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ORIGINAL
RESEARCH
The Anatomic Variations of the Circle of Willis in
Preterm-at-Term and Term-Born Infants: An MR
Angiography Study at 3T
C. Malamateniou
M.E. Adams
L. Srinivasan
J.M. Allsop
S.J. Counsell
F.M. Cowan
J.V. Hajnal
M.A. Rutherford
BACKGROUND AND PURPOSE: It has been shown that the brain of a preterm infant develops differently
from that of a term infant, but little is known about the neonatal cerebrovascular anatomy. Our aims
were to establish reference data for the prevalence of the anatomic variations of the neonatal circle of
Willis (CoW) and to explore the effect of prematurity, MR imaging abnormality, vascular-related
abnormality, laterality, and sex on these findings.
MATERIALS AND METHODS: We scanned 103 infants with an optimized MR angiography (MRA)
protocol. Images were analyzed for different variations of the CoW, and results were compared for the
following: 1) preterm-at-term and term-born infants, 2) infants with normal and abnormal MR imaging,
3) infants with and without a vascular-related abnormality, 4) boys and girls, and 5) left- and right-sided
occurrence.
RESULTS: The most common anatomic variation was absence/hypoplasia of the posterior communi-
cating artery. Preterm infants at term had a higher prevalence of a complete CoW and a lower
prevalence of anatomic variations compared with term-born infants; this finding was significant for the
anterior cerebral artery (P⫽.02). There was increased prevalence of variations of the major cerebral
arteries in those infants with vascular-related abnormalities, statistically significant for the posterior
cerebral artery (P⫽.004). There was no statistically significant difference between boys and girls and
left/right variations.
CONCLUSIONS: Prematurity is associated with more complete CoWs and fewer anatomic variations.
In vascular-related abnormalities, more variations involved major arterial segments, but fewer varia-
tions occurred in the communicating arteries. Overall reference values of the variations match those
of the general adult population.
The circle of Willis (CoW) is a ringlike arterial structure,
which, when complete,
1
consists of 9 component vessels
(Fig 1A,-B). However, as both autopsy
2
and imaging
3
studies
in adults have reported, the CoW may be incomplete and may
present different anatomic variations, depending on the pres-
ence or absence and the size (hypoplasia/hyperplasia) of its
component vessels (Fig 2A, -D). In the past, the origin of these
variations was thought to involve hereditary factors
4
; later
studies reported that these altered CoW configurations are the
result of developmental modifications driven by the func-
tional demand of the growing brain, with a change of their
prevalence during the human lifespan.
5-7
The arteries of the CoW are the major blood suppliers of
the brain. The CoW can serve potentially as a primary collat-
eral pathway in cases of impaired or decreased flow within 1 or
more of the major cerebral vessels.
8
Its ability to redistribute
blood flow to hemodynamically deprived areas and to operate
as a natural protective mechanism in vascular accidents de-
pends largely on the presence and size of its component
vessels.
Previous MR imaging studies in term-born infants and
preterm infants at term-equivalent age have shown that pre-
mature exposure to the ex utero environment alters brain de-
velopment in the white matter,
9-11
cortex,
12,13
and deep gray
matter.
14,15
It is also known that certain cerebral pathologies
with a strong vascular component, such as periventricular leu-
comalacia and intraventricular hemorrhage, present more of-
ten in preterm than term-born infants.
16,17
We have previ-
ously shown that the proximal cerebral arteries of preterm
infants imaged at term-equivalent age have a straighter pattern
compared with those in infants born at term and that this
difference persists well into infancy.
18
The aims of this study were to establish reference data for
the prevalence of the anatomic variations in a neonatal popu-
lation; and to explore the effect of prematurity, degree of pre-
maturity, MR imaging-detected brain abnormality, vascular-
related abnormality, sex, and laterality on these findings.
Materials and Methods
Inclusion Criteria
Infants scanned with a high-resolution dedicated MR angiography
(MRA) protocol at 3T were included in this study (n⫽103). We
excluded 9 of these infants due to motion artifacts because these may
hamper the detection of anatomic variations, especially for the small
communicating cerebral arteries. Of the 94 remaining infants, 44
Received March 2, 2009; accepted after revision May 6.
From the Department of Imaging Sciences (C.M., M.E.A., L.S., J.M.A., S.J.C., F.M.C., J.V.H.,
M.A.R.), Robert Steiner MRI Unit, Hammersmith Hospital Campus, Imperial College London,
London, UK; Division of Medical Imaging and Radiotherapy (C.M.), School of Health
Sciences, University of Liverpool, Liverpool, UK; Department of Radiology (M.E.A.), Great
Ormond Street Hospital, London, UK; and Department of Paediatrics (F.M.C.), Imperial
College London, London, UK.
This work was supported by a research grant from the Greek State Scholarships Foundation
(IKY), the Health Foundation, the Academy of Medical Sciences, and Philips Medical
Systems.
Paper previously presented in part at: Annual Meeting of the Pediatric Academic Societies,
April 29 –May 2, 2006; San Francisco, Calif; and Annual Meeting of the International
Society for Magnetic Resonance in Medicine, May 6 –12, 2006; Seattle, Wash.
Please address correspondence to Christina Malamateniou, PhD, Department of Imaging
Sciences, Robert Steiner MRI Unit, Hammersmith Hospital, DuCane Rd, W12 0HS, London,
UK; e-mail:christina.malamateniou03@imperial.ac.uk
DOI 10.3174/ajnr.A1724
PEDIATRICS ORIGINAL RESEARCH
AJNR Am J Neuroradiol 30:1955– 62 兩Nov-Dec 2009 兩www.ajnr.org 1955
were preterm and imaged at term-equivalent age and 50 were term-
born and scanned soon after birth. There were 50 boys and 44 girls. Of
the preterm infants, 23 were born before 30 weeks of gestation and 21
were born after 30 weeks of gestation.
Fig 1. A, Graph of the CoW with its component vessels: A1 segments of the ACAs, AcomA, internal carotid arteries (ICAs), PcomAs, and P1 segments of PCAs. The middle cerebral artery
(MCA) and the basilar artery are not structurally part of the CoW. B, Complete CoW in a preterm neonate on an axial 3D TOF MRA image.
Fig 2. Axial MIP images of different anatomic variations of the CoW in the neonatal brain. A, Hypoplastic right A1 segment of the ACA (thin arrow) and bilateral fetal-type origin of the
PCA with bilaterally hypoplastic P1 segments (thick arrows ) and enlarged PcomAs (block arrows). B, Unilateral (left) fetal-type origin of the PCA with the PcomA diameter (thin arrow) larger
than the P1 diameter. C, Clearly present AcomA (arrowhead ) with bilaterally absent PcomAs. D, Absent right A1 segment (arrowhead), and bilateral fetal-type origin of the PCA (block
arrows) with absent P1 segments. The whole of the anterior circulation originates from the enlarged left ACA.
1956 Malamateniou 兩AJNR 30 兩Nov-Dec 2009 兩www.ajnr.org
Of the 94 infants, 16 presented with vascular-related abnormali-
ties, such as facial port-wine stain (n⫽4), perinatal arterial territory
ischemic stroke (n⫽7), or cerebral hemorrhage (n⫽2). Three pre-
term infants had retinopathy of prematurity (ROP).
All structural T1- and T2-weighted images were assessed by an
experienced pediatric neuroradiologist for the presence of overt white
matter or basal ganglia focal lesions. MR imaging findings were clas-
sified as abnormal if there was evidence of infarction, porencephalic
cyst, parenchymal hemorrhage, or other overt focal lesions for the
preterm infant; and abnormal signal intensities in the basal ganglia,
loss of gray/white matter differentiation, infarction, and parenchymal
hemorrhage in the term infant. In total, 24 term infants and 41 pre-
term infants had an MR image finding that was considered normal at
term or term-equivalent age respectively. The detailed demographic
data for those infants is given in Table 1.
Patient Preparation
Approval was granted by the Research Ethics Committee (2003/6564
and 06/Q0406/14) of the hospital, and informed parental consent was
obtained before each scanning. Infants were imaged either in natural
sleep or, where necessary, after sedation with oral chloral hydrate
(20 –30 mg/kg) to prevent image degradation from motion artifacts.
Each infant was positioned supine, and the head was immobilized by
using a pillow evacuated by suction to fit snugly around it. Additional
ear protection was used for each infant. Temperature was maintained
and monitoring of infants’ vital signs was performed throughout the
scanning. A neonatologist experienced in MR imaging was present
throughout the examination.
19
MR Imaging Data Acquisition
All infants were scanned by using a 3T scanner (Achieva; Philips Med-
ical Systems, Best, the Netherlands) with a dedicated high-resolution
3D time-of-flight (TOF) MRA protocol with TR/TE/flip angle of 19/
5.7ms/16°, respectively, and true isotropic resolution of 0.6 ⫻0.6 ⫻
0.6 mm
3
. This protocol has been specifically optimized for use in a
neonatal population, in which vascular flow is slower and vessels are
narrower.
20
Standard anatomic T1- and T2-weighted images were
also acquired; more specifically T1-weighted volume scans and T2-
weighted multisection fast-field echo anatomic scans were obtained
for the detection of brain abnormalities.
Image Analysis
Qualitative assessment of angiographic images was performed by an
experienced observer blinded to the clinical and demographic details
of the subjects, by using ImageJ software (Version 1.32, National In-
stitutes of Health, Bethesda, Md; http://rsb.info.nih.gov/ij/download.
html). A second observer confirmed the findings with substantial
interobserver agreement (Cohen
coefficient,
⫽0.79). The aim of
the image assessment was to confirm the completeness or incom-
pleteness of the CoW and to identify and record the prevalence of
different anatomic variations (absence/hypoplasia of the posterior
communicating artery [PcomA], anterior communicating artery
[AcomA], proximal A1 and P1 segments of the anterior cerebral ar-
tery [ACA], and posterior cerebral artery [PCA] respectively; and
fetal-, transitional-, or adult-type origin of the PCA). Both maximum
intensity projections (MIPs) in all imaging planes and source images
were used to confirm the findings (Fig 3A,-B).
Completeness of the CoW and anatomic variations were classified
on the basis of the arterial configurations described in previous adult
studies.
3,7
Segments of the communicating arteries visualized only in
the source images but not in the MIP images were reported as hypo-
plastic; segments visualized in neither the source nor the MIP images
were reported as absent. Both hypoplastic and absent segments were
considered not present when determining the completeness or in-
completeness of the CoW because visibility was used as a surrogate
measure of the functionality of the vasculature
21
; therefore, absent or
hypoplastic vessels were considered not functional.
Care was taken to differentiate the PcomAs from the anterior cho-
roidal and overlapping pericallosal branches of the ACA on the axial
MIP (Fig 4A). This was achieved by scrolling through the sections and
judging the courses of the arteries in sequential display. The commu-
nication of the PcomA with the PCA had to be visualized to determine
the identity of the vessel. The same method was used to help differ-
entiate the PCAs from the superior cerebellar segments and the ana-
tomic variants of enlarged anterior choroidal branches (Fig 4B).
A P1 segment of the PCA larger than the ipsilateral PcomA as
visualized on the MIP was classified as adult-type origin of the PCA, a
P1 segment with the same size as the PcomA was classified as a tran-
sitional-type origin of the PCA, and a P1 with a smaller size than the
PcomA (or totally absent) was classified as fetal-type origin of the
PCA.
Statistical Considerations
Infants were subdivided in the following subgroups: 1) preterm at
term (n⫽41) and term-born (n⫽24) with normal MR imaging
findings; 2) preterm-born before 30 weeks’ gestational age (GA, n⫽
22) and those born after 30 weeks’ GA (n⫽19) with normal MR
imaging findings; 3) term infants with normal MR imaging findings
(n⫽24) and abnormal MR imaging findings (n ⫽26); 4) boys (n⫽
34) and girls (n⫽31) with normal MR imaging findings and infants
with (n⫽16) and without (n⫽78) evidence of vascular-related
abnormality. Laterality (left- or right-side occurrence) was also exam-
ined in those vessels that had bilateral representation in the CoW.
The StatsDirect package (http://www.statsdirect.com/) was used.
The Shapiro Wilk test was applied to test the normality of the demo-
graphic data, and the unpaired ttest, to identify differences between
Table 1: Summary of the demographic data of the preterm-at-term and term-born infants taking part in this study
Demographic Parameters
Preterm Infants
at Term Term infants
Statistical Difference between
Preterm-at-Term and
Term Infants
Median (range) Median (range) PValue
Gestational age (weeks) 29.5 (25.7–34.7) 40 (36.4–42.3)
Postmenstrual age at scanning (weeks) 41.1 (36.3–45.3) 41.6 (37.1–42.8) .13
Birth weight (kg) 1.29 (0.51–2.69) 3.29 (1.85–4.50)
Weight at scanning (kg) 3.06 (1.70–5.5) 3.48 (1.93–5.28 ) .11
Head circumference at birth (cm) 27.1 (22.1–34.5) 34.4 (31–38)
Head circumference at scanning (cm) 35.4 (31.2–40) 36.4 (32–39.4) .02
AJNR Am J Neuroradiol 30:1955– 62 兩Nov-Dec 2009 兩www.ajnr.org 1957
the groups. The Fisher exact test was used to explore associations
between prematurity, degrees of prematurity, MR imaging abnormal-
ity, sex, vessel laterality, and vascular-related abnormality with the
anatomic variations and the completeness of the CoW. The r by c
2
test (StatsDirect) was used to explore whether the laterality of vascular
variations correlated with the laterality of the brain parenchymal or
other vascular abnormalities. A Pvalue ⬍.05 was considered to indi-
cate a statistically significant difference.
Results
Reference Values of CoW Anatomic Variations in
Neonates with Normal MR Imaging Findings
In the 65 infants (including both term and preterm-at term
infants) with normal MR imaging, the CoW was complete in
27 (41.5%). The AcomA was absent or hypoplastic in 12
(18.5%). For the vessels with bilateral representation and
hence 130 (2 ⫻65) potential examples, the PcomA was absent
or hypoplastic in 39 of 130 cases (30%), the A1 segment of the
ACA was absent or hypoplastic in 6 of 130 cases (4.6%), and
the P1 segment of the PCA was absent or hypoplastic in 8 of
130 cases (6.1%). Fetal-type origin of the PCA was observed in
36 of 130 cases (27.7%), and the transitional configuration of
the posterior part of the CoW was present in 7 of 130 cases
(5.4%). The most common variation was the absence of the
PcomA (30%). More details can be found in Table 2.
Effect of Prematurity in Neonates with Normal MR
Imaging Findings
Preterm infants had a higher prevalence of a complete CoW of
44% relative to term-born infants with 37.5%, but this differ-
ence was not statistically significant (P⫽.41). Preterm infants
had a generally lower prevalence of CoW anatomic variations
Fig 3. A, Axial MIP image of a term-born infant in which the AcomA cannot be clearly seen due to excessive vessel overlap of the pericallosal branches of the ACA. B, Axial source image
of the same infant in which the AcomA can be clearly seen (arrow), to exclude AcomA absence/hypoplasia.
Fig 4. A, Axial MIP image in which the anterior choroidal arteries (thick arrows) and pericallosal branches of the ACA (thin arrow) overlap the PcomAs (arrowheads). B, Axial MIP image
in which the superior cerebellar arteries (arrowheads) can be mistaken for PCA branches and an abnormally enlarged anterior choroidal artery can be mistaken for fetal-type origin of the
PCA (block arrow).
1958 Malamateniou 兩AJNR 30 兩Nov-Dec 2009 兩www.ajnr.org
(Table 2). The term-born infants had a significantly higher
prevalence (P⫽.02) of absence/hypoplasia of the A1 segment
(10.4%) compared with the preterm infants (1.2%).
The preterm infants born at ⬍30 weeks’ GA (n⫽22) had a
higher prevalence of CoW completeness (50%) compared
with the preterm infants born after 30 weeks (n⫽19, 36.8%),
but this difference was not statistically significant (P⫽.30).
Overall, they had a lower prevalence of anatomic variations
(Table 3). The preterm infants born after 30 weeks’ GA had
more significantly increased prevalence (P⫽.04) in the bilat-
eral fetal-type origin of the PCA (83.3%) than those infants
born before 30 weeks’ GA (40%).
There was no statistically significant difference between the
early (⬍30 weeks’ GA) infants and the term ones, neither in
the completeness of the CoW (P⫽.29) nor in the incidence of
specific anatomic variations.
Effect of MR Imaging Abnormalities
Term infants with abnormal MR imaging findings had a
slightly higher prevalence of complete CoW and subsequently
a lower prevalence of anatomic variations compared with
those with normal MR imaging findings, but this difference
did not reach statistical significance. However, A1 segment
absence/hypoplasia was observed less frequently in term-born
infants with abnormal MR imaging findings than in those with
normal MR imaging findings (P⫽.05). The same was true for
the bilaterally absent PcomA (P⫽.07), approaching statistical
significance, as seen in Table 4.
It was not feasible to apply similar statistical tests in the
total preterm population (n⫽44) because there were only 3
preterm infants scanned at term with abnormal MR imaging
findings and 41 preterm at term with normal MR imaging
findings.
In total, 26 term infants and 3 preterm infants had an MR
imaging finding that was considered abnormal at term or
term-equivalent age, respectively. Some infants had ⬎1 paren-
chymal abnormality. In total, abnormalities on structural MR
imaging consisted of abnormal signal intensity of the basal
ganglia (n⫽17), infarction (n⫽10), loss of gray/white matter
differentiation (n⫽3), periventricular cyst (n⫽2), cerebral
hemorrhage (n⫽2), and porencephalic cyst (n⫽1). The
detailed prevalence of anatomic variations of the CoW in re-
lation to each type of parenchymal abnormality is presented in
Table 5. Because ⬎1 anatomic variation and/or ⬎1 parenchy-
mal abnormality could be simultaneously present in the same
infant, it was not feasible to associate a specific variation with
a specific parenchymal abnormality.
Effects of Vascular-Related Abnormalities
There was no difference in the completeness of the CoW be-
tween infants with (n⫽16) and without (n⫽78) evidence of
Table 2: Reference values of the prevalence of anatomic variations of the CoW in a group of 65 infants (24 term-born, 41 preterm-at-term)
with normal MR imaging findings
Term
(normal MRI)
n⫽24
Preterm
(normal MRI)
n⫽41 PValue Mean
Completeness of CoW 9 in 24 (37.5%) 18 in 41 (44%) .405 41.50%
AcomA absence/hypoplasia 6 in 24 (25%) 6 in 41 (14.6%) .237 18.50%
PcomA absence/hypoplasia 13 in 48 (27%) 26 in 82 (31.7%) .363 30%
A1 segment of ACA absence/hypoplasia 5 in 48 (10.4%) 1 in 82 (1.2%) .026* 4.60%
P1 segment of PCA absence/hypoplasia 4 in 48 (8.3%) 4 in 82 (4.8%) .332 6.10%
Fetal-type origin of PCA 14 in 48 (29%) 22 in 82 (26.8%) .463 27.70%
Transitional-configuration origin of PCA 6 in 48 (12.5%) 4 in 82 (4.8%) .11 5.40%
Bilateral fetal-type origin 8 in 14 (57.1%) 14 in 22 (63.6%) .482 61.10%
Bilaterally absent PcomA 6 in 13 (46.2%) 14 in 26 (53.8%) .455 51.30%
Note:—CoW indicates circle of Willis; MRI, MR imaging; AcomA, anterior communicating artery; PcomA, posterior communicating artery; ACA, anterior cerebral artery; PCA, posterior
cerebral artery.
* Statistically significant.
Table 3: Prevalence of anatomic variations of the CoW in a group
of 41 preterm-at-term infants (19 born after 30 weeks’ GA, 22 born
before 30 weeks’ GA) with normal MR imaging findings
Preterm
(⬎30 weeks)
Preterm
(⬍30 weeks)
P
Value
Completeness of CoW 7 in 19 (36.8%) 11 in 22 (50%) .298
AcomA absence/hypoplasia 4 in 19 (21%) 2 in 22 (9%) .262
PcomA absence/hypoplasia 15 in 38 (39.5%) 11 in 44 (25%) .122
A1 segment of ACA absence/
hypoplasia
0 in 38 (0%) 1 in 44 (2%) .537
P1 segment of PCA absence/
hypoplasia
2 in 38 (5.2%) 2 in 44 (4.5%) .635
Fetal-type origin of PCA 12 in 38 (31.6%) 10 in 44 (22.7%) .257
Transitional-configuration
origin of PCA
1 in 38 (2.6%) 3 in 44 (6.8%) .365
Bilateral fetal-type origin 10 in 12 (83.3%) 4 in 10 (40%) .048*
Bilaterally absent PcomA 10 in 15 (66.7%) 4 in 11 (36.4%) .129
Note:—GA indicates gestational age.
* Statistically significant.
Table 4: Prevalence of anatomic variations of the CoW in a group
of 50 term-born infants (24 with normal MR imaging findings and 26
with abnormal MR imaging findings)
Term
(normal MRI)
Term
(abnormal MRI)
P
Value
Completeness of CoW 9 in 24 (37.5%) 11 in 26 (42.3%) .477
AcomA absence/hypoplasia 6 in 24 (25%) 6 in 26 (23.1%) .567
PcomA absence/hypoplasia 13 in 48 (27%) 18 in 52 (34.6%) .276
A1 segment of ACA absence/
hypoplasia
5 in 48 (10.4%) 1 in 52 (1.9%) .053*
P1 segment of PCA absence/
hypoplasia
4 in 48 (8.3%) 3 in 52 (5.7%) .455
Fetal-type origin of PCA 14 in 48 (29%) 12 in 52 (23%) .321
Transitional-configuration
origin of PCA
6 in 48 (12.5%) 5 in 52 (9.6%) .443
Bilateral fetal-type origin 8 in 14 (57.1%) 6 in 12 (50%) .512
Bilaterally absent PcomA 6 in 13 (46.2%) 14 in 18 (77.8%) .076
* Statistically significant.
AJNR Am J Neuroradiol 30:1955– 62 兩Nov-Dec 2009 兩www.ajnr.org 1959
a vascular-related abnormalities. There were, however, signif-
icant differences in the prevalence of some anatomic varia-
tions between the 2 groups (Table 6). More specifically, there
was significantly increased (P⫽.004) absence/hypoplasia of
the P1 segment of the PCA in the group with the vascular-
related abnormalities (18.8%) compared with the group with-
out them (3.2%). The absence of the A1 segment was seen
more often in the group with pathology (9.3%) compared
with the group without (2.5%), approaching but not reaching
significance (P⫽.09). Absence/hypoplasia of the PcomA,
however, was seen less often in the group with pathology (P⫽
.07). Prevalence for the other anatomic variations remained
similar between the 2 groups.
The most common anatomic variation in the group with
vascular-related abnormalities was the fetal-type origin of the
PCA (28.1%). The most common anatomic variation in the
group without vascular-related abnormalities was the ab-
sence/hypoplasia of the PcomA (33.3%).
Effect of Sex
There were no significant differences in CoW completeness or
prevalence of anatomic variations when comparing boys (n⫽
34) and girls (n⫽31) with normal MR imaging findings.
Overall, girls presented with more complete CoWs (45.2%)
than boys (38.2%), but this difference was not significant. The
prevalence of the AcomA absence/hypoplasia occurred almost
twice as often in term-born girls (37.5%) as in term-born boys
(18.8%), but this difference was not statistically significant.
Absence/hypoplasia of the PcomA was more common in pre-
term boys (38.9%) than in girls (26%). Absence/hypoplasia of
the A1 segment of the ACA was 4 times more frequent in boys
(7.4%) than in girls (1.6%). Absence/hypoplasia of the P1 seg-
ment of the PCA occurred twice as often in term-born girls
(12.5%) than in boys (6.3%).
Effect of Laterality (Left- or Right-Sided Prevalence)
There were generally no differences in laterality of the lateral-
ized anatomic variations, namely of absence/hypoplasia of the
A1 segment, P1 segment, and PcomA in infants with normal
MR imaging findings. However, there were twice as many left-
sided PCAs with a fetal-type origin (8 in 12 or 66.7%) as right-
sided ones (4 in 12 or 33.3%) in the term-born infants with
abnormal MR imaging findings. There was no correlation be-
tween the laterality of the parenchymal and vascular-related
abnormalities and the laterality of the anatomic variations
(P⫽.43).
Discussion
Reference values on the prevalence of the anatomic variations
of the CoW have been systematically described in a neonatal
population by using high-resolution MRA at 3T. The results
are in keeping with the adult literature and are within the
range cited in the adult studies.
3,22-24
These variations have
been examined in relation to prematurity, MR imaging abnor-
mality, vascular-related abnormality, sex, and laterality in
neonates.
Preterm infants had a higher, though not significantly so,
prevalence of a complete CoW and overall fewer anatomic
variations of the CoW compared with the term-born infants.
Similarly, more very preterm infants (50%), born at ⬍30
weeks’ GA, had a complete CoW compared with the moder-
ately preterm infants (36.8%). It is tempting to hypothesize
that this trend might reflect a well-instructed reaction (vascu-
lar remodelling) to protect the most potentially vulnerable
populations by maintaining adequate blood supply to their
brain. In keeping with these findings, term-born infants with
normal MR imaging findings had more anatomic variations of
the CoW, with significantly increased prevalence (P⫽.02) of
the absence/hypoplasia of the A1 segment.
The significantly increased prevalence (P⫽.04) of the bi-
lateral fetal-type origin of the PCA in preterm infants born
after 30 weeks’ GA matched with a decreased occurrence of the
transitional-type configuration may relate to the chronologic
order of the relative changes in metabolic demand in the fetal
brain. After 20 –21 weeks of gestation, there is a period of
accelerated growth of the occipital lobes, associated with in-
creasing metabolic demand.
7,25
Therefore, this increase in fe-
tal-type origins of the PCA with the relative decrease of the
transitional-type origins, in which all vessels appear to be of
Table 5: Prevalence of anatomic variations of the CoW in relation to MR imagingⴚdetected parenchymal abnormalities in a group of 29
infants (26 term-born and 3 preterm infants imaged at term)
Parenchymal Abnormalities
Complete
CoW
Fetal-Type
Origin of PCA
PcomA
Absence/Hypo
AcomA
Absence/Hypo
P1
Absence/Hypo
A1
Absence/Hypo
Abnormal signal intensity in basal ganglia (n⫽17)467421
Infarction (n⫽10) 243230
Loss of grey/white matter differentiation (n⫽3)022110
Hemorrhage (n⫽2) 101000
Periventricular cysts (n⫽2) 101000
Porencephalic cysts (n⫽1) 100000
Note:—Hypo indicates hypoplasia.
Table 6: Prevalence of anatomic variations of the CoW in relation
to vascular-related abnormalities in a group of 94 infants (16 with a
vascular-related abnormality and 78 without)
With
Vascular-Related
Abnormality
Without
Vascular-Related
Abnormality
P
Value
Completeness of CoW 7 in 16 (43.7%) 33 in 78 (42.3%) .564
AcomA absence/hypoplasia 4 in 16 (25%) 14 in 78 (17.9%) .364
PcomA absence/hypoplasia 6 in 32 (18.8%) 52 in 156 (33.3%) .075
A1 segment of ACA absence/
hypoplasia
3 in 32 (9.3%) 4 in 156 (2.5%) .097
P1 segment of PCA absence/
hypoplasia
6 in 32 (18.8%) 5 in 156 (3.2%) .004*
Fetal-type origin of PCA 9 in 32 (28.1%) 39 in 156 (25%) .432
Transitional-configuration
origin of PCA
3 in 32 (9.3%) 12 in 156 (7.7%) .487
* XXX.
1960 Malamateniou 兩AJNR 30 兩Nov-Dec 2009 兩www.ajnr.org
equal size, may be a response to this increasing metabolic
demand.
Sex and laterality did not influence the prevalence of the
anatomic variations in the neonatal population, and this was
in line with most of the adult literature.
3-5
Some studies, how-
ever, report an increased prevalence of anatomic variations on
the left side.
26
Most interesting, the comparison of the groups with and
without vascular-related abnormalities revealed that the ma-
jor cerebral arteries (A1, P1) were more often absent/hypo-
plastic in the affected group (P⫽.09 and 0.004, respectively).
This might not be surprising given the medical histories of
those infants. The PcomA, however, was more often present
(P⫽.07) in the affected group (infants with vascular-related
abnormality). This finding was similar to those in previous
adult studies in which there was a significantly higher percent-
age of entirely complete CoW in patients with internal carotid
artery obstruction compared with control subjects, with the
communicating arteries playing a major role in supplying by-
pass routes.
21,27
Nevertheless, the variety of the vascular-re-
lated abnormalities included in this subgroup (cerebral infarc-
tion, ROP, facial port-wine stain) makes it difficult to draw
any definitive conclusions at this stage. A larger scale study
focused on a specific cerebrovascular pathology could perhaps
offer more categoric results.
Vessel hypoplasia or absence may render the CoW non-
functional and leave the brain more exposed to a potential
blood-supply deprivation and, therefore, more prone to in-
jury. Several studies have explored the correlation between
certain types of CoW anatomic variations with a variety of
adult brain pathologies. It has been shown that hypoplasia or
absence of the PcomA in patients with angiographically
proved internal carotid artery occlusion is considered a risk
factor for ischemic stroke.
28,29
In our study, MR imaging ab-
normality did not generally correlate with the presence of an-
atomic variations, but A1 segment hypoplasia was more fre-
quently seen in infants with normal MR imaging findings,
whereas bilateral absence/hypoplasia of the PcomA was more
frequently seen in infants with MR imaging abnormality. It
was not possible to attribute MR imaging abnormality to a
poorly functioning CoW because a larger sample size with a
narrower definition of MR imaging abnormality would be re-
quired. Additionally, the etiology of vascular disorders such as
stroke occurring perinatally is often different from that in
adult.
The TOF MRA is adequately sensitive and specific for the
detection of the CoW vessels, but it does have its limitations.
Some of the vessels that cannot be seen with TOF MRA are not
truly absent or hypoplastic; they are just too small to be de-
tected, given the spatial resolution.
30,31
This study was per-
formed with a dedicated neonatal MRA protocol, in which the
acquired resolution was 0.6 ⫻0.6 ⫻0.6 mm
3
isotropic to
maximize the potential to visualize the small neonatal vessels
uniformly in all planes relative to the 0.80 ⫻0.80 ⫻1.20 mm
3
,
which has been used in corresponding adult studies.
3-5
With a
mean diameter of approximately 1 mm for the middle cerebral
arteries of our neonatal population,
18
it would be reasonable
to assume that the size of the communicating arteries would lie
at the limits of the acquired resolution. Therefore, the results
we report in this study are expected to underestimate slightly
the true prevalence of a complete CoW because some of the
smaller communicating arteries will be too small to be
detectable.
The physiologic significance and possible brain perfusion
effects of the differences in the prevalence of the anatomic
variations of the CoW between the preterm and term group
have yet to be determined. It remains unclear whether the
differences that we have observed between preterm and term
infants and in infants with vascular-related disease represent
cause or effect. Further longitudinal MRA studies could also
explore the dynamic nature of the completeness of the CoW
over the human lifespan and in response to different func-
tional demands.
Conclusions
The anatomic variations and completeness of the CoW have
been systematically studied in a group of 94 infants by using a
high-resolution dedicated neonatal protocol at 3T. The most
common anatomic variation was the absence of the PcomA,
accounting for 30% of the studied neonatal population. There
was no statistically significant difference between boys and
girls and left/right anatomic variations. Preterm infants im-
aged at term-equivalent age presented with more complete
CoWs and fewer anatomic variations than term-born infants.
This was statistically significant for the A1 segment (P⫽.02).
Similarly, preterm infants born at ⬍30-weeks’ GA had a more
complete CoW and a lower prevalence of anatomic variations
compared with those born after 30-weeks’ GA. Additionally,
infants with vascular-related abnormalities had more absent/
hypoplastic major arterial segments but fewer variations in the
communicating arteries, with the absence/hypoplasia of the
P1 seen more often in the group with pathology (P⫽.004).
Further studies are needed to explore the functional signifi-
cance of these findings in a neonatal population.
Acknowledgments
We acknowledge all the staff at the Department of Imaging
Sciences of the Hammersmith Hospital for their endless sup-
port. Also, we thank all the parents and children who made
this study possible.
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