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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 is a critical step in analyzing the developing human fetal brain. There have been vast improvements in automatic segmentation methods in the past several years, and the Fetal Brain Tissue Annotation (FeTA) Challenge 2021 helped to establish an excellent standard of fetal brain segmentation. However, FeTA 2021 was a single center study, and the generalizability of algorithms across different imaging centers remains unsolved, limiting real-world clinical applicability. The multi-center FeTA Challenge 2022 focuses on advancing the generalizability of fetal brain segmentation algorithms for magnetic resonance imaging (MRI). In FeTA 2022, the training dataset contained images and corresponding manually annotated multi-class labels from two imaging centers, and the testing data contained images from these two imaging centers as well as two additional unseen centers. The data from different centers varied in many aspects, including scanners used, imaging parameters, and fetal brain super-resolution algorithms applied. 16 teams participated in the challenge, and 17 algorithms were evaluated. Here, a detailed overview and analysis of the challenge results are provided, focusing on the generalizability of the submissions. Both in- and out of domain, the white matter and ventricles were segmented with the highest accuracy, while the most challenging structure remains the cerebral cortex due to anatomical complexity. The FeTA Challenge 2022 was able to successfully evaluate and advance generalizability of multi-class fetal brain tissue segmentation algorithms for MRI and it continues to benchmark new algorithms. The resulting new methods contribute to improving the analysis of brain development in utero., Comment: Results from FeTA Challenge 2022, held at MICCAI; Manuscript submitted to IEEE Transactions on Medical Imaging (2024). Supplementary Info (including submission methods descriptions) available here: https://zenodo.org/records/10628648

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

International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multi-center study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and postprocessing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work., Comment: accepted to CVPR 2023

The number of international benchmarking competitions is steadily increasing in various fields of machine learning (ML) research and practice. So far, however, little is known about the common practice as well as bottlenecks faced by the community in tackling the research questions posed. To shed light on the status quo of algorithm development in the specific field of biomedical imaging analysis, we designed an international survey that was issued to all participants of challenges conducted in conjunction with the IEEE ISBI 2021 and MICCAI 2021 conferences (80 competitions in total). The survey covered participants' expertise and working environments, their chosen strategies, as well as algorithm characteristics. A median of 72% challenge participants took part in the survey. According to our results, knowledge exchange was the primary incentive (70%) for participation, while the reception of prize money played only a minor role (16%). While a median of 80 working hours was spent on method development, a large portion of participants stated that they did not have enough time for method development (32%). 25% perceived the infrastructure to be a bottleneck. Overall, 94% of all solutions were deep learning-based. Of these, 84% were based on standard architectures. 43% of the respondents reported that the data samples (e.g., images) were too large to be processed at once. This was most commonly addressed by patch-based training (69%), downsampling (37%), and solving 3D analysis tasks as a series of 2D tasks. K-fold cross-validation on the training set was performed by only 37% of the participants and only 50% of the participants performed ensembling based on multiple identical models (61%) or heterogeneous models (39%). 48% of the respondents applied postprocessing steps.

Fetal brain magnetic resonance imaging serves as an emerging modality for prenatal counseling and diagnosis in disorders affecting the brain. Machine learning based segmentation plays an important role in the quantification of brain development. However, a limiting factor is the lack of sufficiently large, labeled training data. Our study explored the application of SPADE, a conditional general adversarial network (cGAN), which learns the mapping from the label to the image space. The input to the network was super-resolution T2-weighted cerebral MRI data of 120 fetuses (gestational age range: 20-35 weeks, normal and pathological), which were annotated for 7 different tissue categories. SPADE networks were trained on 256*256 2D slices of the reconstructed volumes (image and label pairs) in each orthogonal orientation. To combine the generated volumes from each orientation into one image, a simple mean of the outputs of the three networks was taken. Based on the label maps only, we synthesized highly realistic images. However, some finer details, like small vessels were not synthesized. A structural similarity index (SSIM) of 0.972+-0.016 and correlation coefficient of 0.974+-0.008 were achieved. To demonstrate the capacity of the cGAN to create new anatomical variants, we artificially dilated the ventricles in the segmentation map and created synthetic MRI of different degrees of fetal hydrocephalus. cGANs, such as the SPADE algorithm, allow the generation of hypothetically unseen scenarios and anatomical configurations in the label space, which data in turn can be utilized for training various machine learning algorithms. In the future, this algorithm would be used for generating large, synthetic datasets representing fetal brain development. These datasets would potentially improve the performance of currently available segmentation networks.

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, brainstem, deep grey matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero., Comment: Results from FeTA Challenge 2021, held at MICCAI; Manuscript submitted

The quantitative assessment of the developing human brain in utero is crucial to fully understand neurodevelopment. Thus, automated multi-tissue fetal brain segmentation algorithms are being developed, which in turn require annotated data to be trained. However, the available annotated fetal brain datasets are limited in number and heterogeneity, hampering domain adaptation strategies for robust segmentation. In this context, we use FaBiAN, a Fetal Brain magnetic resonance Acquisition Numerical phantom, to simulate various realistic magnetic resonance images of the fetal brain along with its class labels. We demonstrate that these multiple synthetic annotated data, generated at no cost and further reconstructed using the target super-resolution technique, can be successfully used for domain adaptation of a deep learning method that segments seven brain tissues. Overall, the accuracy of the segmentation is significantly enhanced, especially in the cortical gray matter, the white matter, the cerebellum, the deep gray matter and the brain stem., Comment: 4 pages, 4 figures. This work has been submitted to the IEEE for possible publication

Accurate characterization of in utero human brain maturation is critical as it involves complex and interconnected structural and functional processes that may influence health later in life. Magnetic resonance imaging is a powerful tool to investigate equivocal neurological patterns during fetal development. However, the number of acquisitions of satisfactory quality available in this cohort of sensitive subjects remains scarce, thus hindering the validation of advanced image processing techniques. Numerical phantoms can mitigate these limitations by providing a controlled environment with a known ground truth. In this work, we present FaBiAN, an open-source Fetal Brain magnetic resonance Acquisition Numerical phantom that simulates clinical T2-weighted fast spin echo sequences of the fetal brain. This unique tool is based on a general, flexible and realistic setup that includes stochastic fetal movements, thus providing images of the fetal brain throughout maturation comparable to clinical acquisitions. We demonstrate its value to evaluate the robustness and optimize the accuracy of an algorithm for super-resolution fetal brain magnetic resonance imaging from simulated motion-corrupted 2D low-resolution series as compared to a synthetic high-resolution reference volume. We also show that the images generated can complement clinical datasets to support data-intensive deep learning methods for fetal brain tissue segmentation., Comment: 23 pages, 9 figures (including Supplementary Material), 4 tables, 1 supplement. Submitted to Scientific Reports (2021)

It is critical to quantitatively analyse the developing human fetal brain in order to fully understand neurodevelopment in both normal fetuses and those with congenital disorders. To facilitate this analysis, automatic multi-tissue fetal brain segmentation algorithms are needed, which in turn requires open databases of segmented fetal brains. Here we introduce a publicly available database of 50 manually segmented pathological and non-pathological fetal magnetic resonance brain volume reconstructions across a range of gestational ages (20 to 33 weeks) into 7 different tissue categories (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, deep grey matter, brainstem/spinal cord). In addition, we quantitatively evaluate the accuracy of several automatic multi-tissue segmentation algorithms of the developing human fetal brain. Four research groups participated, submitting a total of 10 algorithms, demonstrating the benefits the database for the development of automatic algorithms., Comment: This is a preprint of an article published in Nature Scientific Data. The final authenticated version is available online at: https://doi.org/10.1038/s41597-021-00946-3

Segmentation of the developing fetal brain is an important step in quantitative analyses. However, manual segmentation is a very time-consuming task which is prone to error and must be completed by highly specialized indi-viduals. Super-resolution reconstruction of fetal MRI has become standard for processing such data as it improves image quality and resolution. However, dif-ferent pipelines result in slightly different outputs, further complicating the gen-eralization of segmentation methods aiming to segment super-resolution data. Therefore, we propose using transfer learning with noisy multi-class labels to automatically segment high resolution fetal brain MRIs using a single set of seg-mentations created with one reconstruction method and tested for generalizability across other reconstruction methods. Our results show that the network can auto-matically segment fetal brain reconstructions into 7 different tissue types, regard-less of reconstruction method used. Transfer learning offers some advantages when compared to training without pre-initialized weights, but the network trained on clean labels had more accurate segmentations overall. No additional manual segmentations were required. Therefore, the proposed network has the potential to eliminate the need for manual segmentations needed in quantitative analyses of the fetal brain independent of reconstruction method used, offering an unbiased way to quantify normal and pathological neurodevelopment., Comment: Accepted for publication at PIPPI MICCAI 2020

Open spina bifida (SB) is one of the most common congenital defects and can lead to impaired brain development. Emerging fetal surgery methods have shown considerable success in the treatment of patients with this severe anomaly. Afterwards, alterations in the brain development of these fetuses have been observed. Currently no longitudinal studies exist to show the effect of fetal surgery on brain development. In this work, we present a fetal MRI neuro-imaging analysis pipeline for fetuses with SB, including automated fetal ventricle segmentation and deformation-based morphometry, and demonstrate its applicability with an analysis of ventricle enlargement in fetuses with SB. Using a robust super-resolution algorithm, we reconstructed fetal brains at both pre-operative and post-operative time points and trained a U-Net CNN in order to automatically segment the ventricles. We investigated the change of ventricle shape post-operatively, and the impacts of lesion size, type, and GA at operation on the change in ventricle shape. No impact was found, except for moderately larger ventriculomegaly progression in myeloschisis patients. Prenatal ventricle volume growth was also investigated. Our method allows for the quantification of longitudinal morphological changes to fully quantify the impact of prenatal SB repair and could be applied to predict postnatal outcomes., Comment: Pre-print version, published in MICCAI PIPPI 2019

Children with congenital heart disease (CHD) remain at risk for neurodevelopmental impairment despite improved peri- and intraoperative care. Our prospective cohort study aimed to determine the relationship between perioperative brain volumes and neurodevelopmental outcome in neonates with severe CHD. Pre- and postoperative cerebral MRI was acquired in term born neonates with CHD undergoing neonatal cardiopulmonary bypass surgery. Brain volumes were measured using an atlas prior based automated method. One-year outcome was assessed with the Bayley-III. CHD infants (n=77) had lower pre- and postoper-ative total and regional brain volumes compared to controls (n=44, all p<0.01). CHD infants had poorer cognitive and motor outcome (p<=0.0001) and a trend towards lower language composite score compared to controls (p=0.06). The total and selected regional postoperative brain volumes predicted cognitive and language outcome (all p<0.04). This association was independent of length of intensive care unit stay for total, cortical, temporal, frontal and cerebellar volumes. In CHD neonates undergoing cardiopulmonary bypass surgery, pre- and postoperative brain volumes are reduced, and postoperative brain volumes predict cognitive and language outcome at one year. Reduced cerebral volumes in CHD patients could serve as a biomarker for im-paired outcome.