Placenta 28, Supplement A, Trophoblast Research, Vol.

21 (2007) S14eS22

In Utero Imaging of the Placenta: Importance for

Diseases of Pregnancy
J.S. Abramowicz a,*, E. Sheiner a,b
a
Department of Obstetrics and Gynecology, Rush University, 1653 West Congress Parkway, Chicago, IL 60612, USA
b
Department of Obstetrics and Gynecology, Soroka University Medical Center,
Ben Gurion University of the Negev, Beer-Sheva, Israel
Accepted 9 February 2007

Abstract

Maurice Panigel demonstrated by X-rays, almost 40 years ago, placental maternal blood jets in non-human primates. Although to researchers
the importance of the placenta is evident, in clinical obstetrical imaging, the fetus takes precedence. The placenta is imaged almost as an after
thought and mostly to determine its location in the uterus. In animal species, the placenta was imaged with techniques which would be consid-
ered too invasive (or too costly for routine use) in humans, many pioneered by Panigel: radioangiography, radioisotopes scintigraphy, thermog-
raphy, magnetic resonance imaging (MRI) and spectroscopy, positive emission tomography (PET) and single photon emission computed
tomography (SPECT). Ultrasound allows for detailed, and, as far as is known, safe analyses of not only placental structure in the human but
also its function. Earlier, only 2-dimensional grey-scale was available and more than 20 years ago, placental grading was popular. Later, colour
imaging and spectral Doppler analysis of blood velocity both in the umbilical artery and within the placenta as well as the uterus and fetal vessels
became essential and, more recently, the use of ultrasound contrast agents has been described, albeit not yet in a clinical setting. Three-
dimensional ultrasound permits evaluation of the placenta in several planes, more precise depiction of internal vasculature as well as more
accurate volume assessment. Several medical disorders of the pregnant woman or her fetus begin or end in the placenta, and ultrasound is
the optimal investigation method. Obvious examples include pre-eclampsia and other forms of hypertension in pregnancy, less than optimal fetal
growth (i.e. intrauterine growth restriction), triploidy (and its placental manifestation: partial mole), non-immune hydrops as well as several
infectious processes. Ultrasound is also particularly suited to evaluate specific placental conditions, such as abnormal placentation (placenta
previa and accreta for instance), gestational trophoblastic disease and placental tumors (e.g. chorioangioma).
Ó 2007 Published by IFPA and Elsevier Ltd.

Keywords: Placenta; Ultrasound; Pregnancy; Fetalematernal circulation; Pre-eclampsia

1. Introduction years, arguments continued regarding the purely fetal versus

The notion of placental circulation dates from Antiquity. At
the end of the first century AD, Soranus of Ephesus, in his
‘‘Treaty of women illnesses’’, described the chorion, amnion
and the cord, containing 4 vessels and a urinary channel [1].
At the time and for many years to come, approximately the
middle of the 16th century in fact [2], maternal and fetal cir-
culations were thought to be continuous. Over the ensuing
* Corresponding author. Tel.: þ1 312 942 9428; fax: þ1 312 942 6606.
E-mail address: jacques_abramowicz@rush.edu (J.S. Abramowicz).
shared origin of the placenta and the timing of the connection
between the two systems (see historical perspectives [3,4]).
The question of exactly when is the actual uteroplacental cir-
culation established, posed by Ramsey and Donner [5] is still
debated [6,7].
Many imaging techniques have been used in the last
50 years [8], culminating in ultrasound and all its modalities:
starting with regular B-mode [9], spectral [10,11], power,
also known as energy or colour angio [12] and colour Doppler
[13], 3D/4D [14,15] and, more recently, ultrasound contrast
agents [16]. These have allowed in situ observation of the

0143-4004/$ - see front matter Ó 2007 Published by IFPA and Elsevier Ltd.
doi:10.1016/j.placenta.2007.02.004
 J.S. Abramowicz, E. Sheiner / Placenta 28, Supplement A, Trophoblast Research, Vol. 21 (2007) S14eS22
placenta and have elucidated in part some of the long-standing
questions on the aetiology of several gestational conditions,
such as pre-eclampsia and intrauterine growth restriction
(IUGR). In this review, some facts on placental implantation
will be detailed as well as past, present and future imaging
modalities and their importance in diagnosing or predicting
pregnancy complications. Some of these complications will
be discussed, more from the imaging standpoint that in
detailed clinical aspects.
2. Placental development
While a detailed analysis of maternalefetal communica-
tions is well beyond the scope of this article, some details
may be helpful in understanding the aetiology of certain preg-
nancy conditions, their manifestations in the placenta and the
contribution of imaging techniques in interpreting changes oc-
curring as a result of these situations. Anomalies on the mater-
nal side, rather than the fetal side are, generally, at the origin
of later pathological conditions. The interested reader is re-
ferred to a recently published excellent discussion of implan-
tation, trophoblastic invasion and remodelling changes
occurring in the uterine spiral arteries [17].
Invasion of the myometrium (maternal tissue) by the tro-
phoblast (fetal origin) has traditionally been described as
occurring in two phases: first (up to 12 weeks) and early
second (12e16 weeks) trimesters [18]. More recently, this
process has been depicted as progressive rather than biphasic
[19], although there does not seem to be absolute certainty re-
garding one or the other [17]. This trophoblastic invasion
transforms the normally coiled uterine spiral arteries into
open and straight vessels, causing resistance to fall dramati-
cally in the uterine arteries, as can be demonstrated with spec-
tral Doppler [20]. Abnormal placentation may allow either
lower levels of O2 with resulting villous hypervascularisation,
as seen in pre-eclampsia or higher than normal levels with ab-
normal branching and fetal growth restriction [21,22]. If, on
the contrary, the capillary obliteration is incomplete, excessive
entry of maternal blood at a very early stage inside the devel-
oping placenta results in oxidative stress and subsequent de-
generation of villous tissue [23]. Documentation of blood
flow in the intervillous space in cases of first-trimester miscar-
riage by colour Doppler is useful in the prediction of success
or failure of expectant management [24]. Premature and dif-
fuse onset of intervillous blood flow can be detected by
grey-scale and colour imaging and confirmed by spectral
Doppler. This abnormal blood flow pattern may increase the
oxidative stress on the early placental tissue, subsequently im-
pair placental development and is often associated with early
pregnancy failure [25]. The continuing invasion (referred to
by some as the second invasion phase) may occur as late as
20e24 weeks. Spiral arteries are widely open, resulting in
a further drop in the impedance in the uterine arteries and
a major increase in the end-diastolic velocity, as documented
by Doppler velocimetry [20]. Both syncytiotrophoblast and cy-
totrophoblast growth, development and invasion are regulated
by an apoptosis cascade within the villous trophoblast [26].
S15
This cascade is active in the earlier stages of trophoblastic inva-
sion and becomes reactivated several weeks later. Derangement
in the cascade (upregulation) and abnormal secondary invasion
is thought by most to be the phenomenon at the origin of pre-
eclampsia. If severe, it can also be responsible for early miscar-
riages while, if less severe, it may induce other pathological
conditions, such as IUGR [19,26]. Extravillous trophoblast ap-
optosis, however, has been found to be reduced in pre-eclampsia
[27]. In 75e90% of cases of ‘‘placenta-induced’’ IUGR, uterine
artery will demonstrate abnormal Doppler velocimetry [24,27].
Endothelial dysfunction too is involved in the process of abnor-
mal placentation in pre-eclampsia and IUGR [26,29]. Abnormal
uterine artery Doppler velocimetry is observed in most cases of
early onset pre-eclampsia and IUGR, in association with labora-
tory signs of endothelial dysfunction and less in late-onset pre-
eclampsia where such dysfunction is not observed [28].
3. Imaging technologies
There is a large variety of techniques for placental imaging,
many of them pioneered by Panigel in animal imaging, such as
radioisotope scintigraphy, thermography and magnetic reso-
nance imaging with gadolinium [8]. Some early technologies
were used in animals with variable degrees of success but
less in humans, in some cases because of concerns for safety
of the fetus. Presently ultrasound and, to a much lesser extent,
magnetic resonance imaging, are the options of choice for im-
aging of the placenta in health and disease. In the future, the
use of ultrasound contrast agents will, undoubtedly, bring fur-
ther understanding to placental implantation process and
physiopathology.
3.1. Early technologies (for more details
and references, see [8])
These have been used successfully as a placental imaging
technique but mostly in animal and laboratory setups because
they are far too invasive for human studies: conventional
X-rays, particularly angiography, with injection of contrast
agents; computer-assisted tomography; radionuclide scintigra-
phy to localise implantation, study haemodynamics and diag-
nose placenta previa; thermography; magnetic resonance
imaging and its variations, such as microscopic MR, MR angi-
ography, particularly with gadolinium DTPA, MR spectros-
copy; and positron emission tomography (PET) which
allows analysis of materno-fetal transport and placental blood
volume. Some, if not most of these methods (except MR) are
contraindicated in the pregnant human and have essentially
been replaced by ultrasound.
3.2. Where are we now?
3.2.1. Ultrasound
Ian Donald is credited with the first publication, in 1958, in
the Lancet, on the use of ultrasound in abdominal masses, Since
then, its use has burgeoned to a point that virtually every preg-
nant woman who receives prenatal care will have, at least, 1
S16 J.S. Abramowicz, E. Sheiner / Placenta 28, Supplement A, Trophoblast Research, Vol. 21 (2007) S14eS22
(and, often, many more) ultrasound scans. Ultrasound imaging
has an excellent record of safety in pregnancy and it has rapidly
supplanted all other techniques used to study human pregnancy
in general and the placenta in particular. Conventional B-mode
ultrasound can give information on the general appearance of
the placenta and its location but none on its function [9]. In com-
bination with colour flow imaging, it permits direct visualisation
of placental vasculature which can then be interrogated by spec-
tral Doppler to obtain in vivo functional assessment of both ute-
roplacental and fetoplacental circulations in health and disease
with correlation with placental histomorphology [30e34]. In
1977, the first description of ‘‘noninvasive measurement of
human fetal circulation using ultrasound.’’ with continuous
Doppler was published [35]. The Doppler principle was applied
earlier to placental flow [10] but without the discrimination that
Fitzgerald and Drumm brought [35]. Studies of early placental
physiology are possible. The question of when does maternal-
fetal circulation establishes itself can, thus, be addressed
[6,7,33]. Some authors maintain that it is present since the ear-
liest stages of gestation [36]. Others uphold that there is no inter-
villous flow in the first trimester and that actual circulation
begins only around 10e12 weeks [37]. If earlier connection
occurs, this is pathological [23]. It has been reported that the pla-
centa appears hypervascular in pregnancies destined to miscarry
[13,24]. Improving technologies, such as the use of contrast
agents (vide infra) may allow better observation of the very early
placental circulation, as proposed by Jauniaux in an excellent
editorial [38]. Physiopathology of the placenta later in preg-
nancy is clearer.
Abnormal placental development, as expressed by increased
ultrasonographic placental thickness [39,40] and morphologic
characteristics and abnormal uterine Doppler velocimetry, is
associated with subsequent abnormal fetal growth or hyperten-
sive disorders of pregnancy [29,41]. Blood flow indices (ratio
of systolic to diastolic velocity [S/D] or combination thereof,
such as resistive [S-D/S] and pulsatility indices [S-D/mean])
diminish as pregnancy progresses, both in the maternal (uter-
ine) and fetal (umbilical artery) circulations, a sign of in-
creased vascularity in the placenta [20,30,41]. When certain
complications occur, either because of or associated with in-
creased placental resistance, the indices are elevated [31,42].
Correlation between abnormal indices and placental morpho-
pathology has been documented [31]. As previously described,
in normal development, secondary to trophoblastic invasion,
resistance is greatly reduced in the uterine and umbilical ar-
teries [17]. Therefore, in general, after 20e22 weeks’ gesta-
tion, profuse end diastolic velocity should be displayed in
spectral Doppler of both circulations. Decreased end-diastolic
velocity and presence of an early diastolic notch are signs of
increased resistance and predict the onset of pre-eclampsia or
IUGR [19,43,44]. Prognosis for the fetus is much worse with
absent or reverse end-diastolic velocity in the umbilical artery
[32,45], a sign of extremely elevated placental vascular resis-
tance because of vessel obliteration by the disease process
[46]. It is interesting to note that placental vascular disease,
as determined by Doppler analysis has been associated with
a fetal inflammatory response, also expressed by increased
cytokine [47]. Because of placental reserves, the signal in the
umbilical artery can still be normal, although placental disease
is advanced. This is why certain authors recommend analysis
of the internal placental vessels, in addition to, or even rather
than, the umbilical artery [48,49]. Intraplacental blood flow
determination was more sensitive than umbilical artery blood
flow in detecting abnormal umbilical-placental flow imped-
ances as manifested by the presence of IUGR [48]. This takes
several forms: colour Doppler, power (also known as energy)
Doppler and colour velocity imaging (CVI). While colour
Doppler is based on a frequency change, power Doppler is
based on an amplitude changes, hence is more sensitive and
thus offers better imaging of slow flow but is non-directional.
This allows visualisation of details of the villous tree, as soon
as the first trimester [50]. Abnormal (decreased) invasion by
the trophoblast can be observed [51]. Several conditions
have thus been studied, IUGR in particular with correlation
between the clinical picture and a reduced number of detect-
able intraplacental tertiary-stem villi arteries and branches
[52]. With CVI, the position of a group of erythrocytes is re-
corded with an ultrasound beam. A second beam is emitted
a few moments later to verify the new position of the cells,
thus calculating flow velocities. The two most investigated
pregnancy conditions, most particularly with Doppler are
pre-eclampsia [28,34] and IUGR [43,52]. In IUGR, Doppler
permits close follow-up of fetal well-being since there appears
to be a sequence of events with changes in different vascular
beds associated with worsening health status [53,54]. Al-
though it has been analyzed much less than the arterial
beds, the venous system appears to be very important in pre-
dicting acidebase fetal status when arterial Doppler shows
elevated resistance [55].
A relatively new application of ultrasound is three-dimensional
reconstruction (3D) and its expansion, real-time 3D or 4D ultra-
sound. Combination of 3D with colour and Doppler permit
amazing representation of the vascular tree, a method often re-
ferred to as 3D power colour angio and described both in normal
pregnancies [15] as well as numerous pathologies [14,15,56].
Placental volume is easier to estimate with 3D ultrasound
[57,58]. This method has been used in a research setting and
may be a potential tool for prediction of chromosomal anoma-
lies, where placental volume is decreased early in gestation [59].
Other placental pathologies can also be investigated by ultra-
sound, particularly with spectral and colour Doppler, as well as
3D/4D: abnormal placentation (placenta previa, accreta, increta,
percreta) [60], velamentous insertion of the cord [61], vasa pre-
via, as well as placental tumors [62], for instance.
3.2.2. Magnetic resonance (MR) imaging
MR is an adjunct to and, occasionally, a rival of ultrasound
in placental imaging [63]. It can demonstrate maternal pelvic
structures, localise the site of implantation of the placenta, de-
tect the presence of placenta previa or the different forms of
placenta accreta, as well as retroplacental haematomas in pla-
cental abruption. More to the point of the present review, MR
imaging has been used to assess fetal and placental volumes to
evaluate normal and disturbed growth [64]. It can be used by
 J.S. Abramowicz, E. Sheiner / Placenta 28, Supplement A, Trophoblast Research, Vol. 21 (2007) S14eS22 S17

itself or with contrast agents, gadolinium compounds in partic-

ular. Even without injection of contrast agent, MR can create
an angiography-like image, utilising different techniques, such
as maximum intensity projection. With improved resolution
(down to 4 mm), one can now speak of microscopic MR [65].
Functional changes in the placenta, in normal pregnancies and
those affected by pre-eclampsia and/or IUGR have been de-
scribed from 16 to 36 weeks’ gestation [66]. The actual volume
of blood moving within different regions of the placenta can be
estimated with MR [67]. This perfusion fraction mapping iden-
tified differences in function within the normal placenta in vivo
and between the placentae of 13 normal and 7 pregnancies with
growth-restricted fetuses [67]. Placental perfusion has been
measured in mice with dynamic MRI [68]. For now, however,
in the vast majority of clinical situations, ultrasound remains,
by far, the preferred mode of imaging.

3.2.3. Clinical aspects

A detailed discussion of all placental pathologies diagnos-
able by contemporary technologies is well beyond the scope of
the present review; however, a brief description may benefit
the reader. This will consist only of definition of the condition
and criteria for imaging diagnosis, mostly by ultrasound which
is the preferred clinical imaging method. Clinical material will
not be covered. The interested reader may find this in text-
books and various articles [60,69].
The following major conditions will be considered: pla-
centa previa, placenta accreta, vasa previa (although not gen-
uinely a placental condition), abruptio placentae, placental
calcifications, gestational trophoblastic disease, and non-
trophoblastic placental tumors.
1. Placenta previa: This is an important cause of bleeding
during the second half of pregnancy, occurring in 1 in
200 to 250 pregnancies. There are several classifications
in the literature; the most commonly used being: no pre-
via, low lying placenta, marginal previa (although occa-
sionally low lying is included), complete previa [60].
The diagnosis is mainly by transvaginal ultrasound
[60,70]. Fig. 1a represents complete placenta previa and
1b marginal previa.
2. Placenta accreta: Placenta accreta is defined as abnormal
adherence of the placenta to the uterus, probably due to
an absence or deficiency of Nitabuch’s layer or the spon-
gious layer of the deciduas [60,71]. Invasion to the myo-
metrium is defined as placenta increta, and invasion
through the myometrium and serosa is called placenta
percreta [60]. Ultrasound imaging is widely used for the
screening of placenta location and potential abnormal
development [60,71]. This exam is associated with high
sensitivity and specificity for diagnosis of placenta ac-
creta when specific defined criteria are used for the diag-
nosis. Prenatal diagnosis of placenta accreta by imaging
should be based on the irregularly shaped placental lacu-
nae signs (‘‘Swiss cheese’’ appearance) representing vas-
cular spaces rather than the loss of the normally obvious
retro-placental clear space ([60]; Fig. 2). Other signs
Fig. 1. Placenta previa. (a) Complete previa. The cervix is between the arrow
heads. Internal os to the left. (b) Marginal previa. The placental edge is 1.1 cm
from the internal os. The placenta is posterior.
include thinning of the myometrium overlying the pla-
centa, protrusion of the placenta into the bladder, in-
creased vascularity of the uterine serosaebladder
interface, and turbulent flow through the lacunae using
Doppler studies [72]. Placental MRI provides a morpho-
logical description, as well as recently demonstrated
topographical information that optimises diagnosis and
surgical management [72]. Screening of placenta accreta
should be improved with the use of a combination of
these diagnostic techniques (ultrasonography first, and
then MRI for cases with inconclusive ultrasound fea-
tures), and benefit high-risk populations with a reduction
in morbidity.
3. Vasa previa: Vasa previa is a rare, potentially preventable,
severe complication that carries a risk of fetal exsanguina-
tion and death when the membranes rupture [60,73]. This
is due to the fact that fetal vessels run through the mem-
branes, unprotected by placental tissue or Wharton’s jelly,
below the fetal presenting part and close to the internal
cervical os. It should particularly be suspected when the
placental edge covers the os in mid-pregnancy but recedes
later on. Risk factors include multiple pregnancy,
S18 J.S. Abramowicz, E. Sheiner / Placenta 28, Supplement A, Trophoblast Research, Vol. 21 (2007) S14eS22
Fig. 2. Placenta accreta/increta. (a) Accreta. Note absence of retroplacental
echofree space as well as typical cystic spaces (‘‘Swiss cheese’’ appearance).
(b) Increta (possibly percreta). Note cervical invasion by placental tissue.
pregnancy resulting from IFV, presence of velamentous in-
sertion, succenturiate or accessory placental lobes (Fig. 3).
The condition can be diagnosed prenatally by ultrasound
examination (Fig. 4). Recently, prenatal diagnosis and
evaluation was reported using 3D sonography and power
angiography [73].
4. Abruptio placentae: this is a leading cause of vaginal
bleeding in the latter half of pregnancy, complicating
about 0.5e1% of pregnancies [74,75]. It is an important
reason for perinatal mortality and morbidity. The diagnosis
of abruption is a clinical one, and ultrasonography is of
limited value [74,75]. In ultrasound one might see placen-
tal edge separation, subchorionic and retroplacental hae-
matomas. Ultrasound is not sensitive for detection of
placental abruption, but a positive finding is associated
with more aggressive management and worse neonatal
outcome [75].
5. Placental calcifications: Ultrasonically detectable placental
changes are correlated with fetal maturity, and the placenta
is known to mature and calcify [76]. Significant placental
calcifications are rarely seen before 37 weeks’ gestation.
At 40 weeks’ gestation or beyond, about 20% of placentas
Fig. 3. Cord insertion. (a) Normal cord insertion. (b) Velamentous insertion of
the cord in a case of accessory placental lobe.
have extensive calcification (Grannum grade 3). Placental
grading was not found useful to predict postmaturity and
fetal distress [76]. Nevertheless, recently, McKenna et al.
[77] determined the significance of an inappropriately
mature calcified placenta on ultrasound examination, and
concluded that ultrasound detection of a grade 3 placenta
at 36 weeks’ gestation might help to identify the ‘‘at-risk’’
pregnancy. It helps to predict subsequent development of
gestational hypertension and may help in identifying the
growth-restricted baby.
6. Gestational trophoblastic disease: Gestational trophoblastic
disease refers to a wide spectrum of proliferative disorders
of the placental trophoblast [78]. The secretion of beta-
HCG characterises this condition which is highly curable
even in the presence of metastases. Current ultrasonographic
techniques offer a novel approach for the identification of ges-
tational trophoblastic disease. Common ultrasound presenta-
tions include enlarged uterus and absence of fetal parts. Early
ultrasound description was linked to the appearance of
‘‘snowstorm’’ without embryonic structure. Maternal lakes
resulting from stasis of blood between the molar villi are
 J.S. Abramowicz, E. Sheiner / Placenta 28, Supplement A, Trophoblast Research, Vol. 21 (2007) S14eS22
Fig. 4. Vasa previa in a case of twins. Note umbilical cord of Twin B (marked
‘‘B’’) and vessels of twin A (‘‘A’’) in close contact with the cervix.
common as well. Large ovarian theca-lutein cysts, secondary
to the elevated beta-HCG levels may also occur. Since this
group of disorders comprises one of the highly curable neo-
plasms, early diagnosis and prompt treatment is necessary
[78]. The partial hydatidiform mole is a histopathologic entity
characterised by focal trophoblastic hyperplasia with villous
hydrops together with identifiable fetal tissue [79]. In more
than 90% of triploidy, the fetus shows growth restriction and
multiple structural anomalies, commonly accompanied by
oligohydramnios and abnormal placental Doppler indices [79].
7. Non-trophoblastic placental tumors: The most common
benign non-trophoblastic placental neoplasm is chorioan-
gioma. It is a hypervascular lesion with arterial and venous
flow containing numerous cystic spaces that produce col-
our signals [80]. Its sonographic appearance includes
a well-circumscribed, rounded, basically hypoechoic le-
sion next to the chorionic surface, often close to the
cord insertion. Colour Doppler ultrasound useful in the
early diagnosis and treatment as well as evaluation of re-
sponse to treatment, since blood flow is prominent in these
lesions.
In addition, in several conditions the placenta will appear
thick or oedematous, for instance in fetal hydrops (whether
immune or non-immune), and, particularly, in several infec-
tions such as syphilis and cytomegalovirus [81].
3.3. Where are we headed?
Ultrasound and, to a lesser degree, MR will continue to be
the major imaging techniques utilised in placental physiology
and fetal development. Some new modalities are experimented
with and will further enhance imaging: ultrasound contrast
agents and several expansions of MR imaging.
3.3.1. Ultrasound contrast agents
Ultrasound is based on the pulse-echo principle: the incident
beam hits reflectors, echoes are produce and return to be
S19
captured and processed. More reflectors in the tissue should cre-
ate more echoes and bring additional information, particularly
for areas which, naturally, do not contain a large quantity of re-
flectors, such as cavities or small blood vessels. This forms the
basis of the use of ultrasound contrast agents (UCA). These can
be solid particles in suspension, liquid droplets in emulsion, gas
bubbles, encapsulated or not. Colour enhancement of placental
blood flow has been described in pregnant macaque monkeys
with the use of Levovist [82] and Albunex [83]. With Levovist
injections, researchers were able to show changes in flow in
small vessels in a fetal sheep model during hypoxic episodes
[84]. Intervillous flow could be demonstrated by ultrasound
with injection of contrast agent in third-trimester rhesus mon-
keys [85] and baboons [82,86]. In perfused human placenta
experiments, improvement in grey-scale imaging was obtained,
and spectral Doppler studies with the use of UCA (Albunex or
iodipamide ethyl ester) demonstrated increase in the echogenic-
ity of the placenta, when injected in the fetal side and a major
increase in the Doppler signal which was very weak before
the injection [87]. Furthermore, changes induced by injection
of vasoactive substances to the model, either U46619, a throm-
boxane agonist or the vasodilator nitroglycerine, were easily
observed [87]. Other contrast agents have also been useful for
enhancement of ultrasound imaging in placental perfusion
experiments [88]. The technique has been described in the hu-
man, without any evident harmful side effects to the mother or
the fetus [89]. In particular, the agent SH U 508A (Levovist;
Shering, Berlin, Germany) was used in cases of twin pregnancy
to confirm interfetal transfusion in monochorionic twins in
pregnancies with twinetwin transfusion syndrome, because
of the high risk associated with such connection. The agent
was injected, under ultrasound guidance, into the intrahepatic
portion of the umbilical vein of one fetus and allowed detection
of the agent in the second twin, if the direct connection existed.
Surprisingly, imaging of the placental angioarchitecture was
not improved with injection of the contrast agent [90]. A further
technological advance is the use of nanomolecular agents.
While previously mentioned contrast agents are in the range
of several microns (microbubbles), nanomolecular agents are
in the nanometre range and are used in an attempt to image pro-
cesses at the cellular or molecular levels. Many techniques can
be adapted, such as radionuclide (PET) and optical imaging,
MRI, CT and ultrasound. While they are too small to be re-
solved by ultrasound, one can attach to them monoclonal anti-
bodies, ligands, peptides etc. This confers high specificity,
allowing active targeted imaging. They have already been
used in several clinical situations [91] and may have potential
applications in obstetrics and gynaecology, such as analysis
of early maternalefetal communications, uterine vascularisa-
tion, placental blood flow and its control, as well as studies of
the placental barrier [16].
3.3.2. Magnetic resonance spectroscopy and microscopy
These are existing applications of MR, not yet in extensive
use. MR spectroscopy analyses the energy levels of several
elements (ATP for instance) to help characterise metabolic
processes and disturbances thereof. It has been used in animals
S20 J.S. Abramowicz, E. Sheiner / Placenta 28, Supplement A, Trophoblast Research, Vol. 21 (2007) S14eS22
and in dually perfused human term placentae and may, in the
future, be used in functional analysis of the placenta in fetal
disorders, particularly IUGR, although reconstruction time is
still too long for efficient clinical use [92]. Equally important,
MR microscopy with improving resolution is already capable
of examining tissues in vivo at the cellular level, including the
placenta [93] and will most likely play an increasing role in
the future.
4. Conclusions
Several serious pathological conditions of pregnancy origi-
nate in abnormal placentation, particularly faulty trophoblastic
invasion: pre-eclampsia and some forms of IUGR for instance.
Although both these conditions seem to result from a similar
placental pathology, and both have endothelial dysfunction,
pre-eclampsia is associated with signs of inflammation (ele-
vated cytokines) and abnormal maternal metabolism while
pure IUGR may not be [29]. Many imaging techniques permit
exploration of placental morphology and function and have
been used to predict complications or formulate a prognosis
regarding perinatal outcome. Ultrasound, in all its modalities
(B-mode, colour, power and spectral Doppler, 3D/4D and con-
trast-agent enhanced), is unquestionably, at the moment, the
optimal method of examination in a clinical setting but mag-
netic resonance imaging may also play a large role. Both
MR and ultrasound will certainly evolve to a much more com-
mon use of contrast agents with dedicated target organs [94]
with better insight on placental haemodynamics, placental
transfer, early maternalefetal connection and fetal develop-
ment, allowing further understanding of their impact on the
course of pregnancy.
References
[1] Soranus D’Ephèse: Traité des maladies des femmes [Treaty of women
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