A motion-robust 2D sequential chemical shift-encoded MRI (CSE-MRI) technique with a short temporal footprint for each slice is investigated for ferumoxytol-enhanced MRI of placental inflammation. In this study, the proposed 2D technique was compared with the reference 3D-CSE-MRI technique in healthy pregnant rhesus, which were anesthetized eliminating fetal motion. B0 field map boundary measurements, as well as R2* measurements in the placenta were compared across the two techniques to assess the accuracy of the 2D technique. High correlations between the measurements from 2D-CSE-MRI and 3D-CSE-MRI were demonstrated and thus provide promise for motion-robust imaging of human placental inflammation.
In the pathologies of preeclampsia, the altered immune cell (e.g. macrophage) activation and distribution at implantation may play a critical role1. The FDA-approved iron supplement ferumoxytol is an ultra-small superparamagnetic iron oxide that is phagocytosed by macrophages. Therefore, ferumoxytol-enhanced MRI in the placenta may enable safe and sensitive detection of increased macrophage density in inflammation2. Previously proposed 3D chemical shift-encoded (CSE) MRI enables R2*- and B0- mapping, both of which may enable assessment of tissue ferumoxytol concentration3. However, maternal respiration and fetal motion in the uterus may lead to artifacts in 3D imaging due to the long temporal footprint (~5 minutes), precluding the accurate estimation of R2* and B0 field maps.
The proposed 2D sequential CSE-MRI has a small temporal footprint (e.g. ~3 seconds for each slice as shown in Figure 1), which may enable robust imaging even in the presence of fetal motion. However, it is unknown whether the 2D sequential technique enables accurate R2* and B0 field mapping. In this study, we compared the estimated R2* and B0 field in 2D-CSE-MRI to the standard 3D-CSE-MRI in anesthetized healthy pregnant rhesus. In this animal model, fetal motion is suppressed due to the anesthesia, therefore enabling reliable imaging with the standard 3D-CSE-MRI technique. For this reason, this animal model provides a unique opportunity to validate the proposed 2D-CSE-MRI technique, which may be the only reliable alternative for imaging in human placenta in the presence of fetal motion.
All procedures were approved by our institution’s animal care and use committee (IACUC). Three healthy pregnant rhesus monkeys were imaged on a clinical 3.0T MRI system (GE Healthcare Discovery MR 750, Waukesha, WI) using a 32-channel phased array torso coil (Neocoil, Pewaukee, WI). All mother rhesus monkeys were under general anesthesia during the scanning, which also anesthetized the fetus, thereby eliminating fetal motion. Six time points were collected for each monkey. Details on the gestational age of the animals, the scan days and ferumoxytol injection are shown in Table 1.
A multi-echo spoiled gradient-echo 2D sequential acquisition without respiratory gating was optimized for motion robustness and performed in the placenta of each animal. A multi-echo spoiled gradient-echo 3D acquisition with respiratory gating was acquired as the reference for ferumoxytol-enhanced CSE MRI in the placenta. Scan parameters are listed in Table 2. R2* and B0 field maps were obtained by using a CSE reconstruction4. R2* measurements were performed using ROIs drawn in two separate placental lobes of each animal at each time point. B0 field values in the placenta and adjacent amniotic fluid (AF) of each monkey (at day 0-post and day 1) were measured and subtracted to obtain the boundary B0 field difference (ΔB0, obtained along boundaries parallel to the main magnetic field), a measure of magnetic susceptibility difference between the two regions3. Linear regression analysis was used to assess the correlation of R2* as well as ΔB0 estimated in 2D versus 3D imaging.
1. Faas MM, et al. Monocytes and macrophages in pregnancy and pre-eclampsia. Front Immunol. 2014; 5:298.
2. Neuwelt A, et al. Iron-based superparamagnetic nanoparticle contrast agents for MRI of infection and inflammation. AJR. 2015; 204(3):W302.
3. Hernando D, et al. Magnetic susceptibility as a B0 field strength independent MRI biomarker of liver iron overload. Magn Reson Med. 2013; 70(3):648-656.
4. Yu H, et al. Multiecho water-fat separation and simultaneous R2* estimation with multifrequency fat spectrum modeling. Magn Reson Med. 2008; 60(5):1122-1134.