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Diffuse Hyperechogenicity of
Basal Ganglia and Thalami in
Preterm Neonates: A Physiologic
Finding?1
ORIGINAL RESEARCH

Gerda van Wezel-Meijler, MD, PhD

Purpose: To elucidate whether echogenicity (EG) of the basal gan-
Lara M. Leijser, MD, MSc, PhD
glia and thalami (BGT) represents a physiologic phenom-
Francesca T. Wiggers-de Bruïne, MD
enon in preterm neonates (,32 weeks gestation).
Sylke J. Steggerda, MD
Jeroen van der Grond, PhD Materials and The study was approved by the medical ethics commit-
Frans J. Walther, MD, PhD Methods: tee, and informed consent was obtained from the parents.
Sequential neonatal cranial ultrasonographic (US) images
obtained in 130 preterm neonates were evaluated for EG
of the BGT. In 110 of the 130 neonates, MR imaging was
performed around or within the first months after term-
equivalent age to assess myelination and changes in BGT
signal. Cranial US studies obtained in 83 low-risk near-
term neonates were used for comparison.

Results: Diffuse homogeneous bilateral EG of the BGT was seen

in 120 (92%) of 130 preterm neonates and in seven (8%)
of 83 low-risk neonates (P , .001). In preterm neonates,
EG of the BGT faded with age and was no longer seen
1 month after delivery. This finding was associated with
frontal echodensity, which is a normal prematurity-related
cranial US phenomenon that occurs in the white matter
(P , .001). No association with changes on MR images
was found.

Conclusion: In preterm neonates, diffuse homogeneous EG of the BGT

is a frequent and normal prematurity-related finding.

q
RSNA, 2011

Supplemental material: http://radiology.rsna.org/lookup

/suppl/doi:10.1148/radiol.10101086/-/DC1

1
From the Departments of Pediatrics, Subdivision of
Neonatology (G.v.W., L.M.L., S.J.S., F.J.W.), and Radiology,
Subdivision of Neuroradiology (F.T.W., J.v.d.G.), Leiden
University Medical Center, PO Box 9600, J6-S, 2300 RC
Leiden, the Netherlands. Received June 3, 2010; revision
requested July 20; revision received August 31; accepted
September 23; final version accepted October 27. L.M.L.
supported by grant 920-03-388 from ZonMw, the Neth-
erlands Organisation for Health Research and Develop-
ment. Address correspondence to G.V.W.M. (e-mail:
G.van_Wezel-Meijler@lumc.nl ).

q
RSNA, 2011

944 radiology.rsna.org n Radiology: Volume 258: Number 3—March 2011

ULTRASONOGRAPHY: Diffuse Hyperechogenicity of the Basal Ganglia and Thalami
P
rematurity may be a risk factor
for abnormal development of the
basal ganglia and thalami (BGT)
(1). In addition, white matter injury,
which frequently occurs in infants born
prematurely, may affect growth and de-
velopment of the BGT (1–5). Injury and
deviant growth and development of the
BGT are associated with neurodevelop-
mental and visual impairments (1,5,6).
Echogenicity (EG) of the BGT region
is frequently seen on cranial ultrasono-
graphic (US) images obtained in preterm
neonates (7–9). In near-term neonates,
increased EG in this region usually indi-
cates hypoxic-ischemic injury (Figs 1, E1
[online]) and is associated with serious
neurologic sequelae; however, the origin
of EG of the BGT in preterm infants is
largely unclear (10,11). In a retrospec-
tive study, preterm infants with diffuse
bilateral EG of the BGT had a short-term
neurologic outcome similar to that of
infants without this finding. Thus, we
hypothesized that diffuse bilateral EG of
the BGT is a normal finding in this age
group, as opposed to increased EG of
BGT in near-term neonates (7).
The aim of this study was to deter-
mine whether EG of the BGT represents
a physiologic phenomenon in preterm
neonates (gestational age, ,32 weeks).
Materials and Methods
Patients
Preterm neonates admitted to our tertiary
neonatal unit between May 2006 and
Advances in Knowledge
n Diffuse echogenicity (EG) of the
basal ganglia and thalami (BGT) is
seen in more than 90% of preterm
neonates (,32 weeks gestation).
n Diffuse EG of the BGT is associated
with a normal prematurity-related
cranial US phenomenon in the white
matter (89%) and with normal MR
findings in the BGT (100%).
n In preterm neonates, EG of the
BGT is a normal prematurity-
related cranial US finding if it is
homogeneous, diffuse, and seen
before term-equivalent age.
Radiology: Volume 258: Number 3—March 2011
October 2007 were eligible for inclusion
in a prospective neuroimaging study in
which we compared serial high-quality
cranial US findings obtained throughout
the neonatal period with findings from
a 3-T magnetic resonance (MR) imag-
ing examination, preferably performed
around term-equivalent age (12). The
study was approved by the medical eth-
ics committee, and informed consent
was obtained from the parents. Exclu-
sion criteria were congenital anomalies
of the central nervous system (n = 3),
other severe congenital anomalies (n = 0),
chromosomal and metabolic disorders
(n = 0), and neonatal meningitis (n = 0).
We included 130 preterm neonates
in this study. In nine neonates, informed
consent was obtained for serial cranial
US but not for MR imaging; in six, MR
images could not be reliably assessed
because of technical problems (move-
ment artifacts or deviant MR imaging
protocol). An additional five neonates
died before MR imaging could be per-
formed. All neonates underwent serial
cranial US throughout the neonatal pe-
riod; in 110, contemporaneous cranial US
and MR images suitable for assessment
could be obtained around or shortly after
term-equivalent age.
Cranial US
As part of routine care, sequential cra-
nial US was performed in all neonates
born prematurely. In addition, in low-
risk neonates born between November
2009 and March 2010, at least one cra-
nial US examination was performed within
2 days after birth in all 83 neonates
Implications for Patient Care
n Diffuse homogeneous EG of the
BGT should be regarded as a
normal phenomenon in preterm
neonates before term-equivalent
age.
n Apart from the normal standard
of care, including neuroimaging
and neurologic follow-up needed
in this high-risk patient group,
presence of diffuse homogeneous
EG of the BGT does not warrant
additional investigation.
n radiology.rsna.org
Wezel-Meijler et al
admitted to the medium care unit of
our neonatal ward. Neonates were ad-
mitted for the following reasons: pre-
term birth (gestational age, 35–37 weeks),
short-term antibiotic treatment for sus-
pected infection with negative cultures,
hyperbilirubinemia in need of photo-
therapy, and small size for gestational
age.
In the preterm neonates, serial
cranial US was performed at least weekly
from the day of birth until discharge or
transfer to another hospital and again
around term-equivalent age. Weekly cra-
nial US examinations were performed by
a research physician (L.M.L., 4 years
of experience) or neonatologist (S.J.S.,
G.v.W.; 5 and 20 years of experience,
respectively). The other cranial US
examinations were performed by at-
tending (fellow) neonatologists with at
least 2 years of experience. In the low-
risk neonates, a medical student per-
formed cranial US after undergoing
4 weeks of training. When the medical
student experienced problems obtaining
high-quality cranial US images, one of
the aforementioned neonatologists per-
formed cranial US examinations. For all
cranial US examinations, an Aloka a10
scanner with a multifrequency trans-
ducer (Biomedic Nederland, Almere,
the Netherlands) was used. Scanning
was performed in the coronal and
sagittal planes by using the anterior
Published online before print
10.1148/radiol.10101086
Radiology 2011; 258:944–950
Abbreviations:
BGT = basal ganglia and thalami
EG = echogenicity
Author contributions:
Guarantors of integrity of entire study, G.v.W., L.M.L., F.T.W.,
F.J.W.; study concepts/study design or data acquisition
or data analysis/interpretation, all authors; manuscript
drafting or manuscript revision for important intellectual
content, all authors; manuscript final version approval, all
authors; literature research, G.v.W., L.M.L., F.T.W., S.J.S.,
F.J.W.; clinical studies, G.v.W., L.M.L., S.J.S., J.v.d.G.;
statistical analysis, L.M.L., S.J.S., J.v.d.G.; and manuscript
editing, all authors
Potential conflicts of interest are listed at the end
of this article.
945
ULTRASONOGRAPHY: Diffuse Hyperechogenicity of the Basal Ganglia and Thalami Wezel-Meijler et al

fontanel as the acoustic window and Figure 1

multifrequency probes (5–10 MHZ) with
the standard image frequency set at
7.5 MHz. Images of at least six coronal
and five sagittal planes and of each (sus-
pected) abnormality were digitally re-
corded. For more reliable detection of
abnormalities in the occipital areas and
posterior fossa, the posterior and mas-
toid fontanels, respectively, were used as
acoustic windows (13).
Cranial US findings and reliability
of cranial US in the detection of white
matter injury in this cohort of preterm
neonates were published separately (12,
14). Cranial US images were assessed
by at least two investigators in consen- Figure 1: (a) Coronal and (b) parasigittal cranial US images of a full-term male neonate with hypoxic-
sus (L.M.L. with G.v.W. or S.J.S.). All ischemic encephalopathy obtained on the 2nd day of life show increased EG of the basal ganglia
cranial US images were assessed for (long arrows) and thalamus (short arrow).
abnormalities in the ventricular system,
white matter, cortical and deep gray mat-
ter, and cerebellum. Figure 2
In full-term neonates, the basal gan-
glia (caudate nucleus, putamen, globus
pallidus) and thalami have an EG simi-
lar to that of the surrounding white
matter and cannot be distinguished as
separate structures (Fig 2). For this part
of the study, special attention was paid
to the BGT, and EG changes in this area
were recorded. EG of the BGT was con-
sidered present if at least one cranial
US examination revealed EG of the BGT
or areas within the BGT was increased
compared with EG of surrounding white
matter on both coronal and sagittal im-
ages. EG of the BGT was described as
diffuse or focal, homogeneous or inho-
mogeneous, and unilateral or bilateral.
Figure 2: (a) Coronal and (b) parasigittal cranial US images of a full-term male neonate obtained on the
We recorded whether EG was seen in
2nd day of life show normal BGT. The basal ganglia and thalami cannot be distinguished as
the basal ganglia, thalami, or both (Figs 3,
separate structures.
E2 [online]). Lenticulostriate vascul-
opathy, seen as a punctate or linear
echogenic structure in the distribution and abnormalities in the posterior fossa— age, MR imaging was postponed until
of thalamostriate vessels, was not con- were noted. 44–56 weeks postmenstrual age depend-
sidered EG of the BGT (Figs 4, E3 [on- ing on the clinical condition.
line]) (15). Postnatal and postmenstrual MR Imaging All MR examinations included the
age at first and last detection of EG of MR examinations were performed pref- following: (a) a three-dimensional T1-
the BGT and its evolution and duration erably around term-equivalent age (40– weighted turbo field-echo sequence (rep-
were recorded. 44 weeks postmenstrual age) according etition time msec/echo time msec, 9.7/
Cranial US abnormalities—including to a standard protocol with a 3-T MR 4.6; flip angle, 8°; turbo factor, 128),
nonphysiologic echodensities in the system (Philips Achieva; Philips Medi- enabling reconstructions in each de-
periventricular white matter, cystic white cal Systems, Best, the Netherlands), as sired plane; (b) a T2-weighted turbo
matter lesions, periventricular hemor- recently described (16). For neonates spin-echo sequence (6269/120; turbo
rhage, intraventricular hemorrhage, who were unstable, ventilator depen- factor, 18); (c) a diffusion-weighted se-
posthemorrhagic ventricular dilatation, dent, or both around term-equivalent quence (spin-echo echo-planar imaging;

946 radiology.rsna.org n Radiology: Volume 258: Number 3—March 2011

ULTRASONOGRAPHY: Diffuse Hyperechogenicity of the Basal Ganglia and Thalami Wezel-Meijler et al

Figure 3 Figure 4

Figure 4: Parasagittal cranial US image of a preterm

Figure 3: Cranial US images of a preterm male neonate (gestational age, 25 weeks 6 days) obtained at female neonate (gestational age, 27 weeks 5 days)
postmenstrual age 26 weeks. (a) Coronal image obtained at the level of the frontal horns of the lateral ven- obtained at postmenstrual age 31 weeks 5 days
tricles and basal ganglia. (b) Parasagittal image obtained through the left lateral ventricle. The basal ganglia shows lenticulostriate vasculopathy (arrow).
(long arrows) show diffuse homogeneous EG that is more prominent than that in the thalami (short arrow).
This finding, as well as a large bulky choroid plexus (as shown on b), should be considered normal in preterm
neonates before they reach term-equivalent age. because of congenital anomalies of the
central nervous system. Median ges-
2406/64; b value, 1000 sec/m2); and (d) Statistical Analysis tational age and birth weight were 29.0
a diffusion-tensor sequence (spin-echo Statistical analysis was performed with weeks (range, 25.6–31.9 weeks) and 1141 g
echo-planar imaging; 7456/54; b value, statistical software (SPSS, version 16.0; (range, 520–1960 g), respectively.
1000 sec/mm2; echo planar imaging fac- SPSS, Chicago, Ill). Incidences of EG of In all 130 neonates, sequential cranial
tor, 56). All sequences were performed the BGT and other changes on cranial US scans (median, eight scans; range,
in transverse planes with a 180 3 US images and of changes in BGT on four to 22 scans) were performed during
230 mm field of view. Section thick- MR images were calculated. Associa- admission. In 25 neonates, fewer than
ness was 1 mm for T1-weighted imag- tions between EG of the BGT and other five cranial US scans were performed be-
ing and 2 mm for T2-, diffusion-tensor, changes on cranial US images and BGT cause of early transfer to another hospi-
and diffusion-weighted imaging, all with- changes on MR images were assessed tal. In 110 neonates (65 male), contem-
out an intersection gap. by using a Pearson x2 test. Associations poraneous cranial US and MR imaging
In this part of the study, T1- and between EG of the BGT and continu- were performed at a median postmen-
T2-weighted images were assessed by ous variables (gestational age and birth strual age of 43.4 weeks (range, 40.1–
at least two investigators in consen- weight) were assessed by using an un- 55.9 weeks) (Fig 5). MR imaging was
sus (F.T.W., pediatric neuroradiologist paired t test. P ⱕ .05 indicated a signifi- performed around term-equivalent age
with more than 15 years of experience; cant difference. (40–44 weeks postmenstrual age) in 69
L.M.L. or S.J.S., 5 years of experience neonates and after term-equivalent age
with neonatal MR imaging) who were but before 4 months postmenstrual age
blinded to cranial US findings. For the Results in the remaining 41 neonates.
latter two investigators, the interval
between performing cranial US exami- Patients Cranial US
nations and assessing MR images was at A total of 182 preterm neonates were In 120 (92%) of 130 preterm neonates,
least 6 weeks. Abnormalities were noted. eligible for inclusion in this neuroimag- EG of the BGT was seen on sequential
Special attention was paid to the BGT. ing study, and 130 (80 male) were in- cranial US images obtained during ad-
Signal intensity changes in the BGT were cluded (Fig 5). Reasons for not obtain- mission. This was bilateral and diffuse
recorded, if present, and were described ing informed consent were transfer to in all 120 neonates (Table, Fig 3). Median
as diffuse or focal and unilateral or bi- another hospital or death shortly after gestational age and birth weight were
lateral. Myelination in the BGT and in- birth (n = 10), parents declined partici- 28.8 weeks (range, 25.6–31.9 weeks) and
ternal capsula on T1-weighted images was pation (n = 23), and practical problems 1100 g (range, 520–1960 g), respectively,
assessed and compared with that on (language barrier and travel distance) in neonates with EG of the BGT and
reference images (17–19) (Fig E4 [online]). (n = 16). Three neonates were excluded 31.2 weeks (range, 29.9–31.9 weeks) and

Radiology: Volume 258: Number 3—March 2011 n radiology.rsna.org 947

ULTRASONOGRAPHY: Diffuse Hyperechogenicity of the Basal Ganglia and Thalami Wezel-Meijler et al

Figure 5
Incidence and Characteristics of EG
of the BGT as Seen on Sequential
Cranial US Images Obtained during
Admission and around Term-
equivalent Age
Characteristic Finding

Admission
Total 120/130 (92)
Appearance
Diffuse 120/120 (100)
Focal 0/120 (0)
Homogeneous 120/120 (100)
Inhomogeneous 0/120 (0)
Side
Unilateral 0/120 (0)
Bilateral 120/120 (100) Figure 5: Flow chart shows the number of neonates who were eligible for the study, who
Seen at first postnatal 98/120 (82) were included in the study, who were excluded from the study, and who underwent sequential
cranial US scan cranial US and MR imaging around term-equivalent age ( TEA).
First seen*
Postnatal age (d) 1 (0–12)
Postmenstrual age (w) 29.0 (25.6–32.6)
neonates (P , .001). EG of the BGT two [20%] of 10 neonates, P = .72), pos-
Last seen* was never seen in low-risk neonates born themorrhagic ventricular dilatation (21
Postnatal age (d) 41 (0–110) after 40 weeks of gestation (n = 13). [18%] of 120 neonates vs none [0%] of
Postmenstrual age (w) 33.6 (27.0–44.1) Preterm neonates with EG of the 10 neonates, P = .36), and abnormali-
Duration (d)† 40 (1–110) BGT had physiologic frontal echodensities ties in the posterior fossa (10 [9%] of
Around Term- at admission significantly more often 111 neonates vs one [11%] of nine neo-
equivalent Age than did preterm neonates without EG nates, P = .68). There was no association
Total 19/110 (17) of the BGT (107 [89%] of 120 neonates between EG of the BGT and changes
vs three [30%] of 10 neonates, P , .001). in BGT on MR images (none [0%] of
Note.—Unless otherwise indicated, data are numbers of
patients, and data in parentheses are percentages.
Neonates with EG of the BGT that was 101 neonates vs none [0%] of nine neo-
* Data are median ages, with ranges in parentheses.
still present around term-equivalent age nates, P . .99).
†
Datum is median duration, with the range in parentheses.
had other periventricular echodensi-
ties during admission (19 [100%] of MR Imaging
19 neonates vs 69 [76%] of 91 neonates, Signal intensity in the BGT was normal
1488 g (range, 585–1880 g), respectively, P = .02) and frontal echodensities still in all neonates. Myelination in BGT and
in neonates without EG of the BGT; the present around term-equivalent age (eight internal capsule appeared normal in all
difference in gestational age between [42%] of 19 neonates vs six [7%] of neonates, both those with and those
the groups was significant (P , .001). 91 neonates, P , .001) significantly more without EG of the BGT, as compared
EG of the BGT gradually faded with age often than did neonates who did not with reference images (17–19) (Fig 5).
(Fig 6). In 19 (17%) of 110 neonates in have EG of the BGT that was still pres-
whom cranial US images were obtained ent around term-equivalent age. In most
around or within 4 months after term- preterm neonates (those with and those Discussion
equivalent age, EG of the BGT was still without EG of the BGT), cranial US Our prospective study on imaging find-
seen at that time; however it was never abnormalities—which are frequently en- ings in the deep gray matter included
seen after 44 weeks postmenstrual age. countered in preterm neonates—were sequential cranial US performed through-
Median gestational age and birth seen. There was no significant association out the neonatal period and MR imag-
weight of low-risk neonates were 38 weeks between EG of the BGT and nonphysi- ing performed once in a large cohort
(range, 35.3–41.7 weeks) and 3075 g ologic echodensities in the periventricu- of unselected preterm neonates and re-
(range, 1970–4970 g), respectively. EG lar white matter (97 [81%] of 120 neo- vealed EG of the BGT in 120 (92%) of
of the BGT was seen in seven (8%) of nates vs nine [90%] of 10 neonates, P = 130 preterm neonates. This finding was
83 low-risk neonates with a median ges- .69), cystic white matter lesions (nine present on the first postnatal cranial
tational age of 38.4 weeks and a birth [8%] of 111 neonates vs one [11%] of US image in most neonates and within
weight of 3145 g. The incidence of nine neonates, P = .56), periventricular 1 week after birth in all neonates; EG of
EG of the BGT differed significantly be- hemorrhage and intraventricular hem- the BGT was bilateral and diffuse in all ne-
tween preterm neonates and low-risk orrhage (35 [29%] of 120 neonates vs onates and was generally most prominent

948 radiology.rsna.org n Radiology: Volume 258: Number 3—March 2011

ULTRASONOGRAPHY: Diffuse Hyperechogenicity of the Basal Ganglia and Thalami
Figure 6
Figure 6: Graph shows relation between incidence of EG of the
BGT and postmenstrual age (PMA) at cranial US (cUS) in
130 preterm infants.
in the basal ganglia. This incidence is
considerably higher than that reported
previously (7,8). This difference in in-
cidence can be explained by the fact
that we studied a relatively homogeneous
cohort of unselected preterm neonates
(,32 weeks gestation only) and that
we used advanced US equipment and
techniques, enabling more reliable de-
tection of subtle changes.
EG of the BGT gradually faded, and
its incidence decreased as gestational age
increased. It was still seen around term-
equivalent age in only 19 (17%) of 110
neonates and in none of the neonates at
44 weeks postmenstrual age. EG of the
BGT was seen in only seven (8%) of 83
low-risk near-term neonates.
Our current findings on the evolution
of EG of the BGT are consistent with
previous findings. EG of the BGT was
related to lower gestational age (P , .001),
a finding that was consistent with find-
ings of previous studies (7,8). We found
a significant association with physiologic
frontal echodensities (P , .001), which
are also frequently seen in preterm neo-
nates, gradually fade as postmenstrual
age increases, and are generally no lon-
ger present more than 1 month post-
term (20,21). On MR images obtained
around or within a few months after
term-equivalent age, no equivalent was
Radiology: Volume 258: Number 3—March 2011
found for EG of the BGT. In all neo-
nates with EG of the BGT, the BGT had
a normal appearance on MR images,
and myelination appeared appropriate
for postmenstrual age.
This combination of results, includ-
ing the high incidence of EG of the BGT
in preterm neonates compared with the
low incidence of EG of the BGT in near-
term low-risk neonates, the fading of
EG of the BGT with age, the associa-
tion with a physiologic cranial US phe-
nomenon in the white matter, and the
absence of MR abnormalities supports
our hypothesis that EG of the BGT, if
diffuse, homogeneous, and bilateral, is
a prematurity-related normal matura-
tional phenomenon. It can be hypoth-
esized that the echogenic appearance of
the BGT results from a relative differ-
ence in EG between the immature deep
gray matter and white matter and is
related to differences in water content,
myelination, or both. The immature white
matter is not yet myelinating during the
early preterm period and has a high
water content, while myelination in the
BGT starts at the beginning of the third
trimester of pregnancy (19). The echo-
genic appearance may also be related
to differences in cell content and/or den-
sity of fibers between the immature deep
gray matter and white matter.
n radiology.rsna.org
Wezel-Meijler et al
EG of the BGT still present around
term-equivalent age in preterm neonates
was associated with echodensities in
the periventricular white matter dur-
ing admission and persistence of frontal
echodensities, suggesting that persis-
tence of EG of the BGT beyond term-
equivalent age reflects abnormal or de-
layed maturation.
Our study had some limitations. First,
in several preterm neonates, early trans-
fer to local hospitals limited the number
of cranial US scans performed. Thus, it
was not always possible to assess the
exact duration of EG of the BGT and
study the evolution over time. Second,
MR imaging was performed around or
after term-equivalent age when EG of
the BGT was no longer visible in the ma-
jority of neonates. Thus, transient MR
changes within the BGT could not be
excluded. In addition, MR imaging was
not performed in low-risk neonates. We
did, however, study a large number of
preterm neonates. The BGT appeared
completely normal on MR images in all of
them, and EG of the BGT was associated
with a normal maturational phenome-
non in the white matter. Thus, we believe
that this finding is normal in preterm ne-
onates, at least before term-equivalent
age. Third, we compared myelination
as depicted with 3-T MR imaging with
historical data on myelination obtained
with lower field strengths (17–19). So
far, it is not known whether myelina-
tion is depicted earlier or better with
higher field strengths. Thus, we may
have missed subtle delays in myelination.
Another limitation was that cranial US
examinations in the near-term control
group were performed by a medical
student. Although this student was spe-
cially trained, her experience was lim-
ited. This may have influenced quality
of cranial US images in the control group.
Finally, we have no information on the
neurologic outcome of this cohort of
preterm neonates. Follow-up studies,
including standard neurologic exami-
nations, visual assessments, and devel-
opmental tests, in this population are
ongoing.
In conclusion, diffuse homogeneous
EG of the BGT is a frequent and normal
prematurity-related cranial US finding in
949
ULTRASONOGRAPHY: Diffuse Hyperechogenicity of the Basal Ganglia and Thalami
preterm neonates. If seen before term-
equivalent age, it should be regarded
as a physiologic phenomenon that does
not warrant additional investigation.
Acknowledgments: We are grateful to S. Martens,
neonatologist; the staff of the pediatric ambu-
latory unit; the MR imaging department of the
Leiden University Medical Center; and B. van
Kooij, University Medical Center Utrecht, for
helpful contributions to this project. We thank
M. de Waard, medical student, for perform-
ing cranial US scans in low-risk neonates and
W. Teeuwisse for technical support.
Disclosures of Potential Conflicts of Interest:
G.v.W. Financial activities related to the present
article: institution received a grant from ZonMw,
the Netherlands Organisation for Health Re-
search and Development. Financial activities not
related to the present article: none to disclose.
Other relationships: none to disclose. L.M.L. Fi-
nancial activities related to the present article:
received a grant from ZonMw, the Netherlands
Organisation for Health Research and Develop-
ment. Financial activities not related to the pres-
ent article: none to disclose. Other relationships:
none to disclose. F.T.W. No potential conflicts of
interest to disclose. S.J.S. No potential conflicts
of interest to disclose. J.v.d.G. No potential con-
flicts of interest to disclose. F.J.W. No potential
10. Eken P, Jansen GH, Groenendaal F, Rade-
conflicts of interest to disclose.
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