Measuring human placental blood flow with multi-delay 3D GRASE pseudo-continuous arterial spin labeling at 3 Tesla
Xingfeng Shao1, Dapeng Liu2, Thomas Martin2, Teresa Chanlaw3, Sherin U. Devaskar3, Carla Janzen4, Aisling M. Murphy4, Daniel Margolis2, Kyunghyun Sung2, and Danny J.J. Wang1

1Laboratory of FMRI Technology (LOFT), Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, 2Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States, 3Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States, 4Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States


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.


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.


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.


We present a 3D multi-delay pCASL sequence, which is promising for non-invasive measurement of PBF and ATT. Its clinical use for the detection of aberrations in placental function and prediction of fetal developmental disorders awaits further evaluation.


This work was supported by National Institute of Health (NIH) grant NIH U01-HD087221.


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Figure 1. (a) Scheme of inner-volume GRASE pCASL sequence. Background suppression was achieved by two inversion pulses following a whole volume pre-saturation. Switching the slice selective gradient to Y-axis for re-focusing pulses preserved the signal only within the targeting imaging volume to avoid wrapping around artifacts along Y-axis. (b) Demonstration of spatial position of imaging volume and ASL labeling plane. Labeling place was placed at aortic bifurcation and highlighted by the yellow dashed line.

Figure 2. (a) Perfusion signal at PLD=1000/1500/2000 ms of a representative slice. (b) Calculated PBF maps. One of focal hyper-perfusion regions was indicated by a blue arrow. (c) Calculated ATT maps. Images are overlaid on the T2-weighted structural image measured by GRASE sequence.

Figure 3. 3D views of PBF (a) and ATT (b) map. Three pairs of coronal/sagittal slices were displayed adjacent to the transverse plane, and their spatial positions were specified by color arrows around the transverse image.

Figure 4. Comparison of PBF (left plot) and ATT (right plot) acquired from two scans within the second trimester. Each dot in the plot represents PBF or ATT of a single subject while horizontal and vertical axes represent the data from the first (14-16 weeks) and second (19-22 weeks) scans respectively. Slope of the solid blue line was estimated from 34 subjects’ data using the least square method. Red dashed line was plotted for reference with a slope of 1 indicating no change between two scans.

Figure 5. Scatter plot of RI/PI vs. PBF. Left/right column showed RI/PI from left/right uterine artery. Top/bottom row showed results acquired after the first/second MRI scans. Linear regression was illustrated by dashed lines, and no significant correlation was found (P values were listed next to dashed lines). Subjects with the early diastolic notch were labeled by red filled marks. Bilateral/unilateral notches presented in three/one subjects’ Doppler ultrasound waveform pattern acquired after the first MRI scan. Two subjects (#5 and #26) with persistent notches at two scans were identified by arrows.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)