infarction from large vessels is under debate. Microembolic signals (MES) indicative of an active embolic source can be recorded by transcranial Doppler sonography. We report four patients (34, 44, 62 and 66 years old) with Fabry's disease from one kindred in whom we carried out microembolus detection recordings to disclose active embolic sources. Three of the patients had had transient focal neurological deficits. Two patients had angina pectoris and one had exercise dyspnea, but no patient had clear evidence of disease of the large coronary vessels or brain-supplying arteries. No MES were found in 1-hour recordings in any patients, supporting the hypothesis that early cerebrovascular symptoms arise from small vessel occlusion and not from embolic sources as an indicator of disease of large brain-supplying arteries or cardiac embolism.

BACKGROUND:The pathophysiology leading to pulmonary side effects during haemodialysis and haemodiafiltration is not yet fully understood. Chronic microembolization, which can be demonstrated by pulsed Doppler ultrasound, may be one cause.METHODS:The study cohort consisted of 24 long-term dialysis patients undergoing haemodialysis (n=21) and online-haemodiafiltration (n=3), respectively. The subclavian vein downstream to the venous access was investigated during different phases of the procedure using a 2-MHz pulsed ultrasound device.RESULTS:In all periods investigated (connection, dialysis, disconnection), numerous microembolic signals (MES) were found in the subclavian vein. The numbers of MES detected during haemodiafiltration (314-709 MES per 10 min) were higher than during haemodialysis (0-81 MES per 10 min).CONCLUSIONS:The composition (gaseous or solid) and origin (pump, tubing system or shunt) of the microemboli detected remains unclear. Chronic microembolization may be one cause of pulmonary complications of haemodialysis and haemodiafiltration. The detection method described in this article will help us to better understand this process and to determine what role microemboli might play in pulmonary and central nervous system disorders. It may also help to optimize the devices and techniques used.