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Title: Feasibility and agreement of including anterior-posterior complexes and landmarks

of the proximal hemisphere into basic examination of the fetal brain: a prospective study

Short title: Extended fetal cerebral screening

Authors: Lorena Hormazabala Flavia Correab David Escribanoc Gabriel Quiroza Constanza Saint-
Jeana Andrea Espinela Linder Diaza Belkys Zambranoa Alberto Galindoc Fernando Viñalsa
aCentro AGB Ultrasonografía, Clínica Sanatorio Alemán, Facultad de Medicina, Universidad de Concepción,
Concepción, Chile, b Fetal and Neonatal Ultrasonography Department, Hospital Lusíadas, Lisboa, Portugal, cFetal Medicine
Unit – Maternal and Child Health and Development Network, Department of Obstetrics and Gynaecology. University
Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Complutense University of Madrid, Madrid, Spain

Corresponding Author:
Fernando Viñals
Centro AGB Ultrasonografia. Clínica Sanatorio Alemán
Junge 75 – A, Concepcion, Chile. 4030000
Departamento de Obstetricia y Ginecología. Facultad de Medicina. Universidad de Concepción
Concepción, Chile
Email: fvinals@gmail.com

Conflict of Statement Statement


The Authors report no conflict of interests.

Funding Statement
The Authors report no funding.

Data Availability Statement


Research data are not shared

KEYWORDS : anterior complex; posterior complex; proximal cerebral hemisphere; central nervous
system; fetus

This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/pd.5652

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What´s already known about this topic?

·Anterior and Posterior Complexes ultrasound evaluation has been recently described as a useful tool
in the study of the fetal brain.

· The visualization of fetal cerebral proximal hemisphere is frequently obscured by artifacts, which
may not allow its proper evaluation.

What does this study add?

· Anterior and Posterior Complexes evaluation, as well as proximal hemisphere visualization, have
proven to be feasible when performing basic ultrasound study of the fetal brain.

ABSTRACT

Objective

To assess the feasibility of identifying structures included in Anterior Complex (AC) and Posterior Complex
(PC), as well as a series of anatomic landmarks that could help to demonstrate the integrity of the cerebral
proximal hemisphere

Methods

This was a prospective observational multicenter study of healthy pregnant women attending routine
ultrasound screening at 20+0–33+6 weeks' gestation. Six physicians performed transabdominal (TA)
ultrasound, in order to obtain the planes required to visualize the AC, PC and PH. Blind analysis by a non-
expert and two experts in fetal neurosonography was used to assess the structures included in each plane
view

Results

In the population studied (n=747), detection of the structures rates for AC, PC and proximal hemisphere was
of 94%, 93% and 96% respectively, with an agreement of 97%, 94% and 98% when comparing an expert and
a non-expert in fetal brain examiner. Detection of structures in the proximal hemisphere was significantly
higher when observed through the proximal hemisphere plane rather than the transventricular plane

Conclusion

Our results suggest that inclusion of AC and PC complexes visualization, as well as real-time access to the
proximal hemisphere, is feasible and could improve the prenatal detection of fetal cerebral anomalies

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Introduction

Ultrasound assessment of the fetal brain can be classified into two levels: a basic examination,
involving a group of axial transabdominal views intended to identify fetuses at risk of presenting
anomalies; and a dedicated examination, or neurosonogram, including a series of multiplanar
transfontanelle views, ideally through transvaginal examination. 1 It is well known that dedicated
fetal neurosonography offers much greater diagnostic potential than a standard basic examination,
but this technique requires the presence of an expert in fetal brain sonography and consequently,
it is not considered a first-line examination. 1,2 Therefore, an optimized basic ultrasound is of great
importance in order to better identify fetuses at risk of presenting cerebral anomalies.

The common denominator of basic ultrasound screening of the fetal brain are axial plane views
(Figures 1A-C). 1 It is generally considered that two axial planes allow visualization of the
supratentorial cerebral structures: the transventricular (Figure 1A) and transthalamic (Figure 1B)
planes. 1,3,4 The structures that are usually noted in those views are: the lateral ventricles (including
choroid plexi); cavum septi pellucidi; midline falx; and thalami. 1,3

Several guidelines also mention that fetal brain assessment provides visual imaging of the
hemisphere distal to the transducer, since imaging artefacts may obscure the closest hemisphere.
1,3
It is therefore suggested that symmetry of the fetal brain must be assumed in the basic
examination. 1 Considering that some abnormal conditions of development can affect only one
hemisphere, we recently proposed a technique able to reduce near field reverberation to the bony
calvarium, which consisted in angling the transducer cranially from the axial transthalamic plane.
This manoeuvre may reduce the near-field reverberation to the bony calvarium, but also allows
ultrasound access through other sutures, allowing ultrasound access to the proximal hemisphere
(Figure 2). 5

Moreover, we defined a series of anatomical targets with significant potential to diagnose


underlying conditions, grouped into anterior (AC) and posterior (PC) complexes (Figure 1). 6,7 During
basic axial examination of the fetal brain, including the evaluation of both complexes, besides those
of the standard anatomical structures, has proven to be valuable in suggesting not only the
likelihood of midline abnormalities but also of cortical anomalies. 6,7

In this study, we sought to assess the feasibility of including in the basic ultrasound examination of
the fetal brain the visualization the structures of both complexes and the anatomic landmarks that
may help to demonstrate the integrity of the proximal hemisphere.

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Methods

This was a prospective observational multicentre study of healthy women with singleton
pregnancies, with no increased risk of fetal CNS anomalies, attending routine ultrasound screening
at 20+0 – 33+6 weeks' gestation, between March and May 2017. All women provided written
informed consent to participate in the study. Exclusion criteria were fetuses with chromosomal or
structural anomalies, unknown pregnancy outcomes and absence of informed consent. During the
ultrasound scan, gestational age (estimated by crown-rump length in the first trimester), fetal
presentation and body mass index were recorded.

Four non expert operators in neurosonography (L.H., G.Q., C.SJ., A.E) and one expert (F.V.)
performed transabdominal (TA) ultrasound in the Sanatorio Alemán Clinic, Concepción, Chile using
Voluson E6, E8 and E10 (GE Healthcare Ultrasound, Milwaukee, WI, USA) equipped with RAB 4-8 or
6D MHZ probe. Another non-expert examiner (D.E.) was located remotely in a tertiary referral
centre at University Hospital 12 de Octubre in Madrid, Spain. In that centre, Toshiba Aplio MX SSA-
780A (Tokyo, Japan) equipped with 6MHz micro-convex probe was used for TA ultrasound. In total,
539 cases were collected from Chile and 216 cases from Spain.
All participants were asked to perform standard transventricular (plane 1) and transthalamic (plane
2) planes of the fetal brain, as reported previously. 1 A five-second 2D videoclip was stored for each
of the two planes. A third videoclip was made of the magnified image of the AC in the
transventricular plane. The landmarks defining this plane view have already been described 6,7 and
are displayed in Table 1. Subsequently, a fourth video was taken in the PC plane (plane 4), slicing
cranially from the transventricular plane until the interhemispheric fissure is interrupted by the
crossing of the corpus callosum (CC) in front of the parieto-occipital fissure (POF). This axial section,
parallel to the transventricular plane, is immediately inferior to that reported to grade fetal cortical
development 8,9 (Fig.1). Lastly, the operator was instructed to return to the transthalamic plane,
angling the transducer cranially by up to 45° (proximal hemisphere plane, plane 5). This manoeuvre
may reduce the near-field reverberation to the bony calvarium, but also allows ultrasound access
through the sphenoidal and mastoid fontanelles as well as squamosal, coronal and lambdoidal
sutures 5,10 (Fig. 2).

For the purposes of this study, all cases were followed up to six months after birth and only those
cases with normal development were included. Two cases were excluded due to neonatal death
and suspicion of anomaly detected in the review of the videoclip. At the outset, in order to
standardise the plane acquisitions, all the participants were asked to send videoclips of five patients
not included in the study to one investigator (F.V., henceforth examiner A).

Blind analysis by a non-expert (L.H., henceforth examiner C) and two experts in fetal
neurosonography (F.C., henceforth examiner B, and F.V.) was used to assess the structures included

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in each plane view. This comparison was included because the identification of such structures
might be hypothetically influenced by the experience of the operator. Each structure was classed as
seen, unseen or abnormal, with the latter subsequently excluded from the analysis. For the
purposes of statistical analysis, the population of fetuses was separated into three groups: 20-23+6,
24-27+6- and 28-33+6-weeks’ gestation. In this study, we analyse both the overall performance and
that of the group of 20-23+6 weeks´ gestation.

Continuous data are presented as absolute numbers, means, percentages, medians (range),
standard deviation, 95% confidence intervals (95% CI). The Kolmogorov–Smirnov test was used to
test for normal distribution. Analysis of variance (ANOVA) of single factor was used to compare the
means, and Levene test for homogeneity of variances. The Cohen kappa index (k) and percentage
of agreement with 95% CI were used to evaluate interobserver agreement between examiners B
and C. Statistical software SPSS version 24.0 (IBM, Chicago, IL, USA), and Excel version 16.0
(Microsoft Corp, Redmond, WA, USA) was used for analysis. Chi-square test and Fischer's exact test
were used to compare proportions; P ≤ 0.05 was considered statistically significant.

Results

Maternal and fetal ultrasound data of the 747 patients studied are summarized in Table 2. The
visualization rates of the structures studied on the five planes by the three examiners with different
levels of experience are displayed on Tables 3-6.

All three examiners achieved high visualization rates for the anatomical structures included in the
distal hemisphere of the transventricular plane (Table 3) and for the structures surrounding the
cavum septi pellucidi in the transthalamic plane grouped in the AC (Table 4). In this plane, it is
possible to visualise both proximal and distal anterior horns of the lateral ventricles and the
periventricular white matter and germinal matrix area immediately posterior to the anterior horn.
Table 5 shows at least a 95% visualization rate for the structures included in the PC with significant
agreement rates between expert and non-expert examiners, both for the whole study group and
for the 20-23+6 weeks´ gestation subgroup. Specifically, visualization of the corpus callosum
crossing the midline echo was achieved in over 98% and 97% of cases for the AC and PC respectively,
with a high level of agreement between the expert and non-expert examiners in the midtrimester
scan group (Kappa 0.83 for AC, and 0.74 for PC). Visualization rates for the required structures in
the proximal hemisphere (Table 6) was over 96% for all examiners, except visualization of the frontal
proximal outline. On comparison, visualization of the relevant structures in the proximal hemisphere
was significantly higher when observed through the proximal hemisphere plane rather than the
standard transventricular plane (Table7).

When the results of the two examiners (B and C) were compared, the Kappa coefficient was mostly
good or very good, and only occasionally moderate. In comparison to the total population, the 20-

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23+6 weeks’ gestation group achieved higher levels of agreement between the two examiners. All
results were statistically significant.

Discussion

It is clear that optimisation of the anatomical targets to be screened prenatally offer better potential
for ultrasound diagnostics. 11 This study combines a prospective assessment of a large number of
normal fetuses by operators with different levels of experience, analysing different populations of
pregnant women with different ultrasound equipments. Our results indicate that both non-expert
and expert operators are able to identify the structures included in AC, PC and proximal hemisphere
over 95% of the time, across a wide range of gestational weeks, maternal habits and different fetal
positions.

Visualization and analysis of the structures in the three planes abovementioned allow either confirm
their normality or highlight unusual or potentially pathological developments and suspect anomalies
when the two hemispheres are compared. 5,6 One initial example is CC anomalies, recently reported
to be present in 1.47 per 10,000 live births. 12 It is well-known that direct view of the CC offers the
possibility to observe its segments and aspect, as well as measure its size 13,15 but the difficult
reproducibility of the midsagittal view limits its inclusion in the basic fetal brain examination. 16,17
Suspicion of its malformations may arise at the mid trimester screening ultrasound on the basis of
indirect sonographic findings visible on the transventricular view. 18,20 However, these signs are more
evident after 24 weeks’ gestation and 33.3% of cases of partial agenesis of the CC (pACC) show no
indirect signs at the time of the mid trimester anomaly scan. 18 This is important because
approximately one third of apparently isolated pACC cases are associated with moderate or severe
neurological disability. 21 The AC and PC section views provide a direct view of at least two segments
of the CC: the anterior part of the genu and the posterior part of the body or splenium, depending
on the gestational age. 6 Visualization of PC also allows the evaluation of the disposition of the
choroid plexuses and lateral ventricles: in cases of complete ACC, they do not present their normal
oblique disposition, becoming parallel. In cases of pACC or CC dysgenesis, they assume an
intermediate disposition between oblique and parallel. 6 In the present study, three different
examiners detected the CC at 20-23+6 weeks´ gestation in 98% of the time in the AC view (with
almost perfect agreement between expert and non-expert examiners), and in 97% of the cases in
the PC plane (with substantial agreement between expert and non-expert examiners).
Another example is the identification of the POF at the level of the PC, achieving 98-99% of
visualization by the three examiners, similar to previously reported. 9 The POF appears triangular
with the apex pointing opposite to the midline. Pistorious et al. 8 studied the grade and symmetry
of the POF in an axial plane parallel to the transventricular plane and slightly cranial to the PC plane.
Alonso et al.9 evaluated the depth of the same fissure in a plane corresponding to that defined by
our group as PC. 6 The depth of the POF increased significantly with increasing gestation and in all
cases, it could be visualised from 20 weeks onwards. 9 Those studies, alongside our results,
demonstrate that fetal cortex gyration can reliably be observed in the basic ultrasound examination,

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without the need of extensive training and being potentially useful for suspicion of some migration
disorders. 22 Prenatal ultrasound is known to accurately demonstrate structures of the fetal cortex,
mostly through transvaginal examination and performed by expert examiners. 23,24,25
Finally, it has been stated that in the standard transventricular plane, usually only the hemisphere
on the far side of the transducer is clearly visualized, since artifacts frequently obscure the
hemisphere close to the transducer. 1 Ossification of the parietal bones progresses radially from the
central primary focus toward the periphery of the bone and continues along all margins throughout
fetal life. 26 This explains why near-field reverberation to the bony calvarium is significant around the
central portion of the parietal bone and increases with gestational age. Nonetheless, even at term,
the cranial sutures adjacent to the parietal bones are relatively broad, particularly in the parieto-
temporal region. 26 Angling the transducer 45° cranially from the axial transthalamic plane allows
ultrasound access through the sphenoidal and mastoid fontanelles as well as squamosal, coronal
and lambdoidal sutures. 5,27 It is essential to evaluate the proximal hemisphere as deeply as the distal
one since some conditions may be purely unilateral and have an important impact in
neurodevelopmental outcome, such as infarct, parenchymal or subependymal hemorrhage,
schizencephaly, porenchephaly, lenticulostriate vasculopathy, heterotopia, polymicrogyria, white
matter disease, calcifications, ventriculomegaly and tumours. 5 Although the visualization of the
cortical surface of the frontal lobe was poorer compared with other areas, which is likely due to
bone artifacts or limited access despite transducer angling, the proximal hemisphere plane enabled
the three examiners to visualize near field structures such as the anterior and posterior horns of the
lateral ventricles, the proximal atrium and choroid plexus, and the proximal Sylvian fissure in almost
98% of cases, with substantial agreement between all the examiners. The simplicity of the technique
broadens the scope of the qualitative evaluation and enables comparison with the distal
hemisphere. However, it should not be assumed that the brain is symmetrical. 1 Visualization and
comparison of both ventricles will reveal that brain asymmetry is a normal phenomenon in the
gradual development process, which begins during fetal life and continues through adulthood. 28,29

We acknowledge that the usefulness of these additional planes for improving the detection of fetal brain
abnormalities has yet to be demonstrated, and this will be the focus for future research. However, the
inclusion of the AC, PC and proximal hemisphere in the routine ultrasound examination of the fetal brain is
feasible, and this was certainly the main aim of this study.

Conclusion

This study reveals that the evaluation of AC, PC and proximal hemisphere is feasible and could
improve performance of fetal brain ultrasound, enhance adequate clinical suspicion and subsequent
referral to tertiary level care, thus offering better management of prenatal cerebral anomalies.
Further prospective studies are needed to confirm these conclusions, and to prove its usefulness for
the detection of brain abnormalities.

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Tables

TABLE 1 Cerebral structures assessed in each plane

Transventricular plane (Plane 1) Structures included in the anterior complex are part of this plane. Visualization of the anterior and
posterior horns of the lateral ventricle, with smooth inner surface and uniformly anechoic fluid
content. Periventricular zone is smooth and regular in its echogenicity. Choroid plexus fills the
ventricular cavity, is closely apposed to both the medial and lateral walls of the ventricle and its glomus
is visible. Continuity of the interhemispheric fissure posterior to the cavum septi pellucidi or cavum
vergae. Temporal and/or occipital cortical surface visible. Attempt to visualize these structures in the
proximal and distal hemisphere.

Transthalamic plane (Plane 2) Frontal horns of the lateral ventricles, the cavum septi pellucidi, the thalami and the hippocampal
gyruses.

Anterior complex (Plane 3) Interhemispheric fissure, callosal sulcus, corpus callosum, presence of cavum septi pellucidi and its
aspect, aspect of anterior horns of the proximal and distal lateral ventricles, visualization of the proximal
and distal germinal matrix area and the proximal and distal periventricular area immediately lateral to
anterior horn

Posterior complex (Plane 4) Interhemispheric fissure, callosal sulcus, corpus callosum, parietooccipital fissure, oblique disposition
to the midline of the proximal and distal lateral ventricles and/or both proximal and distal choroid
plexus of the lateral ventricles

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Proximal hemisphere (Plane 5) Visualization of the anterior and posterior horn of the lateral ventricle with smooth inner surface and
uniformly anechoic fluid content. Periventricular zone is smooth and regular in its echogenicity.
Choroid plexus fills the ventricular cavity, is closely apposed to both the medial and lateral walls of the
ventricle and its glomus is visible. Atrium visible. The Sylvian fissure is visible and its morphology is
compatible with the gestational age and comparable with that of the proximal hemisphere, while the
brain surface of the frontal, temporal and occipital lobes and the homogenicity of the periventricular
white matter are normal.

TABLE 2 Maternal and ultrasound data in 747 women with singleton pregnancy between 20 – 33+6 weeks' gestation

Parameter Value
Maternal
BMI (kg/m2) median (n=743) 26,1 (range 16.7-52.1)
20-23+6 week's (n=478) 25,6 (range 16.7-52.1)
Ultrasound
GA (weeks) 20-23+6 478
24-27+6 181
28-33+6 88

Fetal presentation (n=747) Vertex 71.2%


Breech 23.8%
Transverse 5%

GA 20-23+6 (n=478) Vertex 68.6%


Breech 25.3%
Transverse 6.1%

BMI, body mass index; GA, gestational age

TABLE 3 Transventricular plane: detection of structures, percentage of agreement and kappa index. Examiners A and B: Expert; and
Examiner C: Non-expert in neurosonography

Transventri- Examine Examine Examine Examine Examine Examine Percentag kapp Percentag kapp
cular plane rA rA rB rB rC rC e of a e of a
20 to 20 to 20 to 20 to 20 to 20 to Agreemen Agreemen
33+6 23+6 33+6 23+6 33+6 23+6 t t
(%) (%) (%) (%) (%) (%) B-C B-C
20 to 20 to
33+6 23+6
(95% CI) (95% CI)
Posterior 746/747 478/478 737/747 472/478 745/747 477/478 98.9 0.33 98.9 0.28
horn of distal (99.9) (100) (98.7) (98.7) (99.7) (99.8) (97.8- (97.4-
lateral 99.5) 99.6)
ventricle
Atrium of 744/747 478/478 744/747 478/478 744/747 478/478 100 1 100 NA
distal lateral (99.6) (100) (99.6) (100) (99.6) (100) (99.3-100) (99.0-100)
ventricle
Distal choroid 746/747 478/478 746/747 478/478 745/747 477/478 99.8 0.66 99.7 0
plexus (99.9) (100) (99.9) (100) (99.7) (99.8) (99.1- (98.6-
99.9) 99.9)
Distal 585/747 365/478 639/747 391/478 583/747 364/478 90.3 0.72 92.1 0.80
posterior (78.3) (76.4) (85.5) (81.8) (78.0) (76.2)

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periventricul (87.7- (88.8-
ar white 92.4) 94.4)
matter
Cortical 742/747 475/478 742/747 475/478 742/747 475/478 100 1 100 1
surface of (99.3) (99.4) (99.3) (99.4) (99.3) (99.4) (99.3-100) (99.0-100)
distal
occipital lobe
Cortical 669/747 409/478 671/747 411/478 669/747 409/478 99.4 0.97 99.5 0.98
surface of (89.6) (85.6) (89.8) (85.9) (89.6) (85.6) (98.3- (98.0-
distal 99.8) 99.9)
temporal
lobe
Posterior 607/747 425/478 473/747 351/478 607/747 425/478 75.9 0.52 81.3 0.47
horn of (81.3) (88.9) (63.3) (73.4) (81.3) (88.9) (72.2- (77.2-
proximal 79.1) 84.8)
lateral
ventricle
Atrium of 588/747 418/478 476/747 360/478 588/747 418/478 80.0 0.62 85.6 0.59
proximal (78.7) (87.4) (63.7) (75.3) (78.7) (87.4) (76.5- (81.8-
lateral 83.1) 88.8)
ventricle
Proximal 621/747 436/478 549/747 399/478 621/747 436/478 87.5 0.69 90.6 0.61
choroid (83.1) (91.2) (73.5) (83.5) (83.1) (91.2) (84.5- (87.4-
plexus 89.9) 93.1)
Proximal 434/747 291/478 350/747 248/478 429/747 288/478 77.4 0.73 81.6 0.77
posterior (58.1) (60.9) (46.9) (51.9) (57.4) (60.3) (73.1- (76.7-
periventricul 81.2) 85.8)
ar white
matter
Cortical 653/747 436/478 588/747 405/478 653/747 436/478 88.8 0.65 91.1 0.61
surface of (87.4) (91.2) (78.7) (84.7) (87.4) (91.2) (86.1- (87.9-
proximal 91.1) 93.5)
occipital lobe
Cortical 261/747 165/478 177/747 120/478 259/747 163/478 62.0 0.67 66.4 0.71
surface of (34.9) (34.5) (23.7) (25.1) (34.7) (34.1) (55.9- (58.7-
proximal 67.8) 73.4)
temporal
lobe
p=0.0001

TABLE 4 Anterior complex: detection of structures, percentage of agreement and kappa index. Examiners A and B: Expert; and
Examiner C: Non-expert in neurosonography

Anterior Examine Examine Examine Examine Examine Examine Percentag kapp Percentag kapp
Complex rA rA rB rB rC rC e of a e of a
20 to 20 to 20 to 20 to 20 to 20 to Agreemen Agreemen
33+6 23+6 33+6 23+6 33+6 23+6 t B-C t B-C
(%) (%) (%) (%) (%) (%) 20 to 20 to
33+6 23+6
(95% CI) (95% CI)
Interhemispher 746/747 478/478 745/747 476/478 746/747 477/478 99.8 0.66 99.7 0.66
ic fissure (99.9) (100) (99.7) (99.6) (99.9) (99.8) (99.1- (98.6-
99.9) 99.9)
Callosal sulcus 736/747 469/478 731/747 466/478 736/747 469/478 99.0 0.73 98.9 0.75

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(98.5) (98.1) (97.8) (97.5) (98.5) (98.1) (97.9- (97.3-
99.5) 99.6)
Genu of corpus 741/747 473/478 738/747 471/478 741/747 473/478 99.6 0.79 99.5 0.83
callosum (99.2) (98.9) (98.8) (98.5) (99.2) (98.9) (98.7- (98.3-
99.9) 99.9)
Cavum septi 747/747 478/478 747/747 478/478 747/747 478/478 100 NA 100 NA
pellucidi (100) (100) (100) (100) (100) (100) (99.3-100) (99.0-100)
Proximal 746/747 477/478 745/747 476/478 746/747 477/478 99.8 0.66 99.7 0.66
anterior horn (99.9) (99.8) (99.7) (99.6) (99.9) (99.8) (99.1- (98.6-
of lateral 99.9) 99.9)
ventricle
Distal anterior 738/747 474/478 735/747 474/478 738/747 474/478 99.5 0.85 100 1
horn of lateral (98.8) (99.1) (98.4) (99.1) (98.8) (99.1) (98.7- (99.0-100)
ventricle 99.8)
Proximal 733/747 466/478 731/747 464/478 733/747 466/478 99.7 0,93 99.5 0.92
subependymal (98.1) (97.5) (97.8) (97.1) (98.1) (97.5) (98.9- (98.2-
germinal 99.9) 99.9)
matrix
Distal 732/747 468/478 731/747 467/478 732/747 468/478 99.8 0.96 99.7 0.95
subependymal (98.0) (97.9) (97.8) (97.7) (98.0) (97.9) (99.1- (98.6-
germinal 99.9) 99.9)
matrix
Proximal 712/747 454/478 700/747 447/478 713/747 454/478 97.3 0.74 98.0 0.82
anterior (95.3) (94.9) (93.7) (93.5) (94.9) (95.8- (96.1-
periventricular (95.4) 98.3) 99.0)
white matter
Proximal 709/747 454/478 715/747 454/478 708/747 453/478 97.6 0.74 98.0 0.80
anterior (94.9) (94.9) (95.7) (94.9) (94.7) (94.7) (96.1- (96.1-
periventricular 98.5) 99.0)
white matter
P=0.0001

NA: not available

TABLE 5 Posterior complex: detection of structures, percentage of agreement and kappa index. Examiners A and B: Expert; and
Examiner C: Non-expert in neurosonography

Posterior Examine Examine Examine Examine Examine Examine Percentag kapp Percentag kapp
Complex rA rA rB rB rC rC e of a e of a
20 to 20 to 20 to 20 to 20 to 20 to Agreemen Agreemen
33+6 23+6 33+6 23+6 33+6 23+6 t B-C t B-C
(%) (%) (%) (%) (%) (%) 20 to 20 to
33+6 23+6
(95% CI) (95% CI)
Interhemispher 747/747 478/478 745/747 477/478 746/747 477/478 99.8 0.66 100 1
ic fissure (100) (99.1- (99.0-100)
(100) (99.7) (99.8) (99.9) (99.8) 99.9)

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Callosal sulcus 729/747 463/478 704/747 451/478 729/747 463/478 96.3 0.54 96.5 0.60
(97.6) (94.5- (94.3-
(96.8) (94.2) (94.3) (97.6) (96.8) 97.5) 97.9)
Corpus 732/747 467/478 721/747 465/478 732/747 467/478 97.9 0.62 98.7 0.74
callosum (98.0) (96.5- (97.0-
(97.7) (96,5) (97.3) (98.0) (97.7) 98.8) 99.4)
Parieto- 742/747 474/478 733/747 470/478 742/747 474/478 98.7 0.52 99.1 0.66
occipital fissure (99.3) (97.6- (97.7-
(99.1) (98.1) (98.3) (99.3) (99.1) 99.4) 99.7)
Oblique 740/747 474/478 693/747 457/478 740/747 474/478 93.6 0.21 96.4 0.31
disposition of (99.1) (91.5- (94.2-
proximal (99.1) (92.8) (95.6) (99.1) (99.1) 95.2) 97.8)
lateral ventricle
and/or choroid
plexus
Oblique 744/747 476/478 734/747 472/478 744/747 476/478 98.6 0.37 99.1 0.49
disposition of (99.6) (99.6) (99.6) (97.4- (97.7-
distal lateral (98.2) (98.7) (99.6) 99.3) 99.7)
ventricle
and/or choroid
plexus
P=0.0001

TABLE 6 Proximal cerebral hemisphere: detection of structures, percentage of agreement and kappa index. Examiners A and B: Expert;
and Examiner C: Non-expert in neurosonography

Proximal Examine Examine Examine Examine Examine Examine Percentag kapp Percentag kapp
cerebral rA rA rB rB rC rC e of a e of a
hemisphere 20 to 20 to 20 to 20 to 20 to 20 to Agreemen Agreemen
33+6 23+6 33+6 23+6 33+6 23+6 t B-C t B-C
(%) (%) (%) (%) (%) (%) 20 to 20 to
33+6 23+6
(95% CI) (95% CI)
Anterior horn 744/747 477/478 742/747 476/478 744/747 477/478 99.7 0.74 99.7 0.66
of lateral (99.6) (99.8) (99.3) (99.6) (99.6) (99.8) (98.9- (98.6-
ventricle 99.9) 99.9)
Posterior 735/747 475/478 725/747 469/478 735/747 475/478 98.6 0.69 98.7 0.49
horn of (98.4) (99.3) (97.1) (98.1) (98.4) (99.3) (97.4- (97.1-
lateral 99.3) 99,4)
ventricle
Proximal 741/747 476/478 740/747 477/478 741/747 476/478 99.3 0.61 99.7 0.66
atrium (99.2) (99.6) (99.1) (99.8) (99.2) (99.6) (98.3- (98.6-
99.7) 99.9)
Proximal 744/747 477/478 741/747 477/478 743/747 477/478 99.7 0.79 100 1
choroid (99.6) (99.8) (99.2) (99.8) (99.4) (99.8) (98.9- (99.0-100)
plexus 99.9)

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Periventricul 734/747 468/478 722/747 462/478 734/747 468/478 98.1 0.62 98.2 0.68
ar white (98.2) (97.9) (96.6) (96.6) (98.2) (97.9) (96.7- (96.5-
matter 98.9) 99.2)
Cortical 527/747 345/478 575/747 363/478 527/747 345/478 88.0 0.75 92.3 0.84
surface of (70.5) (72.2) (76.9) (75.9) (70.5) (72.2) (85.0- (89.0-
frontal lobe 90.5) 94.8)
Cortical 735/747 472/478 725/747 467/478 735/747 472/478 98.3 0.63 98.9 0.70
surface of (98.4) (98.7) (97.1) (97,7) (98.4) (98.7) (97.0- (97.4-
temporal 99.1) 99.6)
lobe
Cortical 740/747 474/478 736/747 472/478 740/747 474/478 99.1 0.66 99.1 0.59
surface of (99.1) (99.1) (98.5) (98.7) (99.1) (99.1) (98.1- (97.7-
occipital lobe 99.6) 99.7)
Sylvian 739/747 475/478 739/747 473/478 739/747 475/478 99.1 0.62 99.5 0.74
fissure (98.9) (99.3) (98.9) (98.9) (98.9) (99.4) (98.1- (98.3-
99.6) 99.9)
P=0.0001

TABLE 7 Comparison of Standard Transventricular Plane and Proximal Hemisphere Plane for the visualization of proximal hemisphere
structures, evaluated by expert (examiner B) and non-expert (examiner C)

Landmarks of the Percentage kappa Percentage kappa Percentage kappa Percentage of kappa
proximal hemisphere by of of of Agreement
transventricular and Agreement Agreement Agreement Examiner C
proximal hemisphere Examiner B Examiner B Examiner C (non-expert)
plane (expert) (expert) (non-expert) 20 to 23 + 6
20 to 33 + 6 20 to 23 + 6 20 to 33 + 6 (%)
(%) (%) (%) (95% CI)
(95% CI) (95% CI) (95% CI)
Atrium 64.3 0.03 75.4 0.01 79.3 0.05 87.8 0.05
(60.7-67.7) (71.3-79.2) (76.2-82.1) (84.4-90.5)
Choroid plexus 74.0 0.04 83.6 0.02 83.5 0.04 91.4 0.04
(70.7-77.1) (79.9-86.7) (80.6-86.1) (88.4-93.6)
Posterior periventricular 48.2 0.05 53.3 0.06 58.4 0.04 61.5 0.06
white matter (44.5-51.9) (48.6-57.9) (54.7-62.0) (56.9-65.9)
Cortical surface of 79.6 0.09 85.4 0.10 87.9 0.10 91.5 0.11
occipital lobe (76.5-82.4) (81.8-88.4) (85.3-90.2) (88.6-93.8)
Cortical surface of 23.9 0 25.1 0 35.0 0.01 34.2 0
temporal lobe (20.8-27.2) (21.3-29.3) (31.6-38.6) (30.0-38.7)

Figure Legends

FIGURE 1 Diagram and ultrasound images of axial views of the fetal head. A, Transventricular
plane. B, Transthalamic plane. C, Transcerebellar plane. D, Posterior complex plane. On the right:
(above) an amplified image of the posterior complex; (below) an amplified image of the
transventriclar plane at the level of the anterior complex. (1) interhemispheric fissure. (2) callosal
sulcus. (3) corpus callosum. (4) cavum septi pellucidi. CP, choroid plexus; LV, lateral ventricle; POF,

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parieto-occipital fissure; Ah p, proximal anterior horn; Ah d, distal anterior horn. Lines, shows the
oblique to midline disposition of the lateral ventricles and their choroid plexuses.

FIGURE 2 (A,B) Ultrasound images and (C) diagram showing the display of the proximal
hemisphere plane. (1) Transthalamic plane. (2) From the transthalamic plane, the transducer was
angled towards the cephalic direction in order to display the proximal hemisphere. SF, Sylvian
fissure; T, temporal lobe; CP, choroid plexus; Ph, posterior horn; O: occipital lobe

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