(Stroke. 2000;31:1640.)
© 2000 American Heart Association, Inc.
Original Contributions |
Contrast Transcranial Doppler Ultrasound in the Detection of Right-to-Left Shunts
Time Window and Threshold in Microbubble Numbers
From the Department of Neurology (D.W.D., K.S., V.K., K.K., E.B.R.) and Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (J.S., M.G., T.W.), University of Münster (Germany).
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Abstract |
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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.
Key Words: cerebral embolism • cerebrovascular disorders • foramen ovale, patent • ultrasonography
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Paradoxical embolism of thrombotic material of deep venous origin via a cardiac right-to-left shunt (RLS) into the cerebral arteries is a well-recognized cause of stroke.1 Transesophageal echocardiography (TEE) enhanced by echo contrast agents is currently the "gold standard" for the detection of cardiac RLS, namely, atrial septal defects and patent foramen ovale.2 3 4 5 6 The performance of a Valsalva maneuver (VM) increases right atrial pressure, thus facilitating or demasking intermittent right-to-left shunting.3 7 8
Contrast-enhanced transcranial Doppler sonography (TCD) is an attractive alternative to TEE in the identification of RLS. The technique is based on the detection of an intravenously injected contrast agent within intracranial arteries, eg, the middle cerebral arteries (MCAs). The echo contrast agents used for this test are unable to pass the pulmonary capillary bed. The echo contrast agent Echovist is a suspension of galactose microparticles in an aqueous 20% galactose solution with adherent tiny microbubbles smaller than human erythrocytes. In case of a RLS, the contrast agent enters the arterial circulation and produces microembolic signals (MES) during the TCD recording, thus mimicking the pathway of paradoxical cerebral emboli.9 10
There is no doubt that the performance of a VM increases the
sensitivity of contrast TCD. Recent data suggest that the combination
of the results of 2 contrast TCD tests with a provocation maneuver
considerably increases the sensitivity of the method.11 12
However, several questions regarding contrast-enhanced TCD are still
unsolved. (1) The appropriate timing of the VM in relation to the
injection of the contrast medium is under debate. The injection of the
contrast agent was performed before,4 11 12 13 14 15 16 17 18
during,15 17 19 or after the VM.15 20 In
those studies in which the VM was performed after injection, the time
delay between injection and VM was frequently not clearly specified in
relation to the start or the end of injection. In the studies with a
clear specification, the time from the beginning of injection to the
beginning of the VM ranged between 0 and 5
seconds.4 11 12 15 (2) Several authors use a threshold for
the number of MES detected in the TCD recording; most authors,
however, qualify the test as positive when at least 1 MES can be
identified. Thresholds proposed for the number of MES are
4,21 6,18 and 11.22
Furthermore, the question of whether the use of a
diagnostic time window for MES appearance increases the
specificity of the test without necessarily decreasing sensitivity is
not yet resolved.14 23 24 Time windows proposed between
the intravenous injection of the contrast medium and its
appearance in the MCAs are 6 heartbeats,20 10
seconds,20 21 15 seconds,13 20
seconds,24 22 seconds,15 and 25
seconds.11 14 A recent study described the necessity of
including MES at least 20 to 25 seconds after the start of injection to
achieve a high sensitivity; it may also be possible that no time window
is necessary.12 In the present study we (1)
investigated the effect of different temporal relationships between
injection of the contrast agent and the VM on the sensitivity and
specificity of contrast TCD compared with TEE as the gold standard and
(2) evaluated whether the use of a threshold in number of MES and the
use of a diagnostic window influenced sensitivity and
specificity.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Patients
Fifty-eight subjects (30 males, 28 females) aged 15 to 83 years (mean age, 51 years) were included in the study. All except for 1 patient had suffered strokes, transient ischemic attacks, attacks of amaurosis fugax, or central retinal artery occlusions. Twenty-four patients had had recurrent events. One patient was asymptomatic but had a strong family history of strokes in young and middle age and asked for a full risk factor profile. Nineteen subjects were cigarette smokers, 6 were diabetics, 24 had arterial hypertension, and 36 suffered from hyperlipidemia. No patient had a mechanical prosthetic cardiac valve.
In all 58 patients, TEE was performed to detect or rule out an intracardiac shunt. Apart from these 58 patients, 48 additional patients had been screened but had been excluded from the study for the following reasons: in 34 of them no TEE could be obtained or the TEE was performed in an external hospital with an unknown protocol. In 2 patients the TEE had to be stopped prematurely because of discomfort and was not repeated. In 3 patients the TCD recording had to be stopped because of noncompliance. One patient was pregnant. In 7 patients there was no bilateral temporal window suitable for TCD, and in 1 patient no venous catheter could be placed because of anatomic reasons.
Echocardiography
All patients underwent TEE, which was performed by trained
echocardiographers from the Department of
Cardiology of our hospital. The investigators used a
Hewlett Packard Sonos 2500 or 5500 imaging system and a 4- to 7-MHz
multiplane probe. After informed consent had been obtained, patients
were examined in the fasting state and received local pharyngeal
anesthesia with 10% topical lidocaine. Additional
intravenous sedation (midazolam) was given if the probe was
not well tolerated. For the diagnosis of an interatrial shunt, 10 mL of
contrast agent (Echovist) was injected as a bolus into a large
antecubital vein during 2-dimensional TEE. The presence of an
interatrial shunt was assumed when microbubble transit from the right
to the left atrium occurred spontaneously or during subsequent VM
within 3 heartbeats. The VM was trained with the patients before the
procedure. The effectiveness of the VM was verified by a reduction in
ventricular and atrial size and by bulging of the
interatrial septum into the left atrium. Intrapulmonary shunts
were not systematically investigated in this study.
Vascular Ultrasound Investigations
All subjects underwent a full color duplex investigation of
their neck arteries (Sonos 2500, Hewlett Packard) and a continuous-wave
Doppler investigation of the periorbital arteries. Subjects were
also examined by TCD, including the intracranial segments of the
internal carotid arteries, the MCAs, and the anterior and posterior
cerebral arteries. One patient had an extracranial internal carotid
artery occlusion and a high-grade stenosis on the contralateral
side, 1 patient had a unilateral high-grade carotid artery
stenosis, and an additional patient had a high-grade carotid
siphon stenosis. No further high-grade stenoses or
occlusions were detected in the anterior circulation.
For TCD embolus detection, the MCA was insonated bilaterally through the temporal bone windows. Two 2-MHz transducers were mounted on the temporal planes and secured with a head ribbon. A small sample volume of 8 mm in length and a low gain provided a setting optimal for embolus discrimination from the background spectrum. The bigate technique was used, in which 2 sample volumes were placed at a distance of 1 cm into each MCA main stem. The patients were lying comfortably on a stretcher. The investigations were well tolerated by the subjects without major side effects.
The same transcranial pulsed Doppler ultrasound device (TC4040, EME/Nicolet, software version 2.30) was used for all studies. The machine employed a 128-point fast Fourier transform analysis and used a graded color scale to display the intensity of the Doppler signals received. In addition to on-line recording onto the hard disk, the Doppler audio signal was recorded by an 8-channel digital audiotape deck recorder (TA-88, TEAC Corporation) with normal speed. An experienced observer’s analysis of MES comprised listening to each of the software-recorded signals, watching each signal on the screen, and evaluating the tapes. The following definition of MES was used: typical visible and audible (click, chirp, whistle) short-duration, high-intensity signal within the Doppler flow spectrum with a time delay in the 2 channels of each side.10 Single MES within clusters were discriminated by reducing the amplification during off-line analysis.
The following protocol with injections of 10 mL of the 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, (5) and repetitive short (<2 seconds) VMs in between 2 and 13 seconds after the beginning of contrast injection. Each of these tests lasted at least 2 minutes, with bolus injection of the contrast agent starting at 0 seconds, Valsalva strain, and resting phase until 120 seconds. Echovist was prepared following the instructions of the manufacturer; 10 mL was immediately injected as a bolus into a right cubital vein, which had previously been cannulated with a 21-gauge indwelling intravenous catheter. The VM started with deep inspiration, followed by pressing against the closed glottis and expiration. The patients were meticulously trained before the procedure.
Occasionally, MES could still be detected 80 to 120 seconds after the injection. In these cases, the resting time preceding the next test was prolonged until an MES-free period of at least 40 seconds’ duration was documented. In each test, only the first 40 seconds after injection were used for MES analysis. Data from the right and left MCAs were pooled.
Statistical Analysis
With TEE used as the gold standard, the sensitivity and
specificity of TCD were calculated as follows. Sensitivity was
calculated as the percentage of true positives (RLS confirmed by both
methods) in comparison to true positives plus false-negatives (TCD
negatives and TEE positives). Specificity was determined as the
percentage of true negatives compared with true negatives plus
false-positives (TCD positives and TEE negatives). For statistical
analysis, the numbers of MES seen during the 5 procedures were
compared with the nonparametric Friedman 2-way ANOVA. The
combination of 2 results of the 5 tests with the highest ranks in the
ANOVA were included in this analysis as well. We also
calculated sensitivity and specificity of the single tests for
different thresholds in MES and for different diagnostic
time windows (20, 25, and 40 seconds). Furthermore, the numbers of MES
were compared for the patients with a RLS on TEE and those with a RLS
only in the TCD investigation (nonparametric Mann-Whitney
U tests). For this test the total MES numbers of all 5 tests
of each patient were calculated and compared to avoid repeated
measures. Statistical significance was determined at the 0.05
level.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Twenty-one patients had no RLS on TEE and did not show MES in any of the tests within 40 seconds after the beginning of the injection. Twenty-one patients had a RLS on both tests, the TEE, and within 40 seconds after the beginning of the injection in at least 1 TCD procedure. In all these 21 patients, a patent foramen ovale was found during TEE. Sixteen patients had MES in at least 1 TCD investigation but no RLS on TEE. No patient had a RLS on TEE but failed to have one in the TCD investigation.
Table 1
summarizes the results of
the individual tests and of the combination of the results of 2 tests
with the highest numbers of MES. The values for the combination of the
results of 2 tests were calculated as follows: the numbers of MES from
the 2 tests at each second after the injection were added to form a new
series of numbers. Eventually sensitivity and specificity were
calculated as previously described. The highest ranks in a Friedman
2-way ANOVA were achieved in the tests with the performance of
the VM starting 5 and 8 seconds after the beginning of the injection as
well as the test including repetitive short VMs. This held true in the
combination of the results of 2 tests with the provocation maneuver.
When we combined the results of the 2 tests with the VM performed 5 and
8 seconds after the start of injection, respectively, all TEE-proven
shunts were reliably identified.
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The values for sensitivity and specificity of the single tests and of
the combined results of tests with VM, with different thresholds and
different diagnostic time windows taken into account, are
given in Table 2. A configuration with a
high sensitivity entailed a lower specificity.
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The 2 patient groups with concordant shunt identification in both investigations (n=21) and with shunt demonstration only in the TCD investigation (n=16) were compared concerning the total number of MES in all 5 TCD tests. There was a significant difference indicating more MES in the group of 21 patients with concordant shunt identification (P=0.0002; Mann-Whitney U test). Although in general there were fewer MES in the patient group with a shunt only in the TCD investigation compared with the group with concordant shunt identification, introducing a threshold in number of MES could not reliably discriminate between the 2 groups. The total numbers of MES in the individual patients within 40 seconds after the injection were 1, 1, 1, 1, 1, 2, 3, 3, 4, 4, 8, 10, 10, 12, 33, and 52 (mean 9, median 3.5; shunt only in the TCD recording), and 1, 3, 6, 7, 7, 18, 38, 40, 45, 49, 51, 57, 96, 100, 146, 162, 173, 330, 450, 484, and 890 (mean 150, median 51; concordant shunt identification).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Our study demonstrates that contrast TCD detects TEE-proven RLS with a sensitivity of 90% to 100% and a specificity of 70% to 76% when the results of 2 tests with the VM performed after the injection of Echovist are combined. This is in concordance with 2 previous studies, which emphasized the need to perform the tests with a provocation maneuver at least twice when the first test was negative.11 12 The performance of a VM for 5 seconds starting 5 seconds after the beginning of the injection and combinations of the results of this test with the results of the other tests, in which the VM was performed at different time intervals in relation to the injection, reached the highest ranks in an ANOVA, indicating that this test was the most appropriate. Table 3
gives an overview of the studies
comparing the results of contrast TCD and TEE and the modalities of the
provocation maneuver used.
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Our values for sensitivity and specificity are comparable to those described in the literature. Comparisons are difficult, however, since (1) some studies used unilateral and other studies bilateral recordings, (2) different diagnostic time windows were used, and (3) in some studies, the tests were repeated if the first test was negative. The duration of the VM was not specified in the earlier studies; in the most recent studies, a duration of at least 5 seconds was used. A Valsalva strain of 5 seconds can be performed by most patients and therefore seems to be a good compromise between the need to allow as many bubbles as possible to trespass the shunt and the patient’s tolerance of the procedure. The temporal relationships between the injection of the contrast medium and the VM differ considerably. In our experience, bolus injection of 10 mL takes approximately 2 to 3 seconds. The contrast agent needs a mean time of 5.1±1.4 seconds to reach the right atrium.14 Therefore, performance of the VM before injection does not make sense.20 25 In most studies, VM was performed after injection. Zanette et al15 were the first to systematically investigate the most appropriate timing for the performance of the VM. They also found the highest sensitivity when the VM was performed after injection compared with its performance before or during the injection.
It is a well-known phenomenon that more patients are identified as
having a RLS when investigated by contrast TCD compared with TEE
(compare the specificities in Tables 2
and 3). In these
cases, the lungs are the most likely location of
venous-arterial shunts, allowing the contrast material to
bypass the pulmonary capillaries and to slip into the cerebral
arteries. Another option would be that these shunts correspond to very
small intracardiac shunts not noted during TEE. In our study smaller
amounts of bubbles passed these shunts compared with the shunts also
demonstrated on TEE. Despite training and control, the Valsalva
maneuver may occasionally not have been as effective during TEE as
during the TCD investigation because of the TEE tube in the esophagus
and sedation. Some authors believe that a high number of MES and their
early occurrence may help to discriminate cardiac from noncardiac
shunts or clinically relevant from irrelevant
shunts.18 19 21 22 Our results, however, show that in
individual cases, discrimination based only on the number of MES or
their occurrence is not feasible. Additionally, shunts not noted on TEE
can allow considerable and early transit of microbubbles. On the other
hand, TEE-proven cardiac RLS can lead to small amounts of MES occurring
late after contrast medium injection. Sensitivities of contrast TCD of
100% could, except for 1, only be achieved when the time window was
expanded to 40 seconds and when the occurrence of a single MES was
regarded as indication of a shunt. Thus far, contrast TCD is a
screening procedure before TEE, since closure of a cardiac RLS by open
heart surgery or the endovascular approach relies on TEE to prove the
target lesion.26 27 28 Thus, sensitivity of contrast TCD
prevails over specificity. Given these premises, our study
demonstrates that (1) double performance, (2) the use of a time
window of 40 seconds, and (3) no threshold in MES numbers yields the
best results. Long-term follow-up of patients having suffered a stroke
by paradoxical embolism and treated by shunt closure is scarce and
inconclusive.27 28 The role of shunts demonstrated only
during TCD for clinically manifest paradoxical embolism is unknown and
requires further research. Anticoagulation would minimize thrombus
formation and thus embolization through cardiac and noncardiac shunts.
Once conclusive recommendations on the treatment of RLS patients are
available, the importance of contrast TCD may further increase (1)
because of its ability to detect RLS not noted during TEE and (2)
because of the possibility of quantifying shunts by the number of MES
detected.29
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Footnotes |
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Reprint requests to Dr Dirk W. Droste, Klinik und Poliklinik für Neurologie der WWU Münster, Albert-Schweitzer-Str 33, D-48129 Münster, Germany.
Received January 28, 2000; revision received March 30, 2000; accepted March 30, 2000.
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References |
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|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. Ward R, Jones D, Haponik EF. Paradoxical embolism: an underrecognized problem. Chest. 1995;108:549–558.
2. Belkin RN, Pollack BD, Ruggiero ML, Alas LL, Tatini U. Comparison of transesophageal and transthoracic echocardiography with contrast and color flow Doppler in the detection of patent foramen ovale. Am Heart J. 1994;128:520–525.[Medline] [Order article via Infotrieve]
3.
Chen WJ, Kuan P, Lien WP, Lin FY. Detection of patent
foramen ovale by contrast transesophageal
echocardiography. Chest. 1992;101:1515–1520.
4. Stendel R, Schröder K, Funk T, Brock M. Is transcranial Doppler reliable in the detection of a patent foramen ovale? In: Klingelhöfer J, Bartels EM, Ringelstein EB, eds. New Trends in Cerebral Hemodynamics. Amsterdam, Netherlands: Elsevier Science; 1998:483–489.
5. Pearson AC, Labovitz AJ, Tatineni S, Gomez CR. Superiority of transesophageal echocardiography in detecting cardiac source of embolism in patients with cerebral ischemia of uncertain etiology. J Am Coll Cardiol. 1991;17:66–72.[Abstract]
6. Nemec JJ, Marwick TH, Lorig RJ, Davison MB, Chimowitz MI, Litowitz H, Salcedo EE. Comparison of transcranial Doppler ultrasound and transesophageal contrast echocardiography in the detection of interatrial right-to-left shunts. Am J Cardiol. 1991;68:1498–1502.[Medline] [Order article via Infotrieve]
7. Lynch JJ, Schuchard GH, Gross CM, Wann LS. Prevalence of right-to-left atrial shunting in a healthy population: detection by Valsalva maneuver contrast echocardiography. Am J Cardiol. 1984;53:1478–1480.[Medline] [Order article via Infotrieve]
8. Nishimura RA, Tajik AJ. The Valsalva maneuver and response revisited. Mayo Clin Proc. 1986;61:211–217.[Medline] [Order article via Infotrieve]
9.
Teague SM, Sharma MK. Detection of paradoxical
cerebral echo contrast embolization by transcranial
Doppler ultrasound. Stroke. 1991;22:740–745.
10.
Ringelstein EB, Droste DW, Babikian VL, Evans DH,
Grosset DG, Kaps M, Markus HS, Russell D, Siebler M. Consensus on
microembolus detection by transcranial Doppler
ultrasound. Stroke. 1998;29:725–729.
11.
Droste DW, Reisener M, Kemény V, Dittrich R,
Schulte-Altedorneburg G, Stypmann J, Wichter T, Ringelstein EB.
Contrast transcranial Doppler ultrasound in the
detection of right-to-left shunts: reproducibility, comparison of 2
agents, and distribution of microemboli. Stroke. 1999;30:1014–1018.
12.
Droste DW, Kriete J, Stypmann J, Castrucci M, Wichter
T, Tietje R, Weltermann B, Young P, Ringelstein EB. Contrast
transcranial Doppler ultrasound in the detection of
right-to-left shunts: comparison of different procedures and different
contrast agents. Stroke. 1999;30:1827–1832.
13. Job FP, Ringelstein EB, Grafen Y, Flachskampf FA, Doherty C, Stockmanns A, Hanrath P. Comparison of transcranial contrast Doppler sonography and transesophageal contrast echocardiography for the detection of patent foramen ovale in young stroke patients. Am J Cardiol. 1994;74:381–384.[Medline] [Order article via Infotrieve]
14. Jauss M, Kaps M, Keberle M, Haberbosch W, Dorndorf W. A comparison of transesophageal echocardiography and transcranial Doppler sonography with contrast medium for detection of patent foramen ovale. Stroke. 1994;25:1265–1267.[Abstract]
15.
Zanette EM, Mancini G, De Castro S, Solaro M, Cartoni
D, Chiarotti F. Patent foramen ovale and transcranial
Doppler: comparison of different procedures. Stroke. 1996;27:2251–2255.
16. Horner S, Ni XS, Weihs W, Harb S, Augustin M, Duft M, Niederkorn K. Simultaneous bilateral contrast transcranial Doppler monitoring in patients with intracardiac and intrapulmonary shunts. J Neurol Sci. 1997;150:49–57.[Medline] [Order article via Infotrieve]
17.
Schwarze JJ, Sander D, Kukla C, Wittich I, Babikian VL,
Klingelhofer J. Methodological parameters influence the
detection of right-to-left shunts by contrast transcranial
Doppler ultrasonography. Stroke. 1999;30:1234–1239.
18. Heckmann JG, Niedermeier W, Brandt Pohlmann M, Hilz MJ, Hecht M, Neundorfer B. Transesophageal echocardiography and contrast-transcranial Doppler sonography yield a higher rate for the detection of patent foramen ovale than one method alone. Med Klin. 1999;94:367–370.[Medline] [Order article via Infotrieve]
19. Karnik R, Stollberger C, Valentin A, Winkler WB, Slany J. Detection of patent foramen ovale by transcranial contrast Doppler ultrasound. Am J Cardiol. 1992;69:560–562.[Medline] [Order article via Infotrieve]
20. Anzola GP, Renaldini E, Magoni M, Costa A, Cobelli M, Guindani M. Validation of transcranial Doppler sonography in the assessment of patent foramen ovale. Cerebrovasc Dis. 1995;5:194–198.
21. Devuyst G, Despland PA, Bogousslavsky J, Jeanrenaud X. Complementarity of contrast transcranial Doppler and contrast transesophageal echocardiography for the detection of patent foramen ovale in stroke patients. Eur Neurol. 1997;38:21–25.
22.
Hamann GF, Schatzer Klotz D, Frohlig G, Strittmatter M,
Jost V, Berg G, Stopp M, Schimrigk K, Schieffer H. Femoral injection of
echo contrast medium may increase the sensitivity of testing for a
patent foramen ovale. Neurology. 1998;50:1423–1428.
23.
Klötzsch C, Janssen G, Berlit P.
Transesophageal echocardiography
and contrast-TCD in the detection of a patent foramen ovale:
experiences with 111 patients. Neurology. 1994;44:1603–1606.
24.
Yeung M, Khan KA, Shuaib A. Transcranial
Doppler ultrasonography in the detection of venous to
arterial shunting in acute stroke and transient ischaemic
attacks. J Neurol Neurosurg Psychiatry. 1996;61:445–449.
25.
Chimowitz MI, Nemec JJ, Marwick TH, Lorig RJ, Furlan
AJ, Salcedo EE. Transcranial Doppler ultrasound
identifies patients with right-to-left cardiac or pulmonary
shunts. Neurology. 1991;41:1902–1904.
26.
Bridges ND, Hellenbrand W, Latson L, Filiano J,
Newburger JW, Lock JE. Transcatheter closure of patent
foramen ovale after presumed paradoxical embolism.
Circulation. 1992;86:1902–1908.
27.
Devuyst G, Bogousslavsky J, Ruchat P, Jeanrenaud X,
Despland PA, Regli F, Aebischer N, Karpuz HM, Castillo V, Guffi M,
Sadeghi H. Prognosis after stroke followed by surgical closure of
patent foramen ovale: a prospective follow-up study with brain MRI and
simultaneous transesophageal and
transcranial Doppler ultrasound. Neurology. 1996;47:1162–1166.
28.
Homma S, Di Tullio MR, Sacco RL, Sciacca RR, Smith C,
Mohr JP. Surgical closure of patent foramen ovale in cryptogenic stroke
patients. Stroke. 1997;28:2376–2381.
29.
Serena J, Segura T, Perez Ayuso MJ, Bassaganyas J,
Molins A, Davalos A. The need to quantify right-to-left shunt in acute
ischemic stroke: a case-control study. Stroke. 1998;29:1322–1328.
30.
Venketasubramanian N, Sacco RL, Di Tullio M, Sherman D,
Homma S, Mohr JP. Vascular distribution of paradoxical emboli by
transcranial Doppler. Neurology. 1993;43:1533–1535.
31.
Di Tullio M, Sacco RL, Venketasubramanian N, Sherman D,
Mohr JP, Homma S. Comparison of diagnostic techniques for
the detection of a patent foramen ovale in stroke patients.
Stroke. 1993;24:1020–1024.
32. Schminke U, Ries S, Daffertshofer M, Staedt U, Hennerici M. Patent foramen ovale: a potential source of cerebral embolism? Cerebrovasc Dis. 1995;5:133–138.
33. Albert A, Muller HR, Hetzel A. Optimized transcranial Doppler technique for the diagnosis of cardiac right-to-left shunts. J Neuroimaging. 1997;7:159–163.[Medline] [Order article via Infotrieve]
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 M. S. Albin, J. Wills, R. M. Schwend, S. Mazzucco, G. P. Anzola, J. R. Kizer, and R. B. Devereux Patent foramen ovale and unexplained stroke. N. Engl. J. Med., April 20, 2006; 354(16): 1753 - 1755. [Full Text] [PDF]
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 B. Draganski, W. Blersch, S. Holmer, H. Koch, A. May, U. Bogdahn, T. Holscher, and F. Schlachetzki Detection of Cardiac Right-to-Left Shunts by Contrast-Enhanced Harmonic Carotid Duplex Sonography J. Ultrasound Med., August 1, 2005; 24(8): 1071 - 1076. [Abstract] [Full Text] [PDF]
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G.P. Anzola, E. Morandi, F. Casilli, and E. Onorato Does Transcatheter Closure of Patent Foramen Ovale Really "Shut the Door?": A Prospective Study With Transcranial Doppler Stroke, September 1, 2004; 35(9): 2140 - 2144. [Abstract] [Full Text] [PDF]
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G. Devuyst, B. Piechowski-Jozwiak, T. Karapanayiotides, J.-W. Fitting, V. Kemeny, L. Hirt, L. A. Urbano, P. Arnold, G. van Melle, P.-A. Despland, et al. Controlled Contrast Transcranial Doppler and Arterial Blood Gas Analysis to Quantify Shunt Through Patent Foramen Ovale Stroke, April 1, 2004; 35(4): 859 - 863. [Abstract] [Full Text] [PDF]
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 M. Zanchetta, L. Pedon, P. Maiolino, R. Wolk, T. Kara, and V. K. Somers Obstructive Sleep Apnea and Patent Foramen Ovale * Response Circulation, February 24, 2004; 109 (7): e69 - e69. [Full Text] [PDF]
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M. Saqqur, N. Dean, M. Schebel, M. D. Hill, A. Salam, A. Shuaib, and A. M. Demchuk Improved Detection of Microbubble Signals Using Power M-Mode Doppler Stroke, January 1, 2004; 35 (1): e14 - e17. [Abstract] [Full Text] [PDF]
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 J. Draganov and T. W. L. Scheeren Incidental detection of paradoxical air embolism with a transoesophageal Doppler probe inserted for measuring descending aortic blood flow Br. J. Anaesth., April 1, 2003; 90(4): 520 - 522. [Abstract] [Full Text] [PDF]
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 W. K. Blersch, B. M. Draganski, S. R. Holmer, H. J. Koch, F. Schlachetzki, U. Bogdahn, and T. Holscher Transcranial Duplex Sonography in the Detection of Patent Foramen Ovale Radiology, December 1, 2002; 225(3): 693 - 699. [Abstract] [Full Text] [PDF]
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D. W. Droste, S. Lakemeier, T. Wichter, J. Stypmann, R. Dittrich, M. Ritter, M. Moeller, M. Freund, and E. B. Ringelstein Optimizing the Technique of Contrast Transcranial Doppler Ultrasound in the Detection of Right-to-Left Shunts Stroke, September 1, 2002; 33(9): 2211 - 2216. [Abstract] [Full Text] [PDF]
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K Nedeltchev, M Arnold, A Wahl, M Sturzenegger, E E Vella, S Windecker, B Meier, and H P Mattle Outcome of patients with cryptogenic stroke and patent foramen ovale J. Neurol. Neurosurg. Psychiatry, March 1, 2002; 72(3): 347 - 350. [Abstract] [Full Text] [PDF]
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