Fetal MRI Safety
MRI is a powerful complement to ultrasound for the evaluation of a variety of fetal and placental abnormalities. It is also a primary modality choice for unexpected maternal maladies that may arise in pregnancy. The primary advantages of MRI include high spatial resolution and excellent soft tissue contrast while still being noninvasive and void of ionizing radiation. Regardless, a discussion of several safety aspects of MRI including exposure of the fetus to electromagnetic energy from the static magnetic field, radiofrequency (RF) pulses and rapidly changing gradients is warranted.
The initial safety issue is that of exposure of the fetus to the static magnetic field [1,2]. Numerous animal model studies are present in the literature. Some have shown general deleterious embryonic effects such as upon development of embryos, delay and reduction in hatching rates, fetal loss, decreased crown rump length (CRL); additional studies have demonstrated organ specific disturbances in the development of the chick cerebellar cortex and murine eyes [3-8]. Other animal studies have shown no such embryonic effects, including a study using human fetal lung fibroblasts . There are no studies in the literature that have reproducibly proven a deleterious biologic effect by static magnetic fields on human tissue [2,10]. While in vivo studies are understandably lacking, Kanal et al, in a survey of nearly 1500 pregnant MRI staff, found no statistically significant adverse pregnancy outcomes including fertility with exposure up to 4.7T .
Another safety issue is that of exposure of the fetus to excitatory radiofrequency energy and its inherent potential for tissue heating. Inherent to this issue is the potential teratogenicity of fever to the developing fetus . A parameter for safety that is used is the specific absorption rate (SAR), defined as a measure of the rate of energy absorption by the body when exposed to radiofrequency electromagnetic field. The FDA and other international agencies have published SAR limits for whole body and local body, but it remains uncertain as to if the fetus should be considered a part of the mother or a separate individual. In one study, use of T2 HASTE, the foundation of fetal imaging, produced no significant temperature increase in the fetal brain or amniotic fluid of a pig model. And in a pregnant model, in normal mode at 1.5 T and 3.0T, the calculated temperature increase and SAR limits were found to be within a safe range [13,14]. There is however a report in the literature using a similar pregnant model where using maternal SAR limits may not protect the fetus from overexposure .
Another common safety concern is that of the use of rapid time varying electromagnetic fields (MR gradients) raising two issues: exposure to the gradients themselves and the acoustic noise created by the gradients. Limited research is available on isolated exposure to gradients, none of which have shown adverse effects with in vitro cellular studies [16,17]. More significant literature exists regarding high levels of acoustic exposure. Recent literature suggests that high levels of repeat sound exposure during pregnancy may produce low birth weights, shorter gestation and hearing loss . The FDA limits sound intensity to 140dB in the MRI suite. The exact degree and frequency of sound attenuation as a function of gestational age is not known. Some level of sound attenuation however does occur in utero with attenuation more significant at higher frequencies offering the fetus some protections [19-21]. Exposure of the fetus to MRI at 1.5T in the second and third trimester has not been associated with hearing abnormality in several studies [22-25].
And finally, numerous studies evaluating longer term outcomes have also demonstrated no abnormalities in functional outcomes and birth weight for children exposed to in utero MRI [11,22,23,25-27].
While rarely encountered in women of child-bearing age, all contraindications that apply to non-pregnant patients apply during pregnancy. These include implanted medical devices such as pacemakers, especially when the patient is pacer dependent . medical devices that contain ferromagnetic material are also contraindications. Usual screening procedures customary to all MRI programs must be applied. The ACR recommends that MRI screening should be performed by at least two separate personnel, one of which should be a level 2 MRI personnel. Screening includes documentation with a standard paper questionnaire followed by confirmation with oral review. Manual screening by a ferromagnetic specific detection device (rather than a conventional metal detector) is advisable. As with all other patients, wearable metallic objects that can be removed should be removed prior to the MRI session, including piercings. All patients should be administered a gown supplied by the institution to be worn during the study and while in Zone III and IV. The reader is encouraged to review the ACR Guidance Document on MR Safe Practices: 2013 for further details.
Intravenous Gadolinium Contrast for Fetal MRI
There are no absolute fetal or placental indications for the administration of intravenous gadolinium contrast agents (category C drug) and therefore administration of these agents for these specific indications is not usually indicated. While there is a report of a small number of patients administered gadolinium contrast in the first trimester, with none having experienced congenital defects, there is no literature to prove its fetal safety . Gadolinium agents are not known at this time to be teratogenic [29-34]. However these agents do enter fetal-placental circulation and amniotic fluid potentially creating an environment where dissociation of toxic free gadolinium may occur by way of delayed excretion [35-37].
Please note that gadolinium contrast agents may be considered in the rare instance of a serious maternal indication, a discussion beyond the scope of this section.
In summary, there is no evidence in the literature of harmful effects of MRI on the fetus and therefore no specific special considerations are needed once an attending radiologist has deemed the MRI study to be warranted. Such a decision should rely on a discussion with the referring physician and a careful review of pre-MRI data that clearly demonstrates its need. In general, fetal MRI has limited utility prior to 16-18 weeks due to the small size of the fetus and incomplete organogenesis and therefore should be performed sparingly in the first trimester. The literature does, however, maintain several important safety questions regarding fetal exposure to electromagnetic and sound energy for which the currently available data remains inconclusive. Continued studies are warranted that more definitively address all embryonic and fetal safety concerns related to MRI.
1. De Wilde JP, Rivers AW, Price DL (2005) A review of the current use of magnetic resonance imaging in pregnancy and safety implications for the fetus. Prog Biophys Mol Biol 87 (2-3):335-353. doi:10.1016/j.pbiomolbio.2004.08.010
2. Schenck JF (2000) Safety of strong, static magnetic fields. J Magn Reson Imaging 12 (1):2-19
3. Mevissen M, Buntenkotter S, Loscher W (1994) Effects of static and time-varying (50-Hz) magnetic fields on reproduction and fetal development in rats. Teratology 50 (3):229-237. doi:10.1002/tera.1420500308
4. Narra VR, Howell RW, Goddu SM, Rao DV (1996) Effects of a 1.5-Tesla static magnetic field on spermatogenesis and embryogenesis in mice. Invest Radiol 31 (9):586-590
5. Pan H (1996) The effect of a 7 T magnetic field on the egg hatching of Heliothis virescens. Magn Reson Imaging 14 (6):673-677
6. Espinar A, Piera V, Carmona A, Guerrero JM (1997) Histological changes during development of the cerebellum in the chick embryo exposed to a static magnetic field. Bioelectromagnetics 18 (1):36-46
7. Heinrichs WL, Fong P, Flannery M, Heinrichs SC, Crooks LE, Spindle A, Pedersen RA (1988) Midgestational exposure of pregnant BALB/c mice to magnetic resonance imaging conditions. Magn Reson Imaging 6 (3):305-313
8. Tyndall DA, Sulik KK (1991) Effects of magnetic resonance imaging on eye development in the C57BL/6J mouse. Teratology 43 (3):263-275. doi:10.1002/tera.1420430310
9. Wiskirchen J, Groenewaeller EF, Kehlbach R, Heinzelmann F, Wittau M, Rodemann HP, Claussen CD, Duda SH (1999) Long-term effects of repetitive exposure to a static magnetic field (1.5 T) on proliferation of human fetal lung fibroblasts. Magn Reson Med 41 (3):464-468
10. Saunders R (2005) Static magnetic fields: animal studies. Prog Biophys Mol Biol 87 (2-3):225-239. doi:10.1016/j.pbiomolbio.2004.09.001
11. Kanal E (1994) Pregnancy and the safety of magnetic resonance imaging. Magn Reson Imaging Clin N Am 2 (2):309-317
12. Edwards MJ (2006) Review: Hyperthermia and fever during pregnancy. Birth Defects Res A Clin Mol Teratol 76 (7):507-516. doi:10.1002/bdra.20277
13. Hand JW, Li Y, Hajnal JV (2010) Numerical study of RF exposure and the resulting temperature rise in the foetus during a magnetic resonance procedure. Phys Med Biol 55 (4):913-930. doi:10.1088/0031-9155/55/4/001
14. Hand JW, Li Y, Thomas EL, Rutherford MA, Hajnal JV (2006) Prediction of specific absorption rate in mother and fetus associated with MRI examinations during pregnancy. Magn Reson Med 55 (4):883-893. doi:10.1002/mrm.20824
15. Pediaditis M, Leitgeb N, Cech R (2008) RF-EMF exposure of fetus and mother during magnetic resonance imaging. Phys Med Biol 53 (24):7187-7195. doi:10.1088/0031-9155/53/24/012
16. Guisasola C, Desco M, Millan O, Villanueva FJ, Garcia-Barreno P (2002) Biological dosimetry of magnetic resonance imaging. J Magn Reson Imaging 15 (5):584-590. doi:10.1002/jmri.10099
17. Rodegerdts EA, Gronewaller EF, Kehlbach R, Roth P, Wiskirchen J, Gebert R, Claussen CD, Duda SH (2000) In vitro evaluation of teratogenic effects by time-varying MR gradient fields on fetal human fibroblasts. J Magn Reson Imaging 12 (1):150-156
18. Dzhambov AM, Dimitrova DD, Dimitrakova ED (2014) Noise exposure during pregnancy, birth outcomes and fetal development: meta-analyses using quality effects model. Folia Med (Plovdiv) 56 (3):204-214
19. Glover P, Hykin J, Gowland P, Wright J, Johnson I, Mansfield P (1995) An assessment of the intrauterine sound intensity level during obstetric echo-planar magnetic resonance imaging. Br J Radiol 68 (814):1090-1094. doi:10.1259/0007-1285-68-814-1090
20. Lecanuet JP, Gautheron B, Locatelli A, Schaal B, Jacquet AY, Busnel MC (1998) What sounds reach fetuses: biological and nonbiological modeling of the transmission of pure tones. Dev Psychobiol 33 (3):203-219
21. Walker D, Grimwade J, Wood C (1971) Intrauterine noise: a component of the fetal environment. Am J Obstet Gynecol 109 (1):91-95
22. Baker PN, Johnson IR, Harvey PR, Gowland PA, Mansfield P (1994) A three-year follow-up of children imaged in utero with echo-planar magnetic resonance. American Journal of Obstetrics and Gynecology 170 (1):32-33. doi:10.1016/s0002-9378(13)70275-8
23. Bouyssi-Kobar M, du Plessis AJ, Robertson RL, Limperopoulos C (2015) Fetal magnetic resonance imaging: exposure times and functional outcomes at preschool age. Pediatr Radiol 45 (12):1823-1830. doi:10.1007/s00247-015-3408-7
24. Reeves MJ, Brandreth M, Whitby EH, Hart AR, Paley MN, Griffiths PD, Stevens JC (2010) Neonatal cochlear function: measurement after exposure to acoustic noise during in utero MR imaging. Radiology 257 (3):802-809. doi:10.1148/radiol.10092366
25. Strizek B, Jani JC, Mucyo E, De Keyzer F, Pauwels I, Ziane S, Mansbach AL, Deltenre P, Cos T, Cannie MM (2015) Safety of MR Imaging at 1.5 T in Fetuses: A Retrospective Case-Control Study of Birth Weights and the Effects of Acoustic Noise. Radiology 275 (2):530-537. doi:10.1148/radiol.14141382
26. Kok RD, de Vries MM, Heerschap A, van den Berg PP (2004) 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 22 (6):851-854. doi:10.1016/j.mri.2004.01.047
27. Clements H, Duncan KR, Fielding K, Gowland PA, Johnson IR, Baker PN (2000) Infants exposed to MRI in utero have a normal paediatric assessment at 9 months of age. Br J Radiol 73 (866):190-194. doi:10.1259/bjr.73.866.10884733
28. De Santis M, Straface G, Cavaliere AF, Carducci B, Caruso A (2007) Gadolinium periconceptional exposure: pregnancy and neonatal outcome. Acta Obstet Gynecol Scand 86 (1):99-101. doi:10.1080/00016340600804639
29. Morisetti A, Bussi S, Tirone P, de Haen C (1999) Toxicological safety evaluation of gadobenate dimeglumine 0.5 M solution for injection (MultiHance), a new magnetic resonance imaging contrast medium. J Comput Assist Tomogr 23 Suppl 1:S207-217
30. Rofsky NM, Pizzarello DJ, Duhaney MO, Falick AK, Prendergast N, Weinreb JC (1995) Effect of magnetic resonance exposure combined with gadopentetate dimeglumine on chromosomes in animal specimens. Acad Radiol 2 (6):492-496
31. Rofsky NM, Pizzarello DJ, Weinreb JC, Ambrosino MM, Rosenberg C (1994) Effect on fetal mouse development of exposure to MR imaging and gadopentetate dimeglumine. J Magn Reson Imaging 4 (6):805-807
32. Soltys RA (1992) Summary of preclinical safety evaluation of gadoteridol injection. Invest Radiol 27 Suppl 1:S7-11
33. Wack C, Steger-Hartmann T, Mylecraine L, Hofmeister R (2012) Toxicological safety evaluation of gadobutrol. Invest Radiol 47 (11):611-623. doi:10.1097/RLI.0b013e318263f128
34. Wible JH, Jr., Troup CM, Hynes MR, Galen KP, MacDonald JR, Barco SJ, Wojdyla JK, Periasamy MP, Adams MD (2001) Toxicological assessment of gadoversetamide injection (OptiMARK), a new contrast-enhancement agent for use in magnetic resonance imaging. Invest Radiol 36 (7):401-412
35. Oh KY, Roberts VH, Schabel MC, Grove KL, Woods M, Frias AE (2015) Gadolinium Chelate Contrast Material in Pregnancy: Fetal Biodistribution in the Nonhuman Primate. Radiology 276 (1):110-118. doi:10.1148/radiol.15141488
36. Webb JA, Thomsen HS (2013) Gadolinium contrast media during pregnancy and lactation. Acta Radiol 54 (6):599-600. doi:10.1177/0284185113484894
37. Webb JA, Thomsen HS, Morcos SK, Members of Contrast Media Safety Committee of European Society of Urogenital R (2005) The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol 15 (6):1234-1240. doi:10.1007/s00330-004-2583-y