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Purpose: To provide real-time quantitative organ-specific information - specifically placental and brain T2* - to allow optimization of the MR examination to the individual patient. Methods: A FIRE-based real-time setup segmenting placenta and fetal brain in real-time, performing T2* fitting and analysis and calculation of the centile was implemented. A nn-UNet were trained and tested on 2989 datasets for the fetal brain and a second one trained on 210 datasets for the placenta for automatic segmentation. T2* normal curves were obtained from 106 cases and prospective evaluation was performed on 10 cases between 35 and 39 weeks GA. Results: Quantitative brain and placental T2* maps and centiles were available in all prospective cases within 30 seconds. The robustness of the method was shown with intra-scan repeats (mean difference 1.04+/-12.39 ms for fetal brain and -3.15+/-8.88 ms for placenta) and direct validation with vendor-processed offline results (mean difference 1.62+/-4.33 ms for fetal brain and 0.16+/-6.19 ms for placenta). Discussion and Conclusion: Real-time available organ-specific quantitative information enables more personalized MR examinations, selection of the most pertinent sequences and thus the promise of reduced recalls and specific insights into tissue properties. The here enabled placental T2*, demonstrated in multiple recent studies to be a biomarker sensitive to a range of pregnancy complications, and fetal brain T2* will be explored in further studies in pregnancies with pre-eclampsia, growth restriction as a way of enabling future MR-guided fetal interventions.

Two subsequent deep learning networks, one localizing the fetal chest and one identifying a set of landmarks on a coronal whole-uterus balanced steady-state free precession scan, were trained on 167 and 71 fetal datasets across field strengths, acquisition parameters, and gestational ages and implemented in a real-time setup. Next, a phase-contrast sequence was modified to use the identified landmarks for planning. The OWL pipeline was evaluated retrospectively in 10 datasets and prospectively in 7 fetal subjects (gestational ages between 36+3 and 39+3 weeks). The prospective cases were additionally manually planned to enable direct comparison both qualitatively, by scoring the planning quality, and quantitatively, by comparing the indexed flow measurements. OWL enabled real-time fully automatic planning of the 2D phase-contrast scans in all but one of the prospective participants. The fetal body localization achieved an overall Dice score of 0.94+-0.05 and the cardiac landmark detection accuracy was 5.77+-2.91 mm for the descending aorta, 4.32+-2.44 mm for the spine, and 4.94+-3.82 mm for the umbilical vein. For the prospective cases, overall planning quality was 2.73/4 for the automated scans, compared to 3.0/4 for manual planning, and the flow quantitative evaluation showed a mean difference of -1.8% (range -14.2% to 14.9%) by comparing the indexed flow measurements obtained from gated automatic and manual acquisitions. Real-time automated planning of 2D phase-contrast MRI was effectively accomplished for 2 major vessels of the fetal vasculature. While demonstrated here on 0.55T, the achieved method has wider implications, and training across multiple field strengths enables generalization. OWL thereby presents an important step towards extending access to this modality beyond specialised centres., Comment: 12 pages

Segmentation of fetal brain tissue from magnetic resonance imaging (MRI) plays a crucial role in the study of in utero neurodevelopment. However, automated tools face substantial domain shift challenges as they must be robust to highly heterogeneous clinical data, often limited in numbers and lacking annotations. Indeed, high variability of the fetal brain morphology, MRI acquisition parameters, and superresolution reconstruction (SR) algorithms adversely affect the model's performance when evaluated out-of-domain. In this work, we introduce FetalSynthSeg, a domain randomization method to segment fetal brain MRI, inspired by SynthSeg. Our results show that models trained solely on synthetic data outperform models trained on real data in out-ofdomain settings, validated on a 120-subject cross-domain dataset. Furthermore, we extend our evaluation to 40 subjects acquired using lowfield (0.55T) MRI and reconstructed with novel SR models, showcasing robustness across different magnetic field strengths and SR algorithms. Leveraging a generative synthetic approach, we tackle the domain shift problem in fetal brain MRI and offer compelling prospects for applications in fields with limited and highly heterogeneous data., Comment: 10 pages, 5 figures, 1 table

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 EPI 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. 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 4.21+-2.56 mm for the fetal eyes and 6.47+-3.23 for the cerebellum, planning quality was 2.44/3 (compared to 2.56/3 for manual planning) and diagnostic image quality was 2.14 compared to 2.07 for manual planning. Conclusions: Real-time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way towards simplifying the acquisition of fetal MRI thereby widening the availability of this modality in non-specialist centres., Comment: 17 pages, 8 figures, 1 table, MRM

Fetal Magnetic Resonance Imaging at low field strengths is emerging as an exciting direction in perinatal health. Clinical low field (0.55T) scanners are beneficial for fetal imaging due to their reduced susceptibility-induced artefacts, 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 introduce a semi-automatic pipeline using quantitative MRI for the fetal body at low field strength resulting in fast and detailed quantitative T2* relaxometry analysis of all major fetal body organs. Multi-echo dynamic sequences of the fetal body were acquired and reconstructed into a single high-resolution volume using deformable slice-to-volume reconstruction, generating both structural and quantitative T2* 3D volumes. A neural network trained using a semi-supervised approach was created to automatically segment these fetal body 3D volumes into ten different organs (resulting in dice values > 0.74 for 8 out of 10 organs). The T2* values revealed a strong relationship with GA in the lungs, liver, and kidney parenchyma (R^2>0.5). This pipeline was used successfully for a wide range of GAs (17-40 weeks), and is robust to motion artefacts. Low field fetal MRI can be used to perform advanced MRI analysis, and is a viable option for clinical scanning., Comment: Accepted by MICCAI 2023

Tracking microsctructural changes in the developing brain relies on accurate inter-subject image registration. However, most methods rely on either structural or diffusion data to learn the spatial correspondences between two or more images, without taking into account the complementary information provided by using both. Here we propose a deep learning registration framework which combines the structural information provided by T2-weighted (T2w) images with the rich microstructural information offered by diffusion tensor imaging (DTI) scans. We perform a leave-one-out cross-validation study where we compare the performance of our multi-modality registration model with a baseline model trained on structural data only, in terms of Dice scores and differences in fractional anisotropy (FA) maps. Our results show that in terms of average Dice scores our model performs better in subcortical regions when compared to using structural data only. Moreover, average sum-of-squared differences between warped and fixed FA maps show that our proposed model performs better at aligning the diffusion data.

Purpose: To study placental function - both perfusion and an oxygenation surrogate (T2*)-simultaneously and quantitatively in-vivo. Methods: 15 pregnant women were scanned on a 3T MR scanner. For perfusion measurements, a velocity selective arterial spin labelling preparation module was placed before a multi-echo gradient echo EPI readout to integrate T2* and perfusion measurements in one joint perfusion-oxygenation (PERFOX) acquisition. Joint motion correction and quantification were performed to evaluate changes in T2* and perfusion over GA. Results: The optimised integrated PERFOX protocol and post-processing allowed successful visualization and quantification of perfusion and T2* in all subjects. Areas of high T2* and high perfusion appear to correspond to placental sub-units and show a systematic offset in location along the maternal-fetal axis. The areas of highest perfusion are consistently closer to the maternal basal plate and the areas of highest T2* closer to the fetal chorionic plate. Quantitative results show a strong negative correlation of gestational age with T2* and weak negative correlation with perfusion. Conclusion: A strength of the joint sequence is that it provides truly simultaneous and co-registered estimates of local T2* and perfusion, however, to achieve this, the time per slice is prolonged compared to a perfusion only scan which can potentially limit coverage. The achieved interlocking can be particularly useful when quantifying transient physiological effects such as uterine contractions. PERFOX opens a new avenue to elucidate the relationship between maternal supply and oxygen uptake, both of which are central to placental function and dysfunction.

In utero diffusion MRI provides unique opportunities to non-invasively study the microstructure of tissue during fetal development. A wide range of developmental processes, such as the growth of white matter tracts in the brain, the maturation of placental villous trees, or the fibres in the fetal heart remain to be studied and understood in detail. Advances in fetal interventions and surgery furthermore increase the need for ever more precise antenatal diagnosis from fetal MRI. However, the specific properties of the in utero environment, such as fetal and maternal motion, increased field-of-view, tissue interfaces and safety considerations, are significant challenges for most MRI techniques, and particularly for diffusion. Recent years have seen major improvements, driven by the development of bespoke techniques adapted to these specific challenges in both acquisition and processing. Fetal diffusion MRI, an emerging research tool, is now adding valuable novel information for both research and clinical questions. This paper will highlight specific challenges, outline strategies to target them, and discuss two main applications: fetal brain connectomics and placental maturation.

Diffusion MRI offers a unique probe into neural microstructure and connectivity in the developing brain. However, analysis of neonatal brain imaging data is complicated by inevitable subject motion, leading to a series of scattered slices that need to be aligned within and across diffusion-weighted contrasts. Here, we develop a reconstruction method for scattered slice multi-shell high angular resolution diffusion imaging (HARDI) data, jointly estimating an uncorrupted data representation and motion parameters at the slice or multiband excitation level. The reconstruction relies on data-driven representation of multi-shell HARDI data using a bespoke spherical harmonics and radial decomposition (SHARD), which avoids imposing model assumptions, thus facilitating to compare various microstructure imaging methods in the reconstructed output. Furthermore, the proposed framework integrates slice-level outlier rejection, distortion correction, and slice profile correction. We evaluate the method in the neonatal cohort of the developing Human Connectome Project (650 scans). Validation experiments demonstrate accurate slice-level motion correction across the age range and across the range of motion in the population. Results in the neonatal data show successful reconstruction even in severely motion-corrupted subjects. In addition, we illustrate how local tissue modelling can extract advanced microstructure features such as orientation distribution functions from the motion-corrected reconstructions., Comment: revision. 15 pages, 10 figures, 2 tables

We propose a patch-based singular value shrinkage method for diffusion magnetic resonance image estimation targeted at low signal to noise ratio and accelerated acquisitions. It operates on the complex data resulting from a sensitivity encoding reconstruction, where asymptotically optimal signal recovery guarantees can be attained by modeling the noise propagation in the reconstruction and subsequently simulating or calculating the limit singular value spectrum. Simple strategies are presented to deal with phase inconsistencies and optimize patch construction. The pertinence of our contributions is quantitatively validated on synthetic data, an in vivo adult example, and challenging neonatal and fetal cohorts. Our methodology is compared with related approaches, which generally operate on magnitude-only data and use data-based noise level estimation and singular value truncation. Visual examples are provided to illustrate effectiveness in generating denoised and debiased diffusion estimates with well preserved spatial and diffusion detail., Comment: 26 pages, 9 figures

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.

Diffusion-weighted MRI measures the direction and scale of the local diffusion process in every voxel through its spectrum in q-space, typically acquired in one or more shells. Recent developments in microstructure imaging and multi-tissue decomposition have sparked renewed attention in the radial b-value dependence of the signal. Applications in motion correction and outlier rejection therefore require a compact linear signal representation that extends over the radial as well as angular domain. Here, we introduce SHARD, a data-driven representation of the q-space signal based on spherical harmonics and a radial decomposition into orthonormal components. This representation provides a complete, orthogonal signal basis, tailored to the spherical geometry of q-space and calibrated to the data at hand. We demonstrate that the rank-reduced decomposition outperforms model-based alternatives in human brain data, whilst faithfully capturing the micro- and meso-structural information in the signal. Furthermore, we validate the potential of joint radial-spherical as compared to single-shell representations. As such, SHARD is optimally suited for applications that require low-rank signal predictions, such as motion correction and outlier rejection. Finally, we illustrate its application for the latter using outlier robust regression., Comment: Accepted author manuscript, including supplementary materials

The emergence of multiparametric diffusion models combining diffusion and relaxometry measurements provide powerful new ways to explore tissue microstructure with the potential to provide new insights into tissue structure and function. However, their ability to provide rich analyses and the potential for clinical translation critically depends on the availability of efficient, integrated, multi-dimensional acquisitions. We propose a fully integrated sequence simultaneously sampling the acquisition parameter spaces required for T1 and T2* relaxometry and diffusion MRI. Slice-level interleaved diffusion encoding, multiple spin/gradient echoes and slice-shuffling are combined for higher efficiency, sampling flexibility and enhanced internal consistency. In-vivo data was successfully acquired on healthy adult brains. Obtained parametric maps as well as clustering results demonstrate the potential of the technique regarding its ability to provide eloquent data with an acceleration of roughly 20 compared to conventionally used approaches. The proposed integrated acquisition, called ZEBRA, offers significant acceleration and flexibility compared to existing diffusion-relaxometry studies and thus facilitates wider use of these techniques both for research-driven and clinical applications.