In Vivo Quantification of Placental Insufficiency by BOLD MRI: A Human Study
Jie Luo, Esra Abaci Turk, Carolina Bibbo, Borjan Gagoski, Drucilla J Roberts, Mark Vangel, Clare M Tempany-Afdhal, Carol Barnewolt, Judy Estroff, Arvind Palanisamy, William H Barth, Chloe Zera, Norberto Malpica, Polina Golland, Elfar Adalsteinsson, Julian N Robinson, Patricia Ellen Grant, Jie Luo, Esra Abaci Turk, Carolina Bibbo, Borjan Gagoski, Drucilla J Roberts, Mark Vangel, Clare M Tempany-Afdhal, Carol Barnewolt, Judy Estroff, Arvind Palanisamy, William H Barth, Chloe Zera, Norberto Malpica, Polina Golland, Elfar Adalsteinsson, Julian N Robinson, Patricia Ellen Grant
Abstract
Fetal health is critically dependent on placental function, especially placental transport of oxygen from mother to fetus. When fetal growth is compromised, placental insufficiency must be distinguished from modest genetic growth potential. If placental insufficiency is present, the physician must trade off the risk of prolonged fetal exposure to placental insufficiency against the risks of preterm delivery. Current ultrasound methods to evaluate the placenta are indirect and insensitive. We propose to use Blood-Oxygenation-Level-Dependent (BOLD) MRI with maternal hyperoxia to quantitatively assess mismatch in placental function in seven monozygotic twin pairs naturally matched for genetic growth potential. In-utero BOLD MRI time series were acquired at 29 to 34 weeks gestational age. Maps of oxygen Time-To-Plateau (TTP) were obtained in the placentas by voxel-wise fitting of the time series. Fetal brain and liver volumes were measured based on structural MR images. After delivery, birth weights were obtained and placental pathological evaluations were performed. Mean placental TTP negatively correlated with fetal liver and brain volumes at the time of MRI as well as with birth weights. Mean placental TTP positively correlated with placental pathology. This study demonstrates the potential of BOLD MRI with maternal hyperoxia to quantify regional placental function in vivo.
Conflict of interest statement
J. Luo, E. Abaci Turk, P.E. Grant, N. Malpica, and E. Adalsteinsson are co-inventors on a patent applications describing the MRI based method for measuring placental transport.
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References
- Gagnon R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol. 2003;110(Suppl 1):S99–107. doi: 10.1016/S0301-2115(03)00179-9.
- Resnik, R. Fetal growth restriction: Evaluation and management. UpToDate, Waltham, MA (Accessed on Oct. 20, 2016).
- Baschat AA, Odibo AO. Timing of delivery in fetal growth restriction and childhood development: some uncertainties remain. Am J Obstet Gynecol. 2011;204:2–3. doi: 10.1016/j.ajog.2010.10.915.
- Walker DM, et al. The growth restriction intervention trial: long-term outcomes in a randomized trial of timing of delivery in fetal growth restriction. Am J Obstet Gynecol. 2011;204(34):e1–9.
- Benirschke, K., Burton, G. J. & Baergen, R. N. Pathology of the Human Placenta, 6th edition (Springer-Verlag Berlin Heidelberg, 2012).
- Serov AS, Salafia C, Grebenkov DS, Filoche M. The role of morphology in mathematical models of placental gas exchange. J Appl Physiol. 2016;120:17–28. doi: 10.1152/japplphysiol.00543.2015.
- Frias AE, et al. Using dynamic contrast-enhanced mri to quantitatively characterize maternal vascular organization in the primate placenta. Magn Reson Med. 2015;73:1570–1578. doi: 10.1002/mrm.25264.
- Brunelli R, et al. Intervillous circulation in intra-uterine growth restriction. correlation to fetal well being. Placenta. 2010;31:1051–1056. doi: 10.1016/j.placenta.2010.09.004.
- Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association between mri exposure during pregnancy and fetal and childhood outcomes. JAMA. 2016;316:952–961. doi: 10.1001/jama.2016.12126.
- Zaharchuk G, Martin AJ, Dillon WP. Noninvasive imaging of quantitative cerebral blood flow changes during 100 imaging. AJNR Am J Neuroradiol. 2008;29:663–667. doi: 10.3174/ajnr.A0896.
- Egbor M, Ansari T, Morris N, Green CJ, Sibbons PD. Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction. BJOG. 2006;113:580–589. doi: 10.1111/j.1471-0528.2006.00882.x.
- Sun L, et al. Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation. 2015;131:1313–1323. doi: 10.1161/CIRCULATIONAHA.114.013051.
- Sorensen A, et al. Changes in human placental oxygenation during maternal hyperoxia estimated by blood oxygen level-dependent magnetic resonance imaging (bold mri) Ultrasound Obstet Gynecol. 2013;42:310–314. doi: 10.1002/uog.12395.
- Sorensen A, et al. Changes in human fetal oxygenation during maternal hyperoxia as estimated by bold mri. Prenat Diagn. 2013;33:141–145. doi: 10.1002/pd.4025.
- Sorensen A, et al. Placental oxygen transport estimated by the hyperoxic placental bold mri response. Physiol Rep. 2015;3:e12582. doi: 10.14814/phy2.12582.
- Turk, E. A. et al. Spatiotemporal alignment of in utero bold-mri series. J Magn Reson Imaging, doi:10.1002/jmri.25585 (2017).
- Chasen, S. & Chervenak, F. A. Twin pregnancy: Prenatal issues. UpToDate, Waltham, MA (Accessed on Aug. 18, 2016).
- Burton GJ, Woods AW, Jauniaux E, Kingdom JC. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta. 2009;30:473–482. doi: 10.1016/j.placenta.2009.02.009.
- Konje JC, Kaufmann P, Bell SC, Taylor DJ. A longitudinal study of quantitative uterine blood flow with the use of color power angiography in appropriate for gestational age pregnancies. Am J Obstet Gynecol. 2001;185:608–613. doi: 10.1067/mob.2001.117187.
- Sutton MS, et al. Changes in placental blood flow in the normal human fetus with gestational age. Pediatr Res. 1990;28:383–387. doi: 10.1203/00006450-199010000-00016.
- Barbera A, et al. Relationship of umbilical vein blood flow to growth parameters in the human fetus. Am J Obstet Gynecol. 1999;181:174–179. doi: 10.1016/S0002-9378(99)70456-4.
- Huen I, et al. R1 and r2* changes in the human placenta in response to maternal oxygen challenge. Magn Reson Med. 2013;70:1427–1433. doi: 10.1002/mrm.24581.
- Aimot-Macron S, et al. In vivo mri assessment of placental and foetal oxygenation changes in a rat model of growth restriction using blood oxygen level-dependent (bold) magnetic resonance imaging. Eur Radiol. 2013;23:1335–1342. doi: 10.1007/s00330-012-2712-y.
- Chalouhi GE, et al. Fetoplacental oxygenation in an intrauterine growth restriction rat model by using blood oxygen level-dependent mr imaging at 4.7 t. Radiology. 2013;269:122–129. doi: 10.1148/radiol.13121742.
- Schabel MC, et al. Functional imaging of the nonhuman primate placenta with endogenous blood oxygen level-dependent contrast. Magn Reson Med. 2016;76:1551–1562. doi: 10.1002/mrm.26052.
- Huen I, et al. Absence of po2 change in fetal brain despite po2 increase in placenta in response to maternal oxygen challenge. BJOG. 2014;121:1588–1594. doi: 10.1111/1471-0528.12804.
- Simchen MJ, et al. Effects of maternal hyperoxia with and without normocapnia in uteroplacental and fetal doppler studies. Ultrasound Obstet Gynecol. 2005;26:495–499. doi: 10.1002/uog.1995.
- Brantberg A, Sonesson SE. Central arterial hemodynamics in small-for-gestational-age fetuses before and during maternal hyperoxygenation: a doppler velocimetric study with particular attention to the aortic isthmus. Ultrasound Obstet Gynecol. 1999;14:237–243. doi: 10.1046/j.1469-0705.1999.14040237.x.
- Arduini D, Rizzo G, Mancuso S, Romanini C. Short-term effects of maternal oxygen administration on blood flow velocity waveforms in healthy and growth-retarded fetuses. Am J Obstet Gynecol. 1988;159:1077–1080. doi: 10.1016/0002-9378(88)90417-6.
- Carter AM. Placental gas exchange and the oxygen supply to the fetus. Compr Physiol. 2015;5:1381–1403. doi: 10.1002/cphy.c140073.
- Carter AM. Placental oxygen consumption. part i: in vivo studies–a review. Placenta. 2000;21(Suppl A):S31–37. doi: 10.1053/plac.1999.0513.
- Moore LG, Charles SM, Julian CG. Humans at high altitude: hypoxia and fetal growth. Respir Physiol Neurobiol. 2011;178:181–190. doi: 10.1016/j.resp.2011.04.017.
- Illsley NP, Caniggia I, Zamudio S. Placental metabolic reprogramming: do changes in the mix of energy-generating substrates modulate fetal growth? Int J Dev Biol. 2010;54:409–419. doi: 10.1387/ijdb.082798ni.
- Zamudio S, et al. Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. PLoS One. 2010;5:e8551. doi: 10.1371/journal.pone.0008551.
- Longo LD, Dale PS, Gilbert RD. Uteroplacental o2 uptake: continuous measurements during uterine quiescence and contractions. Am J Physiol. 1986;250:R1099–1107.
- Friesen-Waldner LJ, et al. Hyperpolarized [1-(13) c]pyruvate mri for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs. J Magn Reson Imaging. 2016;43:750–755. doi: 10.1002/jmri.25009.
- Tustison NJ, et al. N4itk: improved n3 bias correction. IEEE Trans Med Imaging. 2010;29:1310–1320. doi: 10.1109/TMI.2010.2046908.
- Guyader JM, et al. Influence of image registration on apparent diffusion coefficient images computed from free-breathing diffusion mr images of the abdomen. J Magn Reson Imaging. 2015;42:315–330. doi: 10.1002/jmri.24792.
- Klein S, Staring M, Murphy K, Viergever MA, Pluim J. P. elastix: a toolbox for intensity-based medical image registration. IEEE Trans Med Imaging. 2010;29:196–205. doi: 10.1109/TMI.2009.2035616.
- Yushkevich PA, et al. User-guided 3d active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. 2006;31:1116–1128. doi: 10.1016/j.neuroimage.2006.01.015.
- Friston, K., Ashburner, J., Kiebel, S., Nichols, T. & Penny, W. Statistical Parametric Mapping: The Analysis of Functional Brain Images (Academic Press, 2007).
- Frackowiak, R. S. et al. Human Brain Function (Academic Press, 1997).
- Khong TY, et al. Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med. 2016;140:698–713. doi: 10.5858/arpa.2015-0225-CC.
- Ramsay, J. Functional data analysis matlab toolbox; (2014).
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