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Available online at www.sciencedirect.com

www.elsevier.com/locate/semperi

Benets and risks of MRI in pregnancy

Dorothy Bulas, MDn, and Alexia Egloff, MD
Department of Diagnostic Imaging and Radiology, Children's National Medical Center, 111 Michigan Ave NW, Washington, DC 20010

ART IC LE INFO

AB ST R A CT
Ultrasound remains the modality of choice in imaging the fetus due to its availability,

Keywords: Fetal MRI Fetal imaging MRI safety Fetal anomalies

safety, and low cost. With advances in technology, however, magnetic resonance imaging (MRI) has become an important adjuvant in the evaluation of the fetus. MRI is not limited by fetal lie, oligohydramnios, overlying bone, or obesity. MRI can image the fetus in any plane, providing a large eld of view of the fetus and placenta with excellent soft tissue resolution of the brain, airway, lungs, and abdomen. Advanced techniques are being developed that provide volumetric data, spectroscopy, and functional images. MRI has its own set of challenges with a lack of consensus regarding its utility and safety. Artifact from the moving fetus and breathing mother limits the sequences available. While there is currently no evidence that fetal MRI produces harmful effects, long-term safety regarding radiofrequency elds and the loud acoustic environment continues to be studied. In this review, the benets and potential risks of fetal MRI will be discussed. & 2013 Elsevier Inc. All rights reserved.

1.

Introduction

For many years, ultrasound (US) has been the only study to image the fetus. Approximately 60 years after being introduced in obstetrics, US is still the primary method used in prenatal imaging due to its availability, safety, and low cost. MRI, with its technological advances, has become an important adjuvant imaging tool in the further evaluation of the fetus. MRI has its own set of challenges, and there is a lack of consensus regarding its utility and safety. In this article, we discuss the benets and risks of fetal magnetic resonance imaging (MRI) and the challenges that are encountered.

diagnostic and therapeutic procedures. It is relatively inexpensive, has real-time capability, and is considered safe, making it the standard in the evaluation of the fetus.1 Ultrasound, however, is highly dependent on the skill and experience of the sonographer, resulting in signicantly different performance rates, with detection rates of abnormalities varying from 13% to 82%.2,3 Even in experienced hands, diagnosing subtle cortical brain anomalies, intracranial extraaxial collections, and lung masses can be difcult by ultrasound. The sensitivity and specicity of US also depends on the fetal position, presence of oligohydramnios, degree of ossication, and maternal body habitus.1,35

2.

Ultrasound

3.

MRI

Ultrasound is the rst and often the only modality needed in the evaluation of the fetus. With ultrasound, it is possible to conrm number and location of pregnancies early in gestation, evaluate and diagnose fetal and placental abnormalities, assess fetal well-being, and provide guidance during invasive
n

Fetal MRI was initially attempted in the 1980s but was limited due to slow sequences requiring fetal and/or maternal sedation. Since then, the development of faster sequences has been fundamental in the success of imaging the moving fetus without the use of sedation.6 MRI has numerous advantages

Corresponding author. E-mail address: dbulas@childrensnational.org (D. Bulas).

0146-0005/13/$ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.semperi.2013.06.005

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that makes it a complementary study in the evaluation of the fetus MRI, and in comparison to ultrasound, is not limited by fetal lie, overlying maternal or fetal bone, obesity, or oligohydramnios. MRI offers excellent soft tissue contrast and multiplanar visualization of all organs. Advanced MR imaging has been particularly useful in the improved diagnostic accuracy of CNS abnormalities.79 In cases with non-CNS pathology, such as abdominal and lung masses, MRI may provide additional information including volumetric data. With the airway lled with uid in fetal life, MRI can directly visualize the larynx, pharynx, and trachea, assessing the need for ex utero intrapartum treatment (EXIT) procedure when an oral or neck mass is present compressing the airway.1 Various T1w, T2w, and echo planar sequences can distinguish blood, fat, meconium, and cartilage, increasing the accuracy of diagnosis. Large eld of view with multiplanar capability enables other specialists (surgeons, neurosurgeons, neurologists, urologists, etc.) to evaluate MRI images. This team approach is critical for advanced delivery and fetal and postnatal surgical planning. Families are able to review these images as well, which is useful during counseling.3 Additional benets include the fact that fetal MRI, at times, can limit the need for postnatal imaging, which is particularly helpful when a newborn is unstable and unable to tolerate sedation. Advanced techniques are being developed that may provide physiologic information, including fetal spectroscopy and functional MRI.10,11

of view is particularly helpful in complex delivery planning for neck masses, sacrococcygeal teratomas, and conjoined twins that may require emergent surgery following delivery.

3.2.

Safety

3.1.

Timing and indications for fetal MRI

For the multiple reasons stated above, MRI can be a useful adjunct when a targeted sonogram performed by an experienced sonologist raises questions that could benet from further assessment. MRI may provide additional information when an abnormality is identied by US or when ndings are equivocal and require clarication.12 The optimal timing of a fetal MRI depends on what questions need to be answered. Prior to 18 weeks, fetal MRI is limited due to the small size of the fetus, increased fetal motion, and the fact that some anomalies may have not yet evolved (i.e., cortical dysplasias). MRI between 18 and 22 weeks gestation can be useful to further evaluate or conrm ndings noted on target sonograms that can affect pregnancy planning. MRI in the third trimester is optimal for the assessment of cortical anomalies due to improved spatial resolution. Later studies, however, risk identifying anomalies too late for optimal intervention. MR studies performed in the second trimester may, at times, benet from a follow-up examination in the third trimester, particularly those requiring complex delivery planning such as neck masses. Evidence-based data for the performance of fetal MRI is strongest for CNS anomalies and for cases being considered for fetal intervention such as neural tube defects.3 Much research is currently being performed on the use of MR to estimate lung volumes, particularly in cases of congenital diaphragmatic hernia as well lung masses and lung hypoplasia.13,14 Fetal MR images are helpful in the planning of fetal and postnatal surgery allowing multiple specialists to work together as a team reviewing images they are familiar with. The ability to view lesions in multiple plains with a large eld

While there currently is no evidence that fetal MRI produces harmful effects on the fetus, long-term safety has not yet been denitively demonstrated. There is a lack of consensus as to whether the risk to the fetus is real.1518 Saunders noted in a review of the literature that while no adverse effects have been consistently demonstrated, the evidence is inconclusive, numbers small, data variable with potential confounders, and few evaluating elds greater than 1 T.19 In studies performed, two potential safety issues have been raised: teratogenic effects and acoustic damage.1519 Some studies have raised the concern for teratogenic effects of MRI when performed early in pregnancy, secondary to the heating effect of MR gradient changes, and a direct non-thermal interaction of the electromagnetic eld.1921 Static magnetic elds produce short-term high eld exposure to the patient from 0.23 T and long-term low eld exposure to MR staff (0.5200 mT). Animal studies have demonstrated effects such as a decrease in crown-rump length when mice were exposed to MRI in midgestation period20; eye malformations in genetically predisposed mice21; and demise of chick embryos when exposed to strong magnetic elds.15 These studies are not applicable to humans and cannot be extrapolated, but they do raise concerns. Kanal et al.22 produced a worker survey on female MR technologists concerning low eld exposure. There were over 1900 responses with no statistically signicant associations revealed. Radiofrequency elds generate heat and are controlled by Specic Absorption Rate (SAR). Mathematical models on simulations have identied RF levels that are tolerable to humans; however, fetal dosimetry is only now being developed.2325 Fast sequences use high-specication magnetic eld gradients. dB/dT exposure needs to be further researched not only in adults but in the fetus as well. MRI produces a loud tapping noise when coils are exposed to rapidly oscillating electromagnetic currents. Initially, concern was raised regarding potential acoustic damage to the developing ear. A study by Baker et al.26 suggested that hearing was preserved but the sample size was small. A study in 1995 simulated the acoustic environment of the gravid uterus by passing a microphone through the esophagus of a volunteer. This demonstrated a sufcient attenuation of sound to an acceptable level that was not harmful to the developing fetal ear.27 While several series have described no adverse long-term effects of fetal MRI in children imaged as fetus, the samples have been too small to be conclusive and no long-term studies are currently available regarding higher strength magnets such as 3 T.26,2831 MRI should be performed when benets outweigh potential risks, even if long-term adverse effects have not been denitely demonstrated.1517,32 It is unknown whether higher magnet strengths and prolonged imaging times may have biological effects if applied at sensitive stages of development. For these reasons, it is recommended to perform fetal MRI after 18 weeks

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of gestation. The United States Food and Drug Administration (US FDA) and the International Commission on NonIonizing Radiation Protection (ICNIRP) recommend performing studies with caution, including a close control of SAR values.1517,32 In the UK, the Medical Device Agency (MDA) guidelines require SAR to be a maximum of 10 W/kg within the fetus.1517 The use of intravenous gadolinium and its toxic effects to the fetus has been tested in animals, but not adequately in humans. Gadolinium crosses the placenta and is excreted in urine by the fetus and later reabsorbed/swallowed, prolonging the elimination time.33 In a study with rabbits, a high concentration of gadolinium is noted 5 min after its administration, with a subsequent decrease of 50% after 60 min. In the fetus, the concentration of gadolinium in different organs is low, except for the kidneys, which show an increase in concentration over the rst 60 min.33 At high (27 times the dose used in humans) and repeated doses, teratogenic effects (including growth retardation, visual problems, and bone and visceral anomalies) have been described in animals.33,34 No carcinogenic or mutagenic effects have been noted.34 Other preclinical studies using contrast have not shown negative effects on the fetus, including detectable chromosomal damage, abortions, stillbirth, and grossly detectable anomalies, even at 1116 times the clinical dose.34 A few clinical studies using contrast have been performed in humans with no adverse effects to the fetus or neonate reported, even when given during the rst trimester.34 Side effects have not been observed in human studies when clinical doses of gadolinium are administered. However, as contrast may remain within the amniotic uid for long periods of time, unless absolutely needed, its use is not recommended during pregnancy particularly during the period of organogenesis. Use of gadolinium late in gestation may be appropriate for specic maternal or obstetric indications.

the patient to remain still, resulting in the need to repeat sequences prolonging the examination. Maternal safety and comfort should be the priority during the study and should guide the success of completing the study. Technical challenges include motion artifact, limited fast sequences, optimizing signal/noise, and lack of technical expertise. Motion comes mainly from the fetus, but also from the mother who can be uncomfortable and anxious making it difcult to obtain adequate images. The moving fetus makes obtaining appropriate planes challenging for the technologists and repeat sequences may be required to obtain a quality image. Physicians often are required to sit with an inexperienced technologist when rst learning to perform a fetal MRI as anatomy can be confusing in a moving fetus with anomalies. Fast scanning sequences are limited. T1 and T2 must be optimized to decrease the scanning time and motion artifact. Some sequences require the breath to be held to improve image quality (T1w, DWI, and skeletal EPI). This can be difcult for a mother lying uncomfortably with diaphragms elevated by the gravid uterus. Fetal gating currently is not commercially available limiting evaluation of the fetal heart. The use of 3-T magnets represents another technical challenge with its increased susceptibility to motion artifact and the need to closely follow SAR limits. Challenges in interpretation of MR images include limited training opportunities and expertise in the eld of fetal MRI. To properly evaluate fetal MRI studies, expertise in both fetal ultrasound and MRI is needed. There needs to be an understanding of maternal and fetal pathology as well as pediatric pathophysiology and pediatric neuroradiology including cortical development. Standard measures and volumes of organs for all gestations need to accumulate so that there is a decreased reliance on subjective pattern recognition.

3.3.

Challenge

4.

Conclusions

The performance and interpretation of fetal MRI can be challenging. Challenges can be divided in three categories: maternal, technical, and interpretative. Maternal challenges include high cost, limited accessibility, need for schedule exibility, and maternal discomfort/anxiety. MRI is more expensive to perform as compared to US, with less availability of equipment. While many centers have access to 1.5 T MR scanners, due to lack of expertise, the ability to schedule a fetal MRI is currently not widely available Positioning the mother in the scanner can be difcult. Lying on her back may be painful, and positioning on her side may be required. Coils have not been designed for the pregnant patient and can be stiff and heavy. Large bore magnets may not be available and smaller bores may be claustrophobic or simply too small to t a large pregnant patient. The MR rooms are cold and loud with the patient unable to talk or see a loved one during the examination.8 Anxiety due to the concern of having a fetus with an abnormality is exacerbated by being alone in the noisy magnet, not being able to see the facial expression of the physician,8 and not being in contact with their partner. All of these factors can make it difcult for

Ultrasound remains the initial and often the only imaging study required in the evaluation of the fetus. MRI has become an important adjunct in the further assessment of fetal abnormalities and those with a family history risk. MRI can help conrm and clarify ndings, providing additional information useful in the diagnosis, counseling, treatment, and management of the pregnancy, delivery, and postnatal care. With no indication that use of clinical MR during pregnancy produces adverse affects, this technology has provided important advances in the care of the fetus and newborn. Fetal MRI, however, should be performed only when benets outweigh potential risks and care should be taken regarding timing of exams and SAR limits. Additional studies are needed to further document safety of static eld, RF, and dB/dT exposure on the embryo and fetus.

refere nces

1 Reddy UM, Filly RA, Copel JA. Prenatal imaging: ultrasonography and magnetic resonance imaging. Obstet Gynecol. 2008;112(1):145157.

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2 Levi S. Ultrasound in prenatal diagnosis: polemics around routine ultrasound screening for second trimester fetal malformations. Prenat Diagn. 2002;22(4):285295. 3 Bulas D. Imaging of fetal anomalies. In: Medina LS, eds, ed, Evidence Based Imaging in Pediatric. New York: Springer; 2009 [Chapter 41]. 4 Switzer PJ, James CA, Freitag. MA. Value and limitations of obstetrical ultrasound. Can Fam Physician. 1992;38:121128. 5 Dashe JS, McIntire DD, Twickler DM. Maternal obesity limits the ultrasound evaluation of fetal anatomy. J Ultrasound Med. 2009;28:10251030. 6 Coakley FV, Glenn OA, Qayyum A, Barkovich AJ, Goldstein R, Filly RA. Fetal MRI: a developing technique for a developing patient. Am J Roentgenol. 2004;182(1):243252. 7 Levine D. Obstetric MRI. J Magn Reson Imaging. 2006;24:115. 8 Wieseler KM, Bhargava P, Kanal KM, Vaidya S, Sterwart BK, Dighe MK. Imaging in pregnant patients: examination appropriateness. Radiographics. 2010;30:12151233. 9 Benacerraf BR, Shipp TD, Bromley B, Levine D. What does magnetic resonance imaging add to the prenatal sonographic diagnosis of ventriculomegaly? J Ultrasound Med. 2007;26 (11):15131522. 10 Garel C. Fetal MRI: what is the future? Ultrasound Obstet Gynecol. 2008;31:123128 [editorial]. 11 Clouchoux C, Limperopoulos C. Novel applications of quantitative MRI for the fetal brain. Pediatr Radiol. 2012;42(suppl 1):S24S32. 12 Garel C, Brisse H, Sebag G, et al. Magnetic resonance imaging of the fetus. Pediatr Radiol. 1998;28:201211. 13 Kline-Fath BM. Current advances in prenatal imaging of congenital diaphragmatic hernia. Pediatr Radiol. 2012;42(suppl 1): S74S90. 14 Victoria T, Bebbington MW, Danzer E, et al. Use of magnetic resonance imaging in prenatal prognosis of the fetus with isolated left congenital diaphragmatic hernia. Prenat Diagn. 2012;32(8):715723. 15 Yip YP, Capriotti C, Talagala SL, Yip JW. Effects of MR exposure at 1.5 T on early embryonic development of the chick. J Magn Reson Imaging. 1994;4:742748. 16 Yip YP, Capriotti C, Yip JW. Effects of MR exposure on axonal outgrowth in the sympathetic nervous system of the chick. J Magn Reson Imaging. 1995;5:457462. 17 Mevissen M, Buntenkotter S, Loscher W. Effects of static and time varying (50-Hz) magnetic elds on reproduction and fetal development in rats. Teratology. 1994;50:229237. 18 Magin RL, Lee JK, Klintsova A, et al. Biological effects of longduration high eld (4 T) MRI on growth and development of the mouse. J Magn Reson Imaging. 2000;12:140149. 19 Saunders R. Static magnetic elds: animal studies. Prog Biophys Mol Biol. 2005;87:225239.

20 Heinrichs WL, Fong P, Flannery M, et al. Midgestational exposure of pregnant mice to magnetic resonance imaging. Magn Reson Imaging. 1986;8:6569. 21 Tyndall DA, Sulik KK. Effects of magnetic resonance imaging on eye development in the C57BL/6 J mouse. Teratology. 1991;43:263275. 22 Kanal E, Gillen J, Evans JA, Savitz DA, Shellock FG. Survey of reproductive health among female MR workers. Radiology. 1993;187(2):395399. 23 Levine D, Zuo C, Faro CG, Chen Q. Potential heating effect in the gravid uterus during MR HASTE imaging. J Magn Reson Imaging. 2001;13(6):856861. 24 Dimbylow P. Development of pregnant female, hybrid voxelmathematical models and their application to the dosimetry of applied magnetic and electric elds at 50 Hz. Phys Med Biol. 2006;51(10):23832394. 25 Hand JW, Li Y, Hajnal JV. Numerical study of RF exposure and the resulting temperature rise in the foetus during a magnetic resonance procedure. Phys Med Biol. 2010;55:913930. 26 Baker P, Johnson I, Harvey R, Gowland PA, Manselld P. A three-year follow-up of children imaged in utero with echoplanar magnetic resonance. Am J Obstet Gynecol. 1994;170: 3233. 27 Gover P, Hykin J, Gowland P, Wright J, Johnson I, Manseld P. An assessment of the intrauterine sound intensity level during obstetric echo-planar magnetic resonance imaging. Br J Radiol. 1995;68:10901094. 28 Myers C, Duncan KR, Gowland PA, Johnson IR, Baker PN. Failure to detect intrauterine growth restriction following in utero exposure to MRI. Br J Radiol. 1998;71:549551. 29 Clements H, Duncan KR, Fielding K, Gowland PA, Johsnon IR, Baker PN. Infants exposed to MRI in utero have a normal paediatric assessment at 9 months of age. Br J Radiol. 2000;73:190194. 30 Kok RD, de Vries MM, Heerschap A, van den Berg PP. Absence of harmful effects of magnetic resonance exposure at 1.5 T in utero during the third trimester of pregnancy: a follow-up study. Magn Reson Imaging. 2004;22:851854. 31 International Commission on Non-Ionizing Radiation Protection. Magnetic resonance (MR) procedures: protection of patients. Health Physics 2004;87:1970216. 32 Okuda Y, Sagami F, Tirone P, Morisetti A, Bussi S, Masters RE. Reproductive and developmental toxicity study of gadobenate dimeglumine formulation (E7155) (3)study of embryo-fetal toxicity in rabbits by intravenous administration. J Toxicol Sci. 1999;24(suppl 1):7987. 33 Sundgren PC, Leander P. Is administration of gadoliniumbased contrast media to pregnant women and small children justied? J Magn Reson Imaging. 2011;34:750757.