INTRODUCTION

Reliable evaluation of in vivo placental function is important for detecting early deviation from normal fetal development, and is necessary to open a new, currently unavailable therapeutic window. Recently, placental perfusion imaging using velocity-selective arterial spin labeling (VSASL)¹ was applied in pregnancies complicated by fetal heart disease, and revealed a significant difference in placental perfusion from healthy pregnancies². In the current study, we demonstrate the feasibility of performing VSASL in the human placenta and provide supporting evidence that is needed for validation of placental VSASL.

METHODS

Pulse Sequence: VS labeling was achieved with a cutoff velocity of 2 cm/s. Image acquisition was performed using fast-spin-echo 3D stack of spirals with 8 interleaves, TR/TE = 3000/10 ms, FOV = 36-40 cm, matrix size = 64x64, number of slices = 36-44, and slice thickness = 4 mm. Total scan time was 3:55 min. All scans were performed on a GE MR450 1.5 T scanner with an 8-channel cardiac coil. Comparison with pseudocontinuous ASL (PCASL): PCASL is the standard ASL method for measuring cerebral blood flow³. Placental VSASL and PCASL were performed in seven healthy pregnant volunteers (mean GA: 25±5 weeks) for comparison. PCASL was performed twice with two different labeling positions: 2.2 cm above and below the axial imaging slab. In PCASL, identical image acquisition to VSASL was used, labeling duration and post-labeling delay were 1450 ms and 2025 ms respectively, and total scan time was 4:10 min. Reproducibility: Placental VSASL scan was repeated back to back within the same scan session in fourteen healthy pregnant volunteers (mean GA: 28±5 weeks). Reproducibility was assessed using within-subject standard deviation (wsSD), within-subject coefficient of variation (wsCV), repeatability, and intraclass correlation coefficient (ICC)^4,5. Response to Maternal Hyperoxia: Maternal hyperoxia was employed to modulate VSASL signal in the placenta by changing relaxation times of blood inflow in seven healthy pregnant women (mean GA: 30±6 weeks). 100% oxygen was inhaled through facial mask with rate of 15 L/min for 4-6 min. Varying Cutoff Velocity: As another way to modulate VSASL signal, cutoff velocity was varied from 2 cm/s to 4cm/s and infinity (i.e. no labeling) in six healthy pregnant women (mean GA: 32±2 weeks). Larger cutoff velocity was expected to generate the label farther from the imaging region, leading to reduced apparent VSASL signal.

RESULTS AND DISCUSSION

Comparison with PCASL: Depending on the location of the placenta in the uterus, PCASL with one labeling location showed higher apparent placental perfusion than PCASL with the other labeling location. However, VSASL consistently showed substantially higher perfusion signal than PCASL using either labeling location (p < 0.01 for both; see Figure 1). Figure 2 shows comparison of VSASL and PCASL images acquired in two subjects. Reproducibility: Placental VSASL demonstrated high reproducibility based on the following parameters: wsSD = 7.1 ml/100 g/min (note that overall mean of placental perfusion in this experiment was 195 ml/100 g/min); wsCV = 3.5%; repeatability = 19.7 ml/100 g/min; ICC = 0.97. Figure 3 shows correlation and Bland-Altman plots of two repeated VSASL measurements. Response to Maternal Hyperoxia: Figure 4 compares the apparent placental perfusion with and without maternal hyperoixa as well as the results from the reproducibility test in the same subjects. The absolute difference (i.e. either increase or decrease) in placental perfusion between with and without hyperoxia was significantly larger than that of two repeated measurements without hyperoxia (p < 0.01). The inconsistent change of perfusion with hyperoxia may be because VSASL is sensitive to both T1 and T2 changes. Increased oxygenation with hyperoxia reduces T1 and increases T2 of blood, leading to reduction and increase in VSASL signal respectively. Overall VSASL signal change with hyperoxia may be positive or negative depending on actual changes of T1 and T2 in each subject. Varying Cutoff Velocity: Figure 5 shows the apparent placental perfusion measured using VSASL with cutoff velocity of 2 cm/s, 4 cm/s, and infinity. The differences between three measurements were all statistically significant (p < 0.01, for all).

CONCLUSION

Placental VSASL generated significantly higher ASL signal than PCASL and showed high reproducibility within the same imaging session. Placenta VSASL was also found to be dependent on blood inflow based on modulation of VSASL signal using 100% oxygen inhalation and variation of cutoff velocity. This study supports the use of VSASL in placental perfusion imaging and lays the groundwork for future investigation of placental perfusion imaging in pregnancies complicated by placental insufficiency such as fetal growth restriction and preeclampsia.

Acknowledgements

R01 HL116585-01 from NIH National Heart, Lung, and Blood Institute, and UL1TR000075/KL2TR000076 from the NIH National Center for Advancing Translational Sciences.

References

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