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Background and Purpose —This study aimed to determine the correlation of in vivo ultrasound measurements of intima-media thickening (IMT), lumen diameter, and cross-sectional area of the common carotid artery (CCA) with corresponding measurements obtained by gross pathology and histology. Methods —Sixty-six moribund neurological patients (mean age 71 years) underwent B-mode ultrasound of the CCA a few days before death. During autopsy, carotid specimens were removed in toto. Carotid arteries were ligated and cannulated for injection of a hydrophilic embedding material under standardized conditions. The carotid bifurcation was frozen and cut manually in 3-mm cross slices. Digital image analysis was carried out to determine the diameter and the cross-sectional area of the frozen slices of the CCA. IMT was assessed by light microscope. Ultrasonic and planimetric data were compared. Results —Mean measurements of lumen diameter and cross-sectional area were 7.13±1.27 mm and 0.496±0.167 cm 2 , respectively, by ultrasound, and 7.81±1.45 mm and 0.516±0.194 cm 2 , respectively, by planimetric analysis of the unfixed redistended carotid arteries ( R 2 =0.389 and 0.497). The mean IMT was 1.005±0.267 mm by ultrasound and 0.67±0.141 mm histologically, resulting in a mean difference of −31%. Conclusions —Transcutaneous B-mode ultrasound provides a reliable approach for in vivo measurements of the cross-sectional area and, less exactly, of the lumen diameter of the CCA. Compared with histological results, in vivo ultrasound measurements of the IMT are systematically larger.

Background and Purpose —Transcranial color-coded sonography (TCCS) via the suboccipital approach allows direct and continuous visualization of the basilar artery (BA). In this study, we intended to evaluate the ability of native TCCS in visualizing the length of the BA by means of a comparison with postmortem measurements. Methods —The BA was prospectively studied by TCCS shortly before death (median 3 days) in 46 moribund neurological patients (mean±SD age 71.1±13.1 years). The length of the BA was determined by measuring the distance between the vertebrobasilar junction and the deepest available flow signal in the top of the BA. During autopsy, photos of the vertebrobasilar system were taken to evaluate the true anatomic length and variations of the course of BA in situ, eg, straight, curved, or S-shaped. Results —Comparison of the in vivo ultrasound measurements of BA length and postmortem data was possible in 44 of 46 cases. In the 2 remaining patients, the BA was occluded. The mean insonation depth of the vertebrobasilar junction was found at 66.9±7.1 mm. The mean BA length was 21.5±6.8 mm by color-coded duplex and 32.9±6 mm anatomically ( P Conclusions —Color duplex imaging enables correct visualization of the proximal two thirds of the BA, but only exceptionally of its distal one third. A tortuous course of the BA leads to an underestimation of its anatomic length.

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 different contrast agents and different provocation procedures. Currently, data on an appropriate time window for the appearance of contrast bubbles in the TCD recording after the injection of the contrast medium and the comparison of different provocation maneuvers to increase right-to-left shunting are insufficient. Methods —Forty-six patients were investigated by both TEE and bilateral TCD of the middle cerebral artery. The following protocol with 6 injection modes was applied in a randomized way: (1) injection of 10 mL of agitated saline without Valsalva maneuver, (2) injection of 10 mL of agitated saline with Valsalva maneuver, (3) injection of 10 mL of a commercial galactose-based contrast agent (Echovist) without Valsalva maneuver, (4) injection of 10 mL of Echovist with Valsalva maneuver, (5) injection of 10 mL of Echovist with standardized Valsalva maneuver, and (6) injection of 10 mL of Echovist with coughing. Results —In 20 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt-positive). Sixteen patients were negative in both investigations, no patient was positive on TEE and negative on TCD, and 10 patients were only positive on at least 1 TCD investigation but negative during TEE. The amount of microbubbles detected in the various tests decreased in the following order: Echovist and Valsalva maneuver, Echovist with coughing, Echovist and standardized Valsalva maneuver, saline with Valsalva maneuver, Echovist, and saline. With a time window of 20 to 25 seconds for the bubbles to appear in the TCD recording and with a sequence of first Echovist and Valsalva maneuver and then Echovist with coughing, all shunts were reliably identified with a specificity of 65% compared with TEE as the traditional gold standard. The time of first microbubble appearance was not helpful to distinguish between shunts detected on TEE and other shunts. Conclusions —TCD performed twice with 2 provocation maneuvers using Echovist is a sensitive method to identify cardiac right-to-left shunts also identified by TEE.

Background and Purpose —Cardiac right-to-left shunts can be identified by transcranial Doppler ultrasound (TCD) with the use of different contrast agents and by transesophageal echocardiography (TEE). Systematic data are available on neither the reproducibility of contrast TCD, the comparison of different contrast agents, nor the comparison of simultaneous bilateral to unilateral recordings. Furthermore, we assessed the side distribution of thus provoked artificial cardiac emboli. Methods —Fifty-four patients were investigated by TEE and by bilateral TCD of the middle cerebral artery. The following protocol was performed twice: injection of 9 mL of agitated saline without Valsalva maneuver, injection of 9 mL of agitated saline with Valsalva maneuver, injection of 5 mL of a commercial galactose-based contrast agent without Valsalva maneuver, and injection of 5 mL of the galactose-based contrast agent with Valsalva maneuver. Results —In 18 patients, a right-to-left shunt was demonstrated by TEE and contrast TCD (shunt positive). Twenty-nine patients were negative in both investigations, 1 was positive on TEE and negative on TCD, and 6 patients were only positive on TCD. Both bilateral and repeated recordings increased the sensitivity of contrast TCD. There was a symmetrical distribution of microembolic signals in the right and left middle cerebral artery. Conclusions —TCD performed twice and with the use of saline or a galactose-based contrast agent is a sensitive method in the identification of cardiac right-to-left shunts also identified by TEE. The cardiac microemboli in this study did not show any side preference for one of the middle cerebral arteries.

Background and Purpose —Embolus detection using transcranial Doppler ultrasound is a useful method for the identification of active embolic sources in cerebrovascular diseases. Automated embolus detection systems have been developed to reduce the time of evaluation in long-term recordings and to provide more “objective” criteria. The purpose of this study was to evaluate the critical conditions of automated embolus detection by means of a trained neural network (EMBotec V5.1 One, STAC GmbH, Germany). Methods —In 11 normal volunteers and in 11 patients with arterial or cardiac embolic sources, we performed simultaneous recordings from both middle or both posterior cerebral arteries. In the normal subjects, we produced 1342 additional artifacts to use the latter as false-positives. Detection of microembolic signals (MES) was done offline from digital audiotapes (1) by an experienced blinded investigator used as a reference and (2) by a trained 3-layer–feed-forward neural network. Results —From the 1342 provoked artifacts the neural network labeled 216 events as microemboli, yielding an artifact rejection of 85%. In microembolus-positive patients the neural network detected 282 events as emboli, among these 122 signals originating from artifacts; 58 “real” events were not detected. This result revealed a sensitivity of 73.4% and a positive predictive value of 56.7. The spectral power of the detected artifact signals was 16.5±5 dB above background signal. MES from patients with artificial heart valves had a spectral power of 6.4±2.1 dB; however, in patients with other sources of emboli, MES had an averaged energy reflection of 2.7±0.9 dB. Conclusions —The neural network is a promising tool for automated embolus detection, the formal algorithm for signal identification is unknown. However, extreme signal qualities, eg, strong artifacts, lead to misdiagnosis. Similar to other automated embolus detection systems, good signal quality and verification of MES by an experienced investigator is still mandatory.

Abstract —Transcranial Doppler ultrasound is capable of detecting microembolic material, both gaseous and solid, within the intracranial cerebral arteries. To avoid discrediting this promising and exciting new technique, experts in this field met in January 1997 in Frankfurt, Germany, to discuss the limitations and problems of embolus detection and to determine guidelines for its proper use in clinical practice, as well as in scientific investigations. In particular, the authors suggest that studies report the following parameters: (1) ultrasound device, (2) transducer type and size, (3) insonated artery, (4) insonation depth, (5) algorithms for signal intensity measurement, (6) scale settings, (7) detection threshold, (8) axial extension of sample volume, (9) fast Fourier transform (FFT) size (number of points used), (10) FFT length (time), (11) FFT overlap, (12) transmitted ultrasound frequency, (13) high-pass filter settings, and (14) recording time. There was agreement that no current system of automatic embolus detection has the required sensitivity and specificity for clinical use.

Background and Purpose Different frequencies of asymptomatic Doppler embolic signals have been reported in studies. There has been concern that different criteria for identification may account for some of this variation. A previous reproducibility study between two centers found good agreement, but no studies among large numbers of centers have been performed. We performed an international reproducibility study among nine centers, each of which had published recent studies of embolic signal detection in peer-reviewed journals. Methods Each center performed blinded analysis of a taped audio Doppler signal composed of transcranial Doppler middle cerebral artery recordings from 6 patients with symptomatic carotid artery stenosis. The exact time of any embolic signal was recorded. Six centers also measured the intensity increase of any embolic signals detected. Interobserver agreement was determined by a method based on the proportion of specific agreement. Results Seven centers reported between 39 and 55 signals, but one center reported 142 embolic signals. The probability of agreement between observers was .678, which rose to .791 when the data from the highest reporting center were excluded. Introducing a decibel threshold resulted in a significant increase in the probability of agreement; a decibel threshold of >7 dB resulted in a probability of agreement of .902. Intensity measurements made by different centers were usually highly correlated, but this was not always the case, and 3 of the 15 correlations were not significant. The absolute values of the intensities measured varied between centers by as much as 40%. Conclusions Although most centers report similar numbers of embolic signals, some use less specific criteria and report more events. The use of a decibel threshold improves reproducibility. However, intensity thresholds developed by one center cannot be directly transferred without validation to another center; differing methods of measurement are being used, and this results in different intensity values for the same embolic signals, even when the same equipment is used.

Background and Purpose Microembolic signals (MES) are frequently observed by transcranial Doppler ultrasound after prosthetic heart valve implantation. Whether these MES are due to solid or gaseous particles is uncertain. We hypothesized that MES are gaseous and that if they are due to cavitation effects, their occurrence should respond to changes of dissolved oxygen concentration in the blood. Methods Transcranial monitoring of MES was performed in five patients with prosthetic aortic valves, who inspired 100% oxygen through a facial mask. In one patient 100% oxygen was administered under hyperbaric (2.5 kPa) conditions in a hyperbaric chamber. Results Inspiration of 100% oxygen reduced the total number of MES from 96/30 min to 2/30 min. Increasing the concentration of dissolved oxygen in the hyperbaric chamber led to an increase from 0.3 MES per minute (1.0 kPa) to 0.9 MES per minute (2.5 kPa). Conclusions The dependence of occurrence of MES in patients with prosthetic cardiac valves on the oxygen partial pressure in blood provides strong evidence that these microemboli are gaseous.

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 ρ=0.84; P Conclusion— Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.

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 χ 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.

Background and Purpose— The correct detection and quantification of carotid artery disease are of decisive impact on patient prognosis and adequate treatment. In this study, we evaluated the ability of ultrasonography to detect and to grade carotid artery stenosis through a comparison of the in vivo ultrasound findings with the planimetric analysis of the corresponding postmortem specimens. Methods— Shortly before their death, 59 critically ill neurological patients (mean age, 70 years) were prospectively examined by extracranial and intracranial Doppler sonography and color-coded duplex ultrasound. Carotid stenosis was classified by hemodynamic and morphological ultrasound criteria. Carotid specimens were removed in toto during autopsy. Under standardized conditions, specimens were redistended, sectioned, and histologically processed. Computerized planimetric measurements of the arteries were carried out and compared with the ultrasound findings. Correlation of the ultrasound and postmortem planimetric findings was available in 93 carotid bifurcations. Results— Through both techniques, 46 carotid arteries were found to be normal. Steno-occlusive carotid lesions ranged from 8.5% to 100% lumen reduction. Overall, r =0.96 and adjusted R 2 =0.90. For the steno-occlusive carotid lesions, r =0.91. Conclusions— Extracranial and intracranial Doppler and color-coded duplex ultrasound permits reliable detection and quantification of carotid artery stenoses and occlusions even under difficult examination conditions in critically ill patients.

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.

Background and Purpose Detection of clinically silent circulating microemboli by transcranial Doppler sonography is now being widely investigated in the hope of identifying patients at increased risk for stroke. Automatic detection by bigated Doppler, which uses sampling from two different depths in the artery under study and considers the motion of the embolus, may help to define “periods of interest” that can be evaluated off-line. Methods In 12 normal volunteers and 10 patients with prosthetic aortic valves, we performed 1-hour recordings from one middle cerebral artery. In the normal subjects, we produced additional artifacts to use them as false-positives. Detection of microemboli was done off-line from digital audiotapes by an experienced blinded investigator (used as the gold standard) and was compared with on-line detection using specially designed software. Results With the setting used, 91.5% of all recorded artifacts could correctly be identified as such with the software. Embolic signals were detected by the software with a specificity of 59.9% and a sensitivity of 74.3%. Conclusions Bigated Doppler adds a new dimension to the definition and detection of microembolic signals. It constitutes an important step forward toward automatic screening of stroke-prone patients. Assessing on-line periods of interest during the recording and going over the recorded data again off-line helps to save time for the discrimination of embolic signals from both the normal Doppler spectrum background and artifacts.