A flexible generative algorithm for growing in silico placentas.

The placenta is crucial for a successful pregnancy, facilitating oxygen exchange and nutrient transport between mother and fetus. Complications like fetal growth restriction and pre-eclampsia are linked to placental vascular structure abnormalities, highlighting the need for early detection of placental health issues. Computational modelling offers insights into how vascular architecture correlates with flow and oxygenation in both healthy and dysfunctional placentas. These models use synthetic networks to represent the multiscale feto-placental vasculature, but current methods lack direct control over key morphological parameters like branching angles, essential for predicting placental dysfunction. We introduce a novel generative algorithm for creating in silico placentas, allowing user-controlled customisation of feto-placental vasculatures, both as individual components (placental shape, chorionic vessels, placentone) and as a complete structure. The algorithm is physiologically underpinned, following branching laws (i.e. Murray's Law), and is defined by four key morphometric statistics: vessel diameter, vessel length, branching angle and asymmetry. Our algorithm produces structures consistent with in vivo measurements and ex vivo observations. Our sensitivity analysis highlights how vessel length variations and branching angles play a pivotal role in defining the architecture of the placental vascular network. Moreover, our approach is stochastic in nature, yielding vascular structures with different topological metrics when imposing the same input settings. Unlike previous volume-filling algorithms, our approach allows direct control over key morphological parameters, generating vascular structures that closely resemble real vascular densities and allowing for the investigation of the impact of morphological parameters on placental function in upcoming studies.

Structural and functional fetal cardiac imaging using low field (0.55†T) MRI.

Purpose: This study aims to investigate the feasibility of using a commercially available clinical 0.55 T MRI scanner for comprehensive structural and functional fetal cardiac imaging. Methods: Balanced steady-state free precession (bSSFP) and phase contrast (PC) sequences were optimized by in utero studies consisting of 14 subjects for bSSFP optimization and 9 subjects for PC optimization. The signal-to-noise ratio (SNR) of the optimized sequences were investigated. Flow measurements were performed in three vessels, umbilical vein (UV), descending aorta (DAo), and superior vena cava (SVC) using the PC sequences and retrospective gating. The optimized bSSFP, PC and half-Fourier single shot turbo spin-echo (HASTE) sequences were acquired in a cohort of 21 late gestation-age fetuses (>36 weeks) to demonstrate the feasibility of a fetal cardiac exam at 0.55 T. The HASTE stacks were reconstructed to create an isotropic reconstruction of the fetal thorax, followed by automatic great vessel segmentations. The intra-abdominal UV blood flow measurements acquired with MRI were compared to ultrasound UV free-loop flow measurements. Results: Using the parameters from 1.5 T as a starting point, the bSSFP sequences were optimized at 0.55 T, resulting in a 1.6-fold SNR increase and improved image contrast compared to starting parameters, as well as good visibility of most cardiac structures as rated by two experienced fetal cardiologists. The PC sequence resulted in increased SNR and reduced scan time, subsequent retrospective gating enabled successful blood flow measurements. The reconstructions and automatic great vessel segmentations showed good quality, with 18/21 segmentations requiring no or minor refinements. Blood flow measurements were within the expected range. A comparison of the UV measurements performed with ultrasound and MRI showed agreement between the two sets of measurements, with better correlation observed at lower flows. Conclusion: We demonstrated the feasibility of low-field (0.55 T) MRI for fetal cardiac imaging. The reduced SNR at low field strength can be effectively compensated for by strategically optimizing sequence parameters. Major fetal cardiac structures and vessels were consistently visualized, and flow measurements were successfully obtained. The late gestation study demonstrated the robustness and reproducibility at low field strength. MRI performed at 0.55 T is a viable option for fetal cardiac examination.

Fetal body organ T2* relaxometry at low field strength (FOREST).

Fetal Magnetic Resonance Imaging (MRI) at low field strengths is an exciting new field in both clinical and research settings. Clinical low field (0.55T) scanners are beneficial for fetal imaging due to their reduced susceptibility-induced artifacts, increased T2* values, and wider bore (widening access for the increasingly obese pregnant population). However, the lack of standard automated image processing tools such as segmentation and reconstruction hampers wider clinical use. In this study, we present the Fetal body Organ T2* RElaxometry at low field STrength (FOREST) pipeline that analyzes ten major fetal body organs. Dynamic multi-echo multi-gradient sequences were acquired and automatically reoriented to a standard plane, reconstructed into a high-resolution volume using deformable slice-to-volume reconstruction, and then automatically segmented into ten major fetal organs. We extensively validated FOREST using an inter-rater quality analysis. We then present fetal T2* body organ growth curves made from 100 control subjects from a wide gestational age range (17-40 gestational weeks) in order to investigate the relationship of T2* with gestational age. The T2* values for all organs except the stomach and spleen were found to have a relationship with gestational age (p<0.05). FOREST is robust to fetal motion, and can be used for both normal and fetuses with pathologies. Low field fetal MRI can be used to perform advanced MRI analysis, and is a viable option for clinical scanning.

Automated Craniofacial Biometry with 3D T2w Fetal MRI.

Objectives: Evaluating craniofacial phenotype-genotype correlations prenatally is increasingly important; however, it is subjective and challenging with 3D ultrasound. We developed an automated landmark propagation pipeline using 3D motion-corrected, slice-to-volume reconstructed (SVR) fetal MRI for craniofacial measurements. Methods: A literature review and expert consensus identified 31 craniofacial biometrics for fetal MRI. An MRI atlas with defined anatomical landmarks served as a template for subject registration, auto-labelling, and biometric calculation. We assessed 108 healthy controls and 24 fetuses with Down syndrome (T21) in the third trimester (29-36 weeks gestational age, GA) to identify meaningful biometrics in T21. Reliability and reproducibility were evaluated in 10 random datasets by four observers. Results: Automated labels were produced for all 132 subjects with a 0.03% placement error rate. Seven measurements, including anterior base of skull length and maxillary length, showed significant differences with large effect sizes between T21 and control groups (ANOVA, p<0.001). Manual measurements took 25-35 minutes per case, while automated extraction took approximately 5 minutes. Bland-Altman plots showed agreement within manual observer ranges except for mandibular width, which had higher variability. Extended GA growth charts (19-39 weeks), based on 280 control fetuses, were produced for future research. Conclusion: This is the first automated atlas-based protocol using 3D SVR MRI for fetal craniofacial biometrics, accurately revealing morphological craniofacial differences in a T21 cohort. Future work should focus on improving measurement reliability, larger clinical cohorts, and technical advancements, to enhance prenatal care and phenotypic characterisation.

Placental multimodal MRI prior to spontaneous preterm birth <32 weeks' gestation: An observational study.

OBJECTIVE: To utilise combined diffusion-relaxation MRI techniques to interrogate antenatal changes in the placenta prior to extreme preterm birth among both women with PPROM and membranes intact, and compare this to a control group who subsequently delivered at term. DESIGN: Observational study. SETTING: Tertiary Obstetric Unit, London, UK. POPULATION: Cases: pregnant women who subsequently spontaneously delivered a singleton pregnancy prior to 32 weeks' gestation without any other obstetric complications. CONTROLS: pregnant women who delivered an uncomplicated pregnancy at term. METHODS: All women consented to an MRI examination. A combined diffusion-relaxation MRI of the placenta was undertaken and analysed using fractional anisotropy, a combined T2*-apparent diffusion coefficient model and a combined T2*-intravoxel incoherent motion model, in order to provide a detailed placental phenotype associated with preterm birth. Subgroup analyses based on whether women in the case group had PPROM or intact membranes at time of scan, and on latency to delivery were performed. MAIN OUTCOME MEASURES: Fractional anisotropy, apparent diffusion coefficients and T2* placental values, from two models including a combined T2*-IVIM model separating fast- and slow-flowing (perfusing and diffusing) compartments. RESULTS: This study included 23 women who delivered preterm and 52 women who delivered at term. Placental T2* was lower in the T2*-apparent diffusion coefficient model (p < 0.001) and in the fast- and slow-flowing compartments (p = 0.001 and p < 0.001) of the T2*-IVIM model. This reached a higher level of significance in the preterm prelabour rupture of the membranes group than in the membranes intact group. There was a reduced perfusion fraction among the cases with impending delivery. CONCLUSIONS: Placental diffusion-relaxation reveals significant changes in the placenta prior to preterm birth with greater effect noted in cases of preterm prelabour rupture of the membranes. Application of this technique may allow clinically valuable interrogation of histopathological changes before preterm birth. In turn, this could facilitate more accurate antenatal prediction of preterm chorioamnionitis and so aid decisions around the safest time of delivery. Furthermore, this technique provides a research tool to improve understanding of the pathological mechanisms associated with preterm birth in vivo.

T2*-Relaxometry MRI to Assess Third Trimester Placental and Fetal Brain Oxygenation and Placental Characteristics in Healthy Fetuses and Fetuses With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) has been linked to impaired placental and fetal brain development. Assessing the placenta and fetal brain in parallel may help further our understanding of the relationship between development of these organs. HYPOTHESIS: 1) Placental and fetal brain oxygenation are correlated, 2) oxygenation in these organs is reduced in CHD compared to healthy controls, and 3) placental structure is altered in CHD. STUDY TYPE: Retrospective case-control. POPULATION: Fifty-one human fetuses with CHD (32 male; median [IQR] gestational age [GA] = 32.0 [30.9-32.9] weeks) and 30 from uncomplicated pregnancies with normal birth outcomes (18 male; median [IQR] GA = 34.5 [31.9-36.7] weeks). FIELD STRENGTH/SEQUENCE: 1.5 T single-shot multi-echo-gradient-echo echo-planar imaging. ASSESSMENT: Masking was performed using an automated nnUnet model. Mean brain and placental T2* and quantitative measures of placental texture, volume, and morphology were calculated. STATISTICAL TESTS: Spearman's correlation coefficient for determining the association between brain and placental T2*, and between brain and placental characteristics with GA. P-values for comparing brain T2*, placenta T2*, and placental characteristics between groups derived from ANOVA. Significance level P < 0.05. RESULTS: There was a significant positive association between placental and fetal brain T2* (⍴ = 0.46). Placental and fetal brain T2* showed a significant negative correlation with GA (placental T2* ⍴ = -0.65; fetal brain T2* ⍴ = -0.32). Both placental and fetal brain T2* values were significantly reduced in CHD, after adjusting for GA (placental T2*: control = 97 [±24] msec, CHD = 83 [±23] msec; brain T2*: control = 218 [±26] msec, CHD = 202 [±25] msec). Placental texture and morphology were also significantly altered in CHD (Texture: control = 0.84 [0.83-0.87], CHD = 0.80 [0.78-0.84]; Morphology: control = 9.9 [±2.2], CHD = 10.8 [±2.0]). For all fetuses, there was a significant positive association between placental T2* and placental texture (⍴ = 0.46). CONCLUSION: Placental and fetal brain T2* values are associated in healthy fetuses and those with CHD. Placental and fetal brain oxygenation are reduced in CHD. Placental appearance is significantly altered in CHD and shows associations with placental oxygenation, suggesting altered placental development and function may be related. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Characterizing T1 in the fetal brain and placenta over gestational age at 0.55T.

PURPOSE: T1 mapping and T1-weighted contrasts have a complimentary but currently under utilized role in fetal MRI. Emerging clinical low field scanners are ideally suited for fetal T1 mapping. The advantages are lower T1 values which results in higher efficiency and reduced field inhomogeneities resulting in a decreased requirement for specialist tools. In addition the increased bore size associated with low field scanners provides improved patient comfort and accessibility. This study aims to demonstrate the feasibility of fetal brain T1 mapping at 0.55T. METHODS: An efficient slice-shuffling inversion-recovery echo-planar imaging (EPI)-based T1-mapping and postprocessing was demonstrated for the fetal brain at 0.55T in a cohort of 38 fetal MRI scans. Robustness analysis was performed and placental measurements were taken for validation. RESULTS: High-quality T1 maps allowing the investigation of subregions in the brain were obtained and significant correlation with gestational age was demonstrated for fetal brain T1 maps ( p < 0 . 05 $$ p<0.05 $$ ) as well as regions-of-interest in the deep gray matter and white matter. CONCLUSIONS: Efficient, quantitative T1 mapping in the fetal brain was demonstrated on a clinical 0.55T MRI scanner, providing foundations for both future research and clinical applications including low-field specific T1-weighted acquisitions.

Correlation of fetal lung area with MRI derived pulmonary volume.

BACKGROUND: Neonatal chest-Xray (CXR)s are commonly performed as a first line investigation for the evaluation of respiratory complications. Although lung area derived from CXRs correlates well with functional assessments of the neonatal lung, it is not currently utilised in clinical practice, partly due to the lack of reference ranges for CXR-derived lung area in healthy neonates. Advanced MR techniques now enable direct evaluation of both fetal pulmonary volume and area. This study therefore aims to generate reference ranges for pulmonary volume and area in uncomplicated pregnancies, evaluate the correlation between prenatal pulmonary volume and area, as well as to assess the agreement between antenatal MRI-derived and neonatal CXR-derived pulmonary area in a cohort of fetuses that delivered shortly after the antenatal MRI investigation. METHODS: Fetal MRI datasets were retrospectively analysed from uncomplicated term pregnancies and a preterm cohort that delivered within 72 h of the fetal MRI. All examinations included T2 weighted single-shot turbo spin echo images in multiple planes. In-house pipelines were applied to correct for fetal motion using deformable slice-to-volume reconstruction. An MRI-derived lung area was manually segmented from the average intensity projection (AIP) images generated. Postnatal lung area in the preterm cohort was measured from neonatal CXRs within 24 h of delivery. Pearson correlation coefficient was used to correlate MRI-derived lung volume and area. A two-way absolute agreement was performed between the MRI-derived AIP lung area and CXR-derived lung area. RESULTS: Datasets from 180 controls and 10 preterm fetuses were suitable for analysis. Mean gestational age at MRI was 28.6 ± 4.2 weeks for controls and 28.7 ± 2.7 weeks for preterm neonates. MRI-derived lung area correlated strongly with lung volumes (p < 0.001). MRI-derived lung area had good agreement with the neonatal CXR-derived lung area in the preterm cohort [both lungs = 0.982]. CONCLUSION: MRI-derived pulmonary area correlates well with absolute pulmonary volume and there is good correlation between MRI-derived pulmonary area and postnatal CXR-derived lung area when delivery occurs within a few days of the MRI examination. This may indicate that fetal MRI derived lung area may prove to be useful reference ranges for pulmonary areas derived from CXRs obtained in the perinatal period.

The Fetal Spleen in Low-Risk Pregnancies and prior to Preterm Birth: Observational Study of the Role of Anatomical and Functional Magnetic Resonance Imaging.

INTRODUCTION: Spontaneous preterm birth complicates ∼7% of pregnancies and causes morbidity and mortality. Although infection is a common etiology, our understanding of the fetal immune system in vivo is limited. This study aimed to utilize T2-weighted imaging and T2* relaxometry (which is a proxy of tissue oxygenation) of the fetal spleen in uncomplicated pregnancies and in fetuses that were subsequently delivered spontaneously prior to 32 weeks. METHODS: Women underwent imaging including T2-weighted fetal body images and multi-eco gradient echo single-shot echo planar sequences on a Phillips Achieva 3T system. Previously described postprocessing techniques were applied to obtain T2- and T2*-weighted imaging of the fetal spleen and T2-weighted fetal body volumes. RESULTS: Among 55 women with uncomplicated pregnancies, an increase in fetal splenic volume, splenic:body volume, and a decrease in splenic T2* signal intensity was demonstrated across gestation. Compared to controls, fetuses who were subsequently delivered prior to 32 weeks' gestation (n = 19) had a larger spleen when controlled for the overall size of the fetus (p = 0.027), but T2* was consistent (p = 0.76). CONCLUSION: These findings provide evidence of a replicable method of studying the fetal immune system and give novel results on the impact of impending preterm birth on the spleen. While T2* decreases prior to preterm birth in other organs, preservation demonstrated here suggests preferential sparing of the spleen.

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease.

Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR < 0.001), with changes most evident after 30 weeks gestation. A significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, pFDR = 0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.

Fully automated planning for anatomical fetal brain MRI on 0.55T.

PURPOSE: Widening the availability of fetal MRI with fully automatic real-time planning of radiological brain planes on 0.55T MRI. METHODS: Deep learning-based detection of key brain landmarks on a whole-uterus echo planar imaging scan enables the subsequent fully automatic planning of the radiological single-shot Turbo Spin Echo acquisitions. The landmark detection pipeline was trained on over 120 datasets from varying field strength, echo times, and resolutions and quantitatively evaluated. The entire automatic planning solution was tested prospectively in nine fetal subjects between 20 and 37 weeks. A comprehensive evaluation of all steps, the distance between manual and automatic landmarks, the planning quality, and the resulting image quality was conducted. RESULTS: Prospective automatic planning was performed in real-time without latency in all subjects. The landmark detection accuracy was 4.2 ± $$ \pm $$ 2.6 mm for the fetal eyes and 6.5 ± $$ \pm $$ 3.2 for the cerebellum, planning quality was 2.4/3 (compared to 2.6/3 for manual planning) and diagnostic image quality was 2.2 compared to 2.1 for manual planning. CONCLUSIONS: Real-time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way toward simplifying the acquisition of fetal MRI thereby widening the availability of this modality in nonspecialist centers.

Optimisation of quantitative brain diffusion-relaxation MRI acquisition protocols with physics-informed machine learning.

Diffusion-relaxation MRI aims to extract quantitative measures that characterise microstructural tissue properties such as orientation, size, and shape, but long acquisition times are typically required. This work proposes a physics-informed learning framework to extract an optimal subset of diffusion-relaxation MRI measurements for enabling shorter acquisition times, predict non-measured signals, and estimate quantitative parameters. In vivo and synthetic brain 5D-Diffusion-T1-T2∗-weighted MRI data obtained from five healthy subjects were used for training and validation, and from a sixth participant for testing. One fully data-driven and two physics-informed machine learning methods were implemented and compared to two manual selection procedures and Cramér-Rao lower bound optimisation. The physics-informed approaches could identify measurement-subsets that yielded more consistently accurate parameter estimates in simulations than other approaches, with similar signal prediction error. Five-fold shorter protocols yielded error distributions of estimated quantitative parameters with very small effect sizes compared to estimates from the full protocol. Selected subsets commonly included a denser sampling of the shortest and longest inversion time, lowest echo time, and high b-value. The proposed framework combining machine learning and MRI physics offers a promising approach to develop shorter imaging protocols without compromising the quality of parameter estimates and signal predictions.

Craniofacial phenotyping with fetal MRI: a feasibility study of 3D visualisation, segmentation, surface-rendered and physical models.

This study explores the potential of 3D Slice-to-Volume Registration (SVR) motion-corrected fetal MRI for craniofacial assessment, traditionally used only for fetal brain analysis. In addition, we present the first description of an automated pipeline based on 3D Attention UNet trained for 3D fetal MRI craniofacial segmentation, followed by surface refinement. Results of 3D printing of selected models are also presented.Qualitative analysis of multiplanar volumes, based on the SVR output and surface segmentations outputs, were assessed with computer and printed models, using standardised protocols that we developed for evaluating image quality and visibility of diagnostic craniofacial features. A test set of 25, postnatally confirmed, Trisomy 21 fetal cases (24-36 weeks gestational age), revealed that 3D reconstructed T2 SVR images provided 66-100% visibility of relevant craniofacial and head structures in the SVR output, and 20-100% and 60-90% anatomical visibility was seen for the baseline and refined 3D computer surface model outputs respectively. Furthermore, 12 of 25 cases, 48%, of refined surface models demonstrated good or excellent overall quality with a further 9 cases, 36%, demonstrating moderate quality to include facial, scalp and external ears. Additional 3D printing of 12 physical real-size models (20-36 weeks gestational age) revealed good/excellent overall quality in all cases and distinguishable features between healthy control cases and cases with confirmed anomalies, with only minor manual adjustments required before 3D printing.Despite varying image quality and data heterogeneity, 3D T2w SVR reconstructions and models provided sufficient resolution for the subjective characterisation of subtle craniofacial features. We also contributed a publicly accessible online 3D T2w MRI atlas of the fetal head, validated for accurate representation of normal fetal anatomy.Future research will focus on quantitative analysis, optimizing the pipeline, and exploring diagnostic, counselling, and educational applications in fetal craniofacial assessment.

Automated body organ segmentation, volumetry and population-averaged atlas for 3D motion-corrected T2-weighted fetal body MRI.

Structural fetal body MRI provides true 3D information required for volumetry of fetal organs. However, current clinical and research practice primarily relies on manual slice-wise segmentation of raw T2-weighted stacks, which is time consuming, subject to inter- and intra-observer bias and affected by motion-corruption. Furthermore, there are no existing standard guidelines defining a universal approach to parcellation of fetal organs. This work produces the first parcellation protocol of the fetal body organs for motion-corrected 3D fetal body MRI. It includes 10 organ ROIs relevant to fetal quantitative volumetry studies. We also introduce the first population-averaged T2w MRI atlas of the fetal body. The protocol was used as a basis for training of a neural network for automated organ segmentation. It showed robust performance for different gestational ages. This solution minimises the need for manual editing and significantly reduces time. The general feasibility of the proposed pipeline was also assessed by analysis of organ growth charts created from automated parcellations of 91 normal control 3T MRI datasets that showed expected increase in volumetry during 22-38 weeks gestational age range.

Preeclampsia Associated Differences in the Placenta, Fetal Brain, and Maternal Heart Can Be Demonstrated Antenatally: An Observational Cohort Study Using MRI.

BACKGROUND: Preeclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multiorgan approach to magnetic resonance imaging (MRI) investigation of preeclampsia, with the acquisition of maternal cardiac, placental, and fetal brain anatomic and functional imaging. METHODS: An observational study was performed recruiting 3 groups of pregnant women: those with preeclampsia, chronic hypertension, or no medical complications. All women underwent a cardiac MRI, and pregnant women underwent a placental-fetal MRI. Cardiac analysis for structural, morphological, and flow data were undertaken; placenta and fetal brain volumetric and T2* (which describes relative tissue oxygenation) data were obtained. All results were corrected for gestational age. A nonpregnant cohort was identified for inclusion in the statistical shape analysis. RESULTS: Seventy-eight MRIs were obtained during pregnancy. Cardiac MRI analysis demonstrated higher left ventricular mass in preeclampsia with 3-dimensional modeling revealing additional specific characteristics of eccentricity and outflow track remodeling. Pregnancies affected by preeclampsia demonstrated lower placental and fetal brain T2*. Within the preeclampsia group, 23% placental T2* results were consistent with controls, these were the only cases with normal placental histopathology. Fetal brain T2* results were consistent with normal controls in 31% of cases. CONCLUSIONS: We present the first holistic assessment of the immediate implications of preeclampsia on maternal heart, placenta, and fetal brain. As well as having potential clinical implications for the risk stratification and management of women with preeclampsia, this gives an insight into the disease mechanism.

Advanced magnetic resonance imaging detects altered placental development in pregnancies affected by congenital heart disease.

Congenital heart disease (CHD) is the most common congenital malformation and is associated with adverse neurodevelopmental outcomes. The placenta is crucial for healthy fetal development and placental development is altered in pregnancy when the fetus has CHD. This study utilized advanced combined diffusion-relaxation MRI and a data-driven analysis technique to test the hypothesis that placental microstructure and perfusion are altered in CHD-affected pregnancies. 48 participants (36 controls, 12 CHD) underwent 67 MRI scans (50 control, 17 CHD). Significant differences in the weighting of two independent placental and uterine-wall tissue components were identified between the CHD and control groups (both pFDR<0.001), with changes most evident after 30 weeks gestation. A Significant trend over gestation in weighting for a third independent tissue component was also observed in the CHD cohort (R = 0.50, pFDR=0.04), but not in controls. These findings add to existing evidence that placental development is altered in CHD. The results may reflect alterations in placental perfusion or the changes in fetal-placental flow, villous structure and maturation that occur in CHD. Further research is needed to validate and better understand these findings and to understand the relationship between placental development, CHD, and its neurodevelopmental implications.

Adrenal volumes in fetuses delivering prior to 32 weeks' gestation: An MRI pilot study.

INTRODUCTION: Spontaneous preterm birth prior to 32 weeks' gestation accounts for 1% of all deliveries and is associated with high rates of morbidity and mortality. A total of 70% are associated with chorioamnionitis which increases the incidence of morbidity, but for which there is no noninvasive antenatal test. Fetal adrenal glands produce cortisol and dehydroepiandosterone-sulphate which upregulate prior to spontaneous preterm birth. Ultrasound suggests that adrenal volumes may increase prior to preterm birth, but studies are limited. This study aimed to: (i) demonstrate reproducibility of magnetic resonance imaging (MRI) derived adrenal volumetry; (ii) derive normal ranges of total adrenal volumes, and adrenal: body volume for normal; (iii) compare with those who have spontaneous very preterm birth; and (iv) correlate with histopathological chorioamnionitis. MATERIAL AND METHODS: Patients at high risk of preterm birth prior to 32 weeks were prospectively recruited, and included if they did deliver prior to 32 weeks; a control group who delivered an uncomplicated pregnancy at term was also recruited. T2 weighted images of the entire uterus were obtained, and a deformable slice-to-volume method was used to reconstruct the fetal abdomen. Adrenal and body volumes were obtained via manual segmentation, and adrenal: body volume ratios generated. Normal ranges were created using control data. Differences between groups were investigated accounting for the effect of gestation by use of regression analysis. Placental histopathology was reviewed for pregnancies delivering preterm. RESULTS: A total of 56 controls and 26 cases were included in the analysis. Volumetry was consistent between observers. Adrenal volumes were not higher in the case group (p = 0.2); adrenal: body volume ratios were higher (p = 0.011), persisting in the presence of chorioamnionitis (p = 0.017). A cluster of three pairs of adrenal glands below the fifth centile were noted among the cases all of whom had a protracted period at risk of preterm birth prior to MRI. CONCLUSIONS: Adrenal: body volume ratios are significantly larger in fetuses who go on to deliver preterm than those delivering at term. Adrenal volumes were not significantly larger, we hypothesize that this could be due to an adrenal atrophy in fetuses with fulminating chorioamnionitis. A straightforward relationship of adrenal size being increased prior to preterm birth should not be assumed.

Functional MRI assessment of the lungs in fetuses that deliver very Preterm: An MRI pilot study.

OBJECTIVES: To compare mean pulmonary T2* values and pulmonary volumes in fetuses that subsequently spontaneously delivered before 32 weeks with a control cohort with comparable gestational ages and to assess the value of mean pulmonary T2* as a predictor of preterm birth < 32 weeks' gestation. METHODS: MRI datasets scanned at similar gestational ages were selected from fetuses who spontaneously delivered < 32 weeks of gestation and a control group who subsequently delivered at term with no complications. All women underwent a fetal MRI on a 3 T MRI imaging system. Sequences included T2-weighted single shot fast spin echo and T2* sequences, using gradient echo single shot echo planar sequencing of the fetal thorax. Motion correction was performed using slice-to-volume reconstruction and T2* maps generated using in-house pipelines. Lungs were manually segmented and volumes and mean T2* values calculated for both lungs combined and left and right lung separately. Linear regression was used to compare values between the preterm and control cohorts accounting for the effects of gestation. Receiver operating curves were generated for mean T2* values and pulmonary volume as predictors of preterm birth < 32 weeks' gestation. RESULTS: Datasets from twenty-eight preterm and 74 control fetuses were suitable for analysis. MRI images were taken at similar fetal gestational ages (preterm cohort (mean ± SD) 24.9 ± 3.3 and control cohort (mean ± SD) 26.5 ± 3.0). Mean gestational age at delivery was 26.4 ± 3.3 for the preterm group and 39.9 ± 1.3 for the control group. Mean pulmonary T2* values remained constant with increasing gestational age while pulmonary volumes increased. Both T2* and pulmonary volumes were lower in the preterm group than in the control group for all parameters (both combined, left, and right lung (p < 0.001 in all cases). Adjusted for gestational age, pulmonary volumes and mean T2* values were good predictors of premature delivery in fetuses < 32 weeks (area under the curve of 0.828 and 0.754 respectively). CONCLUSION: These findings indicate that mean pulmonary T2* values and volumes were lower in fetuses that subsequently delivered very preterm. This may suggest potentially altered oxygenation and indicate that pulmonary morbidity associated with prematurity has an antenatal antecedent. Future work should explore these results correlating antenatal findings with long term pulmonary outcomes.

Functional assessment of brain development in fetuses that subsequently deliver very preterm: An MRI pilot study.

OBJECTIVES: To evaluate changes occurring in the fetal brain prior to very preterm delivery using MRI T2* relaxometry, an indirect assessment of tissue perfusion. METHOD: Fetuses that subsequently delivered spontaneously <32 weeks gestation and a control cohort were identified from pre-existing datasets. Participants had undergone a 3T MRI assessment including T2* relaxometry of the fetal brain using a 2D multi-slice gradient echo single shot echo planar imaging sequence. T2* maps were generated, supratentorial brain tissue was manually segmented and mean T2* values were generated. Groups were compared using quadratic regression. RESULTS: Twenty five fetuses that subsequently delivered <32 weeks and 67 that delivered at term were included. Mean gestation at MRI was 24.5 weeks (SD 3.3) and 25.4 weeks (SD 3.1) and gestation at delivery 25.5 weeks (SD 3.4) and 39.7 weeks (SD 1.2) in the preterm and term cohorts respectively. Brain mean T2* values were significantly lower in fetuses that subsequently delivered before 32 weeks gestation (p < 0.001). CONCLUSION: Alterations in brain maturation appear to occur prior to preterm delivery. Further work is required to explore these associations, but these findings suggest a potential window for therapeutic neuroprotective agents in fetuses at high risk of preterm delivery in the future.

Non-invasive mapping of human placenta microenvironments throughout pregnancy with diffusion-relaxation MRI.

INTRODUCTION: In-vivo measurements of placental structure and function have the potential to improve prediction, diagnosis, and treatment planning for a wide range of pregnancy complications, such as fetal growth restriction and pre-eclampsia, and hence inform clinical decision making, ultimately improving patient outcomes. MRI is emerging as a technique with increased sensitivity to placental structure and function compared to the current clinical standard, ultrasound. METHODS: We demonstrate and evaluate a combined diffusion-relaxation MRI acquisition and analysis pipeline on a sizable cohort of 78 normal pregnancies with gestational ages ranging from 15 + 5 to 38 + 4 weeks. Our acquisition comprises a combined T2*-diffusion MRI acquisition sequence - which is simultaneously sensitive to oxygenation, microstructure and microcirculation. We analyse our scans with a data-driven unsupervised machine learning technique, InSpect, that parsimoniously identifies distinct components in the data. RESULTS: We identify and map seven potential placental microenvironments and reveal detailed insights into multiple microstructural and microcirculatory features of the placenta, and assess their trends across gestation. DISCUSSION: By demonstrating direct observation of micro-scale placental structure and function, and revealing clear trends across pregnancy, our work contributes towards the development of robust imaging biomarkers for pregnancy complications and the ultimate goal of a normative model of placental development.