Maternal tadalafil treatment does not increase uterine artery blood flow or oxygen delivery in the pregnant ewe.

Increasing placental perfusion (PP) could improve outcomes of growth-restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)-5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116-117 days' gestational age (dGA; term, 150 days), pregnant ewes (n = 6) underwent fetal catheterization surgery. At 120-123 dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15-75 min (TAD 1) and ∼75-135 min (TAD 2) post maternal administration (24 mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion-Relaxation Combined Imaging for Detailed Placental Evaluation-'DECIDE' technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal-placental blood volume fraction was increased in the TAD 2 period. Fetal D O 2 ${D_{{{\mathrm{O}}_2}}}$ and V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal-placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA D O 2 ${D_{{{\mathrm{O}}_2}}}$ .

Developments in functional imaging of the placenta.

The placenta is both the literal and metaphorical black box of pregnancy. Measurement of the function of the placenta has the potential to enhance our understanding of this enigmatic organ and serve to support obstetric decision making. Advanced imaging techniques are key to support these measurements. This review summarises emerging imaging technology being used to measure the function of the placenta and new developments in the computational analysis of these data. We address three important examples where functional imaging is supporting our understanding of these conditions: fetal growth restriction, placenta accreta, and twin-twin transfusion syndrome.

Placental MRI Predicts Fetal Oxygenation and Growth Rates in Sheep and Human Pregnancy.

Magnetic resonance imaging (MRI) assessment of fetal blood oxygen saturation (SO2 ) can transform the clinical management of high-risk pregnancies affected by fetal growth restriction (FGR). Here, a novel MRI method assesses the feasibility of identifying normally grown and FGR fetuses in sheep and is then applied to humans. MRI scans are performed in pregnant ewes at 110 and 140 days (term = 150d) gestation and in pregnant women at 28+3  ± 2+5 weeks to measure feto-placental SO2 . Birth weight is collected and, in sheep, fetal blood SO2 is measured with a blood gas analyzer (BGA). Fetal arterial SO2 measured by BGA predicts fetal birth weight in sheep and distinguishes between fetuses that are normally grown, small for gestational age, and FGR. MRI feto-placental SO2 in late gestation is related to fetal blood SO2 measured by BGA and body weight. In sheep, MRI feto-placental SO2 in mid-gestation is related to fetal SO2 later in gestation. MRI feto-placental SO2 distinguishes between normally grown and FGR fetuses, as well as distinguishing FGR fetuses with and without normal Doppler in humans. Thus, a multi-compartment placental MRI model detects low placental SO2 and distinguishes between small hypoxemic fetuses and normally grown fetuses.

Motion correction of free-breathing magnetic resonance renography using model-driven registration.

INTRODUCTION: Model-driven registration (MDR) is a general approach to remove patient motion in quantitative imaging. In this study, we investigate whether MDR can effectively correct the motion in free-breathing MR renography (MRR). MATERIALS AND METHODS: MDR was generalised to linear tracer-kinetic models and implemented using 2D or 3D free-form deformations (FFD) with multi-resolution and gradient descent optimization. MDR was evaluated using a kidney-mimicking digital reference object (DRO) and free-breathing patient data acquired at high temporal resolution in multi-slice 2D (5 patients) and 3D acquisitions (8 patients). Registration accuracy was assessed using comparison to ground truth DRO, calculating the Hausdorff distance (HD) between ground truth masks with segmentations and visual evaluation of dynamic images, signal-time courses and parametric maps (all data). RESULTS: DRO data showed that the bias and precision of parameter maps after MDR are indistinguishable from motion-free data. MDR led to reduction in HD (HDunregistered = 9.98 ± 9.76, HDregistered = 1.63 ± 0.49). Visual inspection showed that MDR effectively removed motion effects in the dynamic data, leading to a clear improvement in anatomical delineation on parametric maps and a reduction in motion-induced oscillations on signal-time courses. DISCUSSION: MDR provides effective motion correction of MRR in synthetic and patient data. Future work is needed to compare the performance against other more established methods.

Magnetic resonance imaging of placentome development in the pregnant Ewe.

INTRODUCTION: Novel imaging measurements of placental development are difficult to validate due to the invasive nature of gold-standard procedures. Animal studies have been important in validation of magnetic resonance imaging (MRI) measurements in invasive preclinical studies, as they allow for controlled experiments and analysis of multiple time-points during pregnancy. This study characterises the longitudinal diffusion and perfusion properties of sheep placentomes using MRI, measurements that are required for future validation studies. METHODS: Pregnant ewes were anaesthetised for a MRI session on a 3T scanner. Placental MRI was used to classify placentomes morphologically into three types based on their shape and size at two gestational ages. To validate classification accuracy, placentome type derived from MRI data were compared with placentome categorisation results after delivery. Diffusion-Weighted MRI and T2-relaxometry were used to measure a broad range of biophysical properties of the placentomes. RESULTS: MRI morphological classification results showed consistent gestational age changes in placentome shape, as supported by post-delivery gold standard data. The mean apparent diffusion coefficient was significantly higher at 110 days gestation than at late gestation (~140 days; term, 150 days). Mean T2 was higher at mid gestation (152.2 ± 58.1 ms) compared to late gestation (127.8 ms ± 52.0). Significantly higher perfusion fraction was measured in late gestation placentomes that also had a significantly higher fractional anisotropy when compared to the earlier gestational age. DISCUSSION: We report baseline measurements of techniques common in placental MRI for the sheep placenta. These measurements are essential to support future validation measurements of placental MRI techniques.

The effects of maternal position, in late gestation pregnancy, on placental blood flow and oxygenation: an MRI study.

KEY POINTS: Maternal supine sleep position in late pregnancy is associated with an increased risk of stillbirth. Maternal supine position in late pregnancy reduces maternal cardiac output and uterine blood flow. Using MRI, this study shows that compared to the left lateral position, maternal supine position in late pregnancy is associated with reduced utero-placental blood flow and oxygen transfer across the placenta with an average 6.2% reduction in oxygen delivery to the fetus and an average 11% reduction in fetal umbilical venous blood flow. ABSTRACT: Maternal sleep position in late gestation is associated with an increased risk of stillbirth, though the pathophysiological reasons for this are unclear. Studies using magnetic resonance imaging (MRI) have shown that compared with lateral positions, lying supine causes a reduction in cardiac output, reduced abdominal aortic blood flow and reduced vena caval flow which is only partially compensated for by increased flow in the azygos venous system. Using functional MRI techniques, including an acquisition termed diffusion-relaxation combined imaging of the placenta (DECIDE), which combines diffusion weighted imaging and T2 relaxometry, blood flow and oxygen transfer were estimated in the maternal, fetal and placental compartments when subjects were scanned both supine and in left lateral positions. In late gestation pregnancy, lying supine caused a 23.7% (P < 0.0001) reduction in total internal iliac arterial blood flow to the uterus. In addition, lying in the supine position caused a 6.2% (P = 0.038) reduction in oxygen movement across the placenta. The reductions in oxygen transfer to the fetus, termed delivery flux, of 11.2% (P = 0.0597) and in fetal oxygen saturation of 4.4% (P = 0.0793) did not reach statistical significance. It is concluded that even in healthy late gestation pregnancy, maternal position significantly affects oxygen transfer across the placenta and may in part provide an explanation for late stillbirth in vulnerable fetuses.

Improved fetal blood oxygenation and placental estimated measurements of diffusion-weighted MRI using data-driven Bayesian modeling.

PURPOSE: Motion correction in placental DW-MRI is challenging due to maternal breathing motion, maternal movements, and rapid intensity changes. Parameter estimates are usually obtained using least-squares methods for voxel-wise fitting; however, they typically give noisy estimates due to low signal-to-noise ratio. We introduce a model-driven registration (MDR) technique which incorporates a placenta-specific signal model into the registration process, and we present a Bayesian approach for Diffusion-rElaxation Combined Imaging for Detailed placental Evaluation model to obtain individual and population trends in estimated parameters. METHODS: MDR exploits the fact that a placenta signal model is available and thus we incorporate it into the registration to generate a series of target images. The proposed registration method is compared to a pre-existing method used for DCE-MRI data making use of principal components analysis. The Bayesian shrinkage prior (BSP) method has no user-defined parameters and therefore measures of parameter variation in a region of interest are determined by the data alone. The MDR method and the Bayesian approach were evaluated on 10 control 4D DW-MRI singleton placental data. RESULTS: MDR method improves the alignment of placenta data compared to the pre-existing method. It also shows a further reduction of the residual error between the data and the fit. BSP approach showed higher precision leading to more clearly apparent spatial features in the parameter maps. Placental fetal oxygen saturation (FO2 ) showed a negative linear correlation with gestational age. CONCLUSIONS: The proposed pipeline provides a robust framework for registering DW-MRI data and analyzing longitudinal changes of placental function.

Quantifying the Intra-Operative Hemodynamic Effects of Glue Embolization in Vein of Galen Malformations.

Vein of Galen malformation is a rare congenital pathological intracranial arteriovenous shunt which carries 30% risk of death before 28 days-of-age. Treatment is by high risk minimally invasive endovascular glue embolization of shunt feeding arteries under angiographic control. A tool to support intra-operative decision making would be useful. We present a novel method for visualizing angiography data to demonstrate the effect of the intervention based upon change the after embolization in the delay in time of peak contrast density relative to the injected artery and a novel method for quantifying the immediate effect of embolization on the hemodynamics of the shunt. The method is demonstrated on the angiograms of five neonates who underwent embolization. We show consistent results including a post-embolization increase in the delay in time of peak contrast density relative to the injected artery at the venous outflow in keeping with reduced shunting and redistribution of blood following embolization.

Separating fetal and maternal placenta circulations using multiparametric MRI.

PURPOSE: The placenta is a vital organ for the exchange of oxygen, nutrients, and waste products between fetus and mother. The placenta may suffer from several pathologies, which affect this fetal-maternal exchange, thus the flow properties of the placenta are of interest in determining the course of pregnancy. In this work, we propose a new multiparametric model for placental tissue signal in MRI. METHODS: We describe a method that separates fetal and maternal flow characteristics of the placenta using a 3-compartment model comprising fast and slowly circulating fluid pools, and a tissue pool is fitted to overlapping multiecho T2 relaxometry and diffusion MRI with low b-values. We implemented the combined model and acquisition on a standard 1.5 Tesla clinical system with acquisition taking less than 20 minutes. RESULTS: We apply this combined acquisition in 6 control singleton placentas. Mean myometrial T2 relaxation time was 123.63 (±6.71) ms. Mean T2 relaxation time of maternal blood was 202.17 (±92.98) ms. In the placenta, mean T2 relaxation time of the fetal blood component was 144.89 (±54.42) ms. Mean ratio of maternal to fetal blood volume was 1.16 (±0.6), and mean fetal blood saturation was 72.93 (±20.11)% across all 6 cases. CONCLUSION: The novel acquisition in this work allows the measurement of histologically relevant physical parameters, such as the relative proportions of vascular spaces. In the placenta, this may help us to better understand the physiological properties of the tissue in disease.

Fitting the two-compartment model in DCE-MRI by linear inversion.

PURPOSE: Model fitting of dynamic contrast-enhanced-magnetic resonance imaging-MRI data with nonlinear least squares (NLLS) methods is slow and may be biased by the choice of initial values. The aim of this study was to develop and evaluate a linear least squares (LLS) method to fit the two-compartment exchange and -filtration models. METHODS: A second-order linear differential equation for the measured concentrations was derived where model parameters act as coefficients. Simulations of normal and pathological data were performed to determine calculation time, accuracy and precision under different noise levels and temporal resolutions. Performance of the LLS was evaluated by comparison against the NLLS. RESULTS: The LLS method is about 200 times faster, which reduces the calculation times for a 256 × 256 MR slice from 9 min to 3 s. For ideal data with low noise and high temporal resolution the LLS and NLLS were equally accurate and precise. The LLS was more accurate and precise than the NLLS at low temporal resolution, but less accurate at high noise levels. CONCLUSION: The data show that the LLS leads to a significant reduction in calculation times, and more reliable results at low noise levels. At higher noise levels the LLS becomes exceedingly inaccurate compared to the NLLS, but this may be improved using a suitable weighting strategy. Magn Reson Med 76:998-1006, 2016. © 2015 Wiley Periodicals, Inc.