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.

In vivo T2 measurements of the fetal brain using single-shot fast spin echo sequences.

PURPOSE: We propose a quantitative framework for motion-corrected T2 fetal brain measurements in vivo and validate the single-shot fast spin echo (SS-FSE) sequence to perform these measurements. METHODS: Stacks of two-dimensional SS-FSE slices are acquired with different echo times (TE) and motion-corrected with slice-to-volume reconstruction (SVR). The quantitative T2 maps are obtained by a fit to a dictionary of simulated signals. The sequence is selected using simulated experiments on a numerical phantom and validated on a physical phantom scanned on a 1.5T system. In vivo quantitative T2 maps are obtained for five fetuses with gestational ages (GA) 21-35 weeks on the same 1.5T system. RESULTS: The simulated experiments suggested that a TE of 400 ms combined with the clinically utilized TEs of 80 and 180 ms were most suitable for T2 measurements in the fetal brain. The validation on the physical phantom confirmed that the SS-FSE T2 measurements match the gold standard multi-echo spin echo measurements. We measured average T2s of around 200 and 280 ms in the fetal brain grey and white matter, respectively. This was slightly higher than fetal T2* and the neonatal T2 obtained from previous studies. CONCLUSION: The motion-corrected SS-FSE acquisitions with varying TEs offer a promising practical framework for quantitative T2 measurements of the moving fetus.

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.

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.

High resolution and contrast 7 tesla MR brain imaging of the neonate.

Introduction: Ultra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system. Methods: Images were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM). Results: There was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy. Discussion: We demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life.