(Stroke. 1997;28:1009-1014.)
© 1997 American Heart Association, Inc.
Articles |
Application of Interhemispheric Index for Transcranial Doppler Sonography Velocity Measurements and Evaluation of Recording Time
From the Department of Neurology, University Hospital Rigs-hospitalet, Copenhagen, Denmark.
Correspondence to Jesper Bay-Hansen, Department of Neurology, N2082, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose To validate the reliability of transcranial Doppler sonography velocity measurements in clinical settings, assessment of the reproducibility of repeated bilateral simultaneous measurements and the optimal recording time is needed. Our hypothesis was that interhemispheric indices would prove more valid than the absolute velocity measurements usually applied. The potential interference between ultrasound beams in bilateral samplings also needs evaluation.
Methods Thirty healthy volunteers were studied at rest within hours or with a 2-month interval between measurements. Absolute blood flow velocities and side-to-side indices between velocities obtained in the middle cerebral arteries were measured over a 30-second period by two independent examiners. The correlation coefficient (r) and the coefficients of variation of the difference between either absolute velocities (CV) or indices (CVi) were calculated. The beat-to-beat variation of the diastolic, systolic, and mean velocities was also recorded. For evaluation of ultrasound beam interference, measurements were performed with and without one probe unplugged.
Results In the interobserver study in which measurements were repeated within hours, r=.92, CV=8.8%, and CVi=4.1%. In the intraobserver study in which measurements were repeated with a 2-month interval, r=.8, CV=13.0%, and CVi=7.3%. A recording time of 30 seconds reduced CVi to 2.6%, whereas for absolute velocities 5-second recordings produced an acceptable variation. There was no significant interference between bilaterally placed probes.
Conclusions The introduction of interhemispheric indices improves interobserver and intraobserver reproducibility by approximately 50%. We recommend use of the index in clinical settings in which unilateral velocity changes are expected. For measurement of an interhemispheric index, a recording time of 30 seconds is recommended, whereas 5-second measurement periods yield a sufficient estimate of absolute velocities.
Key Words: blood flow velocity • middle cerebral artery • observer variation • transcranial Doppler
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Transcranial Doppler sonography was introduced in 1982 for noninvasive and continuous monitoring of blood flow velocity in the basal cerebral arteries.1 Since then, the TCD technique has been widely used to evaluate regional cerebral blood flow changes in both physiological and pathological conditions, assuming that vessel diameter and perfusion territory remain unchanged with time. The technique has been applied to studies of cerebral autoregulation2 and CO2 reactivity3 and certainly adds another tool in the evaluation of patients with extracranial and intracranial stenosis, vasospasm after subarachnoid hemorrhage, acute stroke, arteriovenous malformations, head injury, brain death,4 and possibly other clinical conditions. In addition, the technique has proven valuable in clinical pharmacology trials testing the cerebral hemodynamic effects of drugs, eg, anesthetics,5 nonsteroidal anti-inflammatory drugs,6 and angiotensin-converting enzyme inhibitors.7
A major prerequisite for the use of the TCD technique in clinical settings is the reliability and reproducibility of measurements. Obviously, the assumption that cerebral blood flow velocity is constant during measurements and that all variations detected reflect the degree of insufficient reproducibility8 9 may not be valid, since physiological changes in blood flow velocity occur, ie, variations are caused by both insufficient reproducibility and physiological changes.
Therefore, the aim of this study was to evaluate the interobserver and intraobserver reproducibility of TCD velocimetry for repeated bilateral simultaneous measurements in the MCA under the assumption that side-to-side indices between the MCA blood flow velocities would be constant during and between measurements. Such indices, defined as the ratio between left and right or right and left absolute MCA velocities, were hypothesized to be relatively resistant against physiological systemic fluctuations in absolute blood flow velocity. In addition, spontaneous changes in MCA velocities with time were evaluated to determine the optimal recording time for both indices and absolute velocities. Beat-to-beat variations; the relationship between depth of the sample volume, intertemple distance, and probe position at the temporal window; and the relationship between probe position and absolute MCA velocities were also assessed. The potential interference between ultrasound beams occurring during bilateral recordings was also evaluated.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Subjects
Thirty volunteers (16 men and 14 women; median age, 45 years; range, 21 to 72 years) were examined. The subjects had no history of cerebrovascular disease and did not receive any medication. Our study was approved by the local ethics committee, and each individual provided written informed consent.
Equipment
Blood flow velocity measurements were performed with 2-MHz
pulsed-wave TCD equipment (Multi-Dop X hardware, DWL; version 7.40 of
MDX TCD-7 software) able to make two-channel fast Fourier
transformation calculations. The positioning of probes was maintained
over each temple by an elastic headband.
Experimental Procedure
Between September 1995 and February 1996, all subjects were
examined twice (examinations 1 and 2). Each session lasted between 1.5
and 4 hours. Tea, coffee, alcohol, and smoking were not allowed on
examination days. Before the first examination, the basic principles of
the equipment were demonstrated, and each individual was helped to find
his own MCA Doppler signal with a hand-held probe. We attempted to
provide a calm environment with minimal acoustic distractions.
Throughout the examinations, subjects were resting in the supine
position; during measurements, subjects were requested to close their
eyes, relax, and "think of nothing." Subjects were not allowed to
speak, nor were they spoken to. To maximize cardiac stability, subjects
were resting at least half an hour before the first measurement was
made.
We obtained Doppler signals from the MCA by placing each probe over the temple just superior to the zygomatic arch and adjusting its position and its angulation for a maximally reflected signal, characteristic of the MCA. The depth of the sample volume was increased from 50 mm by 2-mm steps until bidirectional flow appeared from the bifurcation of the internal carotid artery. Then the depth of the sample volume was decreased and the tilt of the probe was carefully adjusted to obtain a maximally reflected signal, characteristic of the M1 segment of the MCA. Signals were identified by means of the spectral screen display and an audible pitch. After we adjusted the axial length of the sample volume and gain to standardized values (10 and 8 mm, respectively), the spectral outline, ie, envelope, was ready for recording. Bilateral simultaneous waveform recordings were made over a period of at least 60 seconds. The depth of the sample volume and the probe position (at the anterior, middle, or posterior temporal window) were noted for each recording. The intertemple distance was measured by a slide gauge.
As shown in Table 1
, subjects underwent two series of
measurements. In examination 1, subjects were investigated by two
observers (A and B). Each of the observers placed a probe over a temple
three times, and five bilateral simultaneous waveform
recordings were made, ie, five indices were obtained. To avoid
any bias, order of probe positioning was randomized so that the order
of measurements was reversed in half of the cases.
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An interval of 57 to 96 days passed between examinations 1 and 2.
Subjects were reinvestigated by the same observers, A and B. Each
observer placed a probe twice, and two recordings were done as
shown in Table 1
. Each A4/A5 recording lasted at least 7
minutes and represented two separate measurement periods
with 5 minutes in between and no change in probe position.
Subjects were asked not to help the observers during examinations. Once a probe had been fixed on one side, its wire was disconnected from the computer to ensure blinding and minimize ultrasound exposure while the second probe was positioned on the opposite side. The screen was covered during recordings, so that the exact relationship between velocities remained unknown to both observers.
For assessment of reproducibility and spontaneous evolution with time, the absolute MV and the side-to-side indices between MV of the left and the right MCA were considered.
To test for interference, the last A4/A5 measurement periods each included three intervals of 30 seconds, the last of which was performed in the left MCA (A4) only, ie, the wire of the right probe was disconnected.
Data and Statistical Evaluation
Evaluation of the hemispheric side-to-side difference in
velocity was based on the first indices recorded (B1/A1). This
approach seemed reasonable because the data showed that the observers
on average measured equal velocities.
The data were used in four different studies, as discussed below. The potential interference between ultrasound beams occurring during bilateral recordings was also evaluated.
Interobserver Reproducibility Study
Evaluation of interobserver reproducibility was based on data
obtained in examination 1. Duration of waveform recordings used
in calculations was 30 seconds. Standard deviations and coefficients of
variation were calculated with either indices or absolute velocities.
SDi denotes the standard deviation of the differences
within indices and was calculated between each pair of A1/A2 and B2/A2
and between each pair of A2/A1 and B1/A1 determinations. The
coefficient of variation of the difference between indices was
calculated as CVi=SDi/M*100%, where M is the
mean of the indices measured by observer A. SD denotes the standard
deviation of the differences within absolute velocities and was
calculated between A1 and B2 and between A2 and B1 determinations. CV
was calculated as CV=SD/M*100%, where M is the mean of the absolute
velocity determinations of observer A. Linear regression
analyses for comparison of absolute velocities (A1 versus B2
and A2 versus B1) were performed.
Intraobserver Reproducibility Study
Evaluation of intraobserver reproducibility was based on data
obtained in examinations 1 and 2. To obtain an unbiased estimate of the
intraobserver reproducibility, approximately 2 months elapsed between
examinations. Duration of waveform recordings used in the
calculations was 30 seconds. The intraobserver reproducibility was
evaluated for both observers by means of the indices indicated in Table 1 and was estimated as SDi and CVi.
Furthermore, SD and CV for the measurements A1 versus A4 and B2 versus
B4 were determined, and linear regression analyses for
comparison of the absolute velocities were performed. SD, CV, and a
linear regression analysis were applied to A1 and A3
determinations to assess short-term intraobserver reproducibility.
Time-Dependent Variations
Beat-to-beat variation of MCA velocity parameters
obtained in two successive cardiac cycles was determined in A3
recordings. Computerized calculations of MVs of the two A4/A5
measurement periods were done over 5, 10, 20, 30, 45, and 60 seconds,
and corresponding velocities were compared. Evaluation was performed by
calculating SDi, CVi, r, SD, and CV
as previously described, and CVi was used to evaluate the
short-term conservation of indices. Student's t test was
applied to compare the CVis and CVs obtained with different
observation times.
Depth of Sample Volume Versus Head Size and Probe Position
A linear regression analysis of the correlation between
the depth of sample volume and the head size determined as the
intertemple distance was performed. For comparison of depth of sample
volume, depth of sample volume divided by intertemple distance, and MV
at the middle and posterior temporal windows, the Mann-Whitney test was
applied.
Interference
A Mann-Whitney test was applied to test for differences within
absolute velocities (A4) of the three 30-second intervals.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Two subjects had inappropriate temporal windows on either side and one on both sides. In total, 216 bilateral waveform recordings were obtained for data analysis. No artifacts with spike configuration appeared.
The averaged MVs were 74±15 cm/s on both the left and right MCA. The mean of left/right (B1/A1) indices was 1.00; the SD was ±16%. After exclusion of one subject who had a localized increase in MV and an index of 1.56, who was suspected of having a unilateral MCA stenosis, the SD was 11%.
Fig 1 illustrates the correlation between absolute MCA
velocities as measured by observers A and B on the left side.
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Table 2 summarizes the results of the interobserver
reproducibility study. Correlations were statistically significant
(P<.001). CVis of the left and the right MCA
were of the same order of magnitude. As expected, CVi was
comparable to SDi, since the mean index was close to 1.
CVi was approximately half the value of CV.
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Fig 2 illustrates the correlation between absolute MCA
velocities as measured by observer A on the left side, with
approximately 2 months between measurements.
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Table 3 summarizes the results of the intraobserver
reproducibility study based on either indices or absolute velocities
obtained from the left MCA. The study yields an estimate of the
CVi of roughly 7%. Again, CVi was
approximately half the size of CV. Correlations were statistically
significant (P<.001).
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Statistical parameters of beat-to-beat variations are given
in Table 4. The best correlation, evaluated as the
correlation coefficient and the CV, was found between MV values,
followed by SV and DV, respectively. Correlation coefficients of SV,
MV, and DV from heartbeat to heartbeat were all statistically
significant (P<.001). Because of differences in mean values
of SV and DV, the higher SD between SVs than between DVs is not
reflected in the corresponding values of CV.
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Variations of the differences between absolute velocities and indices
of two measurement periods performed with an interval of 5 minutes,
with no change in probe position, are illustrated in Figs 3 and 4. Differences between absolute
velocities recorded over periods of 5 and 60 seconds did not differ
significantly. Absolute differences between indices recorded over
periods of 45 or 60 seconds were significantly smaller than differences
recorded over a period of 5 seconds (Student's t test;
P<.05). Absolute differences between indices recorded
over a period of 30 seconds were not significantly smaller than
differences recorded over a period of 5 seconds (Student's
t test; P=.06). When recordings were done
over a period of 30 seconds, the variation of the differences,
evaluated as CVi, reached a level within acceptable limits
(2.6%). This value was not statistically different from the
CVi resulting from 60 seconds of recording time.
The corresponding SDi was 0.03, and the corresponding
variation of the differences between absolute velocities on the left
side yielded values for r, SD, and CV of .91, 5.8 cm/s, and
8.5%, respectively.
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There was a statistically significant correlation between depth of sample volume on the left side and intertemple distance (n=16, r=.72, P<.005) according to the equation Depth of Sample Volume=0.47 xIntertemple Distance (mm)-13.8 mm
The number of probe positions at the anterior, middle, and posterior temporal windows was 1, 14, and 12, respectively. Insonation through the middle temporal window was performed with a mean depth (52 mm) that was lower than that through the posterior window (55 mm), although the difference was not significant; nor was the difference between ratios of mean depths and intertemple distance significant. Mean velocities showed a trend toward higher values when probes were fixed at the middle (average MV, 76 cm/s) compared with the posterior (average MV, 69 cm/s) temporal window, although the difference was not statistically significant.
The absolute velocity on the left MCA was not significantly different in the presence compared with the absence of contralateral insonation.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In this study, MVs in the left and right MCA were both 74±15 cm/s. This level is somewhat higher than those observed by Aaslid et al (62±12 cm/s)1 but corresponds well to those obtained by Sorteberg et al (73±11 cm/s).10 Our SD of the average side differences in flow velocity was 16%. After exclusion of one subject suspected to have a unilateral MCA stenosis, the SD was 11%, which was in better agreement with the SD of Sorteberg et al (7%).
The CV obtained in two measurement periods with 5 minutes between measurements and no change in probe position is an estimate of the spontaneous variation of MV with time. Based on 30-second recordings, this variation was as high as 8.5%. This value is similar to the interobserver reproducibility estimated as the CV, which was 8.8%. Thus, when the probe is carefully positioned, interobserver variation is almost entirely caused by spontaneous fluctuations with time, with only a negligible contribution from interobserver disagreement.
The interobserver reproducibility for side-to-indices, CVi, was 4.1%, ie, approximately half the value of the corresponding CV. Similarly, in the intraobserver reproducibility study, CVi and CV were 7.3% and 13.0%, respectively. The smaller variation of MCA indices than of absolute velocities is probably caused by physiological fluctuations in absolute blood flow velocities being reflected bilaterally, eg, systemic changes in arterial CO2 partial pressure3 or changes in cardiac output and mean arterial blood pressure. Whenever measurements of indices are relevant, the need for continuous end-tidal CO2 partial pressure and mean arterial blood pressure monitoring during measurements is minimized, which is beneficial because monitoring of end-tidal CO2 partial pressure may have an unpredictable influence on blood flow velocity and correction for changes in arterial CO2 partial pressure may be insecure11 or insignificant for recordings at rest.10 Furthermore, side-to-side indices are resistant to changes in hematocrit (known to be inversely related to the MCA velocity parameters12 ) between examinations, and possible diurnal variations in blood flow velocity were proposed by Demolis et al.13 On the other hand, indices may be influenced by hemispheric blood flow velocity shifts induced by cognitive tasks.14 15 Since side-to-side indices between absolute velocities are resistant to physiological changes reflected bilaterally, the CVis are far better reproducibility estimates than CVs. We therefore recommend the performance of simultaneous bilateral measurements and the use of side-to-side indices whenever unilateral velocity changes are expected. The use of indices would be of potential value in the evaluation of patients with conditions such as extracranial and intracranial stenosis, vasospasm after subarachnoid hemorrhage, and acute stroke.
Table 5 summarizes the reproducibility of MCA absolute
velocity reported in published TCD studies. Our interobserver
reproducibility parameters are in accordance with those of
Demolis et al13 and Maeda et al.8
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An unbiased estimate of intraobserver reproducibility can only be obtained if the examiner is unaware of the result obtained from the previous examination. Therefore, a period of approximately 2 months between examinations was allowed to pass. It should be emphasized that the intraobserver reproducibility variance includes contributions caused not only by the examiner but also by the time interval between examinations and the duration of recordings. When the time interval between examinations was approximately 2 hours, our intraobserver reproducibility was 6.9%, whereas it increased to 13% when this time interval was approximately 2 months.
Since it is unlikely that the intraobserver disagreement (CV of
observer A=13.0%) exceeds the interobserver disagreement (CV of the
left MCA=8.8%), changes in MV during the 2-month period must account
for the difference. Long-term dependent changes may explain why our
reproducibility corresponds well to the findings of Maeda et
al8 but less well to those of others9 13 16
(Table 5). Alternatively, both observers may have experienced a change
in their skills between examinations, but this is less likely, since
the average MV did not differ significantly between examinations 1 and
2. Since measurements were performed at different times during
examination days, diurnal variations might contribute to intraobserver
disagreement only.
For absolute velocities obtained in two measurement periods with 5
minutes between measurements at unchanged probe positions, the CV did
not change significantly whether the recording time was 5 or 60
seconds (Fig 3). Therefore, after 5 seconds a sufficiently reliable
measure of the absolute velocity seemed to be reached and prolongation
of the measurement period did not lead to an improved estimate. With a
recording time of 30 seconds, our findings (r=.91;
SD=5.8 cm/s; CV=8.5%) were in agreement with the findings of Demolis
et al13 (r=.90; SD=4.8 cm/s). In contrast, the
CVi showed a decline with increasing observation time (Fig 4). A recording time of 30 seconds seems, however, to yield a
satisfactory CVi, which was not statistically different
from the CVi resulting from a recording time of 60
seconds. Still, all CVis were lower than the CVs
independent of recording time.
The beat-to-beat variation was smallest for absolute MVs, followed by SVs and DVs, respectively. To our knowledge, this is the first report of beat-to-beat variation on TCD velocimetry.
A significant correlation between depth of sample volume and intertemple distance was found and, as noted by Vriens et al,11 when depth of insonation is evaluated, the head size must be taken into consideration. The maximum reflected signal was found when insonation was performed through the middle temporal window (52%) or through the posterior temporal window (44%). This emphasizes the need to scan these windows systematically during examinations.
In conclusion, the introduction of MCA interhemispheric indices improves interobserver and intraobserver reproducibility by approximately 50%. We recommend the performance of simultaneous bilateral measurements and the use of the index in clinical settings in which unilateral velocity changes are expected. For measurement of the index, a recording time of approximately 30 seconds is recommended, whereas 5-second measurement periods yield a sufficient estimate of absolute MCA blood flow velocities. A significant interference between ultrasound beams could not be demonstrated.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by the Danish Health Research Council.
Received September 12, 1996; revision received January 10, 1996; accepted January 13, 1997.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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1. Aaslid R, Markwalder T-M, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg. 1982;57:769-774.[Medline] [Order article via Infotrieve]
2. Larsen FS, Olsen KS, Hansen BA, Paulson OB, Knudsen GM. Transcranial Doppler is valid for determination of the lower limit of cerebral blood flow autoregulation. Stroke. 1994;25:1985-1988.[Abstract]
3. Markwalder T-M, Grolimund P, Seiler RW, Roth F, Aaslid R. Dependency of blood flow velocity in the middle cerebral artery on end-tidal carbon dioxide partial pressure: a transcranial ultrasound Doppler study. J Cereb Blood Flow Metab. 1984;4:368-372.[Medline] [Order article via Infotrieve]
4. Newell DW, Aaslid R. Transcranial Doppler: clinical and experimental use. Cerebrovasc Brain Metab Rev. 1992;4:122-143.[Medline] [Order article via Infotrieve]
5.
Thiel A, Zickmann B, Zimmermann R, Hempelmann
G. Transcranial Doppler sonography: effects of
halothane, enflurane and isoflurane on blood flow velocity in the
middle cerebral artery. Br J Anaesth. 1991;68:388-393.
6. Markus HS, Vallance P, Brown MM. Differential effect of three cyclooxygenase inhibitors on human cerebral blood flow velocity and carbon dioxide reactivity. Stroke. 1994;25:1760-1764.[Abstract]
7. Demolis P, Annane D, Duhaze P, Giudicelli JF. Systemic, regional and cerebral hemodynamic effects of a new angiotensin converting enzyme inhibitor, imidapril, in healthy volunteers. Fundam Clin Pharmacol. 1994;8:80-89.[Medline] [Order article via Infotrieve]
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10. Sorteberg W, Langmoen IA, Lindegaard K-F, Nornes H. Side-to-side differences and day-to-day variations of transcranial Doppler parameters in normal subjects. J Ultrasound Med. 1990;9:403-409.[Abstract]
11. Vriens EM, Kraaier V, Musbach M, Wieneke GH, van Huffelen AC. Transcranial pulsed Doppler measurements of blood velocity in the middle cerebral artery: reference values at rest and during hyperventilation in healthy volunteers in relation to age and sex. Ultrasound Med Biol. 1989;15:1-8.
12.
Brass LM, Pavlakis SG, DeVivo D, Piomelli S, Mohr
JP. Transcranial Doppler measurements of the
middle cerebral artery: effect of hematocrit.
Stroke. 1988;19:1466-1469.
13. Demolis P, Chalon S, Giudicelli J-F. Repeatability of transcranial Doppler measurements of arterial blood flow velocities in healthy subjects. Cli Sci. 1993;84:599-604.
14.
Droste DW, Harders AG, Rastogi E. A
transcranial Doppler study of blood flow velocity in
the middle cerebral arteries performed at rest and during mental
activities. Stroke. 1989;20:1005-1011.
15.
Rihs F, Gutbrod K, Gutbrod B, Steiger H-J, Sturzenegger
M, Mattle HP. Determination of cognitive hemispheric dominance
by `stereo' transcranial Doppler sonography.
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16. Baumgartner RW, Mathis J, Sturzenegger M, Mattle HP. A validation study on the intraobserver reproducibility of transcranial color-coded duplex sonography velocity measurements. Ultrasound Med Biol. 1994;20:233-237.[Medline] [Order article via Infotrieve]
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