Andras Jakab

Thomas Sanchez, Oscar Esteban, Yvan Gomez et al.

Fetal brain MRI is becoming an increasingly relevant complement to neurosonography for perinatal diagnosis, allowing fundamental insights into fetal brain development throughout gestation. However, uncontrolled fetal motion and heterogeneity in acquisition protocols lead to data of variable quality, potentially biasing the outcome of subsequent studies. We present FetMRQC, an open-source machine-learning framework for automated image quality assessment and quality control that is robust to domain shifts induced by the heterogeneity of clinical data. FetMRQC extracts an ensemble of quality metrics from unprocessed anatomical MRI and combines them to predict experts' ratings using random forests. We validate our framework on a pioneeringly large and diverse dataset of more than 1600 manually rated fetal brain T2-weighted images from four clinical centers and 13 different scanners. Our study shows that FetMRQC's predictions generalize well to unseen data while being interpretable. FetMRQC is a step towards more robust fetal brain neuroimaging, which has the potential to shed new insights on the developing human brain.

Kelly Payette, Hongwei Li, Priscille de Dumast et al.

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.

Thomas Sanchez, Vladyslav Zalevskyi, Angeline Mihailov et al.

Quality control (QC) has long been considered essential to guarantee the reliability of neuroimaging studies. It is particularly important for fetal brain MRI, where acquisitions and image processing techniques are less standardized than in adult imaging. In this work, we focus on automated quality control of super-resolution reconstruction (SRR) volumes of fetal brain MRI, an important processing step where multiple stacks of thick 2D slices are registered together and combined to build a single, isotropic and artifact-free T2 weighted volume. We propose FetMRQC$_{SR}$, a machine-learning method that extracts more than 100 image quality metrics to predict image quality scores using a random forest model. This approach is well suited to a problem that is high dimensional, with highly heterogeneous data and small datasets. We validate FetMRQC$_{SR}$ in an out-of-domain (OOD) setting and report high performance (ROC AUC = 0.89), even when faced with data from an unknown site or SRR method. We also investigate failure cases and show that they occur in $45\%$ of the images due to ambiguous configurations for which the rating from the expert is arguable. These results are encouraging and illustrate how a non deep learning-based method like FetMRQC$_{SR}$ is well suited to this multifaceted problem. Our tool, along with all the code used to generate, train and evaluate the model are available at https://github.com/Medical-Image-Analysis-Laboratory/fetmrqc_sr/ .

Raghav Mehta, Angelos Filos, Ujjwal Baid et al.

Deep learning (DL) models have provided state-of-the-art performance in various medical imaging benchmarking challenges, including the Brain Tumor Segmentation (BraTS) challenges. However, the task of focal pathology multi-compartment segmentation (e.g., tumor and lesion sub-regions) is particularly challenging, and potential errors hinder translating DL models into clinical workflows. Quantifying the reliability of DL model predictions in the form of uncertainties could enable clinical review of the most uncertain regions, thereby building trust and paving the way toward clinical translation. Several uncertainty estimation methods have recently been introduced for DL medical image segmentation tasks. Developing scores to evaluate and compare the performance of uncertainty measures will assist the end-user in making more informed decisions. In this study, we explore and evaluate a score developed during the BraTS 2019 and BraTS 2020 task on uncertainty quantification (QU-BraTS) and designed to assess and rank uncertainty estimates for brain tumor multi-compartment segmentation. This score (1) rewards uncertainty estimates that produce high confidence in correct assertions and those that assign low confidence levels at incorrect assertions, and (2) penalizes uncertainty measures that lead to a higher percentage of under-confident correct assertions. We further benchmark the segmentation uncertainties generated by 14 independent participating teams of QU-BraTS 2020, all of which also participated in the main BraTS segmentation task. Overall, our findings confirm the importance and complementary value that uncertainty estimates provide to segmentation algorithms, highlighting the need for uncertainty quantification in medical image analyses. Finally, in favor of transparency and reproducibility, our evaluation code is made publicly available at: https://github.com/RagMeh11/QU-BraTS.

Hélène Lajous, Christopher W. Roy, Tom Hilbert et al.

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.

Vladyslav Zalevskyi, Thomas Sanchez, Misha Kaandorp et al.

Accurate fetal brain tissue segmentation and biometric analysis are essential for studying brain development in utero. The FeTA Challenge 2024 advanced automated fetal brain MRI analysis by introducing biometry prediction as a new task alongside tissue segmentation. For the first time, our diverse multi-centric test set included data from a new low-field (0.55T) MRI dataset. Evaluation metrics were also expanded to include the topology-specific Euler characteristic difference (ED). Sixteen teams submitted segmentation methods, most of which performed consistently across both high- and low-field scans. However, longitudinal trends indicate that segmentation accuracy may be reaching a plateau, with results now approaching inter-rater variability. The ED metric uncovered topological differences that were missed by conventional metrics, while the low-field dataset achieved the highest segmentation scores, highlighting the potential of affordable imaging systems when paired with high-quality reconstruction. Seven teams participated in the biometry task, but most methods failed to outperform a simple baseline that predicted measurements based solely on gestational age, underscoring the challenge of extracting reliable biometric estimates from image data alone. Domain shift analysis identified image quality as the most significant factor affecting model generalization, with super-resolution pipelines also playing a substantial role. Other factors, such as gestational age, pathology, and acquisition site, had smaller, though still measurable, effects. Overall, FeTA 2024 offers a comprehensive benchmark for multi-class segmentation and biometry estimation in fetal brain MRI, underscoring the need for data-centric approaches, improved topological evaluation, and greater dataset diversity to enable clinically robust and generalizable AI tools.

Ziyao Shang, Misha Kaandorp, Kelly Payette et al.

Magnetic resonance imaging (MRI) has played a crucial role in fetal neurodevelopmental research. Structural annotations of MR images are an important step for quantitative analysis of the developing human brain, with Deep learning providing an automated alternative for this otherwise tedious manual process. However, segmentation performances of Convolutional Neural Networks often suffer from domain shift, where the network fails when applied to subjects that deviate from the distribution with which it is trained on. In this work, we aim to train networks capable of automatically segmenting fetal brain MRIs with a wide range of domain shifts pertaining to differences in subject physiology and acquisition environments, in particular shape-based differences commonly observed in pathological cases. We introduce a novel data-driven train-time sampling strategy that seeks to fully exploit the diversity of a given training dataset to enhance the domain generalizability of the trained networks. We adapted our sampler, together with other existing data augmentation techniques, to the SynthSeg framework, a generator that utilizes domain randomization to generate diverse training data, and ran thorough experimentations and ablation studies on a wide range of training/testing data to test the validity of the approaches. Our networks achieved notable improvements in the segmentation quality on testing subjects with intense anatomical abnormalities (p < 1e-4), though at the cost of a slighter decrease in performance in cases with fewer abnormalities. Our work also lays the foundation for future works on creating and adapting data-driven sampling strategies for other training pipelines.

Misha P. T Kaandorp, Damola Agbelese, Hosna Asma-ull et al.

Developing new methods for the automated analysis of clinical fetal and neonatal MRI data is limited by the scarcity of annotated pathological datasets and privacy concerns that often restrict data sharing, hindering the effectiveness of deep learning models. We address this in two ways. First, we introduce Fetal&Neonatal-DDPM, a novel diffusion model framework designed to generate high-quality synthetic pathological fetal and neonatal MRIs from semantic label images. Second, we enhance training data by modifying healthy label images through morphological alterations to simulate conditions such as ventriculomegaly, cerebellar and pontocerebellar hypoplasia, and microcephaly. By leveraging Fetal&Neonatal-DDPM, we synthesize realistic pathological MRIs from these modified pathological label images. Radiologists rated the synthetic MRIs as significantly (p < 0.05) superior in quality and diagnostic value compared to real MRIs, demonstrating features such as blood vessels and choroid plexus, and improved alignment with label annotations. Synthetic pathological data enhanced state-of-the-art nnUNet segmentation performance, particularly for severe ventriculomegaly cases, with the greatest improvements achieved in ventricle segmentation (Dice scores: 0.9253 vs. 0.7317). This study underscores the potential of generative AI as transformative tool for data augmentation, offering improved segmentation performance in pathological cases. This development represents a significant step towards improving analysis and segmentation accuracy in prenatal imaging, and also offers new ways for data anonymization through the generation of pathologic image data.

Hongwei Bran Li, Fernando Navarro, Ivan Ezhov et al.

Uncertainty in medical image segmentation tasks, especially inter-rater variability, arising from differences in interpretations and annotations by various experts, presents a significant challenge in achieving consistent and reliable image segmentation. This variability not only reflects the inherent complexity and subjective nature of medical image interpretation but also directly impacts the development and evaluation of automated segmentation algorithms. Accurately modeling and quantifying this variability is essential for enhancing the robustness and clinical applicability of these algorithms. We report the set-up and summarize the benchmark results of the Quantification of Uncertainties in Biomedical Image Quantification Challenge (QUBIQ), which was organized in conjunction with International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020 and 2021. The challenge focuses on the uncertainty quantification of medical image segmentation which considers the omnipresence of inter-rater variability in imaging datasets. The large collection of images with multi-rater annotations features various modalities such as MRI and CT; various organs such as the brain, prostate, kidney, and pancreas; and different image dimensions 2D-vs-3D. A total of 24 teams submitted different solutions to the problem, combining various baseline models, Bayesian neural networks, and ensemble model techniques. The obtained results indicate the importance of the ensemble models, as well as the need for further research to develop efficient 3D methods for uncertainty quantification methods in 3D segmentation tasks.

Hongwei Bran Li, Gian Marco Conte, Qingqiao Hu et al.

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions.

Florian Kofler, Felix Meissen, Felix Steinbauer et al.

A myriad of algorithms for the automatic analysis of brain MR images is available to support clinicians in their decision-making. For brain tumor patients, the image acquisition time series typically starts with an already pathological scan. This poses problems, as many algorithms are designed to analyze healthy brains and provide no guarantee for images featuring lesions. Examples include, but are not limited to, algorithms for brain anatomy parcellation, tissue segmentation, and brain extraction. To solve this dilemma, we introduce the BraTS inpainting challenge. Here, the participants explore inpainting techniques to synthesize healthy brain scans from lesioned ones. The following manuscript contains the task formulation, dataset, and submission procedure. Later, it will be updated to summarize the findings of the challenge. The challenge is organized as part of the ASNR-BraTS MICCAI challenge.

Priscille de Dumast, Hamza Kebiri, Kelly Payette et al.

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.

Ujjwal Baid, Satyam Ghodasara, Suyash Mohan et al.

The BraTS 2021 challenge celebrates its 10th anniversary and is jointly organized by the Radiological Society of North America (RSNA), the American Society of Neuroradiology (ASNR), and the Medical Image Computing and Computer Assisted Interventions (MICCAI) society. Since its inception, BraTS has been focusing on being a common benchmarking venue for brain glioma segmentation algorithms, with well-curated multi-institutional multi-parametric magnetic resonance imaging (mpMRI) data. Gliomas are the most common primary malignancies of the central nervous system, with varying degrees of aggressiveness and prognosis. The RSNA-ASNR-MICCAI BraTS 2021 challenge targets the evaluation of computational algorithms assessing the same tumor compartmentalization, as well as the underlying tumor's molecular characterization, in pre-operative baseline mpMRI data from 2,040 patients. Specifically, the two tasks that BraTS 2021 focuses on are: a) the segmentation of the histologically distinct brain tumor sub-regions, and b) the classification of the tumor's O[6]-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. The performance evaluation of all participating algorithms in BraTS 2021 will be conducted through the Sage Bionetworks Synapse platform (Task 1) and Kaggle (Task 2), concluding in distributing to the top ranked participants monetary awards of $60,000 collectively.

Sarthak Pati, Ujjwal Baid, Maximilian Zenk et al.

This manuscript describes the first challenge on Federated Learning, namely the Federated Tumor Segmentation (FeTS) challenge 2021. International challenges have become the standard for validation of biomedical image analysis methods. However, the actual performance of participating (even the winning) algorithms on "real-world" clinical data often remains unclear, as the data included in challenges are usually acquired in very controlled settings at few institutions. The seemingly obvious solution of just collecting increasingly more data from more institutions in such challenges does not scale well due to privacy and ownership hurdles. Towards alleviating these concerns, we are proposing the FeTS challenge 2021 to cater towards both the development and the evaluation of models for the segmentation of intrinsically heterogeneous (in appearance, shape, and histology) brain tumors, namely gliomas. Specifically, the FeTS 2021 challenge uses clinically acquired, multi-institutional magnetic resonance imaging (MRI) scans from the BraTS 2020 challenge, as well as from various remote independent institutions included in the collaborative network of a real-world federation (https://www.fets.ai/). The goals of the FeTS challenge are directly represented by the two included tasks: 1) the identification of the optimal weight aggregation approach towards the training of a consensus model that has gained knowledge via federated learning from multiple geographically distinct institutions, while their data are always retained within each institution, and 2) the federated evaluation of the generalizability of brain tumor segmentation models "in the wild", i.e. on data from institutional distributions that were not part of the training datasets.

Kelly Payette, Priscille de Dumast, Hamza Kebiri et al.

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.

Spyridon Bakas, Mauricio Reyes, Andras Jakab et al.

Gliomas are the most common primary brain malignancies, with different degrees of aggressiveness, variable prognosis and various heterogeneous histologic sub-regions, i.e., peritumoral edematous/invaded tissue, necrotic core, active and non-enhancing core. This intrinsic heterogeneity is also portrayed in their radio-phenotype, as their sub-regions are depicted by varying intensity profiles disseminated across multi-parametric magnetic resonance imaging (mpMRI) scans, reflecting varying biological properties. Their heterogeneous shape, extent, and location are some of the factors that make these tumors difficult to resect, and in some cases inoperable. The amount of resected tumor is a factor also considered in longitudinal scans, when evaluating the apparent tumor for potential diagnosis of progression. Furthermore, there is mounting evidence that accurate segmentation of the various tumor sub-regions can offer the basis for quantitative image analysis towards prediction of patient overall survival. This study assesses the state-of-the-art machine learning (ML) methods used for brain tumor image analysis in mpMRI scans, during the last seven instances of the International Brain Tumor Segmentation (BraTS) challenge, i.e., 2012-2018. Specifically, we focus on i) evaluating segmentations of the various glioma sub-regions in pre-operative mpMRI scans, ii) assessing potential tumor progression by virtue of longitudinal growth of tumor sub-regions, beyond use of the RECIST/RANO criteria, and iii) predicting the overall survival from pre-operative mpMRI scans of patients that underwent gross total resection. Finally, we investigate the challenge of identifying the best ML algorithms for each of these tasks, considering that apart from being diverse on each instance of the challenge, the multi-institutional mpMRI BraTS dataset has also been a continuously evolving/growing dataset.

Lin Zhang, Valery Vishnevskiy, Andras Jakab et al.

Intravoxel incoherent motion (IVIM) imaging allows contrast-agent free in vivo perfusion quantification with magnetic resonance imaging (MRI). However, its use is limited by typically low accuracy due to low signal-to-noise ratio (SNR) at large gradient encoding magnitudes as well as dephasing artefacts caused by subject motion, which is particularly challenging in fetal MRI. To mitigate this problem, we propose an implicit IVIM signal acquisition model with which we learn full posterior distribution of perfusion parameters using artificial neural networks. This posterior then encapsulates the uncertainty of the inferred parameter estimates, which we validate herein via numerical experiments with rejection-based Bayesian sampling. Compared to state-of-the-art IVIM estimation method of segmented least-squares fitting, our proposed approach improves parameter estimation accuracy by 65% on synthetic anisotropic perfusion data. On paired rescans of in vivo fetal MRI, our method increases repeatability of parameter estimation in placenta by 46%.