Reference values of Doppler parameters of the fetal anterior cerebral artery throughout gestation.
Aim
The objective of this study was to construct normal reference values of the Doppler parameters in two anatomical segments of the ACA throughout pregnancy, and to compare the feasibility of Doppler examination for each segment.
Introduction
There is recent evidence that the process of brain vasodilatation in intrauterine growth restricted (IUGR) fetuses can be reflected earlier in the anterior cerebral artery (ACA) than in the middle cerebral artery (MCA). Figueroa et al. and Dubiel at al. reported that in IUGR fetuses, ACA pulsatility index (PI) was significantly reduced, as compared with gestational agematched normally grown fetuses. A significant proportion of fetuses had ACA PI values below the 5th centile, despite presenting a MCA PI within the normal range, thus, in the absence of brain vasodilation, as currently defined.
Method
Three hundred and seventy three (373) normally grown fetuses at 20-40 weeks of gestation were studied cross sectionally. Normal growth was estimated according to local normal curves. The project was approved by the hospital ethics committee and written consent was obtained in all cases. Median maternal age at the time of the study was 26 (range, 18–32) years. Only one measurement of each fetus was included.
For ultrasound and Doppler studies, Siemens Sonoline Antares (Siemens Medical Systems Malvern, PA, USA), or Voluson 730 Expert (GE Medical Systems, WI USA) ultrasound equipments with 6-2 and 7-4 MHz curved array probes were used. All estimations were done in the absence of fetal corporal and respiratory movements and with the mother in voluntary suspended respiration. For vascular recordings, special attention was taken to avoid unnecessary pressure on the fetal head as this could affect blood flow velocities. Directional colour Doppler was used to clearly locate the different vessels; the anterior cerebral (ACA) was studied in its two anatomical segments.
For segment 1 (S1) the circle of Willis was visualised in a transverse view and the Doppler gate was placed immediately after the origin of the ACA from the internal carotid artery. Segment 2 (S2) was visualised in a transverseview slightly more cranial than the previous one, and the transducer was thenrotated in order to achieve the best possible angle of insonation. The Doppler gate was placed as close to the origin as possible. The angle of insonation was maintained below 45 degrees and corrected manually when necessary, the wall filter was set at 70 Hz and a minimum of 5 consecutive regular waveforms included in the automatic calculation. PI, peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV), and angle of insonation were calculated in all cases. In addition, the time elapsed between the identification of the correct anatomical plane of the fetal head, until the acquisition of good quality waveforms was registered for both segments. The mechanical and thermal indices were maintained below 1. For reproducibility analyses, in 35 fetuses both segments were evaluated twice by 2 operators and agreement calculated.
In brief, ACA was studied in 373 normally grown fetuses cross-sectionally from 20 to 40 weeks of gestation with pulsed Doppler ultrasound. ACA was recorded in its segment 1 (ACA-S1) just after its origin from the internal carotid artery in the same plane as the middle cerebral artery (MCA), and in segment 2 (ACA-S2) distal to the outlet of the anterior communicating artery. Reference values throughout gestation for PI and velocities were constructed for both anatomical sites and reproducibility evaluated.
Statistical Analysis
Descriptive statistics were used for all parameters. The statistical method to estimate reference intervals described by Royston and Wright was used. For assymetrically distributed variables, a log-transformation was previously performed. Separate linear, quadratic and cubic regression models were fitted to estimate the relationship between Doppler variables and gestational age (in weeks). The best fitting model for each variable was selected: models (linear, quadratic and cubic) were selected only if the highest power coefficient was significantly different from zero (more than twice its standard error). Standard deviation (SD) curves as functions of gestational age were calculated by means of a polynomial regression procedure of the scaled absolute residuals. The best fitting model for SD was selected by means of the same procedure used for the mean values. The Z scores (measurement – mean/ SD) were calculated for assessing model fit. Normal distribution of the Z scores was checked with the Shapiro-Francia W’ test. Equations of the polynomial regression curves were used to calculate the mean and the 5th and 95th centiles for each gestational age (centiles = estimated mean ± SD• 1.645). Data was plotted as smooth curves. All analyses were performed with SPSS 14.0 statistical package (SPSS, Inc. Chicago ILL) and Med Calc 7.6 (MedCalc Software Belgium).
Results
It was always possible to record both ACA segments in all cases, but the time spent for acquiring a good quality waveform was significantly lower for ACA-S1 (Mean 63 s (SD16s); ACA-S2 Mean 187s (SD 24s); p<0.001).
Formulas for the calculation of means and standard deviations of all studied Doppler parameters are presented in Table 1. ACA PI behaved similarly in both segments throughout gestation (Figure 2). PI values in both ACA segments showed a biphasic pattern, and therefore a quadratic analysis was performed in order to construct curves for normal values. The values increased until 28-32 weeks of gestation then decreased until the end of the pregnancy. ACA-SI PI reference values for each gestational age are expressed in Table 2.
All velocities showed a similarly constant increase from 20 to 40 weeks of gestation. No significant differences in velocities were documented between the 2 segments, however PSV in ACA-S2 was slightly lower than ACA-S1, this can be partially explained by the angle of insonation which was significantly lower in ACA-S1 (ACA mean 18º (SD 8.8º) ACA-S2 mean 31º (SD 14.8º); p=0.01).
Reproducibility analysis showed an intraclass correlation coefficient for ACA-S1 of 0.84 (95% CI 0.67-0.94) and for ACA-S2 0.73 (95% CI 0.63-0.90). There was a mean difference between observers of 0.21 with a SD of 0.074.
Table 1:
Formula for calculation of the mean and standard deviation (SD) of the studied Doppler parameters in both segments of the anterior cerebral artery (ACA) throughout gestation.
| Mean PI = -3.49 + 0.37 ∙ GA -0.0063 ∙GA2 |
Mean PI = -1.54 + 0.22 ∙ GA 0.0037 ∙ GA2 |
| SD = -0.603 + 0.061 ∙ GA–0.001∙ GA2 |
SD = 0.206 + 0.0037 ∙ GA |
| Mean PSV = Antilog (0.84 + 0.023 ∙ GA) |
Mean PSV= Antilog (0.89 + 0.019 ∙ GA) |
| SD = Antilog (0.062 + 0. 0015 ∙ GA) |
SD= Antilog (0.174 + 0.0045 ∙ GA) |
| ACA 1 MV= AntiLN (1,1809+0,0520 ∙ GA) |
Mean MV =12.41 – 0.528 ∙ GA + 0.0197 ∙ GA2 |
| SD= AntiLN (0,13058+0,004 ∙ GA) |
SD= -2.578 + 0.241∙ GA2 |
| Mean EDV= 4.413–0.0214 ∙ GA+0.0048 ∙GA2 |
Mean EDV= 4.309 – 0.195 ∙ GA +0.0043 ∙ GA2 |
| SD= Antilog (0.137 + 0.0011 ∙ GA) |
SD= -0.751 + 0.101 ∙ GA |
ACA-S1; anterior cerebral artery segment 1, ACA-S2; anterior cerebral artery segment 2 (for the anatomical description of the 2 segments please see the text) , PI, pulsatility index; PSV, peak systolic velocity, MV, mean velocity; EDV, end diastolic velocity; GA gestational age; Antilog, antilogarithm; AntiLN, anti Neperian logarithm.
Table 2:
Normal reference values of the pulsatility index in the first segment of the anterior cerebral artery (ACA-S1 PI).
|
20 |
1.07 |
1.43 |
1.78 |
0.21 |
|
21 |
1.15 |
1.54 |
1.93 |
0.23 |
|
22 |
1.22 |
1.64 |
2.06 |
0.25 |
|
23 |
1.29 |
1.73 |
2.17 |
0.27 |
|
24 |
1.34 |
1.80 |
2.27 |
0.28 |
|
25 |
1.38 |
1.87 |
2.35 |
0.29 |
|
26 |
1.41 |
1.91 |
2.42 |
0.30 |
|
27 |
1.44 |
1.95 |
2.47 |
0.31 |
|
28 |
1.45 |
1.97 |
2.50 |
0.32 |
|
29 |
1.46 |
1.98 |
2.52 |
0.32 |
|
30 |
1.45 |
1.98 |
2.52 |
0.32 |
|
31 |
1.44 |
1.97 |
2.50 |
0.32 |
|
32 |
1.42 |
1.94 |
2.47 |
0.32 |
|
33 |
1.38 |
1.90 |
2.42 |
0.32 |
|
34 |
1.34 |
1.85 |
2.36 |
0.31 |
|
35 |
1.29 |
1.79 |
2.28 |
0.30 |
|
36 |
1.23 |
1.71 |
2.19 |
0.29 |
|
37 |
1.16 |
1.62 |
2.08 |
0.28 |
|
38 |
1.08 |
1.52 |
1.95 |
0.26 |
|
39 |
0.99 |
1.40 |
1.81 |
0.25 |
GA, gestational age; P, percentile; SD, standard deviation.
ACA PI behaved similarly in both segments, with a constant increment until 28 weeks followed by a decrease until the end of pregnancy (ACA-S1 PI= -3.49+0.37 ∙ GA -0.00635 ∙ GA2 (SD= -0.60 + 0.061 ∙ GA – 0.001 ∙ GA2); ACA-S2 PI = -1.54+0.22 ∙ GA -0.0037 ∙ GA2 (SD = 0.21+0.0037 ∙ GA)). All velocities showed a constant increment from 20 to 40 weeks of gestation (ACA-S1 PSV= Antilog (0.84 + 0.023 ∙ GA); SD= Antilog (0.061 + 0.0015 ∙ GA); ACA-S2 PSV= Antilog (=0.89 + 0.019 ∙ GA) SD= Antilog (0.17 + 0.0045 ∙ GA)). Despite that no significant differences in any Doppler parameter were documented between segments, the angle of insonation and the time spent for examination were significantly lower, and the reproducibility increased for ACA-S1.
Discussion
The results of this study show that there is an increment in the PI of the ACA in both segments until 28-32 weeks of gestation, followed by a reduction until the end of the pregnancy; this pattern is similar to that previously reported for MCA-PI. PI values did not differ between both ACA segments, but in ACA-S1 the reproducibility was better, and the mean angle of insonation, and the time of examination lower than in ACA-S2.
We were always able to locate both segments of ACA despite the reported existence of anatomical variations of ACA. Blood velocities did not show significant differences between both segments. However, in ACA-S1 values were slightly higher than in ACA-S2. These differences might be due to the lower angle of insonation or to real differences in velocities. To make consistent the velocity recordings, we locate the Doppler sample gate in the same position of either segment, as different velocities have been reported when the same vessel is insonated at different sampling points. Even though the differences in velocities are true, the better angle of insonation for ACA-S1 makes the velocity estimation more reliable in this segment.
The tendency of our values throughout gestation is different from those previously reported by van den Wijngaard et al. The different shape of the curve throughout gestation is likely to be related to the larger number of cases included in our study (377 vs. 55). In addition, the successful rate for recording ACA was better in our study as we achieved a 100% successful rate for both segments, whereas van den Wijngaard et al. reported a rate of success of 64%. This difference probably reflects the significant technological improvements in Doppler imaging between the time of the former study (1989) and the present time. One of the advantages of ACA-S1 is that it can be observed in the same plane as the MCA, and with only a slight movement of the probe, the best angle of insonation can be achieved. In contrast, for ACA-2 an apical projection of the fetal head should be acquired either anterior or posterior in order to improve the angle of insonation. This renders the recording more cumbersome and time- consuming, and requires a more experienced examiner to achieve high rates of satisfactory measurements.
Evaluation of the clinical value of the ACA is now underway. There is recent evidence that not only in IUGR fetuses, but in a significant number of small-for-gestational age neonates, there is a reduced PI in the ACA with apparently no changes in the MCA. The reference values described here will contribute to better analysis of the clinical value of the ACA in the hemodynamic events of IUGR fetuses.
Conclusion
In conclusion, this study provides gestational age-adjusted reference values for Doppler parameters of the ACA. Both segments of the ACA showed similar values in the Doppler parameters throughout gestation, however, the shorter time spent for examination and the easier location of ACA-S1 makes it more suitable for investigation and clinical application.
There is an increment in the PI of the ACA in both segments until 28- 32 weeks of gestation, followed by a reduction until the end of the pregnancy. The first segment of the anterior cerebral artery (ACA-S1) is more reproducible and can be reliably recorded in the same anatomical projection as the MCA.
This information is not meant to replace the advice of any physician or qualified health professional. The information provided by Cerebra is for information purposes only and is not a substitute for medical advice or treatment for any medical condition. You should promptly seek professional medical assistance if you have concerns regarding any health issue.