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Science to Practice: Can MR Oxygenation Imaging Be Used to Assess At-Risk Pregnancies?

Department of Radiology,
Beth Israel Deaconess Medical Center,
330 Brookline Ave,
Boston, MA 02215,
dlevine{at}bidmc.harvard.edu

SUMMARY:

By combining emerging technologies and in response to the need for noninvasive measurement of fetal and placental oxygenation, Wedegärtner et al have shown that 3-T BOLD MR imaging can be used to depict changes in fetal sheep organ oxygenation induced by maternal hypoxia. Future studies in animals and humans are needed to determine which organs show changes and if these changes can be detected in time to allow intervention earlier than with more traditional modes (ie, ultrasonography) used to study at-risk pregnant patients. Further refinements and studies will undoubtedly lead to improvements in this technique and optimizations for clinical applications.

THE SETTING

Inadequate placental transfer of oxygen results in fetal hypoxemia that has been associated with alterations in both fetal physiology and fetal structure, as well as with impaired neurodevelopment (1,2). In particular, low levels of fetal oxygenation represent a major cause of intrauterine growth restriction (IUGR), with an attendant increase in perinatal morbidity and mortality. IUGR, which is the second leading contributor to perinatal mortality, is a major problem in perinatal care, with an estimated 350 000 cases of IUGR occurring each year in the United States (3). In this issue of Radiology, Wedegärtner et al (4) describe the use of blood oxygen level–dependent (BOLD) magnetic resonance (MR) imaging in the assessment of fetal brain, liver, heart, lung, and placental oxygenation in sheep.

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In MR imaging, the BOLD effect is based on the principle that a change in the oxygen saturation level of hemoglobin and, therefore, the level of deoxyhemoglobin causes a change in local magnetic field susceptibility and affects T2* signal intensity. The deoxygenation of hemoglobin to deoxyhemoglobin, which is paramagnetic, causes an increase in local magnetic field inhomogeneity and, therefore, decreased T2* values. This technique has been used to assess both organ oxygenation in patients who are not pregnant (5) and fetal tissue and placental oxygenation in patients who are pregnant (6,7).

Wedegärtner et al (4) studied six pregnant sheep during a control period with maternal oxygen saturation of 90%–100% and during a period of hypoxia with maternal oxygen saturation of 60%–80%. The greatest changes in T2* values occurred in the liver and heart (both organs have high blood flow in utero), with smaller changes occurring in the brain, placenta, and lungs. The less marked changes in the brain are compatible with the known fetal physiology, where cerebral blood flow increases during periods of hypoxia. The less marked changes in the placenta are likely caused by the small size of sheep cotyledons, which makes distinction between maternal and fetal portions of the placenta difficult to assess. The less marked changes in the lungs are likely secondary to relative lack of blood flow through the fetal lungs in utero.

THE PRACTICE

Clinical Use:
Screening for IUGR involves evaluation of the endpoints of placental dysfunction, a small fetus, and a low amniotic fluid level. To my knowledge, no proved method for evaluation of placental function in vivo exists at this time; therefore, IUGR is currently diagnosed when a fetus is small. Thus, many small but healthy fetuses are characterized as having IUGR, whereas IUGR is not detected in other fetuses until the endpoints of abnormal growth have been reached, a poor obstetric outcome has occurred, or both. This scenario highlights the critical importance of the development of novel approaches for in vivo evaluation of placental and fetal oxygenation.

Future Opportunities and Challenges:
It is possible that the technology described by Wedegärtner et al (4) will ultimately enable us to assess pregnant patients at risk for IUGR and preeclampsia. This may lead to earlier diagnosis, intervention, and—perhaps—treatment.

The challenges of moving this research to the clinical setting include the fact that Wedegärtner et al (4) used 3-T MR imaging. The safety of 3-T MR imaging in pregnant patients has not been proved. It is standard practice to perform MR imaging at 1.5 T; therefore, this type of work needs to be repeated with 1.5-T MR imaging. The sheep placenta has multiple cotyledons. Studies of the human placenta will likely be easier to perform because of the larger size of the placenta, which will allow for assessment of maternal and fetal portions of the placenta. Many of the challenges relate to obstetric MR imaging in general and include the limitations of signal-to-noise ratio in small structures, artifacts imposed by physiologic motion, and heterogeneous oxygenation across the placenta.

References

1. Parer JT. The effect of acute maternal hypoxia on fetal oxygenation and the umbilical circulation in the sheep. Eur J Obstet Gynecol Reprod Biol 1980;10:125–136.[CrossRef][Medline]
2. Soothill PW, Ajayi RA, Campbell S, et al. Relationship between fetal acidemia at cordocentesis and subsequent neurodevelopment. Ultrasound Obstet Gynecol 1992;2:80–83.[CrossRef][Medline]
3. Spellacy WN. Fetal growth retardation. In: Scott JR, DiSaia PJ, Hammon B, Spellacy WN, eds. Danforth's obstetrics and gynecology. 7th ed. Philadelphia, Pa: Lippincott, 1994; 317.
4. Wedegärtner U, Tchirikov M, Shafer S, et al. Functional MR imaging: comparison of BOLD signal intensity changes in fetal organs with fetal and maternal oxyhemoglobin saturation during hypoxia in sheep. Radiology 2006;238:000–000.
5. Prasad PV, Chen Q, Goldfarb JW, Epstein FH, Edelman RR. Breath-hold R2* mapping with a multiple gradient-recalled echo sequence: application to the evaluation of intrarenal oxygenation. J Magn Reson Imaging 1997;7:1163–1165.[Medline]
6. Semple SI, Wallis F, Haggarty P, et al. The measurement of fetal liver T(*)(2) in utero before and after maternal oxygen breathing: progress towards a non-invasive measurement of fetal oxygenation and placental function. Magn Reson Imaging 2001;19:921–928.[CrossRef][Medline]
7. Wedegartner U, Tchirikov M, Koch M, Adam G, Schroder H. Functional magnetic resonance imaging (fMRI) for fetal oxygenation during maternal hypoxia: initial results. Rofo 2002;174:700–703.[Medline]

This article has been cited by other articles:

				A. Rajakumar, A. Jeyabalan, N. Markovic, R. Ness, C. Gilmour, and K. P. Conrad Placental HIF-1{alpha}, HIF-2{alpha}, membrane and soluble VEGF receptor-1 proteins are not increased in normotensive pregnancies complicated by late-onset intrauterine growth restriction Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R766 - R774. [Abstract] [Full Text] [PDF]

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