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.

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.

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.

Comprehensive volumetric phenotyping of the neonatal brain in Down syndrome.

Down syndrome (DS) is the most common genetic cause of intellectual disability with a wide range of neurodevelopmental outcomes. To date, there have been very few in vivo neuroimaging studies of the neonatal brain in DS. In this study we used a cross-sectional sample of 493 preterm- to term-born control neonates from the developing Human Connectome Project to perform normative modeling of regional brain tissue volumes from 32 to 46 weeks postmenstrual age, accounting for sex and age variables. Deviation from the normative mean was quantified in 25 neonates with DS with postnatally confirmed karyotypes from the Early Brain Imaging in DS study. Here, we provide the first comprehensive volumetric phenotyping of the neonatal brain in DS, which is characterized by significantly reduced whole brain, cerebral white matter, and cerebellar volumes; reduced relative frontal and occipital lobar volumes, in contrast with enlarged relative temporal and parietal lobar volumes; enlarged relative deep gray matter volume (particularly the lentiform nuclei); and enlargement of the lateral ventricles, amongst other features. In future, the ability to assess phenotypic severity at the neonatal stage may help guide early interventions and, ultimately, help improve neurodevelopmental outcomes in children with DS.

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.

Development of human white matter pathways in utero over the second and third trimester.

During the second and third trimesters of human gestation, rapid neurodevelopment is underpinned by fundamental processes including neuronal migration, cellular organization, cortical layering, and myelination. In this time, white matter growth and maturation lay the foundation for an efficient network of structural connections. Detailed knowledge about this developmental trajectory in the healthy human fetal brain is limited, in part, due to the inherent challenges of acquiring high-quality MRI data from this population. Here, we use state-of-the-art high-resolution multishell motion-corrected diffusion-weighted MRI (dMRI), collected as part of the developing Human Connectome Project (dHCP), to characterize the in utero maturation of white matter microstructure in 113 fetuses aged 22 to 37 wk gestation. We define five major white matter bundles and characterize their microstructural features using both traditional diffusion tensor and multishell multitissue models. We found unique maturational trends in thalamocortical fibers compared with association tracts and identified different maturational trends within specific sections of the corpus callosum. While linear maturational increases in fractional anisotropy were seen in the splenium of the corpus callosum, complex nonlinear trends were seen in the majority of other white matter tracts, with an initial decrease in fractional anisotropy in early gestation followed by a later increase. The latter is of particular interest as it differs markedly from the trends previously described in ex utero preterm infants, suggesting that this normative fetal data can provide significant insights into the abnormalities in connectivity which underlie the neurodevelopmental impairments associated with preterm birth.

Reliability and Feasibility of Low-Field-Strength Fetal MRI at 0.55 T during Pregnancy.

Background The benefits of using low-field-strength fetal MRI to evaluate antenatal development include reduced image artifacts, increased comfort, larger bore size, and potentially reduced costs, but studies about fetal low-field-strength MRI are lacking. Purpose To evaluate the reliability and feasibility of low-field-strength fetal MRI to assess anatomic and functional measures in pregnant participants using a commercially available 0.55-T MRI scanner and a comprehensive 20-minute protocol. Materials and Methods This prospective study was performed at a large teaching hospital (St Thomas' Hospital; London, England) from May to November 2022 in healthy pregnant participants and participants with pregnancy-related abnormalities using a commercially available 0.55-T MRI scanner. A 20-minute protocol was acquired including anatomic T2-weighted fast-spin-echo, quantitative T2*, and diffusion sequences. Key measures like biparietal diameter, transcerebellar diameter, lung volume, and cervical length were evaluated by two radiologists and an MRI-experienced obstetrician. Functional organ-specific mean values were given. Comparison was performed with existing published values and higher-field MRI using linear regression, interobserver correlation, and Bland-Altman plots. Results A total of 79 fetal MRI examinations were performed (mean gestational age, 29.4 weeks ± 5.5 [SD] [age range, 17.6-39.3 weeks]; maternal age, 34.4 years ± 5.3 [age range, 18.4-45.5 years]) in 47 healthy pregnant participants (control participants) and in 32 participants with pregnancy-related abnormalities. The key anatomic two-dimensional measures for the 47 healthy participants agreed with large cross-sectional 1.5-T and 3-T control studies. The interobserver correlations for the biparietal diameter in the first 40 consecutive scans were 0.96 (95% CI: 0.7, 0.99; P = .002) for abnormalities and 0.93 (95% CI: 0.86, 0.97; P < .001) for control participants. Functional features, including placental and brain T2* and placental apparent diffusion coefficient values, strongly correlated with gestational age (mean placental T2* in the control participants: 5.2 msec of decay per week; R2 = 0.66; mean T2* at 30 weeks, 176.6 msec; P < .001). Conclusion The 20-minute low-field-strength fetal MRI examination protocol was capable of producing reliable structural and functional measures of the fetus and placenta in pregnancy. Clinical trial registration no. REC 21/LO/0742 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Gowland in this issue.

Risk Factors for Perioperative Brain Lesions in Infants With Congenital Heart Disease: A European Collaboration.

BACKGROUND: Infants with congenital heart disease are at risk of brain injury and impaired neurodevelopment. The aim was to investigate risk factors for perioperative brain lesions in infants with congenital heart disease. METHODS: Infants with transposition of the great arteries, single ventricle physiology, and left ventricular outflow tract and/or aortic arch obstruction undergoing cardiac surgery <6 weeks after birth from 3 European cohorts (Utrecht, Zurich, and London) were combined. Brain lesions were scored on preoperative (transposition of the great arteries N=104; single ventricle physiology N=35; and left ventricular outflow tract and/or aortic arch obstruction N=41) and postoperative (transposition of the great arteries N=88; single ventricle physiology N=28; and left ventricular outflow tract and/or aortic arch obstruction N=30) magnetic resonance imaging for risk factor analysis of arterial ischemic stroke, cerebral sinus venous thrombosis, and white matter injury. RESULTS: Preoperatively, induced vaginal delivery (odds ratio [OR], 2.23 [95% CI, 1.06-4.70]) was associated with white matter injury and balloon atrial septostomy increased the risk of white matter injury (OR, 2.51 [95% CI, 1.23-5.20]) and arterial ischemic stroke (OR, 4.49 [95% CI, 1.20-21.49]). Postoperatively, younger postnatal age at surgery (OR, 1.18 [95% CI, 1.05-1.33]) and selective cerebral perfusion, particularly at ≤20 °C (OR, 13.46 [95% CI, 3.58-67.10]), were associated with new arterial ischemic stroke. Single ventricle physiology was associated with new white matter injury (OR, 2.88 [95% CI, 1.20-6.95]) and transposition of the great arteries with new cerebral sinus venous thrombosis (OR, 13.47 [95% CI, 2.28-95.66]). Delayed sternal closure (OR, 3.47 [95% CI, 1.08-13.06]) and lower intraoperative temperatures (OR, 1.22 [95% CI, 1.07-1.36]) also increased the risk of new cerebral sinus venous thrombosis. CONCLUSIONS: Delivery planning and surgery timing may be modifiable risk factors that allow personalized treatment to minimize the risk of perioperative brain injury in severe congenital heart disease. Further research is needed to optimize cerebral perfusion techniques for neonatal surgery and to confirm the relationship between cerebral sinus venous thrombosis and perioperative risk factors.

3D black blood cardiovascular magnetic resonance atlases of congenital aortic arch anomalies and the normal fetal heart: application to automated multi-label segmentation.

BACKGROUND: Image-domain motion correction of black-blood contrast T2-weighted fetal cardiovascular magnetic resonance imaging (CMR) using slice-to-volume registration (SVR) provides high-resolution three-dimensional (3D) images of the fetal heart providing excellent 3D visualisation of vascular anomalies [1]. However, 3D segmentation of these datasets, important for both clinical reporting and the application of advanced analysis techniques is currently a time-consuming process requiring manual input with potential for inter-user variability. METHODS: In this work, we present novel 3D fetal CMR population-averaged atlases of normal and abnormal fetal cardiovascular anatomy. The atlases are created using motion-corrected 3D reconstructed volumes of 86 third trimester fetuses (gestational age range 29-34 weeks) including: 28 healthy controls, 20 cases with postnatally confirmed neonatal coarctation of the aorta (CoA) and 38 vascular rings (21 right aortic arch (RAA), 17 double aortic arch (DAA)). We used only high image quality datasets with isolated anomalies and without any other deviations in the cardiovascular anatomy.In addition, we implemented and evaluated atlas-guided registration and deep learning (UNETR) methods for automated 3D multi-label segmentation of fetal cardiac vessels. We used images from CoA, RAA and DAA cohorts including: 42 cases for training (14 from each cohort), 3 for validation and 6 for testing. In addition, the potential limitations of the network were investigated on unseen datasets including 3 early gestational age (22 weeks) and 3 low SNR cases. RESULTS: We created four atlases representing the average anatomy of the normal fetal heart, postnatally confirmed neonatal CoA, RAA and DAA. Visual inspection was undertaken to verify expected anatomy per subgroup. The results of the multi-label cardiac vessel UNETR segmentation showed 100[Formula: see text] per-vessel detection rate for both normal and abnormal aortic arch anatomy. CONCLUSIONS: This work introduces the first set of 3D black-blood T2-weighted CMR atlases of normal and abnormal fetal cardiovascular anatomy including detailed segmentation of the major cardiovascular structures. Additionally, we demonstrated the general feasibility of using deep learning for multi-label vessel segmentation of 3D fetal CMR images.

Phenotyping the Preterm Brain: Characterizing Individual Deviations From Normative Volumetric Development in Two Large Infant Cohorts.

The diverse cerebral consequences of preterm birth create significant challenges for understanding pathogenesis or predicting later outcome. Instead of focusing on describing effects common to the group, comparing individual infants against robust normative data offers a powerful alternative to study brain maturation. Here we used Gaussian process regression to create normative curves characterizing brain volumetric development in 274 term-born infants, modeling for age at scan and sex. We then compared 89 preterm infants scanned at term-equivalent age with these normative charts, relating individual deviations from typical volumetric development to perinatal risk factors and later neurocognitive scores. To test generalizability, we used a second independent dataset comprising of 253 preterm infants scanned using different acquisition parameters and scanner. We describe rapid, nonuniform brain growth during the neonatal period. In both preterm cohorts, cerebral atypicalities were widespread, often multiple, and varied highly between individuals. Deviations from normative development were associated with respiratory support, nutrition, birth weight, and later neurocognition, demonstrating their clinical relevance. Group-level understanding of the preterm brain disguises a large degree of individual differences. We provide a method and normative dataset that offer a more precise characterization of the cerebral consequences of preterm birth by profiling the individual neonatal brain.

Preterm birth alters the development of cortical microstructure and morphology at term-equivalent age.

INTRODUCTION: The dynamic nature and complexity of the cellular events that take place during the last trimester of pregnancy make the developing cortex particularly vulnerable to perturbations. Abrupt interruption to normal gestation can lead to significant deviations to many of these processes, resulting in atypical trajectory of cortical maturation in preterm birth survivors. METHODS: We sought to first map typical cortical micro- and macrostructure development using invivo MRI in a large sample of healthy term-born infants scanned after birth (n = 259). Then we offer a comprehensive characterization of the cortical consequences of preterm birth in 76 preterm infants scanned at term-equivalent age (37-44 weeks postmenstrual age). We describe the group-average atypicality, the heterogeneity across individual preterm infants, and relate individual deviations from normative development to age at birth and neurodevelopment at 18 months. RESULTS: In the term-born neonatal brain, we observed heterogeneous and regionally specific associations between age at scan and measures of cortical morphology and microstructure, including rapid surface expansion, greater cortical thickness, lower cortical anisotropy and higher neurite orientation dispersion. By term-equivalent age, preterm infants had on average increased cortical tissue water content and reduced neurite density index in the posterior parts of the cortex, and greater cortical thickness anteriorly compared to term-born infants. While individual preterm infants were more likely to show extreme deviations (over 3.1 standard deviations) from normative cortical maturation compared to term-born infants, these extreme deviations were highly variable and showed very little spatial overlap between individuals. Measures of regional cortical development were associated with age at birth, but not with neurodevelopment at 18 months. CONCLUSION: We showed that preterm birth alters cortical micro- and macrostructural maturation near the time of full-term birth. Deviations from normative development were highly variable between individual preterm infants.

Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome.

The neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer's disease (AD). A key metabolite of interest within the brain in DS is Myo-inositol (mIns). The NA+/mIns co-transporter is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain mIns was previously associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain mIns is increased earlier in development. The aim of this study was to estimate mIns concentration levels and key brain metabolites [N-acetylaspartate (NAA), Choline (Cho) and Creatine (Cr)] in the developing brain in DS and aged-matched controls. We used in vivo magnetic resonance spectroscopy (MRS) in neonates with DS (n = 12) and age-matched controls (n = 26) scanned just after birth (36-45 weeks postmenstrual age). Moreover, we used Mass Spectrometry in early (10-20 weeks post conception) ex vivo fetal brain tissue samples from DS (n = 14) and control (n = 30) cases. Relative to [Cho] and [Cr], we report elevated ratios of [mIns] in vivo in the basal ganglia/thalamus, in neonates with DS, when compared to age-matched typically developing controls. Glycine concentration ratios [Gly]/[Cr] and [Cho]/[Cr] also appear elevated. We observed elevated [mIns] in the ex vivo fetal cortical brain tissue in DS compared with controls. In conclusion, a higher level of brain mIns was evident as early as 10 weeks post conception and was measurable in vivo from 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention.

An efficient and combined placental T1 -ADC acquisition in pregnancies with and without pre-eclampsia.

PURPOSE: To provide a new approach to jointly assess microstructural and molecular properties of the human placenta in vivo fast and efficiently and to present initial evidence in cohorts of healthy pregnancies and those affected by pre-eclampsia. METHODS: Slice and diffusion preparation shuffling, built on the previously proposed ZEBRA method, is presented as a robust and fast way to obtain T1 and apparent diffusivity coefficient (ADC) values. Joint modeling and evaluation is performed on a cohort of healthy and pre-eclamptic participants at 3T. RESULTS: The datasets show the ability to obtain robust and fast T1 -ADC measurements. Significant decay over gestation in T1 (-11 ms/week, P<.05 ) and a trend toward significance in ADC (-0.23 mm/ s2 /week, P = .08) values can be observed in a control cohort. Values for the pre-eclamptic pregnancies show a negative trend for both ADC and T1 . CONCLUSIONS: The presented sequence allows the simultaneous acquisition of 2 of the most promising quantitative parameters to study placental insufficiency-identified individually as relevant in previous studies-in under 2 minutes. This allows dynamic assessment of physiological processes, reduced inconsistency in spatial comparisons due to reduced motion artefacts and opens novel avenues for analysis. Initial results in pre-eclamptic placentas, with depicted changes in both ADC and T1 , illustrate its potential to identify cases of placental insufficiency. Future work will focus on expanding the field-of-view using multi-band acceleration techniques and the expansion to larger and more diverse patient groups.

The effect of maternal position on venous return for pregnant women during MRI.

Magnetic resonance imaging (MRI) in pregnancy is commonly undertaken in the left lateral tilt (LLT) position to prevent inferior vena cava (IVC) compression and supine hypotensive events, although this may be suboptimal for image quality. The supine position may also have an adverse effect on fetal well-being. The spinal venous plexus may provide an alternative pathway for venous return in the presence of IVC compression. This study assesses morphology and blood flow of the IVC and spinal venous plexus for pregnant women in LLT and supine positions to ascertain the effect of maternal position on venous return during MRI. Eighty-two pregnant women underwent phase contrast MRI (PC-MRI) of the IVC and spinal venous plexus in the supine position; 25 were also imaged in the LLT position. Differences in life monitoring, IVC, spinal venous plexus and total venous return between the two positions were assessed. A linear regression assessed the relationship between flow in the IVC and the spinal venous plexus in the supine position. Increasing gestational age and the right-sided position of the uterus on IVC and spinal venous plexus venous return were also evaluated. Hypotension symptoms were similar in supine (10%) and LLT (8%) positioning. Supine positioning decreased IVC height (p < 0.004) and flow (p = 0.045) but flow in the spinal venous plexus increased (p < 0.001) compared with the LLT position. Total venous return showed no difference (p = 0.989) between the two positions. Additional measurements of flow in the aorta also showed no significant difference between the two groups (p = 0.866). Reduced IVC flow in the supine position was associated with increasing gestational age (p = 0.004) and degree of right-sided uterine position (p = 0.004). Women in the left lateral decubitus position who then rotated supine had greater flow in the IVC (p = 0.008) and spinal venous plexus (p = 0.029) than those who started supine. For the majority of women, the spinal venous plexus acts as a complementary venous return system for pregnant women in the supine position, maintaining vascular homeostasis. Further study is needed to assess the effects on the health of the fetus.

Heterogeneity in Brain Microstructural Development Following Preterm Birth.

Preterm-born children are at increased risk of lifelong neurodevelopmental difficulties. Group-wise analyses of magnetic resonance imaging show many differences between preterm- and term-born infants but do not reliably predict neurocognitive prognosis for individual infants. This might be due to the unrecognized heterogeneity of cerebral injury within the preterm group. This study aimed to determine whether atypical brain microstructural development following preterm birth is significantly variable between infants. Using Gaussian process regression, a technique that allows a single-individual inference, we characterized typical variation of brain microstructure using maps of fractional anisotropy and mean diffusivity in a sample of 270 term-born neonates. Then, we compared 82 preterm infants to these normative values to identify brain regions with atypical microstructure and relate observed deviations to degree of prematurity and neurocognition at 18 months. Preterm infants showed strikingly heterogeneous deviations from typical development, with little spatial overlap between infants. Greater and more extensive deviations, captured by a whole brain atypicality index, were associated with more extreme prematurity and predicted poorer cognitive and language abilities at 18 months. Brain microstructural development after preterm birth is highly variable between individual infants. This poorly understood heterogeneity likely relates to both the etiology and prognosis of brain injury.

The use of functional placental magnetic resonance imaging for assessment of the placenta after prolonged preterm rupture of the membranes in vivo: A pilot study.

INTRODUCTION: Preterm prelabor rupture of membranes (PPROM) complicates 3% of pregnancies in the UK. Where delivery does not occur spontaneously, expectant management until 37 weeks of gestation is advocated, unless signs of maternal infection develop. However, clinical presentation of maternal infection can be a late sign and injurious fetal inflammatory responses may already have been activated. There is therefore a need for more sensitive markers to aid optimal timing of interventions. At present there is no non-invasive test in clinical practice to assess for infection in the fetal compartment and definitive diagnosis of chorioamnionitis is by histological assessment of the placenta after delivery. This study presents comprehensive functional placental magnetic resonance imaging (MRI) quantification, already used in other organ systems, to assess for infection/inflammation, in women with and without PPROM aiming to explore its use as a biomarker for inflammation within the feto-placental compartment in vivo. MATERIAL AND METHODS: Placental MRI scans were performed in a cohort of 12 women (with one having two scans) with PPROM before 34 weeks of gestation (selected because of their high risk of infection), and in a control group of 87 women. Functional placental assessment was performed with magnetic resonance techniques sensitive to changes in the microstructure (diffusion) and tissue composition (relaxometry), with quantification performed both over the entire organ and in regions of interest between the basal and chorionic plate. Placental histology was analyzed after delivery where available. RESULTS: Normative evolution of functional magnetic resonance biomarkers over gestation was studied. Cases of inflammation, as assessed by histological presence of chorioamnionitis, and umbilical cord vasculitis with or without funisitis, were associated with lower T2* (mean T2* at 30 weeks 50 ms compared with 58 ms in controls) and higher fractional anisotropy (mean at 30 weeks 0.55 compared with 0.45 in controls). These differences did not reach significance and there was substantial heterogeneity both in T2* and Apparent Diffusivitiy across the cohort. CONCLUSIONS: This first exploration of functional placental assessment in a cohort of women with PPROM demonstrates that functional placental MRI can reveal a range of placental changes associated with inflammatory processes. It is a promising tool to gain information and in the future to identify inflammation in vivo, and could therefore assist in improving optimal timing for interventions designed to prevent fetal injury.

Cognitive function in toddlers with congenital heart disease: The impact of a stimulating home environment.

Infants born with congenital heart disease (CHD) are at increased risk of neurodevelopmental difficulties in childhood. The extent to which perioperative factors, cardiac physiology, brain injury severity, socioeconomic status, and home environment influence early neurodevelopment is not clear. Sixty-nine newborns with CHD were recruited from St Thomas' Hospital. Infants underwent presurgical magnetic resonance imaging on a 3-Tesla scanner situated on the neonatal unit. At 22 months, children completed the Bayley Scales of Infant and Toddler Development-3rd edition and parents completed the cognitively stimulating parenting scale to assess cognitive stimulation at home. Level of maternal education and total annual household income were also collected. Hospital records were reviewed to calculate days on the intensive care unit post-surgery, time on bypass during surgery, and days to corrective or definitive palliative surgical intervention. In the final analysis of 56 infants, higher scores on the cognitively stimulating parenting scale were associated with higher cognitive scores at age 22 months, correcting for gestational age at birth, sex, and maternal education. There were no relationships between outcome scores and clinical factors; socioeconomic status; or brain injury severity. Supporting parents to provide a stimulating home environment for children may promote cognitive development in this high-risk population.

Optimizing maternal fat suppression with constrained image-based shimming in fetal MR.

PURPOSE: Echo planar imaging (EPI) is the primary sequence for functional and diffusion MRI. In fetal applications, the large field of view needed to encode the maternal abdomen leads to prolonged EPI readouts, which may be further extended due to safety considerations that limit gradient performance. The resulting images become very sensitive to water-fat shift and susceptibility artefacts. The purpose of this study was to reduce artefacts and increase stability of EPI in fetal brain imaging, balancing local field homogeneity across the fetal brain with longer range variations to ensure compatibility with fat suppression of the maternal abdomen. METHODS: Spectral Pre-saturation with Inversion-Recovery (SPIR) fat suppression was optimized by investigating SPIR pulse frequency offsets. Subsequently, fetal brain EPI data were acquired using image-based (IB) shimming on 6 pregnant women by (1) minimizing B0 field variations within the fetal brain (localized IB shimming) and (2) with added constraint to limit B0 variation in maternal fat (fat constrained IB shimming). RESULTS: The optimal offset for the SPIR pulse at 3 Tesla was 550 Hz. Both shimming approaches had similar performances in terms of B0 homogeneity within the brain, but constrained IB shimming enabled higher fat suppression efficiency. CONCLUSION: Optimized SPIR in combination with constrained IB shimming can improve maternal fat suppression while minimizing EPI distortions in the fetal brain.

Combined diffusion-relaxometry MRI to identify dysfunction in the human placenta.

PURPOSE: A combined diffusion-relaxometry MR acquisition and analysis pipeline for in vivo human placenta, which allows for exploration of coupling between T2* and apparent diffusion coefficient (ADC) measurements in a sub 10-minute scan time. METHODS: We present a novel acquisition combining a diffusion prepared spin echo with subsequent gradient echoes. The placentas of 17 pregnant women were scanned in vivo, including both healthy controls and participants with various pregnancy complications. We estimate the joint T2* -ADC spectra using an inverse Laplace transform. RESULTS: T2* -ADC spectra demonstrate clear quantitative separation between normal and dysfunctional placentas. CONCLUSIONS: Combined T2* -diffusivity MRI is promising for assessing fetal and maternal health during pregnancy. The T2* -ADC spectrum potentially provides additional information on tissue microstructure, compared to measuring these two contrasts separately. The presented method is immediately applicable to the study of other organs.

Fetal whole-heart 4D imaging using motion-corrected multi-planar real-time MRI.

PURPOSE: To develop an MRI acquisition and reconstruction framework for volumetric cine visualization of the fetal heart and great vessels in the presence of maternal and fetal motion. METHODS: Four-dimensional (4D) depiction was achieved using a highly-accelerated multi-planar real-time balanced steady-state free precession acquisition combined with retrospective image-domain techniques for motion correction, cardiac synchronization and outlier rejection. The framework was validated using a numerical phantom and evaluated in a study of 20 mid- to late-gestational age human fetal subjects (23-33 weeks gestational age). Reconstructed MR data were compared with matched ultrasound. A preliminary assessment of flow-sensitive reconstruction using the velocity information encoded in the phase of real-time images is included. RESULTS: Reconstructed 4D data could be visualized in any two-dimensional plane without the need for highly specific scan plane prescription prior to acquisition or for maternal breath hold to minimize motion. Reconstruction was fully automated aside from user-specified masks of the fetal heart and chest. The framework proved robust when applied to fetal data and simulations confirmed that spatial and temporal features could be reliably recovered. Evaluation suggested the reconstructed framework has the potential to be used for comprehensive assessment of the fetal heart, either as an adjunct to ultrasound or in combination with other MRI techniques. CONCLUSIONS: The proposed methods show promise as a framework for motion-compensated 4D assessment of the fetal heart and great vessels.