Prenatal cannabis use is rising, in part due to legalization and perceptions of safety. The impact of prenatal cannabis exposure on offspring development, especially respiratory health, remains largely unknown. The objective of this study was to determine whether in utero exposure to delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, is deleterious to offspring lung development and function using a rhesus macaque model. Female rhesus macaques received a daily edible containing either THC (2.5 mg/7 kg/day, equivalent to a heavy medical cannabis dose) or placebo during gestation and postnatally. Serial in utero magnetic resonance imaging (MRI) was performed during pregnancy at approximately gestational days (G)110 and G150. At 6 mo of age, infants underwent pulmonary function testing, followed by tissue collection for molecular analysis (bulk RNAseq, whole genome bisulfite sequencing, and spatial RNAseq). THC-exposed infants displayed significantly reduced forced residual capacity, which correlated with nonsignificant decreases in total lung capacity, lung diffusion capacity and lower fetal lung perfusion, oxygen availability, and lung volume measured by MRI. Consistent with these decreases in volume indices, levels of pulmonary growth factors were decreased in bronchial alveolar lavage at 6 mo. Molecular analysis of infant lungs revealed altered epigenetic regulation of gene expression, including at genes involved in extracellular matrix organization and lung development, and activation of immune signaling. Our study suggests that exposure to prenatal edible THC alters epigenetic regulation of lung gene expression and may negatively affect offspring lung development and function. Data from this study will help guide healthcare provider counseling on cannabis use in pregnancy.NEW & NOTEWORTHY In a translational rhesus macaque model, chronic prenatal delta-9-tetrahydrocannabinol exposure resulted in decreased lung volumes in offspring measured at 6 mo of age. These decreases correlated with altered DNA methylation in the lung, including at genes involved in extracellular matrix organization, lung development, and activation of immune signaling, and changes in lung cell composition as measured by spatial transcriptomics. These findings add to the growing evidence that prenatal cannabis exposure may adversely affect offspring development.

The placenta plays a crucial role in ensuring adequate oxygen delivery to the fetus. Despite being one of the most important organs in pregnancy, the placenta remains poorly understood. Research into placental developmental structure and function has accelerated in recent years. The use of a preclinical pregnant nonhuman primate model allows researchers to quantify blood and oxygen transfer through the placenta and potentially improve our understanding of it. Furthermore, deploying Magnetic Resonance Imaging (MRI) to better understand the explicit function and mechanism of the placental vascular supply has become commonplace. Among these MRI techniques, T2, T2* and diffusivity are the most commonly deployed for accessing the pseudo-quantitative physical properties of the placenta. To enable better analysis of the placenta from MR images, and reduce the labour-intensive workload of manually delineating regions of interest, here we deployed a robust deep learning model trained on T2* MR images acquired from pregnant rhesus macaques, with the ground truth placenta segmentation drawn by our experts. After obtaining the trained model, we experimented with three segmentation fusion strategies aimed at merging the estimated segmentations from multi-echo times into one final outcome. For each fusion method, we conducted experiments to evaluate the effect of the automated segmentation on T2* estimation, including varying the echo time and the number of imaging slices. The best Dice score (averaging fusion method over 6 segmentations from different TE in one scan) reached 0.869. This work highlights the robustness of our trained segmentation model on nonhuman primate datasets and its potential for application in future preclinical studies. With appropriate fine-tuning, it could also be adapted for analysing human placental datasets.

Although the central role of adequate blood flow and oxygen delivery is known, the lack of optimized imaging modalities to study placental structure has impeded our understanding of its vascular function. Magnetic resonance imaging is increasingly being applied in this field, but gaps in knowledge remain, and further methodological developments are needed. In particular, the ability to distinguish maternal from fetal placental perfusion and the understanding of how individual placental lobules are functioning are lacking. The potential clinical benefits of developing noninvasive tools for the in vivo assessment of blood flow and oxygenation, two key determinants of placental function, are tremendous. Here, we summarize a number of structural and functional magnetic resonance imaging techniques that have been developed and applied in animal models and studies of human pregnancy over the past decade. We discuss the potential applications and limitations of these approaches. Their combination provides a novel source of contrast to allow analysis of placental structure and function at the level of the lobule. We outline the physiological mechanisms of placental T2 and T2* decay and devise a model of how tissue composition affects the observed relaxation properties. We apply this modeling to longitudinal magnetic resonance imaging data obtained from a preclinical pregnant nonhuman primate model to provide initial proof-of-concept data for this methodology, which quantifies oxygen transfer and placental structure across and between lobules. This method has the potential to improve our understanding and clinical management of placental insufficiency once validation in a larger nonhuman primate cohort is complete.

Introduction: Our goal was to evaluate the potential utility of magnetic resonance imaging (MRI) placental volume as an assessment of placental insufficiency. Methods: Secondary analysis of a prospective cohort undergoing serial placental MRIs at two academic tertiary care centers. The population included 316 participants undergoing MRI up to three times throughout gestation. MRI was used to calculate placental volume in milliliters (ml). Placental-mediated adverse pregnancy outcome (cAPO) included preeclampsia with severe features, abnormal antenatal surveillance, and perinatal mortality. Serial measurements were grouped as time point 1 (TP1) <22 weeks, TP2 22 0/7-29 6/7 weeks, and TP3 >= 30 weeks. Mixed effects models compared change in placental volume across gestation between cAPO groups. Association between cAPO and placental volume was determined using logistic regression at each TP with discrimination evaluated using area under receiver operator curve (AUC). Placental volume was then added to known clinical predictive variables and evaluated with test characteristics and calibration. Results: 59 (18.7 %) of 316 participants developed cAPO. Placental volume growth across gestation was slower in the cAPO group (p < 0.001). Placental volume was lower in the cAPO group at all time points, and alone was moderately predictive of cAPO at TP3 (AUC 0.756). Adding placental volume to clinical variables had moderate discrimination at all time points, with strongest test characteristics at TP3 (AUC 0.792) with sensitivity of 77.5 % and specificity of 75.3 % at a predicted probability cutoff of 15 %. Discussion: MRI placental volume warrants further study for assessment of placental insufficiency, particularly later in gestation.

Low placental volume (PV) as assessed by ultrasound has been linked to adverse pregnancy outcomes (APOs), but the predictive power and test characteristics of PV in the second or third trimester remain poorly understood. We aimed to assess the relationship between PVs and APOs in a longitudinal cohort study. Secondary cohort analysis of the Placenta Imaging Study, a prospective study of pregnant individuals enriched for risk factors for preeclampsia and fetal growth restriction (FGR). Participants underwent up to 3 serial MRI studies during pregnancy and acquired MRI data was used to calculate the PV. Severe placental mediated APO composite (cAPO) included preeclampsia with severe features, preterm delivery due to FGR, perinatal death, need for delivery due to FGR/oligohydramnios/abnormal fetal testing, 5 min Apgar < 7, and/or neonatal intubation. Logistic regression predictive models were built containing a) PV only, b) clinical variables only, c) clinical variables + PV. These were built at time windows 22-29 6/7 (T2) and 30+ weeks gestation (T3). Model performance and test characteristics were reported after bootstrapping to reduce optimism. We chose a cutoff of 10% predicted probability for positive test given goal of minimizing missing individuals at risk. Data were available for 316 people for the clinical model, 269 for T2, and 240 for T3. 65 (20.6%) experienced cAPOs. Those with cAPOs were more likely to smoke, have chronic HTN, diabetes, or asthma, have less education, be unpartnered, and use government insurance. Median (interquartile ratio) PV was 454.7ml (357.4-559.6) at T2 with range 68.7-1139.3ml and 684.7ml (582.5-817.0) at T3 with range 231.6-1332.9ml (Figure 1). Both the PV only models and the clinical variables + PV models outperformed the clinical only model at T2 and T3 time points with regards to discrimination and specificity, although sensitivity was lower (Table 1). Incorporating PV measurements into assessment of pregnancy risk for APOs improves specificity and reduces false positives.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Maternal malnutrition increases fetal and neonatal morbidity, partly by affecting placental function and morphology, but its impact on placental hemodynamics are unknown. Our objective was to define the impact of maternal malnutrition on placental oxygen reserve and perfusion in vivo in a rhesus macaque model of protein restriction (PR) using advanced imaging. Animals were fed control (CON, 26% protein), 33% PR diet (17% protein), or a 50% PR diet (13% protein, n = 8/group) preconception and throughout pregnancy. Animals underwent Doppler ultrasound and fetal biometry followed by MRI at gestational days 85 (G85) and 135 (G135; term is G168). Pregnancy loss rates were 0/8 in CON, 1/8 in 33% PR, and 3/8 in 50% PR animals. Fetuses of animals fed a 50% PR diet had a smaller abdominal circumference (G135, p < 0.01). On MRI, placental blood flow was decreased at G135 (p < 0.05) and placental oxygen reserve was reduced (G85, p = 0.05; G135, p = 0.01) in animals fed a 50% PR diet vs. CON. These data demonstrate that a 50% PR diet reduces maternal placental perfusion, decreases fetal oxygen availability, and increases fetal mortality. These alterations in placental hemodynamics may partly explain human growth restriction and stillbirth seen with severe PR diets in the developing world.

Unlike other tomographic imaging methods, quantitative contrast-enhanced magnetic resonance imaging is an indirect measurement technique that infers contrast agent concentrations via changes in 1H2O relaxation rate. The presence of physical barriers to water exchange between tissue compartments (e.g., from the blood plasma to the interstitium or from the interstitium to the intracellular space) can significantly impact this dependence. As a fundamental physical property of the underlying tissues, water exchange is not only a factor that complicates data analysis, but also a potentially significant parameter in its own right, providing a mechanism to interrogate tissues at the microstructural level. This chapter is intended to guide practitioners by clarifying considerations and describing techniques pertinent to assessing and modeling the impact of water exchange in real-world dynamic contrast-enhanced magnetic resonance imaging studies, including potential confounders and methods for modulating the sensitivity of acquired data to these effects.

Placental T2* (PT2*) measurements and serum placental growth factor (PlGF) are associated with adverse pregnancy outcomes (APOs) due to placental insufficiency. We aimed to determine the correlation between these two predictors and their performance in predictive models of APOs. Secondary cohort analysis of the Placenta Imaging Study, a prospective study of pregnant individuals enriched for risk factors for placental insufficiency. Participants had serial blood draws and up to three MRIs. Severe placental mediated APO composite (cAPO) included preeclampsia with severe features, perinatal death, delivery due placental insufficiency, and 5 min Apgar < 7. We used Pearson correlation to evaluate PlGF and PT2*. Logistic regression models were built containing clinical variables only, PlGF, PT2* z-score, and combinations of these. Measurements from T2 (22-29 6/7 wks) and T3 (30+ wks) were used. Model performance and test characteristics were reported after bootstrapping to reduce optimism and optimized model was chosen using these. Predicted probability of 10% was considered a positive test. 316 people were in the clinical model, 146 in T3 PlGF, and 207 in T3 PT2*. 65 (20.6%) experienced cAPO. Those with cAPOs were more likely to smoke, have chronic hypertension (cHTN), pregestational diabetes (DM), or asthma, have less education, be unpartnered, and use government insurance. Correlation between PlGF and PT2* was r=0.3473 (medium strength), p=< 0.001. PlGF and PT2* both had higher specificity for cAPOs than the clinical model but lower sensitivity (Table 1). The optimized model included cHTN, DM, tobacco use, body mass index < 18.5 kg/m2, post-term, T2 PT2*, and T3 PlGF measurements, with c-statistic of 0.787 after shrinkage, sensitivity of 83.3%, specificity of 55.7%, positive predictive value of 29.9%, and negative predictive value of 93.7% (Fig. 2). Incorporating PlGF and PT2* into predictive models of APOs improves discrimination, calibration, and test characteristics, particularly with regards to specificity. Such models may prove useful in risk stratification.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

BACKGROUND: Prenatal alcohol exposure is the most common cause of birth defects and intellectual disabilities and can increase the risk of stillbirth and negatively impact fetal growth. OBJECTIVE: To determine the effect of early prenatal alcohol exposure on nonhuman primate placental function and fetal growth. We hypothesized that early chronic prenatal alcohol would alter placental perfusion and oxygen availability that adversely affects fetal growth. STUDY DESIGN: Rhesus macaques self-administered 1.5 g/kg/d of ethanol (n=12) or isocaloric maltose-dextrin (n=12) daily before conception through the first 60 days of gestation (term is approximately 168 days). All animals were serially imaged with Doppler ultrasound to measure fetal biometry, uterine artery volume blood flow, and placental volume blood flow. Following Doppler ultrasound, all animals underwent both blood oxygenation leveledependent magnetic resonance imaging to characterize placental blood oxygenation and dynamic contrast-enhanced magnetic resonance imaging to quantify maternal placental perfusion. Animals were delivered by cesarean delivery for placental collection and fetal necropsy at gestational days 85 (n=8), 110 (n=8), or 135 (n=8). Histologic and RNA-sequencing analyses were performed on collected placental tissue. RESULTS: Placental volume blood flow was decreased at all gestational time points in ethanol-exposed vs control animals, but most significantly at gestational day 110 by Doppler ultrasound (P<.05). A significant decrease in total volumetric blood flow occurred in ethanol-exposed vs control animals on dynamic contrast-enhanced magnetic resonance imaging at both gestation days 110 and 135 (P<.05); moreover, a global reduction in T2*, high blood deoxyhemoglobin concentration, occurred throughout gestation (P<.05). Similarly, evidence of placental ischemic injury was notable by histologic analysis, which revealed a significant increase in microscopic infarctions in ethanol-exposed, not control, animals, largely present at middle to late gestation. Fetal biometry and weight were decreased in ethanol-exposed vs control animals, but the decrease was not significant. Analysis with RNA sequencing suggested the involvement of the inflammatory and extracellular matrix response pathways. CONCLUSION: Early chronic prenatal alcohol exposure significantly diminished placental perfusion at mid to late gestation and also significantly decreased the oxygen supply to the fetal vasculature throughout pregnancy, these findings were associated with the presence of microscopic placental infarctions in the nonhuman primate. Although placental adaptations may compensate for early environmental perturbations to fetal growth, placental blood flow and oxygenation were reduced, consistent with the evidence of placental ischemic injury.

Existing methods for evaluating in vivo placental function fail to reliably detect pregnancies at-risk for adverse outcomes prior to maternal and/or fetal morbidity. Here we report the results of a prospective dual-site longitudinal clinical study of quantitative placental T2* as measured by blood oxygen-level dependent magnetic resonance imaging (BOLD-MRI). The objectives of this study were: 1) to quantify placental T2* at multiple time points across gestation, and its consistency across sites, and 2) to investigate the association between placental T2* and adverse outcomes. 797 successful imaging studies, at up to three time points between 11 and 38 weeks of gestation, were completed in 316 pregnancies. Outcomes were stratified into three groups: (UN) uncomplicated/normal pregnancy, (PA) primary adverse pregnancy, which included hypertensive disorders of pregnancy, birthweight <5th percentile, and/or stillbirth or fetal death, and (SA) secondary abnormal pregnancy, which included abnormal prenatal conditions not included in the PA group such as spontaneous preterm birth or fetal anomalies. Of the 316 pregnancies, 198 (62.6%) were UN, 70 (22.2%) PA, and 48 (15.2%) SA outcomes. We found that the evolution of placental T2* across gestation was well described by a sigmoid model, with T2* decreasing continuously from a high plateau level early in gestation, through an inflection point around 30 weeks, and finally approaching a second, lower plateau in late gestation. Model regression revealed significantly lower T2* in the PA group than in UN pregnancies starting at 15 weeks and continuing through 33 weeks. T2* percentiles were computed for individual scans relative to UN group regression, and z-scores and receiver operating characteristic (ROC) curves calculated for association of T2* with pregnancy outcome. Overall, differences between UN and PA groups were statistically significant across gestation, with large effect sizes in mid- and late- pregnancy. The area under the curve (AUC) for placental T2* percentile and PA pregnancy outcome was 0.71, with the strongest predictive power (AUC of 0.76) at the mid-gestation time period (20–30 weeks). Our data demonstrate that placental T2* measurements are strongly associated with pregnancy outcomes often attributed to placental insufficiency. Trial registration: ClinicalTrials.gov: NCT02749851.

Cannabis use in pregnancy is associated with adverse perinatal outcomes, which are likely mediated by the placenta. However, the underlying mechanisms and specific vasoactive effects of cannabis on the placenta are unknown. Our objective was to determine the impact of chronic prenatal delta-tetrahydrocannabinol (THC, main psychoactive component of cannabis) exposure on placental function and development in a rhesus macaque model using advanced imaging. Animals were divided into two groups, control (CON, n = 5) and THC-exposed (THC, n = 5). THC-exposed animals received a THC edible daily pre-conception and throughout pregnancy. Animals underwent serial ultrasound and MRI at gestational days 85 (G85), G110, G135 and G155 (full term is ~ G168). Animals underwent cesarean delivery and placental collection at G155 for histologic and RNA-Seq analysis. THC-exposed pregnancies had significantly decreased amniotic fluid volume (p < 0.001), placental perfusion (p < 0.05), and fetal oxygen availability (p < 0.05), all indicators of placental insufficiency. Placental histological analysis demonstrated evidence of ischemic injury with microinfarctions present in THC-exposed animals only. Bulk RNA-seq demonstrated that THC alters the placental transcriptome and pathway analysis suggests dysregulated vasculature development and angiogenesis pathways. The longer-term consequences of these adverse placental findings are unknown, but they suggest that use of THC during pregnancy may deleteriously impact offspring development.

Glial cell-derived neurotrophic factor (GDNF) promotes survival of neurons. In stillbirths, low levels of GDNF are associated with placental causes of stillbirth. Thus, our objective was to assess the association between serum GDNF during pregnancy and adverse pregnancy outcome (APO) due to placental disease. Nested case-control study of the Placenta Imaging Project. Primary APO cases were defined as hypertensive disorders of pregnancy, birthweight below the 5th %ile, and stillbirth. Controls were term pregnancies with birthweight 5th-95th %ile, without hypertensive disorders, chorioamnionitis, placental abruption, or fetal anomaly. The following APOs were defined as severe: preeclampsia with severe features, indicated delivery < 37 weeks, and stillbirth. GDNF levels were assessed via ELISA at three visits during pregnancy and at delivery and compared between groups with ANOVA. Proportion of GDNF values falling below, within, and above the standard ELISA curve were analyzed by c2 test. Mixed effects modeling was used to assess change in GDNF over gestational age by group. Serum was available for n=141-159 controls and n=40-57 cases, depending on visit number (visit 1 early second trimester, visit 2 late second trimester, visit 3 mid third trimester). Controls delivered at a mean of 39.3 weeks and APO cases at 36.2 weeks. Serum GDNF levels did not change throughout gestation for cases or controls (Figure 1). Although there was statistically significant variation in proportion of ELISA levels below, within, and above the standard ELISA curve by outcome group when cases were separated by severity (p=0.012), mean values were not different (Table 1), and there was not a logical dose response. Severe adverse cases had the highest levels, control groups had levels in the middle, and adverse non-severe cases had the lowest mean levels of GDNF across gestation, but there was significant overlap of values and groups were not statistically different. Serum GDNF values during pregnancy do not predict occurrence of APO related to placental disease.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The placenta is a remarkable organ that coordinates and regulates maternal-fetal interactions during pregnancy to optimize fetal development. A host of obstetric complications are associated with placental dysfunction, and existing methods for evaluating in vivo placental function fail to reliably detect at-risk pregnancies prior to maternal or fetal morbidity. Although routinely used as a monitoring tool, the predictive power of ultrasound for identifying compromised pregnancies is poor. Recent preclinical studies performed in our laboratory, using blood oxygen-level dependent magnetic resonance imaging (BOLD-MRI) in the pregnant nonhuman primate (NHP), established a strong correlation between placental T2* values and maternal-fetal oxygen transport. Here we extend this work to a large, longitudinal, two-site study of quantitative in vivo T2* mapping in human pregnancies across 11 to 38 weeks of gestation to characterize the evolution of placental oxygenation in uncomplicated pregnancies and to elucidate the relationship between aberrant placental T2* and adverse obstetric outcomes attributable to placental dysfunction. This methodology has high discriminatory power and strong potential diagnostic utility.

Prenatal exposure to marijuana may lead to epigenetic alterations in the placenta and fetal brain, affecting short- and long-term offspring health. This Viewpoint addresses the critical need to study and characterize the impact of maternal marijuana use and consequences of in utero exposure on later development and health. We highlight the development of new PET imaging tools and the opportunity for longitudinal in vivo non-human primate studies to help elucidate epigenetic changes resulting from prenatal marijuana exposure throughout gestation.

Novel non-invasive T2*-magnetic resonance (MR) sequences have been used to assess placental health by detecting the differences in signal given by oxygenated and deoxygenated regions within the same tissue. We aimed to explore the feasibility of T2*-MR to study the fetal lung in a subset of cases with intrauterine growth restriction (IUGR). Prospective cohort of singleton pregnancies including IUGR (defined by birthweight below 10th centile together with abnormal feto-placental Doppler) and normally grown fetuses paired by gestational age at T2*-MR acquisition (25-37 weeks of gestation). Acquisitions were made in basal conditions and during maternal hyperoxygenation. Regions of interest (ROI) of the lung were drawn manually and analysed to obtain T2* values. Out of a total of 47 acquisitions, fetal lung T2* could be analysed in 23 IUGR and 10 normally grown fetuses (70% of the overall acquisitions). Mean gestational age at acquisition was 32 weeks (29-35 weeks) both in cases and controls. A non-significant tendency to lower T2* values in the lung (basal and after maternal hyperoxygenation) could be observed in IUGR when compared with normally grown fetuses (figure 1). These results suggest that there may exist a hypoxic environment in the lung of IUGR fetuses. T2*-MR seems to be a promising tool for the assessment of the lung in this population offering complementary information about its development. Supporting information can be found in the online version of this abstract Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Anti‐angiogenic agents combined with chemotherapy is an important strategy for the treatment of solid tumors. However, survival benefit is limited, urging the improvement of combination therapies. We aimed to clarify the effects of vascular endothelial growth factor receptor 2 (VEGFR2) targeting on hemodynamic function and penetration of drugs in esophagogastric adenocarcinoma (EAC). Patient‐derived xenograft (PDX) models of EAC were subjected to long‐term and short‐term treatment with anti‐VEGFR2 therapy followed by chemotherapy injection or multi‐agent dynamic contrast‐enhanced (DCE‐) MRI and vascular casting. Long‐term anti‐VEGFR2‐treated tumors showed a relatively lower flow and vessel density resulting in reduced chemotherapy uptake. On the contrary, short‐term VEGFR2 targeting resulted in relatively higher flow, rapid vasodilation, and improved chemotherapy delivery. Assessment of the extracellular matrix (ECM) revealed that short‐term anti‐angiogenic treatment drastically remodels the tumor stroma by inducing nitric oxide synthesis and hyaluronan degradation, thereby dilating the vasculature and improving intratumoral chemotherapy delivery. These previously unrecognized beneficial effects could not be maintained by long‐term VEGFR2 inhibition. As the identified mechanisms are targetable, they offer direct options to enhance the treatment efficacy of anti‐angiogenic therapy combined with chemotherapy in EAC patients.

Current methods for placental tissue collection assess a delivered organ without direct functional correlates; therefore, the four-quadrant biopsy protocol utilized by many researchers may provide reasonable representation of tissue across a large organ, and offer a snapshot for molecular analysis of the placenta. However, the recent impetus to understand the placenta in real time, and the use of functional imaging to comprehend placental biology, warrants a different sampling approach. Here we present a method to standardize placental tissue collection in a format designed to facilitate correlation of in vivo function with ex vivo assessments. Additionally, we draw comparisons to the quadrant biopsy regimen, and highlight a pathological case of placental infarction detected by in utero imaging.

Background In a Japanese macaque model of diet-induced obesity, we have previously demonstrated that consumption of a high-fat, “Western-style” diet (WSD) is associated with placental dysfunction and adverse pregnancy outcomes, independent of an obese maternal phenotype. Specifically, we have reported decreased uterine placental blood flow and increased inflammation with maternal WSD consumption. We also previously investigated the use of a promising therapeutic intervention that mitigated the adverse placental effects of a WSD but had unexpected detrimental effects on fetal pancreatic development. Thus, the objective of the current study was to determine whether simple preconception diet reversal (REV) would improve placental function. Methods Female Japanese macaques were divided into three groups: REV animals ( n = 5) were switched from a chronic WSD (36% fat) to a low fat, CON diet (14% fat) prior to conception and throughout pregnancy. The CON ( n = 6) and WSD ( n = 6) cohorts were maintained on their respective diets throughout pregnancy. Maternal body weight and composition were regularly assessed and advanced noninvasive imaging was performed at midgestation (gestational day 90, G90, or 0.5 of gestation, where full term is G175), and G129, 1 day prior to C-section delivery at G130 (0.75 of gestation). Imaging studies comprised Doppler ultrasound (US), contrast-enhanced US, and dynamic contrast-enhanced magnetic resonance imaging to assess uteroplacental hemodynamics and maternal-side placental perfusion. Results Dietary intervention resulted in significant maternal weight loss prior to pregnancy, and improved lean to fat mass ratio. By advanced imaging we demonstrated that a chronic WSD led to decreased blood flow velocity in the intervillous space, delayed blood flow transfer through the maternal spiral arteries, and reduced total placental blood flow compared to CON fed animals. Dietary reversal ameliorated these concerning derangements, restoring these hemodynamic parameters to CON levels. Conclusions Preconception dietary modification has beneficial effects on the maternal metabolic phenotype, and results in improved placental hemodynamics.