Individualized cortical gyrification in neonates with congenital heart disease.

Congenital heart disease is associated with impaired early brain development and adverse neurodevelopmental outcomes. This study investigated how individualized measures of preoperative cortical gyrification index differ in 142 infants with congenital heart disease, using a normative modelling approach with reference data from 320 typically developing infants. Gyrification index Z-scores for the whole brain and six major cortical areas were generated using two different normative models: one accounting for post-menstrual age at scan, post-natal age at scan and sex, and another additionally accounting for supratentorial brain volume. These Z-scores were compared between congenital heart disease and control groups to test the hypothesis that cortical folding in infants with congenital heart disease deviates from the normal developmental trajectory. The relationships between whole-brain gyrification index Z-scores from the two normative models and both cerebral oxygen delivery and neurodevelopmental outcomes were also investigated. Global and regional brain gyrification was significantly reduced in neonates with congenital heart disease, but not when supratentorial brain volume was accounted for. This finding suggests that whilst cortical folding is reduced in congenital heart disease, it is primarily driven by a reduction in brain size. There was a significant positive correlation between cerebral oxygen delivery and whole-brain gyrification index Z-scores in congenital heart disease, but not when supratentorial brain volume was accounted for. Cerebral oxygen delivery is therefore likely to play a more important role in the biological processes underlying volumetric brain growth than cortical folding. No significant associations between whole-brain gyrification index Z-scores and motor/cognitive outcomes or autism traits were identified in the 70 infants with congenital heart disease who underwent neurodevelopmental assessment at 22-months. Our results suggest that chronic in utero and early post-natal hypoxia in congenital heart disease is associated with reductions in cortical folding that are proportional to reductions in supratentorial brain volume.

Structural Covariance Networks in the Fetal Brain Reveal Altered Neurodevelopment for Specific Subtypes of Congenital Heart Disease.

BACKGROUND: Altered structural brain development has been identified in fetuses with congenital heart disease (CHD), suggesting that the neurodevelopmental impairment observed later in life might originate in utero. There are many interacting factors that may perturb neurodevelopment during the fetal period and manifest as structural brain alterations, such as altered cerebral substrate delivery and aberrant fetal hemodynamics. METHODS AND RESULTS: We extracted structural covariance networks from the log Jacobian determinants of 435 in utero T2 weighted image magnetic resonance imaging scans, (n=67 controls, 368 with CHD) acquired during the third trimester. We fit general linear models to test whether age, sex, expected cerebral substrate delivery, and CHD diagnosis were significant predictors of structural covariance. We identified significant effects of age, sex, cerebral substrate delivery, and specific CHD diagnosis across a variety of structural covariance networks, including primary motor and sensory cortices, cerebellar regions, frontal cortex, extra-axial cerebrospinal fluid, thalamus, brainstem, and insula, consistent with widespread coordinated aberrant maturation of specific brain regions over the third trimester. CONCLUSIONS: Structural covariance networks offer a sensitive, data-driven approach to explore whole-brain structural changes without anatomical priors. We used them to stratify a heterogenous patient cohort with CHD, highlighting similarities and differences between diagnoses during fetal neurodevelopment. Although there was a clear effect of abnormal fetal hemodynamics on structural brain maturation, our results suggest that this alone does not explain all the variation in brain development between individuals with CHD.

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.

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.

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.

Dynamic changes in subplate and cortical plate microstructure at the onset of cortical folding in vivo.

Cortical gyrification takes place predominantly during the second to third trimester, alongside other fundamental developmental processes, such as the development of white matter connections, lamination of the cortex and formation of neural circuits. The mechanistic biology that drives the formation cortical folding patterns remains an open question in neuroscience. In our previous work, we modelled the in utero diffusion signal to quantify the maturation of microstructure in transient fetal compartments, identifying patterns of change in diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester. In this work, we apply the same modelling approach to explore whether microstructural maturation of these compartments is correlated with the process of gyrification. We quantify the relationship between sulcal depth and tissue anisotropy within the cortical plate (CP) and underlying subplate (SP), key transient fetal compartments often implicated in mechanistic hypotheses about the onset of gyrification. Using in utero high angular resolution multi-shell diffusion-weighted imaging (HARDI) from the Developing Human Connectome Project (dHCP), our analysis reveals that the anisotropic, tissue component of the diffusion signal in the SP and CP decreases immediately prior to the formation of sulcal pits in the fetal brain. By back-projecting a map of folded brain regions onto the unfolded brain, we find evidence for cytoarchitectural differences between gyral and sulcal areas in the late second trimester, suggesting that regional variation in the microstructure of transient fetal compartments precedes, and thus may have a mechanistic function, in the onset of cortical folding in the developing human brain.

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.

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.

The influence of antenatal imaging on prenatal bonding in uncomplicated pregnancies: a mixed methods analysis.

BACKGROUND: Prenatal bonding describes the emotional connection expectant parents form to their unborn child. Research acknowledges the association between antenatal imaging and enhanced bonding, but the influencing factors are not well understood, particularly for fathers or when using advanced techniques like fetal magnetic resonance imaging (MRI). This study aimed to identify variables which may predict increased bonding after imaging. METHODS: First-time expectant parents (mothers = 58, fathers = 18) completed a two-part questionnaire (QualtricsXM™) about their expectations and experiences of ultrasound (n = 64) or fetal MRI (n = 12) scans in uncomplicated pregnancies. A modified version of the Prenatal Attachment Inventory (PAI) was used to measure bonding. Qualitative data were collected through open-ended questions. Multivariate linear regression models were used to identify significant parent and imaging predictors for bonding. Qualitative content analysis of free-text responses was conducted to further understand the predictors' influences. RESULTS: Bonding scores were significantly increased after imaging for mothers and fathers (p < 0.05). MRI-parents reported significantly higher bonding than ultrasound-parents (p = 0.02). In the first regression model of parent factors (adjusted R2 = 0.17, F = 2.88, p < 0.01), employment status (ß = -0.38, p < 0.05) was a significant predictor for bonding post-imaging. The second model of imaging factors (adjusted R2 = 0.19, F = 3.85, p < 0.01) showed imaging modality (ß = -0.53), imaging experience (ß = 0.42) and parental excitement after the scan (ß = 0.29) were significantly (p < 0.05) associated with increased bonding. Seventeen coded themes were generated from the qualitative content analysis, describing how scans offered reassurance about fetal wellbeing and the opportunity to connect with the baby through quality interactions with imaging professionals. A positive scan experience helped parents to feel excited about parenthood. Fetal MRI was considered a superior modality to ultrasound. CONCLUSIONS: Antenatal imaging provides reassurance of fetal development which affirms parents' emotional investment in the pregnancy and supports the growing connection. Imaging professionals are uniquely positioned to provide parent-centred experiences which may enhance parental excitement and facilitate bonding.

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.

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.

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.

Executive Function in Preschool Children with Congenital Heart Disease and Controls: The Role of a Cognitively Stimulating Home Environment.

OBJECTIVE: To assess the relationships between (1) environmental and demographic factors and executive function (EF) in preschool children with congenital heart disease (CHD) and controls and (2) clinical and surgical risk factors and EF in preschool children with CHD. STUDY DESIGN: At 4-6 years of age, parents of children with CHD (n = 51) and controls (n = 124) completed the Behavior Rating Inventory of Executive Function, Preschool Version questionnaire and the Cognitively Stimulating Parenting Scale (CSPS). Multivariable general linear modeling assessed the relationship between Behavior Rating Inventory of Executive Function, Preschool Version composite scores (Inhibitory Self-Control Index [ISCI], Flexibility Index [FI], and Emergent Metacognition Index [EMI]) and group (CHD/control), sex, age at assessment, gestational age, Index of Multiple Deprivation, and CSPS scores. The relationships between CHD type, surgical factors, and brain magnetic resonance imaging injury rating and ISCI, FI, and EMI scores were assessed. RESULTS: The presence of CHD, age at assessment, sex, and Index of Multiple Deprivation were not associated with EF scores. Lower gestational age was associated with greater ISCI and FI scores, and age at assessment was associated with lower FI scores. Group significantly moderated the relationship between CSPS and EF, such that CSPS significantly predicted EF in children with CHD (ISCI: P = .0004; FI: P = .0015; EMI: P = .0004) but not controls (ISCI: P = .2727; FI: P = .6185; EMI: P = .3332). There were no significant relationships between EF scores and surgical factors, CHD type, or brain magnetic resonance imaging injury rating. CONCLUSIONS: Supporting parents to provide a cognitively stimulating home environment may improve EF in children with CHD. The home and parenting environment should be considered when designing intervention studies aimed at improving EF in this patient group.

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.

Perioperative Brain Injury in Relation to Early Neurodevelopment Among Children with Severe Congenital Heart Disease: Results from a European Collaboration.

OBJECTIVE: To examine the relationship between perioperative brain injury and neurodevelopment during early childhood in patients with severe congenital heart disease (CHD). STUDY DESIGN: One hundred and seventy children with CHD and born at term who required cardiopulmonary bypass surgery in the first 6 weeks after birth were recruited from 3 European centers and underwent preoperative and postoperative brain MRIs. Uniform description of imaging findings was performed and an overall brain injury score was created, based on the sum of the worst preoperative or postoperative brain injury subscores. Motor and cognitive outcomes were assessed with the Bayley Scales of Infant and Toddler Development Third Edition at 12 to 30 months of age. The relationship between brain injury score and clinical outcome was assessed using multiple linear regression analysis, adjusting for CHD severity, length of hospital stay (LOS), socioeconomic status (SES), and age at follow-up. RESULTS: Neither the overall brain injury score nor any of the brain injury subscores correlated with motor or cognitive outcome. The number of preoperative white matter lesions was significantly associated with gross motor outcome after correction for multiple testing (P = .013, ß = -0.50). SES was independently associated with cognitive outcome (P < .001, ß = 0.26), and LOS with motor outcome (P < .001, ß = -0.35). CONCLUSION: Preoperative white matter lesions appear to be the most predictive MRI marker for adverse early childhood gross motor outcome in this large European cohort of infants with severe CHD. LOS as a marker of disease severity, and SES influence outcome and future intervention trials need to address these risk factors.