Abstract:Diffusion Magnetic Resonance Imaging (dMRI) is a non-invasive method for depicting brain microstructure in vivo. Fiber orientation distributions (FODs) are mathematical representations extensively used to map white matter fiber configurations. Recently, FOD estimation with deep neural networks has seen growing success, in particular, those of neonates estimated with fewer diffusion measurements. These methods are mostly trained on target FODs reconstructed with multi-shell multi-tissue constrained spherical deconvolution (MSMT-CSD), which might not be the ideal ground truth for developing brains. Here, we investigate this hypothesis by training a state-of-the-art model based on the U-Net architecture on both MSMT-CSD and single-shell three-tissue constrained spherical deconvolution (SS3T-CSD). Our results suggest that SS3T-CSD might be more suited for neonatal brains, given that the ratio between single and multiple fiber-estimated voxels with SS3T-CSD is more realistic compared to MSMT-CSD. Additionally, increasing the number of input gradient directions significantly improves performance with SS3T-CSD over MSMT-CSD. Finally, in an age domain-shift setting, SS3T-CSD maintains robust performance across age groups, indicating its potential for more accurate neonatal brain imaging.
Abstract:Diffusion magnetic resonance imaging (dMRI) is pivotal for probing the microstructure of the rapidly-developing fetal brain. However, fetal motion during scans and its interaction with magnetic field inhomogeneities result in artifacts and data scattering across spatial and angular domains. The effects of those artifacts are more pronounced in high-angular resolution fetal dMRI, where signal-to-noise ratio is very low. Those effects lead to biased estimates and compromise the consistency and reliability of dMRI analysis. This work presents HAITCH, the first and the only publicly available tool to correct and reconstruct multi-shell high-angular resolution fetal dMRI data. HAITCH offers several technical advances that include a blip-reversed dual-echo acquisition for dynamic distortion correction, advanced motion correction for model-free and robust reconstruction, optimized multi-shell design for enhanced information capture and increased tolerance to motion, and outlier detection for improved reconstruction fidelity. The framework is open-source, flexible, and can be used to process any type of fetal dMRI data including single-echo or single-shell acquisitions, but is most effective when used with multi-shell multi-echo fetal dMRI data that cannot be processed with any of the existing tools. Validation experiments on real fetal dMRI scans demonstrate significant improvements and accurate correction across diverse fetal ages and motion levels. HAITCH successfully removes artifacts and reconstructs high-fidelity fetal dMRI data suitable for advanced diffusion modeling, including fiber orientation distribution function estimation. These advancements pave the way for more reliable analysis of the fetal brain microstructure and tractography under challenging imaging conditions.
Abstract:Diffusion-weighted Magnetic Resonance Imaging (dMRI) is increasingly used to study the fetal brain in utero. An important computation enabled by dMRI is streamline tractography, which has unique applications such as tract-specific analysis of the brain white matter and structural connectivity assessment. However, due to the low fetal dMRI data quality and the challenging nature of tractography, existing methods tend to produce highly inaccurate results. They generate many false streamlines while failing to reconstruct streamlines that constitute the major white matter tracts. In this paper, we advocate for anatomically constrained tractography based on an accurate segmentation of the fetal brain tissue directly in the dMRI space. We develop a deep learning method to compute the segmentation automatically. Experiments on independent test data show that this method can accurately segment the fetal brain tissue and drastically improve tractography results. It enables the reconstruction of highly curved tracts such as optic radiations. Importantly, our method infers the tissue segmentation and streamline propagation direction from a diffusion tensor fit to the dMRI data, making it applicable to routine fetal dMRI scans. The proposed method can lead to significant improvements in the accuracy and reproducibility of quantitative assessment of the fetal brain with dMRI.
Abstract:Deep learning models have shown great promise in estimating tissue microstructure from limited diffusion magnetic resonance imaging data. However, these models face domain shift challenges when test and train data are from different scanners and protocols, or when the models are applied to data with inherent variations such as the developing brains of infants and children scanned at various ages. Several techniques have been proposed to address some of these challenges, such as data harmonization or domain adaptation in the adult brain. However, those techniques remain unexplored for the estimation of fiber orientation distribution functions in the rapidly developing brains of infants. In this work, we extensively investigate the age effect and domain shift within and across two different cohorts of 201 newborns and 165 babies using the Method of Moments and fine-tuning strategies. Our results show that reduced variations in the microstructural development of babies in comparison to newborns directly impact the deep learning models' cross-age performance. We also demonstrate that a small number of target domain samples can significantly mitigate domain shift problems.
Abstract:Fetal brain extraction is a necessary first step in most computational fetal brain MRI pipelines. However, it has been a very challenging task due to non-standard fetal head pose, fetal movements during examination, and vastly heterogeneous appearance of the developing fetal brain and the neighboring fetal and maternal anatomy across various sequences and scanning conditions. Development of a machine learning method to effectively address this task requires a large and rich labeled dataset that has not been previously available. As a result, there is currently no method for accurate fetal brain extraction on various fetal MRI sequences. In this work, we first built a large annotated dataset of approximately 72,000 2D fetal brain MRI images. Our dataset covers the three common MRI sequences including T2-weighted, diffusion-weighted, and functional MRI acquired with different scanners. Moreover, it includes normal and pathological brains. Using this dataset, we developed and validated deep learning methods, by exploiting the power of the U-Net style architectures, the attention mechanism, multi-contrast feature learning, and data augmentation for fast, accurate, and generalizable automatic fetal brain extraction. Our approach leverages the rich information from multi-contrast (multi-sequence) fetal MRI data, enabling precise delineation of the fetal brain structures. Evaluations on independent test data show that our method achieves accurate brain extraction on heterogeneous test data acquired with different scanners, on pathological brains, and at various gestational stages. This robustness underscores the potential utility of our deep learning model for fetal brain imaging and image analysis.
Abstract:Early brain development is characterized by the formation of a highly organized structural connectome. The interconnected nature of this connectome underlies the brain's cognitive abilities and influences its response to diseases and environmental factors. Hence, quantitative assessment of structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the connectome from diffusion MRI data involves complex computations. For the perinatal period, these computations are further challenged by the rapid brain development and imaging difficulties. Combined with high inter-subject variability, these factors make it difficult to chart the normal development of the structural connectome. As a result, there is a lack of reliable normative baselines of structural connectivity metrics at this critical stage in brain development. In this study, we developed a computational framework, based on spatio-temporal averaging, for determining such baselines. We used this framework to analyze the structural connectivity between 33 and 44 postmenstrual weeks using data from 166 subjects. Our results unveiled clear and strong trends in the development of structural connectivity in perinatal stage. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. We observed increases in global and local efficiency, a decrease in characteristic path length, and widespread strengthening of the connections within and across brain lobes and hemispheres. We also observed asymmetry patterns that were consistent between different connection weighting approaches. The new computational method and results are useful for assessing normal and abnormal development of the structural connectome early in life.
Abstract:Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to assess the brain white matter. One of the most common computations in dMRI involves cross-subject tract-specific analysis, whereby dMRI-derived biomarkers are compared between cohorts of subjects. The accuracy and reliability of these studies hinges on the ability to compare precisely the same white matter tracts across subjects. This is an intricate and error-prone computation. Existing computational methods such as Tract-Based Spatial Statistics (TBSS) suffer from a host of shortcomings and limitations that can seriously undermine the validity of the results. We present a new computational framework that overcomes the limitations of existing methods via (i) accurate segmentation of the tracts, and (ii) precise registration of data from different subjects/scans. The registration is based on fiber orientation distributions. To further improve the alignment of cross-subject data, we create detailed atlases of white matter tracts. These atlases serve as an unbiased reference space where the data from all subjects is registered for comparison. Extensive evaluations show that, compared with TBSS, our proposed framework offers significantly higher reproducibility and robustness to data perturbations. Our method promises a drastic improvement in accuracy and reproducibility of cross-subject dMRI studies that are routinely used in neuroscience and medical research.
Abstract:The brain white matter consists of a set of tracts that connect distinct regions of the brain. Segmentation of these tracts is often needed for clinical and research studies. Diffusion-weighted MRI offers unique contrast to delineate these tracts. However, existing segmentation methods rely on intermediate computations such as tractography or estimation of fiber orientation density. These intermediate computations, in turn, entail complex computations that can result in unnecessary errors. Moreover, these intermediate computations often require dense multi-shell measurements that are unavailable in many clinical and research applications. As a result, current methods suffer from low accuracy and poor generalizability. Here, we propose a new deep learning method that segments these tracts directly from the diffusion MRI data, thereby sidestepping the intermediate computation errors. Our experiments show that this method can achieve segmentation accuracy that is on par with the state of the art methods (mean Dice Similarity Coefficient of 0.826). Compared with the state of the art, our method offers far superior generalizability to undersampled data that are typical of clinical studies and to data obtained with different acquisition protocols. Moreover, we propose a new method for detecting inaccurate segmentations and show that it is more accurate than standard methods that are based on estimation uncertainty quantification. The new methods can serve many critically important clinical and scientific applications that require accurate and reliable non-invasive segmentation of white matter tracts.
Abstract:Magnetic resonance imaging (MRI) is critically important for brain mapping in both scientific research and clinical studies. Precise segmentation of brain tumors facilitates clinical diagnosis, evaluations, and surgical planning. Deep learning has recently emerged to improve brain tumor segmentation and achieved impressive results. Convolutional architectures are widely used to implement those neural networks. By the nature of limited receptive fields, however, those architectures are subject to representing long-range spatial dependencies of the voxel intensities in MRI images. Transformers have been leveraged recently to address the above limitations of convolutional networks. Unfortunately, the majority of current Transformers-based methods in segmentation are performed with 2D MRI slices, instead of 3D volumes. Moreover, it is difficult to incorporate the structures between layers because each head is calculated independently in the Multi-Head Self-Attention mechanism (MHSA). In this work, we proposed a 3D Transformer-based segmentation approach. We developed a Fusion-Head Self-Attention mechanism (FHSA) to combine each attention head through attention logic and weight mapping, for the exploration of the long-range spatial dependencies in 3D MRI images. We implemented a plug-and-play self-attention module, named the Infinite Deformable Fusion Transformer Module (IDFTM), to extract features on any deformable feature maps. We applied our approach to the task of brain tumor segmentation, and assessed it on the public BRATS datasets. The experimental results demonstrated that our proposed approach achieved superior performance, in comparison to several state-of-the-art segmentation methods.
Abstract:Deep learning has a great potential for estimating biomarkers in diffusion weighted magnetic resonance imaging (dMRI). Atlases, on the other hand, are a unique tool for modeling the spatio-temporal variability of biomarkers. In this paper, we propose the first framework to exploit both deep learning and atlases for biomarker estimation in dMRI. Our framework relies on non-linear diffusion tensor registration to compute biomarker atlases and to estimate atlas reliability maps. We also use nonlinear tensor registration to align the atlas to a subject and to estimate the error of this alignment. We use the biomarker atlas, atlas reliability map, and alignment error map, in addition to the dMRI signal, as inputs to a deep learning model for biomarker estimation. We use our framework to estimate fractional anisotropy and neurite orientation dispersion from down-sampled dMRI data on a test cohort of 70 newborn subjects. Results show that our method significantly outperforms standard estimation methods as well as recent deep learning techniques. Our method is also more robust to stronger measurement down-sampling factors. Our study shows that the advantages of deep learning and atlases can be synergistically combined to achieve unprecedented accuracy in biomarker estimation from dMRI data.