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3D R2* Mapping of the Placenta During Early Gestation Using Free-Breathing Multiecho Stack-of-Radial MRI at 3 T
Tess Armstrong1,2, Dapeng Liu1, Thomas Martin1,2, Rinat Masamed1, Carla Janzen3, Cass Wong1, Teresa Chanlaw4, Sherin U. Devaskar4, Kyunghyun Sung1,2, and Holden H. Wu1,2

1Radiological Sciences, University of California Los Angeles, Los Angeles, CA, United States, 2Physics and Biology in Medicine, University of California Los Angeles, Los Angeles, CA, United States, 3Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States, 4Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States

Synopsis

Ischemic placental disease can lead to hypoxia and abnormal pregnancy outcomes. R2* mapping using MRI can characterize placental hypoxia. However, conventional Cartesian MRI requires breath-holding which limits volumetric coverage, resolution, and signal-to-noise ratio. In addition, little is known about the nominal range of placental R2* at 3T and during early gestation. Therefore, we developed and evaluated a new free-breathing 3D stack-of-radial (free-breathing radial) technique for full volume placental R2* mapping at 3T. Free-breathing radial demonstrated good repeatability and established a nominal range of placental R2* in pregnant subjects during early gestation at 3T.

Introduction

Preeclampsia, intrauterine growth restriction, and placental abruption, collectively known as ischemic placental disease (IPD), are characterized by abnormal vascular development, malperfusion, and hypoxia1–6. IPD-induced preterm deliveries contribute to higher rates of infant and maternal morbidity and mortality3. Higher prevalence rates of IPD have been reported using ultrasound for anterior compared to posterior placentas11. Placental oxygenation can be characterized by MRI R2* mapping7–10. However, placental R2* mapping using conventional Cartesian MRI requires breath-holding to avoid motion artifacts, limiting the volumetric coverage, spatial resolution, and/or signal-to-noise ratio. Previous studies were predominantly limited to R2* mapping in a few 2D slices at 1.5T during later gestational age (GA), and did not distinguish between placenta implantation positions (anterior versus posterior)7–10. 3T MRI may provide greater sensitivity to changes in R2*, and predicting IPD during early GA is imperative to improve outcomes2. Therefore, we developed and evaluated a new free-breathing 3D stack-of-radial (FB radial)12 technique for full volume placental R2* mapping at 3T in pregnant women during early GA and investigated differences between anterior and posterior placentas.

Methods

Experimental Design: A phantom with a R2* range of 5–70s-1 was scanned at 3T (Skyra, Siemens) to evaluate R2* quantification agreement between conventional Cartesian and FB radial MRI (Table 1). 33 pregnant subjects (Table 2) were enrolled in this IRB-approved study and informed consent was obtained. Subjects were scanned at two GA ranges (14-18 and 19-23 weeks GA) using T2 HASTE and FB radial sequences at 3T (Skyra/Prisma, Siemens) (Table 1). IPD was diagnosed at delivery. In all experiments, FB radial was scanned twice back-to-back in the same session to assess repeatability.

Reconstruction: FB radial images were reconstructed offline12,13 and R2* maps were calculated14–16 using a 7-peak fat model17,18 with a single effective R2* per voxel19–21.

Analysis: R2* mapping agreement was assessed using linear correlation and Bland-Altman22 analyses by determining Lin’s concordance correlation coefficient (ρc)23 and mean difference (MD). For pregnant subjects, T2 HASTE images were registered to FB radial images with non-rigid registration24–26. 3D entire placenta contours were delineated on registered T2 HASTE images, copied to FB radial maps to measure placental R2*, and verified by an abdominal radiologist and a maternal fetal medicine specialist, masked to the pregnancy outcome. The coefficient of variation (CV=standard deviation/mean) of R2* within the placental volume was calculated. Placental R2* (mean, range, and CV) at each GA range were calculated for all healthy subjects, and for anterior and posterior placentas. Differences were determined using Wilcoxon Signed-Rank and Rank-Sum tests. Z-scores (Z ̂) for placental R2* in the IPD subjects were determined with respect to the healthy subjects. For phantom experiments and healthy subjects, the coefficient of repeatability (CR)27 was calculated. P<0.05 was considered significant.

Results

FB radial demonstrated accurate (ρc≥0.995; P<0.001; |MD|<0.2s-1) and repeatable (CR<4s-1) R2* mapping in a phantom. 3D FB radial R2* maps of the entire placenta were obtained in pregnant subjects in ~3 minutes (representative healthy subject in Figure 1). FB radial achieved repeatable R2* mapping (CR≤4.6s-1) in healthy pregnant subjects. Placental R2* values for healthy subjects are shown in Table 3. The CV was significantly greater at 14-18 weeks than 19-23 weeks GA. At 19-23 weeks, the CV was significantly lower for anterior than posterior placentas. One IPD subject had a lower mean R2* than healthy subjects (<-2) (Figure 2).

Discussion

Placental R2* measured by FB radial demonstrated stronger repeatability for 14-18 (CR=2.92s-1) than 19-23 weeks GA (CR=8.24s-1) due to two outliers from scans during 19-23 weeks GA with substantial motion (>8mm, determined using FB radial self-navigation)28. With these outliers removed, CR=4.20s-1 at 19-23 weeks GA. Significant differences in the CV between anterior and posterior placentas were observed at 19-23 weeks GA (Table 3). This may be due to vascular differences between anterior and posterior placentas, or because subjects were scanned feet-first supine. Lower R2* in the center of the placenta and higher R2* along the periphery were observed in an IPD subject with preeclampsia (Figure 2); regions of higher R2* could reflect tissue hypoxia. Additional healthy subjects and IPD subjects may be studied to improve the understanding of spatial and temporal characteristics of placental R2*.

Conclusion

FB radial achieved accurate and repeatable R2* mapping in a phantom and repeatable R2* mapping in the entire placenta of healthy pregnant subjects. The range of placental R2* in healthy pregnancies during early gestation at 3T has been established. FB radial may improve the understanding and management of pregnant women with IPD.

Acknowledgements

This work acknowledges the use of the ISMRM Fat-Water Toolbox (http://ismrm.org/workshops/FatWater12/data.htm). The authors would like to thank Irish Del Rosario, Margarida Y. Y. Lei, Dr. Daniel Margolis, Sitaram Vangala, and Aaron Scheffler for their help with this project.

Funding: Research reported in this publication was supported in part by NIH grant NICHD U01-HD087221.

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Figures

Figure 1: Representative in vivo placenta images and R2* maps of a subject with normal pregnancy at 16+2 weeks gestational age acquired using free-breathing (FB) radial MRI at 3T. Axial, coronal and sagittal views are shown. The placenta is delineated by a white contour.

Figure 2: Representative in vivo placenta images and R2* maps of a subject with preeclampsia at 19+1 weeks gestational age acquired using free-breathing (FB) radial MRI at 3T. Axial, coronal and sagittal views are shown. The placenta is delineated by a white contour. White arrows on the R2* maps point to spatial variation. In this subject, R2* was lower than in normal subjects (Z ̂<-2) and there were regions of higher R2* along the periphery and regions of lower R2* in the center of the placenta.

Table 1: Representative sequence parameters for the phantom and in vivo placenta MRI experiments. The acquisitions were obtained in the axial orientation. A slice oversampling factor of 9.1% was used for all radial acquisitions for the in vivo placenta experiments and a slice oversampling factor of 20% was used for Cartesian and radial acquisitions for the R2* phantom experiments. Radial acquisitions were two-fold undersampled based on the Nyquist criteria (i.e. Number of Radial Spokes = Nx × π/2 × 1/2).

Table 2: Summary of the characteristics for the subjects with normal pregnancies and the subjects with abnormal pregnancies due to ischemic placental disease (IPD) reported as mean ± standard deviation, count (percentage,%), or minimum,% – maximum,%. 1One normal subject did not have characteristics due to delivery in another location. 2Three normal subjects did not have characteristics due to delivery in another location or elected to keep placenta. 3One normal subject had incomplete placental weight due to missing part of placenta.

Table 3: Placental R2* measurements in normal subjects using free-breathing radial MRI at 3 T. Mean (± standard deviation) R2*, mean (± standard deviation) coefficient of variation (CV), and R2* range are reported for 14-18 weeks and 19-23 weeks GA and change in R2* over gestational age (GA) (ΔR2*) is reported. Analysis was performed for all subjects (N = 30), and again for the subjects separated into anterior (N = 15) versus posterior (N = 15) placenta implantation positions. wStatistically significant differences with P < 0.05 between 14-18 weeks and 19-23 weeks GA. #Statistically significant differences with P < 0.001 between anterior and posterior placentas.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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