Synopsis

Placenta influences the health of both a woman and her fetus during pregnancy. Maternal blood supply to placenta can be measured non-invasively using arterial spin labeling (ASL). The purpose of this study is to present a multi-delay pseudo-continuous arterial spin labeling (pCASL) combined with a fast 3D inner-volume gradient- and spin-echo (GRASE) imaging technique to simultaneously measure placental blood flow (PBF) and arterial transit time (ATT), and to study PBF and ATT evolution with gestational age during the second trimester. The PBF values were compared with uterine arterial Doppler ultrasound to assess its potential clinical utility.

Background

Placenta supports the pregnancy by providing the developing fetus with nutrients and oxygen via maternal blood supply. Pathological development of the utero-placental unit or defective trophoblastic invasion, which can lead to intrauterine growth restriction (IUGR) and Pre-eclampsia (PE), increases the resistance to blood flow, and restricts placental perfusion.

The purpose of this study was to present a multi-delay pseudo-continuous artierial spin labeling (pCASL) sequence, which is capable of selectively labeling maternal feeding aorta, combined with a fast 3D inner-volume Gradient-and Spin Echo (GRASE) imaging technique for non-invasive and simultaneous assessment of placental blood flow (PBF) and arterial transit time (ATT) in pregnant women.

Methods

Figure 1 (a) shows the diagram of pCASL GRASE sequence. Background suppression was applied to minimize temporal fluctuations.¹ Inner-volume excitation was achieved by switching the slice-selective gradient to phase encoding axis for re-focusing pulses,² which enables single-shot readout to cover the whole placenta. The imaging volume was selected as perpendicular to the maternal-fetal axis, and the labeling plane was placed proximal perpendicular to the abdominal aorta and above the aortic bifurcation (Fig. 1b).

34 normal pregnant women (32.6±4.5yrs) were scanned on Siemens 3T scanners (Prisma and Skyra). Each subject was scanned twice within the second trimester (first/second scans were conducted between 14-16/19-22 weeks of gestational age). Imaging parameters were: FOV=300mm, eight slices (20% oversampling), single shot, resolution=3.1×3.1×3mm³, echo spacing=0.49ms, TE=36.5ms, TR=4000ms, label/control duration=1500ms, PLD=1000/1500/2000ms, each PLD contained 14 repetitions and one $$$M_0$$$ scan (2min4sec). Global specific absorption rate (SAR) was monitored for RF heating.

Pixel-wise PBF was estimated by:³

$$f=\frac{\Delta M\lambda R_{1a} }{2\alpha M_0[exp((min(\delta -w,0)-\delta)R_{1a})-exp(-(\tau +w)R_{1a})]}$$[1]

where $$$\Delta M$$$ is the perfusion signal, $$$M_0$$$ is the equilibrium magnetization, $$$f$$$ is blood flow, $$$\alpha$$$=0.63 is the labeling efficiency at the aortic bifurcation (vessel center velocity=11.5 cm/s) estimated by the numerical integration,⁴ $$$\lambda$$$=1ml/g is tissue water partition coefficient,⁵ $$$w$$$ is PLD, $$$\tau$$$ is labeling duration, $$$R_{1a}$$$=1/1660ms^-1 is the longitudinal relaxation rate of blood, $$$\delta$$$ is ATT, which was calculated based on a monotonic relationship with weighted delay (WD):⁶

$$WD=\frac{\sum_{i=1}^Nw_i\Delta M_i}{\sum_{i=1}^N\Delta M_i}$$[2]

where $$$N$$$=3. $$$f_i$$$ was calculated for each PLD, and averaged to produce the final PBF. Repeated scans from 34 subjects were analyzed for PBF and ATT variations with placental development.

The PBF values were compared with ultrasound measurement to assess its potential clinical utility. Uterine arterial Doppler ultrasound was collected from 21/20 subjects after the first/second MRI scans (16 subjects had ultrasound after both MRI scans). RI (resistive index), PI (pulsatility index), and notching at early diastole were measured on both sides of uterine arteries. Poor placental perfusion is typically indicated by increased RI, PI or the persistence of an early diastolic notch in uterine blood flow waveform pattern.

Paired t-test was conducted to evaluate the significance of PBF/ATT variations with placental development. RI and PI were correlated with average PBF using linear regression. Two-sample t-test was conducted to evaluate the significance of PBF difference in subjects with and without early diastolic notch.

Results and discussion

Figure 2 shows perfusion images, PBF and ATT maps. With perfusion signals acquired at three delay times, it is feasible to perform dynamic analysis of regions of interest to better understand how labeled blood passes through the placenta. The global SAR was averaged to be 1.19±0.23 W/kg, about 60% of normal mode limit.

Figure 3 shows 3D view of PBF (a) and ATT (b). Apparent hyper-perfusion regions are displayed in coronal/sagittal views, with arrows indicating the spatial locations corresponds to the transversal image. Whole placenta PBF maps provide spatially resolved diagnostic information, which provides an understanding of the underlying vasculature.

PBF/ATT values of the second scan are plotted against the first scan (Fig. 4). The average PBF increased by 10.4% (P<0.05) while no significant change in ATT (P=0.72) along gestational age. Overall, PBF and ATT for the second trimester were 111.4±26.7 ml/100g/min and 1387.5±88.0 ms, matching well with the literature.⁷

Scatter plot of PI and RI against PBF was shown in Figure 5. No significant correlation between PI/RI and PBF was found. PBF across subjects with unilateral/bilateral notch is 89.1±12.4ml/100g/min, which is significantly lower than 111.9±22.4ml/100g/min from the subjects without notch (P<0.01). A 20.3% reduction in PBF is consistent with the presence of notches, which represents the sign of high impedance to flow.⁸ Since ultrasound is an established imaging modality, this result supports the validity of the presented ASL approach for assessing placental function.

Conclusion

Acknowledgements

References

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