Normal Doppler Reference Values of the Pericallosal Artery

Abstract

Purpose: To provide the normal reference values of the Doppler flow of the pericallosal artery in relation to gestational age from 18 to 41 weeks of gestation.

Materials and Methods: The pericallosal artery (PCA) was studied in 466 normal pregnancies. The pulsed Doppler evaluation of the pericallosal artery was done in A3 and A4 segments, and records from PI, RI and Vmax were studied.

Results: The resistance index of the pericallosal artery in A3 / A4 segments exhibits a plateau from 18 to 31 weeks of gestation. After 31 weeks, a marked decrease becomes apparent. The pulsatility index of the pericallosal artery in A3 / A4 segments shows a plateau until 36 weeks of gestation. During the final weeks of gestation, there is a decrease in the pulsatility index. Vmax exhibits a plateau for the maximal flow velocity in A3 / A4 segments of the pericallosal artery from 18 to 28 weeks of gestation. After 28 weeks of gestation, there is a slight increase in Vmax.

Conclusion: Normal reference values of the pericallosal artery might have an impact on clinical judgment during adaptive hemodynamic changes and regarding the progression of the fetal deterioration occurring in the presence of fetal hypoxia.

Zusammenfassung

Ziel: Ziel dieser Studie war es, Dopplerfluss-Normwerte der A. pericallosa in Abhängigkeit vom Gestationsalter zwischen 18 und 41 Schwangerschaftswochen (SSW) zu erstellen.

Material und Methoden: Die A. pericallosa (PCA) wurde mit gepulstem Doppler bei 466 normalen Feten im Rahmen einer prospektiven Querschnittstudie untersucht. Die Messungen erfolgten in den A3- und A4-Segmenten der A. pericallosa, wobei die Parameter Resistance-Index (RI), Pulsatilitäts-Index (PI) und maximale Geschwindigkeit (Vmax) erfasst wurden.

Ergebnisse: Der RI der A. pericallosa zeigt in den A3/A4-Segmenten ein Plateau zwischen 18 und 31 SSW. Nach 31 SSW erkennt man einen deutlichen Abfall. Der PI der A. pericallosa weist in den A3/A4-Segmenten ein Plateau bis 36 SSW auf. Danach kommt es ebenfalls zu einem Abfall. Die Vmax zeigt in den A3/A4-Segmenten ein Plateau von 18 bis 28 SSW. Nach 28 SSW erkennt man einen leichten Anstieg der Vmax-Werte.

Schlussfolgerung: Die Normkurven von RI, PI und Vmax der A. pericallosa ergeben neben der A. cerebri media eine weitere Möglichkeit, adaptive hämodynamische Veränderungen im Gehirn zu erkennen. Inwieweit die Butflusssmessungen in der A. pericallosa eine Rolle in der frühzeitigen Erkennung einer fetalen Hypoxie spielen wird, müssen weitere Studien zeigen.

Key words

brain - blood vessels - prenatal

Introduction

The pericallosal artery (PCA) appears as a semicircular vessel that originates from the anterior cerebral artery [1] (ACA) and is located distal to the anterior communicating artery (ACoA) [2]. It is the primary supplier of blood to the midline of the fetal brain, including the corpus callosum, the optodiencephalic area, and the anterior two-thirds of the medial and superomedial aspects of both hemispheres [3].

According to Fischer’s classification [4] ([Fig. 1]), the ACA is divided into five segments [5].

Fig. 1 Diagram illustrating five segments (A1 – A5) of the anterior cerebral artery according to the classification of Fischer [4]. The optic nerve (ON) is below the anterior communicating artery (ACoA). PCA = cerebral artery (PCA) [3]. Used with permission from A. L. Rhoton.

Abb. 1 Demonstration der 5 Segmente (A1 – A5) der A. cerebri anterior nach der Klassifikation von Fischer [4]. Der Nervus opticus (ON) liegt unter der A. commincans anterior (ACoA). PCA = A. cerebri posterior [3]. Mit Genehmigung von A. L. Rhoton.

There is recent evidence that the process of brain vasodilatation in the intrauterine growth restricted fetuses (IUGR) can be reflected earlier in the anterior cerebral artery than in the middle cerebral artery [6]. Figueroa et al. [7] and Dubiel et al. [8] reported that in IUGR fetuses, the ACA pulsatility index was significantly reduced, as compared to gestational age-matched normally grown fetuses. A significant proportion of fetuses had ACA PI values below the 5th percentile, despite presenting an MCA PI within the normal range, thus in the absence of brain vasodilatation, as currently defined [6]. The aim of this study was to provide the normal reference values of the Doppler measurements of the pericallosal artery in relation to gestational age from 18 to 41 weeks of gestation.

Methods

This was a cross-sectional study for which we recruited, between June 2010 and February 2012, a total of 604 pregnant women referred to a tertiary center for fetal sonographic examination between 17 + 0 and 41 + 6 weeks of gestation. 466 normal pregnancies between 18 and 41 weeks of gestation were used to develop normal charts and tables of the Doppler flow of the fetal pericallosal artery ([Table 1]).

Table 1 Normal values for the variable RI A. pericallosa (RI-APericall) (5th, 50th and 95th percentiles).

	RI-APericall
weeks	5 %	50 %	95 %
18.0	0.7	0.8	1.0
18.5	0.7	0.8	1.0
19.0	0.7	0.8	1.0
19.5	0.7	0.8	1.0
20.0	0.7	0.8	1.0
20.5	0.7	0.8	1.0
21.0	0.7	0.8	1.0
21.5	0.7	0.8	1.0
22.0	0.7	0.8	1.0
22.5	0.7	0.8	1.0
23.0	0.7	0.8	1.0
23.5	0.7	0.8	1.0
24.0	0.7	0.8	1.0
24.5	0.7	0.8	1.0
25.0	0.7	0.8	1.0
25.5	0.7	0.8	1.0
26.0	0.7	0.8	1.0
26.5	0.7	0.8	1.0
27.0	0.7	0.8	1.0
27.5	0.7	0.8	1.0
28.0	0.7	0.8	1.0
28.5	0.7	0.8	1.0
29.0	0.7	0.8	1.0
29.5	0.7	0.8	1.0
30.0	0.7	0.8	1.0
30.5	0.6	0.8	1.0
31.0	0.6	0.8	1.0
31.5	0.6	0.8	1.0
32.0	0.6	0.8	1.0
32.5	0.6	0.8	1.0
33.0	0.6	0.8	1.0
33.5	0.6	0.8	1.0
34.0	0.6	0.8	1.0
34.5	0.6	0.8	0.9
35.0	0.6	0.8	0.9
35.5	0.6	0.7	0.9
36.0	0.6	0.7	0.9
36.5	0.6	0.7	0.9
37.0	0.5	0.7	0.9
37.5	0.5	0.7	0.9
38.0	0.5	0.7	0.9
38.5	0.5	0.7	0.9
39.0	0.5	0.7	0.8
39.5	0.5	0.7	0.8
40.0	0.5	0.7	0.8
40.5	0.5	0.7	0.8
41.0	0.5	0.6	0.8
41.5	0.5	0.6	0.8

The reason for the reduction in the original sample size was that in all cases, pregnancies had to be uncomplicated, no fetal cerebral malformation should be suspected or diagnosed, and the fetus had to be appropriate for its gestational age. Exclu­sion criteria comprised fetuses at 17 weeks of gestation, multiple pregnancy and fetuses with structural and chromosomal anomalies.

Each fetus was examined only once. Informed consent was available for all patients and the whole study was previously approved by the local ethical committee.

Gestational age was determined on the basis of the last menstrual period and confirmed at least by one ultrasound examination during the first trimester of pregnancy. All examinations were performed by one operator. The mean maternal body mass index (BMI) was 27 kg/m², ranging from 18 to 53 kg/m². All scans were performed using Voluson E8 General Electric equipment (Zipf, Austria) with a 5 – 8 MHz 3 D transabdominal and 5 – 9 MHz 3 D transvaginal transducer. A transabdominal 3 D ultrasound volume acquisition from axial planes (transventricular, transthalamic and transcerebellar planes) was performed in all fetuses. Normal fetal development was confirmed by normal fetal anatomy and normal biometric measurements: biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference (HC), transverse and antero-posterior diameter of the cerebellum, abdominal transverse diameter (ATD), abdominal sagittal diameter (ASD), femur, tibia, fibula, humerus, radius and ulna. According to the fetal position, the pericallosal artery was visualized either transabdominally or transvaginally in the median plane of the fetal head. The pulsed Doppler evaluation of the pericallosal artery was done in the A3 and A4 segments ([Fig. 2]) and records from PI, RI and Vmax were studied. During vascular measurements, attention was taken to avoid unnecessary pressure on the fetal head. Directional color Doppler was used to clearly locate the vessels. The angle of insonation was maintained between 0 – 30 degrees and corrected manually when necessary. The wall filter was set at 60 Hz and a minimum of 5 consecutive regular forms included the automatic calculation. The mechanical and thermal indices were maintained below 1. The mean scanning time for anatomical survey and biometrical measurements was 30 minutes and the mean time for the acquisition of the pericallosal artery Doppler data ranged from 1 to 3 minutes. All the collected measurement data were recorded in Excel tables for statistical calculations. In order to assess the reproducibility of the measure­ments, these seven variables were repeatedly measured by the same observer in a subset of n = 30 patients.

Fig. 2 Visualization of the pericallosal artery and its flow velocity waveform (FVW). The FVW displays a continuous forward flow at 30 weeks of gestation and has a relatively high pulsatility index of 1.56. The measurement is done in the A3 segment of the pericallosal artery.

Abb. 2 Darstellung der fetalen A. pericallosa und deren Blutflussmuster (FVW). Das Blutflussmuster zeigt einen kontinuierlichen Vorwärtsfluss mit 30 SSW und weist einen relativ hohen Pulsatilitätsindex von 1,56 auf. Die Messung erfolgte im A3-Segment der A. pericallosa.

Statistical analysis

Statistical procedure for the construction of age-dependent reference percentiles

In order to carry out the necessary computations, special SAS macros were made available at the Institute of Medical Biometry, Epidemiology and Informatics of the University of Mainz. These programs were run on a standard Intel PC using SAS, Version 9.2 (SAS Institute Inc., Cary, NC, USA). For each measurement under consideration, a 90 % reference band was constructed using gestational age (weeks) as the covariable of interest according to the approach established by Wellek and Merz in 1995 [9]. A detailed description of the procedure was published recently [10].

Results

In the present study we used 466 singleton pregnancies of 604 pregnant women. 123 cases were excluded due to presence of fetal (chromosomal anomalies, anatomical malformation, growth disorders) or maternal pathologies such as infections (toxoplasmosis, listeriosis, CMV infections) endocrine disorders (Addison’s disease, Hashimoto tiroiditis metabolic disorder (diabetes) and COPD (chronic obstructive pulmonary disease). 15 cases were twin pregnancies. In 366 examinations, the fetus was in cephalic presentation and in 100 it was in breech or transverse presentation. In the case of cephalic presentation, the mid-sagittal plane was acquired in 296 cases by transvaginal and in 70 cases by transabdominal imaging. In the case of a breech or transverse position of the fetus, only transabdominal scans could be performed.

The mean patient age was 31 years.

The calculated values for the 5th, 50th and 95th percentiles of the pericallosal artery Doppler measurements, resistance index (RI PCA), pulsatility index (PI PCA), and maximal velocimetry flow (Vmax PCA) in relation to gestational age, are demonstrated in [Fig. 3], [4], [5].

Fig. 3 Individual measurements and calculated 90 % reference band of the pulsatility index (PI A. pericall) in the A3 / A4 segments of the pericallosal artery in relation to gestational age (18 to 41 weeks) (n = 466 cases). The lines represent the 5th, 50th and 95th percentiles.

Abb. 3 Individuelle Messungen und konstruiertes 90 % Referenzband für den Pulsatilitätsindex (PI A. pericall) in der A. pericallosa in Abhängigkeit vom Gestationsalter (18 – 41 SSW) (n = 466 Fälle). Die Messungen erfolgten in den A3/A4-Segmenten. Die Linien repräsentieren die 5., 50., und 95. Perzentile.

Fig. 4 Individual measurements and calculated 90 % reference band of the resistance index (RI A. pericall) in the A3 / A4 segments of the pericallosal artery in relation to gestational age (18 to 41 weeks) (n = 466 cases). The lines represent the 5th, 50th and 95th percentiles.

Abb. 4 Individuelle Messungen und konstruiertes 90 % Referenzband für den Resistenzindex (RI A. pericall) in der A. pericallosa in Abhängigkeit vom Gestationsalter (18 – 41 SSW) (n = 466 Fälle). Die Messungen erfolgten in den A3/A4-Segmenten. Die Linien repräsentieren die 5., 50., und 95. Perzentile.

Fig. 5 Individual measurements and calculated 90 % reference band of the maximal flow velocity of the pericallosal artery (Vmax A. pericall.) in the A3 / A4 segments in relation to gestational age (18 to 41 weeks) (n = 466 cases). The lines represent the 5th, 50th and 95th percentiles.

Abb. 5 Individuelle Messungen und konstruiertes 90 % Referenzband für die maximale Flussgeschwindigkeit (Vmax A. pericall) in der A. pericallosa in Abhängigkeit vom Gestationsalter (18 – 41 SSW) (n = 466 Fälle). Die Messungen erfolgten in den A3/A4-Segmenten. Die Linien repräsentieren die 5., 50., und 95. Perzentile.

The data are presented as a collection of points in a scatterplot with the gestational age on the X-axis and measurements of the RI, PI, Vmax of the pericalloal artery on the Y-axis. The blue lines represent the 5th and 95th percentiles, the green line shows the 50th percentile.

The resistance index of the pericallosal artery in the A3 / A4 segments ([Fig. 3]) exhibits a plateau from 18 to 31 weeks of gestation. After 31 weeks a marked decrease becomes apparent.

The pulsatility index of the pericallosal artery in the A3 / A4 segments ([Fig. 4]) shows a plateau until 36 weeks of gestation. During the final weeks of gestation, there is a decrease in the pulsatility index.

[Fig. 5] depicts a plateau for the maximal flow velocity in the A3 / A4 segments of the pericallosal artery from 18 to 28 weeks of gestations. After 28 weeks of gestation, there is a slight increase of Vmax.

[Table 2], [3], [4] demonstrate the normal values (5th, 50th and 95th percentiles) for the variables RI, PI and Vmax of the pericallosal artery.

Table 2 Normal values for the variable PI A. pericallosa (PI-APericall) (5th, 50th and 95th percentiles).

	PI-APericall
weeks	5 %	50 %	95 %
18.0	1.1	1.4	1.9
18.5	1.1	1.4	1.9
19.0	1.1	1.4	1.9
19.5	1.1	1.4	1.9
20.0	1.1	1.4	1.9
20.5	1.1	1.4	1.9
21.0	1.1	1.4	1.9
21.5	1.1	1.4	1.9
22.0	1.1	1.4	1.9
22.5	1.1	1.4	1.9
23.0	1.1	1.4	1.9
23.5	1.1	1.4	1.9
24.0	1.1	1.4	1.9
24.5	1.1	1.4	1.9
25.0	1.1	1.4	1.9
25.5	1.1	1.4	1.9
26.0	1.1	1.4	1.9
26.5	1.1	1.4	1.9
27.0	1.1	1.4	1.9
27.5	1.1	1.4	1.9
28.0	1.1	1.4	1.9
28.5	1.0	1.4	1.9
29.0	1.0	1.4	1.9
29.5	1.0	1.4	1.9
30.0	1.0	1.4	1.9
30.5	1.0	1.4	1.9
31.0	1.0	1.4	1.9
31.5	1.0	1.4	1.9
32.0	1.0	1.4	1.9
32.5	1.0	1.4	1.9
33.0	1.0	1.4	1.9
33.5	1.0	1.4	1.9
34.0	1.0	1.4	1.9
34.5	1.0	1.4	1.9
35.0	1.0	1.4	1.9
35.5	1.0	1.4	1.9
36.0	1.0	1.4	1.9
36.5	1.0	1.4	1.9
37.0	0.9	1.3	1.9
37.5	0.9	1.3	1.8
38.0	0.8	1.2	1.7
38.5	0.7	1.1	1.7
39.0	0.7	1.1	1.6
39.5	0.7	1.1	1.6
40.0	0.7	1.1	1.6
40.5	0.7	1.1	1.6
41.0	0.7	1.1	1.6
41.5	0.7	1.1	1.6

Table 3 Normal values for the variable Vmax A. pericallosa (Vmax-Apericall) (5th, 50th and 95th percentiles).

	Vmax-APericall
weeks	5 %	50 %	95 %
18.0	6.9	15.6	29.8
18.5	6.9	15.6	29.9
19.0	6.8	15.6	29.9
19.5	6.8	15.6	30.0
20.0	6.7	15.6	30.1
20.5	6.7	15.6	30.2
21.0	6.6	15.6	30.3
21.5	6.6	15.6	30.4
22.0	6.5	15.6	30.5
22.5	6.5	15.6	30.5
23.0	6.4	15.6	30.6
23.5	6.3	15.6	30.7
24.0	6.3	15.6	30.8
24.5	6.2	15.6	30.9
25.0	6.2	15.6	31.0
25.5	6.2	15.6	31.1
26.0	6.1	15.6	31.2
26.5	6.1	15.7	31.3
27.0	6.1	15.7	31.4
27.5	6.1	15.8	31.6
28.0	6.2	15.9	31.8
28.5	6.3	16.1	32.1
29.0	6.5	16.4	32.4
29.5	6.8	16.7	32.8
30.0	7.2	17.1	33.3
30.5	7.6	17.6	33.9
31.0	8.1	18.1	34.5
31.5	8.6	18.7	35.2
32.0	9.2	19.3	35.9
32.5	9.7	19.9	36.6
33.0	10.2	20.5	37.2
33.5	10.7	21.0	37.8
34.0	11.0	21.4	38.3
34.5	11.3	21.7	38.7
35.0	11.5	22.0	39.1
35.5	11.6	22.1	39.3
36.0	11.7	22.2	39.5
36.5	11.7	22.3	39.7
37.0	11.7	22.3	39.8
37.5	11.6	22.4	39.9
38.0	11.6	22.4	40.0
38.5	11.6	22.4	40.1
39.0	11.5	22.4	40.1
39.5	11.4	22.4	40.2
40.0	11.4	22.4	40.3
40.5	11.3	22.4	40.4
41.0	11.3	22.4	40.5
41.5	11.2	22.4	40.6

Table 4 Number of the case used in each gastational week of the measurement of the pericallosal artery.

gestational age (weeks)	cases (n)
18	5
19	15
20	24
21	20
22	20
23	22
24	18
25	24
26	23
27	21
28	21
29	22
30	20
31	20
32	21
33	21
34	22
35	23
36	21
37	21
38	22
39	16
40	21
41	3
total	466

For the subset of 30 cases, repeat measurements were performed to find the interobserver reliability. As a result, the intraobserver reliability was found to be excellent, with interclass correlation coefficients ranging from 0.9512 to 0.9999.

Discussion

This is the first study to explore the Doppler measurement of the pericallosal artery. There is no change in PI values until 36 weeks of gestation, followed by a fall in the pericallosal artery PI with more than 36 weeks of gestation, which probably reflects a decreasing vascular resistance at that gestational age. There is an increase of Vmax after 28 weeks of gestation. The tendency of our values throughout gestation is different from those previously reported for the anterior cerebral artery in axial planes [6]. This difference probably reflects the different anatomical planes and segments of the vascular cerebral system used for the measurements of Doppler data.

The fetal cerebral circulation can be estimated noninvasively with Doppler ultrasound flow velocimetry in the large cerebral arteries and veins, where an increase in the cerebral arterial circulation is characterized by an increase of diastolic flow velocity and a decrease of vascular flow resistance [11]. Doppler blood flow examination can be a useful tool in the evaluation of fetal condition and in the prediction of fetal distress and neonatal outcome [12] [13].

Intrauterine growth restriction associated with placental insufficiency and chronic hypoxia complicates nearly 3 – 5 % of all pregnancies [14]. In these fetuses, a circulatory distribution occurs and is a fetal adaptive reaction to placental insufficiency known as the “brain sparing effect”. These changes can be detected noninvasively with Doppler ultrasound, in both the middle cerebral artery (MCA) and the anterior cerebral artery [15] [16].

Recent studies suggest that children with fetal circulatory redistribution to the anterior cerebral artery had higher risk of attention problems and emotional reactivity, which may indicate less mature frontal-subcortical circuitry [17].

The MCA supplies the central and lateral areas of the frontal, parietal and temporal lobes, insula, basal ganglia and internal capsule in the central parts of the hemispheres. The internal capsule contains largely myelinated pathways passing to and from the cerebral cortex. A functional impairment of cortical tissues supplied by the MCA will then strike large parts of motor, somatosensory and auditory centers, and important areas for language. A functional impairment of the basal ganglia will result in a variety of dysfunctions among which motor dysfunctions are the most obvious. Involvement of the internal capsule will result in interrupted cortico-subcortical connections [18].

The ACA supplies the antero-medial cerebral cortex, from the frontal lobe to the parietal lobe all the way to the sulcus parieto-occipitalis. Moreover, it supplies some anterior parts of the internal capsule and caudate nucleus, and finally, the septal and preoptic areas. Dysfunction of areas nourished by the ACA may cause motor and sensory losses in the contralateral leg and disabilities of cognitive and emotion functions [19].

Up to 15 % of IUGR fetuses develop some degree of overt neurological damage, expressed mainly as hypoxic-ischemic encephalopathy, leukomalacia, and/or cerebral palsy [20]. There is evidence that a wider spectrum of subtle brain developmental disturbances may occur, including neuromuscular disorders, learning disabilities and behavioral misconduct [21] [22].

In animal models under hypoxia, the blood supply to different brain areas may differ substantially, and those regional differences are likely to be influenced greatly by gestational age and the type and severity of the insult [23] [24].

Regional hemodynamic changes could be one of the pathways behind the existence of a regional hierarchy in brain deterioration [8]. There are few studies that have shown that the fetal brain arteries differ in their Doppler parameters, supporting the concept that human fetal brain may experience hemodynamic internal variations during hypoxic IUGR [6] [7] [25] [26].

Recent evidence indicates that a reduction in RI in the ACA with apparently no change in the MCA [6] [7] [25] [26] occurs not only in IUGR fetuses but also in a significant number of small fetuses for gestational age neonates. Interpreting the results of two clinical studies [17] [27], those parts of the brain that are involved in higher-order brain functions may be more vulnerable to hypoxemia. The fetal adaptive mechanism serves to protect the frontal regions at the expense of temporal and occipital regions in cases of chronic fetal hypoxia.

The knowledge of the normal charts of Doppler parameters of the pericallosal artery in the A3 and A4 segments might have an important role in clinical judgment during adaptive hemodynamic changes and regarding the progression of the fetal deterioration occurring in the presence of fetal hypoxia, when middle cerebral artery Doppler velocimetry might have normal values in severe cases, as well as in predicting neurological outcome.

Erratum: Pashaj et al. Normal Doppler Reference Values of the Pericallosal Artery. Ultraschall in Med 2015; 36: 375–380.

In this article, the third author’s name and affiliation was incorrectly stated. It was subsequently corrected in the online version to read “S. Wellek, Department of Medical Biostatistics”.

Furthermore the legend of table 4 was incorrectly stated and therefore corrected.

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