Automated fetal brain extraction from full-uterus MRI is a challenging task due to variable head sizes, orientations, complex anatomy, and prevalent artifacts. While deep-learning (DL) models trained on synthetic images have been successful in adult brain extraction, adapting these networks for fetal MRI is difficult due to the sparsity of labeled data, leading to increased false-positive predictions. To address this challenge, we propose a test-time strategy that reduces false positives in networks trained on sparse, synthetic labels. The approach uses a breadth-fine search (BFS) to identify a subvolume likely to contain the fetal brain, followed by a deep-focused sliding window (DFS) search to refine the extraction, pooling predictions to minimize false positives. We train models at different window sizes using synthetic images derived from a small number of fetal brain label maps, augmented with random geometric shapes. Each model is trained on diverse head positions and scales, including cases with partial or no brain tissue. Our framework matches state-of-the-art brain extraction methods on clinical HASTE scans of third-trimester fetuses and exceeds them by up to 5\% in terms of Dice in the second trimester as well as EPI scans across both trimesters. Our results demonstrate the utility of a sliding-window approach and combining predictions from several models trained on synthetic images, for improving brain-extraction accuracy by progressively refining regions of interest and minimizing the risk of missing brain mask slices or misidentifying other tissues as brain.

Over recent years, deep learning based image registration has achieved impressive accuracy in many domains, including medical imaging and, specifically, human neuroimaging with magnetic resonance imaging (MRI). However, the uncertainty estimation associated with these methods has been largely limited to the application of generic techniques (e.g., Monte Carlo dropout) that do not exploit the peculiarities of the problem domain, particularly spatial modeling. Here, we propose a principled way to propagate uncertainties (epistemic or aleatoric) estimated at the level of spatial location by these methods, to the level of global transformation models, and further to downstream tasks. Specifically, we justify the choice of a Gaussian distribution for the local uncertainty modeling, and then propose a framework where uncertainties spread across hierarchical levels, depending on the choice of transformation model. Experiments on publicly available data sets show that Monte Carlo dropout correlates very poorly with the reference registration error, whereas our uncertainty estimates correlate much better. % with the reference registration error. Crucially, the results also show that uncertainty-aware fitting of transformations improves the registration accuracy of brain MRI scans. Finally, we illustrate how sampling from the posterior distribution of the transformations can be used to propagate uncertainties to downstream neuroimaging tasks. Code is available at: https://github.com/HuXiaoling/Regre4Regis.

Purpose. Proton Magnetic Resonance Spectroscopic Imaging (1H-MRSI) provides non-invasive spectral-spatial mapping of metabolism. However, long-standing problems in whole-brain 1H-MRSI are spectral overlap of metabolite peaks with large lipid signal from scalp, and overwhelming water signal that distorts spectra. Fast and effective methods are needed for high-resolution 1H-MRSI to accurately remove lipid and water signals while preserving the metabolite signal. The potential of supervised neural networks for this task remains unexplored, despite their success for other MRSI processing. Methods. We introduce a deep-learning method based on a modified Y-NET network for water and lipid removal in whole-brain 1H-MRSI. The WALINET (WAter and LIpid neural NETwork) was compared to conventional methods such as the state-of-the-art lipid L2 regularization and Hankel-Lanczos singular value decomposition (HLSVD) water suppression. Methods were evaluated on simulated and in-vivo whole-brain MRSI using NMRSE, SNR, CRLB, and FWHM metrics. Results. WALINET is significantly faster and needs 8s for high-resolution whole-brain MRSI, compared to 42 minutes for conventional HLSVD+L2. Quantitative analysis shows WALINET has better performance than HLSVD+L2: 1) more lipid removal with 41% lower NRMSE, 2) better metabolite signal preservation with 71% lower NRMSE in simulated data, 155% higher SNR and 50% lower CRLB in in-vivo data. Metabolic maps obtained by WALINET in healthy subjects and patients show better gray/white-matter contrast with more visible structural details. Conclusions. WALINET has superior performance for nuisance signal removal and metabolite quantification on whole-brain 1H-MRSI compared to conventional state-of-the-art techniques. This represents a new application of deep-learning for MRSI processing, with potential for automated high-throughput workflow.

Introduction: Altered neurometabolism is an important pathological mechanism in many neurological diseases and brain cancer, which can be mapped non-invasively by Magnetic Resonance Spectroscopic Imaging (MRSI). Advanced MRSI using non-cartesian compressed-sense acquisition enables fast high-resolution metabolic imaging but has lengthy reconstruction times that limits throughput and needs expert user interaction. Here, we present a robust and efficient Deep Learning reconstruction to obtain high-quality metabolic maps. Methods: Fast high-resolution whole-brain metabolic imaging was performed at 3.4 mm$^3$ isotropic resolution with acquisition times between 4:11-9:21 min:s using ECCENTRIC pulse sequence on a 7T MRI scanner. Data were acquired in a high-resolution phantom and 27 human participants, including 22 healthy volunteers and 5 glioma patients. A deep neural network using recurring interlaced convolutional layers with joint dual-space feature representation was developed for deep learning ECCENTRIC reconstruction (Deep-ER). 21 subjects were used for training and 6 subjects for testing. Deep-ER performance was compared to conventional iterative Total Generalized Variation reconstruction using image and spectral quality metrics. Results: Deep-ER demonstrated 600-fold faster reconstruction than conventional methods, providing improved spatial-spectral quality and metabolite quantification with 12%-45% (P<0.05) higher signal-to-noise and 8%-50% (P<0.05) smaller Cramer-Rao lower bounds. Metabolic images clearly visualize glioma tumor heterogeneity and boundary. Conclusion: Deep-ER provides efficient and robust reconstruction for sparse-sampled MRSI. The accelerated acquisition-reconstruction MRSI is compatible with high-throughput imaging workflow. It is expected that such improved performance will facilitate basic and clinical MRSI applications.

Affine image registration is a cornerstone of medical-image analysis. While classical algorithms can achieve excellent accuracy, they solve a time-consuming optimization for every image pair. Deep-learning (DL) methods learn a function that maps an image pair to an output transform. Evaluating the function is fast, but capturing large transforms can be challenging, and networks tend to struggle if a test-image characteristic shifts from the training domain, such as resolution. Most affine methods are agnostic to anatomy, meaning the registration will be inaccurate if algorithms consider all structures in the image. We address these shortcomings with SynthMorph, an easy-to-use DL tool for joint affine-deformable registration of any brain image without preprocessing, right off the MRI scanner. First, we leverage a strategy to train networks with wildly varying images synthesized from label maps, yielding robust performance across acquisition specifics unseen at training. Second, we optimize the spatial overlap of select anatomical labels. This enables networks to distinguish anatomy of interest from irrelevant structures, removing the need for preprocessing that excludes content which would impinge on anatomy-specific registration. Third, we combine the affine model with a deformable hypernetwork that lets users choose the optimal deformation-field regularity for their specific data, at registration time, in a fraction of the time required by classical methods. We rigorously analyze how competing architectures learn affine transforms and compare state-of-the-art registration tools across an extremely diverse set of neuroimaging data, aiming to truly capture the behavior of methods in the real world. SynthMorph demonstrates consistent and improved accuracy. It is available at https://w3id.org/synthmorph, as a single complete end-to-end solution for registration of brain MRI.

Motion artifacts are a pervasive problem in MRI, leading to misdiagnosis or mischaracterization in population-level imaging studies. Current retrospective rigid intra-slice motion correction techniques jointly optimize estimates of the image and the motion parameters. In this paper, we use a deep network to reduce the joint image-motion parameter search to a search over rigid motion parameters alone. Our network produces a reconstruction as a function of two inputs: corrupted k-space data and motion parameters. We train the network using simulated, motion-corrupted k-space data generated with known motion parameters. At test-time, we estimate unknown motion parameters by minimizing a data consistency loss between the motion parameters, the network-based image reconstruction given those parameters, and the acquired measurements. Intra-slice motion correction experiments on simulated and realistic 2D fast spin echo brain MRI achieve high reconstruction fidelity while providing the benefits of explicit data consistency optimization. Our code is publicly available at https://www.github.com/nalinimsingh/neuroMoCo.

We introduce HyperMorph, a framework that facilitates efficient hyperparameter tuning in learning-based deformable image registration. Classical registration algorithms perform an iterative pair-wise optimization to compute a deformation field that aligns two images. Recent learning-based approaches leverage large image datasets to learn a function that rapidly estimates a deformation for a given image pair. In both strategies, the accuracy of the resulting spatial correspondences is strongly influenced by the choice of certain hyperparameter values. However, an effective hyperparameter search consumes substantial time and human effort as it often involves training multiple models for different fixed hyperparameter values and may lead to suboptimal registration. We propose an amortized hyperparameter learning strategy to alleviate this burden by learning the impact of hyperparameters on deformation fields. We design a meta network, or hypernetwork, that predicts the parameters of a registration network for input hyperparameters, thereby comprising a single model that generates the optimal deformation field corresponding to given hyperparameter values. This strategy enables fast, high-resolution hyperparameter search at test-time, reducing the inefficiency of traditional approaches while increasing flexibility. We also demonstrate additional benefits of HyperMorph, including enhanced robustness to model initialization and the ability to rapidly identify optimal hyperparameter values specific to a dataset, image contrast, task, or even anatomical region, all without the need to retrain models. We make our code publicly available at http://hypermorph.voxelmorph.net.

Predictive geometric models deliver excellent results for many Machine Learning use cases. Despite their undoubted performance, neural predictive algorithms can show unexpected degrees of instability and variance, particularly when applied to large datasets. We present an approach to measure changes in geometric models with respect to both output consistency and topological stability. Considering the example of a recommender system using word2vec, we analyze the influence of single data points, approximation methods and parameter settings. Our findings can help to stabilize models where needed and to detect differences in informational value of data points on a large scale.