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T2-weighted imaging and T2* maps. A, Example T2-weighted imaging and T2* maps in coronal and sagittal planes across gestation. B, Features of T2-weighted imaging in women with preeclampsia.
Source publication
Placental dysfunction underlies the cause of pregnancies complicated by preeclampsia. The use of placental magnetic resonance imaging to provide an insight into the pathophysiology of preeclampsia and thus assess its potential use to inform prognosis and clinical management was explored. In this prospective observational cohort study, 14 women with...
Contexts in source publication
Context 1
... cholestasis of pregnancy Example T2-weighted images from the control and preeclamptic cohorts are shown in Figure 1, with areas of high signal on T2-weighted imaging corresponding to long T2* and low signal on T2-weighted imaging corresponding to short T2* values. In the control cohort, placental lobularity (the visual presence of lobules, ie, presumed functional units) was more apparent with increasing gestational age at imaging. ...
Context 2
... placental lobules were of low granularity (ie, consistent signal intensity within each lobule). Compared to gestationmatched controls, the placentae in women with preeclampsia showed more marked lobularity (Figure 1, with numerical data given in Table S2 in the Data Supplement), variable lobule size and high granularity with a decline in T2* towards lobule periphery. In addition, the placentae in women with preeclampsia had substantial additional areas of low-signal intensity (Figure 1). ...
Context 3
... to gestationmatched controls, the placentae in women with preeclampsia showed more marked lobularity (Figure 1, with numerical data given in Table S2 in the Data Supplement), variable lobule size and high granularity with a decline in T2* towards lobule periphery. In addition, the placentae in women with preeclampsia had substantial additional areas of low-signal intensity (Figure 1). ...
Context 4
... mean T2* positively correlated (Spearman rank correlation coefficient of 0.76) with PlGF concentration ( Figure 3B). Placental volume did not differ significantly between women in the control group and women with preeclampsia ( Figure S1 in the Data Supplement). Two women with preeclampsia were imaged twice, 2 weeks apart (as indicated in the participant flow diagram in Figure S2 in the Data Supplement). ...
Citations
... [8][9][10][11][12] Additionally, the observation of low circulating PlGF levels in the context of either pre-eclampsia or FGR is known to be strongly associated with placental pathological findings following delivery, 8,9 and the mechanistic association between low circulating PlGF levels and chronic placental ischaemia and hypoxia is well supported. [13][14][15][16] Therefore, the measurement of maternal PlGF has the potential to identify patients with both clinically and morphologically significant placental disease. ...
Objective
To identify which components of maternal vascular malperfusion (MVM) pathology are associated with adverse pregnancy outcomes and to investigate the morphological phenotypes of MVM placental pathology and their relationship with distinct clinical presentations of pre‐eclampsia and/or fetal growth restriction (FGR).
Design
Retrospective cohort study.
Setting
Tertiary care hospital in Toronto, Canada.
Population
Pregnant individuals with low circulating maternal placental growth factor (PlGF) levels (<100 pg/mL) and placental pathology analysis between March 2017 and December 2019.
Methods
Association between each pathological finding and the outcomes of interest were calculated using the chi‐square test. Cluster analysis and logistic regression was used to identify phenotypic clusters, and their association with adverse pregnancy outcomes. Cluster analysis was performed using the K‐modes unsupervised clustering algorithm.
Main outcome measures
Preterm delivery <34⁺⁰ weeks of gestation, early onset pre‐eclampsia with delivery <34⁺⁰ weeks of gestation, birthweight <10th percentile (small for gestational age, SGA) and stillbirth.
Results
The diagnostic features of MVM most strongly associated with delivery <34⁺⁰ weeks of gestation were: infarction, accelerated villous maturation, distal villous hypoplasia and decidual vasculopathy. Two dominant phenotypic clusters of MVM pathology were identified. The largest cluster (n = 104) was characterised by both reduced placental mass and hypoxic ischaemic injury (infarction and accelerated villous maturation), and was associated with combined pre‐eclampsia and SGA. The second dominant cluster (n = 59) was characterised by infarction and accelerated villous maturation alone, and was associated with pre‐eclampsia and average birthweight for gestational age.
Conclusions
Patients with placental MVM disease are at high risk of pre‐eclampsia and FGR, and distinct pathological findings correlate with different clinical phenotypes, suggestive of distinct subtypes of MVM disease.
... Quantitative T2*-MRI has been used to measure placental oxygenation by utilizing the paramagnetic properties of deoxyhemoglobin, providing insights into oxygen levels [5]. Clinical studies showed lower placental oxygenation values in later stages of normal pregnancy, cases of PE, and FGR [6,7]. T2* values also revealed reduced response to maternal respiratory challenge in affected placentas compared to controls, as observed in both human and rat studies [8,9]. ...
... This reduction in oxygenation may indicate hypoxia in the RUPP placenta which has been found previously by the increased expression of hypoxia-inducible factor (HIF1-a) [19,23]. Moreover, a reduction in placental T2* values was reported in human PE and FGR [6,7,24].Oxygenation in fetal organs remained unchanged in the RUPP fetuses, which suggests a mild FGR phenotype without brain-sparing. This is in accordance with a reduction in fetal length and litter size but not weight in RUPP animals in our study. ...
Introduction:
Placental insufficiency may lead to preeclampsia and fetal growth restriction. There is no cure for placental insufficiency, emphasizing the need for monitoring fetal and placenta health. Current monitoring methods are limited, underscoring the necessity for imaging techniques to evaluate fetal-placental perfusion and oxygenation. This study aims to use MRI to evaluate placental oxygenation and perfusion in the reduced uterine perfusion pressure (RUPP) model of placental insufficiency.
Methods:
Pregnant rats were randomized to RUPP (n = 11) or sham surgery (n = 8) on gestational day 14. On gestational day 19, rats imaged using a 7T MRI scanner to assess oxygenation and perfusion using T2* mapping and 3D-DCE MRI sequences, respectively. The effect of the RUPP on the feto-placental units were analyzed from the MRI images.
Results:
RUPP surgery led to reduced oxygenation in the labyrinth (24.7 ± 1.8 ms vs. 28.0 ± 2.1 ms, P = 0.002) and junctional zone (7.0 ± 0.9 ms vs. 8.1 ± 1.1 ms, P = 0.04) of the placenta, as indicated by decreased T2* values. However, here were no significant differences in fetal organ oxygenation or placental perfusion between RUPP and sham animals.
Discussion:
The reduced placental oxygenation without a corresponding decrease in perfusion suggests an adaptive response to placental ischemia. While acute reduction in placental perfusion may cause placental hypoxia, persistence of this condition could indicate chronic placental insufficiency after ischemic reperfusion injury. Thus, placental oxygenation may be a more reliable biomarker for assessing fetal condition than perfusion in hypertensive disorders of pregnancies including preeclampsia and FGR.
... In particular, this has proven valuable in improving our understanding of the human placenta, an organ for which there were previously very limited methods for in vivo study. The application of T2*-relaxometry has offered important insights into both physiological placental development across gestation 1-3 , as well as abnormal placentation as seen in pregnancies affected by hypertensive diseases 2,4,5 , prior to spontaneous preterm birth 6 , fetal growth restriction and discordant growth in twins 7,8 albeit in small cohorts. A rst multi-center study was recently published 1 . ...
Placental MRI is increasingly implemented in clinical obstetrics and research. Functional imaging, especially T2*, has been shown to vary across gestation and in pathology. Translation into the clinical arena has been slow because of time taken to mask the region of interest and owing to differences in T2* results depending on field strength. This paper contributes methodology to remove these barriers by utilising data from 0.55, 1.5 and 3T MRI to provide a fully automated segmentation tool; determining field strength dependency of placental assessment techniques; and deriving normal ranges for T2* by gestational age but independent of field strength. T2* datasets were acquired across field strengths. Automatic quantification including fully automatic masking was achieved and tested in 270 datasets across fields. Normal curves for quantitative placental mean T2*, volume and other derived measurements were obtained in 273 fetal MRI scans and z-scores calculated. The fully automatic segmentation achieved excellent quantification results (Dice scores of 0.807 at 3T, 0.796 at 1.5T and 0.815 at 0.55T.). Similar changes were seen between placental T2* and gestational age across all three field strengths (p < 0.05). Z-scores were generated. This study provides confidence in the translatability of T2* trends across field strengths in fetal imaging.
... This time between identification of at-risk individuals and overt disease expression is characterized by progressive ischemia-reperfusion injury to the placental villi, which can now be identified in vivo by magnetic resonance oximetry. 33 Progressive placental injury may lead to areas of placental infarction, thereby further reducing PlGF secretion and mediating fetal growth restriction. 27 Currently, our limited ability to intervene effectively to prevent preeclampsia from developing in high-risk women is based on low-dose aspirin. ...
BACKGROUND
Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress, hypertension, and maternal systemic organ damage. The transcription factor, PPARγ (peroxisome proliferator-activated receptor-γ) promotes healthy trophoblast differentiation but is dysregulated in the preeclampsia placenta. Our study identifies the beneficial impact of Rosiglitazone-mediated PPARγ-activation in the stressed preeclampsia placenta.
METHODS
We used first trimester placentas, preeclamptic and preterm control placentas, and human trophoblast cell lines to study PPARγ activation.
RESULTS
Induction of PPARγ activates cell growth and antioxidative stress pathways, including the gene, heme oxygenase 1 ( Hmox1 ). Protein expression of both PPARγ and HO1 (heme oxygenase 1) are reduced in preeclamptic placentas, but Rosiglitazone restores HO1 signaling in a PPARγ-dependent manner.
CONCLUSIONS
Restoring disrupted pathways by PPARγ in preeclampsia offers a potential therapeutic pathway to reverse placental damage, extending pregnancy duration, and reduce maternal sequelae. Future research should aim to understand the full scope of impaired PPARγ signaling in the human placenta and focus on compounds for safe use during pregnancy to prevent severe perinatal morbidity and mortality.
... This suggests that the levels of oxygen saturation and HIF-α expression may provide complementary information about placental hypoxia. Clinical studies have demonstrated that ex vivo pathological examinations of affected placentas reveal abnormalities associated with vascular malperfusion, which are consistent with the outcomes obtained from T2* MRI within the same study [54,56,68]. However, it is important to note that, to our knowledge, no clinical studies have integrated hypoxia molecular biomarkers with imaging biomarkers in the assessment of placental insufficiency. ...
Placental hypoxia poses significant risks to both the developing fetus and the mother during pregnancy, underscoring the importance of early detection and monitoring. Effectively identifying placental hypoxia and evaluating the deterioration in placental function requires reliable biomarkers. Molecular biomarkers in placental tissue can only be determined post-delivery and while maternal blood biomarkers can be measured over time, they can merely serve as proxies for placental function. Therefore, there is an increasing demand for non-invasive imaging techniques capable of directly assessing the placental condition over time. Recent advancements in imaging technologies, including photoacoustic and magnetic resonance imaging, offer promising tools for detecting and monitoring placental hypoxia. Integrating molecular and imaging biomarkers may revolutionize the detection and monitoring of placental hypoxia, improving pregnancy outcomes and reducing long-term health complications. This review describes current research on molecular and imaging biomarkers of placental hypoxia both in human and animal studies and aims to explore the benefits of an integrated approach throughout gestation.
... Placental MRI is a promising technique for diagnosis, prognosis and monitoring of multiple pregnancy complications including fetal growth restriction (FGR) [6] and preeclampsia (PE) [7]. In particular, T2* relaxometry is a promising technique for detecting pregnancy complications, with T2* reduced in FGR and PE [8,9]. ...
... [23]). Specifically, many T2* maps (Figures 2, 3, 5) reveal the lobular structure of the placenta, potentially revealing the oxygenation level of maternal blood, as previously observed in standard T2* [7,32,33] and combined T2*-diffusion [21,23] experiments. There is also a higher diffusivity at the boundaries of the placenta in ADC maps potentially reflecting areas with high volumes of maternal blood perfusing into the placenta (Figures 4 and 6). ...
... Again, as expected, this is much higher than directly comparable studies at higher field strengths. Specifically, to compare to the most recent studies of T2* at 3T, Schabel et al. showed T2* values ranging from ~80 ms (GA= 20 weeks) to ~30 ms (at term) [34], and Ho et al. had T2* ~90 ms (GA = 20 weeks) to ~30 ms (at term) [7]. Regarding 1.5 T, the recent study by Sinding et al. showed T2* ~150 ms at 20 weeks to ~60 ms at term [35]. ...
Purpose: Demonstrating quantitative multi-parametric mapping in the placenta with combined T2*-diffusion MRI at low-field (0.55T).
Methods: We present 57 placental MRI scans performed on a commercially available 0.55T scanner. We acquired the images using a combined T2*-diffusion technique scan that simultaneously acquires multiple diffusion preparations and echo times. We processed the data to produce quantitative T2* and diffusivity maps using a combined T2*-ADC model. We compared the derived quantitative parameters across gestation in healthy controls and a cohort of clinical cases.
Results: Quantitative parameter maps closely resemble those from previous experiments at higher field strength, with similar trends in T2* and ADC against gestational age observed.
Conclusion: Combined T2*-diffusion placental MRI is reliably achievable at 0.55T. The advantages of lower field strength - such as cost, ease of deployment, increased accessibility and patient comfort due to the wider bore, and increased T2* for larger dynamic ranges - can support the widespread roll out of placental MRI as an adjunct to ultrasound during pregnancy.
... Data acquired at multiple echo times allows the calculation of T2* maps which in turn indirectly inform on oxygenation via the Blood Oxygen Level Dependent (BOLD) effect, utilising the paramagnetic properties and thus decreased T2* time of deoxyhaemoglobin 9 . For the placenta, promising results show an inverse relation between mean T2* and gestational age as well as reduced T2* associated with low birth weight 10 , pre-eclampsia 11 and fetal growth restriction 12 . However, the T2* value does not depend solely on the concentration of deoxyhaemoglobin, but on additional factors including water content, blood volume and surface area, thus enabling only an indirect quantification of oxygenation. ...
... In addition to the benefit of this indirect insight into labour, assessing placental function both statically and dynamically during pregnancy allows assessment of its reserve capacity. This may be of particular value in placentas affected by inadequate remodelling of the spiral arteries as seen in pregnancies with pre-eclampsia and fetal growth restriction which may have structural and functional changes as demonstrated in recent MRI studies 7,11 and which may struggle to maintain the constant supply of oxygen required by the fetus. The effect of contractile activity in such circumstances is thus of high relevance. ...
Pre-labour uterine contractions, occurring throughout pregnancy, are an important phenomenon involving the placenta in addition to the myometrium. They alter the uterine environment and thus potentially the blood supply to the fetus and may thus provide crucial insights into the processes of labour. Assessment in-vivo is however restricted due to their unpredictability and the inaccessible nature of the utero-placental compartment. While clinical cardiotocography (CTG) only allows global, pressure-based assessment, functional magnetic resonance imaging (MRI) provides an opportunity to study contractile activity and its effects on the placenta and the fetus in-vivo. This study aims to provide both descriptive and quantitative structural and functional MR assessments of pre-labour contractions in the human uterus. A total of 226 MRI scans (18–41 weeks gestation) from ongoing research studies were analysed, focusing on free-breathing dynamic quantitative whole uterus dynamic T2* maps. These provide an indirect measure of tissue properties such as oxygenation. 22 contractile events were noted visually and both descriptive and quantitative analysis of the myometrial and placental changes including volumetric and T2* variations were undertaken. Processing and analysis was successfully performed, qualitative analysis shows distinct and highly dynamic contraction related characteristics including; alterations in the thickness of the low T2* in the placental bed and other myometrial areas, high intensity vessel-like structures in the myometrium, low-intensity vessel structures within the placental parenchyma and close to the chorionic plate. Quantitative evaluation shows a significant negative correlation between T2* in both contractile and not-contractile regions with gestational age ( p < 0.05) as well as a significant reduction in T2* during contractions. The T2* values in the myometrium were however not correlated to gestational age ( p > 0.5). The quantitative and qualitative description of uterine pre-labour contractions including dynamic changes and key characteristics aims to contribute to the sparsely available in-vivo information and to provide an in-vivo tool to study this important phenomenon. Further work is required to analyse the origins of these subclinical contractions, their effects in high-risk pregnancies and their ability to determine the likelihood of a successful labour. Assessing T2* distribution as a marker for placental oxygenation could thus potentially complement clinically used cardiotocography measurements in the future.
... Cependant, la quantification absolue de l'oxygénation à partir de l'effet BOLD est délicate et constitue un sujet de recherche à part entière. En effet, la relation entre le temps de relaxation [135], [136], [139], [140], et éventuellement de la PE [141], [142]. Des premières recommandations ont même été formulées pour la réalisation d'une mesure du temps de relaxation T2* du placenta chez la femme à 1,5T et à 3T Les temps de relaxation T2 / T2* / T2' ayant été introduits, on peut désormais aborder quelques considérations concernant la mesure de ces paramètres pour le placenta dans la section suivante. ...
Les pathologies de la grossesse liées à des dysfonctions placentaires telles que le Retard de Croissance Intra-Utérin et la Pré-éclampsie, ou encore les troubles du spectre du placenta Accreta (PAS) sont associées à d’importantes morbi-mortalité fœtales et maternelles. Pour le dépistage de ces pathologies, l’échographie 2D a atteint ses limites avec une sensibilité et une spécificité basses. L’IRM, quant à elle, permet de fournir des informations morphologiques et fonctionnelles variées avec une bonne résolution spatiale, ce qui en fait un outil de choix pour l’exploration de la fonction placentaire. De plus, cet examen est non invasif et peut être réalisé en cours de grossesse sans injection de produit de contraste, et à l’exclusion du premier trimestre par principe de précaution. L’objectif est alors d’étudier des paramètres qui se révéleraient pertinents pour le dépistage de ces pathologies, obtenus par différentes techniques IRM non-injectées, permettant de mieux caractériser et quantifier la fonction placentaire. En particulier, il semble judicieux dans ce contexte clinique d’utiliser des techniques délivrant une information (idéalement quantitative) sur la perfusion placentaire et/ou l’oxygénation placentaire.Dans ces travaux, nous nous sommes notamment intéressés à la technique IVIM (Intra-Voxel Incoherent Motion) pour obtenir une information sur la perfusion placentaire, et à la mesure des temps de relaxation T2 et T2* qui sont le reflet de l’oxygénation placentaire, avec l’objectif d’établir un protocole d’acquisition IRM approprié dans le contexte du dépistage des PAS, et de l’évaluer dans le cadre du protocole clinique DIANE (Dépistage par Irm des Anomalies d’adhésioN placEntaire) mis en place avec le CIC-IT de Nancy. Dans un premier temps, des données précliniques obtenues chez la lapine gestante ont été analysées afin de mettre en avant l’intérêt d’une mesure des temps de relaxation T2 et T2* dans le placenta. Une étude a ensuite été menée sur fantôme et sur volontaires sains en dehors de la grossesse, afin de comparer différentes stratégies de quantification du T2 en région abdomino-pelvienne compatibles avec une utilisation clinique. Enfin, un protocole d’acquisition IRM pour l’imagerie du placenta dédié au contexte des PAS a été mis en place, et a commencé à être évalué sur les premières volontaires du protocole clinique DIANE.
... Further, T2-weighted MRI captures anatomical information such as the vascular structure of the placenta [8]. Since MRI provides direct measurements of placental function, it is a promising research tool for studying the placenta [2]- [4], [7], [9], [10]. ...
... A promising research direction is to use MRI to develop biomarkers of pathology. BOLD and T2* MRI show promise for identifying intrauterine growth restriction (IUGR) [14], for quantifying differences in discordant twins with IUGR [4], and for characterizing preeclampsia [10]. While emerging as a promising tool to study placental function and health, effective visualization of MRI signals in the placenta is an open problem. ...
We present a volumetric mesh-based algorithm for parameterizing the placenta to a flattened template to enable effective visualization of local anatomy and function. MRI shows potential as a research tool as it provides signals directly related to placental function. However, due to the curved and highly variable in vivo shape of the placenta, interpreting and visualizing these images is difficult. We address interpretation challenges by mapping the placenta so that it resembles the familiar ex vivo shape. We formulate the parameterization as an optimization problem for mapping the placental shape represented by a volumetric mesh to a flattened template. We employ the symmetric Dirichlet energy to control local distortion throughout the volume. Local injectivity in the mapping is enforced by a constrained line search during the gradient descent optimization. We validate our method using a research study of 111 placental shapes extracted from BOLD MRI images. Our mapping achieves sub-voxel accuracy in matching the template while maintaining low distortion throughout the volume. We demonstrate how the resulting flattening of the placenta improves visualization of anatomy and function. Our code is freely available at https://github.com/ mabulnaga/placenta-flattening.
... Further, T2-weighted MRI captures anatomical information such as the vascular structure of the placenta [8]. Since MRI provides direct measurements of placental function, it is a promising research tool for studying the placenta [2]- [4], [7], [9], [10]. ...
... A promising research direction is to use MRI to develop biomarkers of pathology. BOLD and T2* MRI show promise for identifying intrauterine growth restriction (IUGR) [14], for quantifying differences in discordant twins with IUGR [4], and for characterizing preeclampsia [10]. While emerging as a promising tool to study placental function and health, effective visualization of MRI signals in the placenta is an open problem. ...
We present a volumetric mesh-based algorithm for parameterizing the placenta to a flattened template to enable effective visualization of local anatomy and function. MRI shows potential as a research tool as it provides signals directly related to placental function. However, due to the curved and highly variable in vivo shape of the placenta, interpreting and visualizing these images is difficult. We address interpretation challenges by mapping the placenta so that it resembles the familiar ex vivo shape. We formulate the parameterization as an optimization problem for mapping the placental shape represented by a volumetric mesh to a flattened template. We employ the symmetric Dirichlet energy to control local distortion throughout the volume. Local injectivity in the mapping is enforced by a constrained line search during the gradient descent optimization. We validate our method using a research study of 111 placental shapes extracted from BOLD MRI images. Our mapping achieves sub-voxel accuracy in matching the template while maintaining low distortion throughout the volume. We demonstrate how the resulting flattening of the placenta improves visualization of anatomy and function. Our code is freely available at https://github.com/mabulnaga/placenta-flattening .
