Deep learning approaches for diffusion MRI have so far focused primarily on voxel-based segmentation of lesions or white-matter fiber tracts. A drawback of representing tracts as volumetric labels, rather than sets of streamlines, is that it precludes point-wise analyses of microstructural or geometric features along a tract. Traditional tractography pipelines, which do allow such analyses, can benefit from detailed whole-brain segmentations to guide tract reconstruction. Here, we introduce fast, deep learning-based segmentation of 170 anatomical regions directly on diffusion-weighted MR images, removing the dependency of conventional segmentation methods on T 1-weighted images and slow pre-processing pipelines. Working natively in diffusion space avoids non-linear distortions and registration errors across modalities, as well as interpolation artifacts. We demonstrate consistent segmentation results between 0 .70 and 0 .87 Dice depending on the tissue type. We investigate various combinations of diffusion-derived inputs and show generalization across different numbers of gradient directions. Finally, integrating our approach to provide anatomical priors for tractography pipelines, such as TRACULA, removes hours of pre-processing time and permits processing even in the absence of high-quality T 1-weighted scans, without degrading the quality of the resulting tract estimates.
Fiber tractography is an important tool of computational neuroscience that enables reconstructing the spatial connectivity and organization of white matter of the brain. Fiber tractography takes advantage of diffusion Magnetic Resonance Imaging (dMRI) which allows measuring the apparent diffusivity of cerebral water along different spatial directions. Unfortunately, collecting such data comes at the price of reduced spatial resolution and substantially elevated acquisition times, which limits the clinical applicability of dMRI. This problem has been thus far addressed using two principal strategies. Most of the efforts have been extended towards improving the quality of signal estimation for any, yet fixed sampling scheme (defined through the choice of diffusion-encoding gradients). On the other hand, optimization over the sampling scheme has also proven to be effective. Inspired by the previous results, the present work consolidates the above strategies into a unified estimation framework, in which the optimization is carried out with respect to both estimation model and sampling design {\it concurrently}. The proposed solution offers substantial improvements in the quality of signal estimation as well as the accuracy of ensuing analysis by means of fiber tractography. While proving the optimality of the learned estimation models would probably need more extensive evaluation, we nevertheless claim that the learned sampling schemes can be of immediate use, offering a way to improve the dMRI analysis without the necessity of deploying the neural network used for their estimation. We present a comprehensive comparative analysis based on the Human Connectome Project data. Code and learned sampling designs aviliable at https://github.com/tomer196/Learned_dMRI.
Artifacts, blur and noise are the common distortions degrading MRI images during the acquisition process, and deep neural networks have been demonstrated to help in improving image quality. To well exploit global structural information and texture details, we propose a novel biomedical image enhancement network, named Feedback Graph Attention Convolutional Network (FB-GACN). As a key innovation, we consider the global structure of an image by building a graph network from image sub-regions that we consider to be node features, linking them non-locally according to their similarity. The proposed model consists of three main parts: 1) The parallel graph similarity branch and content branch, where the graph similarity branch aims at exploiting the similarity and symmetry across different image sub-regions in low-resolution feature space and provides additional priors for the content branch to enhance texture details. 2) A feedback mechanism with a recurrent structure to refine low-level representations with high-level information and generate powerful high-level texture details by handling the feedback connections. 3) A reconstruction to remove the artifacts and recover super-resolution images by using the estimated sub-region correlation priors obtained from the graph similarity branch. We evaluate our method on two image enhancement tasks: i) cross-protocol super resolution of diffusion MRI; ii) artifact removal of FLAIR MR images. Experimental results demonstrate that the proposed algorithm outperforms the state-of-the-art methods.
Subtle changes in white matter (WM) microstructure have been associated with normal aging and neurodegeneration. To study these associations in more detail, it is highly important that the WM tracts can be accurately and reproducibly characterized from brain diffusion MRI. In addition, to enable analysis of WM tracts in large datasets and in clinical practice it is essential to have methodology that is fast and easy to apply. This work therefore presents a new approach for WM tract segmentation: Neuro4Neuro, that is capable of direct extraction of WM tracts from diffusion tensor images using convolutional neural network (CNN). This 3D end-to-end method is trained to segment 25 WM tracts in aging individuals from a large population-based study (N=9752, 1.5T MRI). The proposed method showed good segmentation performance and high reproducibility, i.e., a high spatial agreement (Cohen's kappa, k = 0.72 ~ 0.83) and a low scan-rescan error in tract-specific diffusion measures (e.g., fractional anisotropy: error = 1% ~ 5%). The reproducibility of the proposed method was higher than that of a tractography-based segmentation algorithm, while being orders of magnitude faster (0.5s to segment one tract). In addition, we showed that the method successfully generalizes to diffusion scans from an external dementia dataset (N=58, 3T MRI). In two proof-of-principle experiments, we associated WM microstructure obtained using the proposed method with age in a normal elderly population, and with disease subtypes in a dementia cohort. In concordance with the literature, results showed a widespread reduction of microstructural organization with aging and substantial group-wise microstructure differences between dementia subtypes. In conclusion, we presented a highly reproducible and fast method for WM tract segmentation that has the potential of being used in large-scale studies and clinical practice.
There is an urgent need for a paradigm shift from group-wise comparisons to individual diagnosis in diffusion MRI (dMRI) to enable the analysis of rare cases and clinically-heterogeneous groups. Deep autoencoders have shown great potential to detect anomalies in neuroimaging data. We present a framework that operates on the manifold of white matter (WM) pathways to learn normative microstructural features, and discriminate those at genetic risk from controls in a paediatric population.
Autism spectrum disorder (ASD) affects the brain connectivity at different levels. Nonetheless, non-invasively distinguishing such effects using magnetic resonance imaging (MRI) remains very challenging to machine learning diagnostic frameworks due to ASD heterogeneity. So far, existing network neuroscience works mainly focused on functional (derived from functional MRI) and structural (derived from diffusion MRI) brain connectivity, which might not capture relational morphological changes between brain regions. Indeed, machine learning (ML) studies for ASD diagnosis using morphological brain networks derived from conventional T1-weighted MRI are very scarce. To fill this gap, we leverage crowdsourcing by organizing a Kaggle competition to build a pool of machine learning pipelines for neurological disorder diagnosis with application to ASD diagnosis using cortical morphological networks derived from T1-weighted MRI. During the competition, participants were provided with a training dataset and only allowed to check their performance on a public test data. The final evaluation was performed on both public and hidden test datasets based on accuracy, sensitivity, and specificity metrics. Teams were ranked using each performance metric separately and the final ranking was determined based on the mean of all rankings. The first-ranked team achieved 70% accuracy, 72.5% sensitivity, and 67.5% specificity, while the second-ranked team achieved 63.8%, 62.5%, 65% respectively. Leveraging participants to design ML diagnostic methods within a competitive machine learning setting has allowed the exploration and benchmarking of wide spectrum of ML methods for ASD diagnosis using cortical morphological networks.
Deep cerebellar nuclei are a key structure of the cerebellum that are involved in processing motor and sensory information. It is thus a crucial step to accurately segment deep cerebellar nuclei for the understanding of the cerebellum system and its utility in deep brain stimulation treatment. However, it is challenging to clearly visualize such small nuclei under standard clinical magnetic resonance imaging (MRI) protocols and therefore precise segmentation is not feasible. Recent advances in 7 Tesla (T) MRI technology and great potential of deep neural networks facilitate automatic patient-specific segmentation. In this paper, we propose a novel deep learning framework (referred to as DCN-Net) for fast, accurate, and robust patient-specific segmentation of deep cerebellar dentate and interposed nuclei on 7T diffusion MRI. DCN-Net effectively encodes contextual information on the patch images without consecutive pooling operations and adding complexity via proposed dilated dense blocks. During the end-to-end training, label probabilities of dentate and interposed nuclei are independently learned with a hybrid loss, handling highly imbalanced data. Finally, we utilize self-training strategies to cope with the problem of limited labeled data. To this end, auxiliary dentate and interposed nuclei labels are created on unlabeled data by using DCN-Net trained on manual labels. We validate the proposed framework using 7T B0 MRIs from 60 subjects. Experimental results demonstrate that DCN-Net provides better segmentation than atlas-based deep cerebellar nuclei segmentation tools and other state-of-the-art deep neural networks in terms of accuracy and consistency. We further prove the effectiveness of the proposed components within DCN-Net in dentate and interposed nuclei segmentation.
Unpaired image-to-image translation has been applied successfully to natural images but has received very little attention for manifold-valued data such as in diffusion tensor imaging (DTI). The non-Euclidean nature of DTI prevents current generative adversarial networks (GANs) from generating plausible images and has mainly limited their application to diffusion MRI scalar maps, such as fractional anisotropy (FA) or mean diffusivity (MD). Even if these scalar maps are clinically useful, they mostly ignore fiber orientations and therefore have limited applications for analyzing brain fibers. Here, we propose a manifold-aware CycleGAN that learns the generation of high-resolution DTI from unpaired T1w images. We formulate the objective as a Wasserstein distance minimization problem of data distributions on a Riemannian manifold of symmetric positive definite 3x3 matrices SPD(3), using adversarial and cycle-consistency losses. To ensure that the generated diffusion tensors lie on the SPD(3) manifold, we exploit the theoretical properties of the exponential and logarithm maps of the Log-Euclidean metric. We demonstrate that, unlike standard GANs, our method is able to generate realistic high-resolution DTI that can be used to compute diffusion-based metrics and potentially run fiber tractography algorithms. To evaluate our model's performance, we compute the cosine similarity between the generated tensors principal orientation and their ground-truth orientation, the mean squared error (MSE) of their derived FA values and the Log-Euclidean distance between the tensors. We demonstrate that our method produces 2.5 times better FA MSE than a standard CycleGAN and up to 30% better cosine similarity than a manifold-aware Wasserstein GAN while synthesizing sharp high-resolution DTI.
Diffusion MRI (dMRI) is a unique imaging technique for in vivo characterization of tissue microstructure and white matter pathways. However, its relatively long acquisition time implies greater motion artifacts when imaging, for example, infants and Parkinson's disease patients. To accelerate dMRI acquisition, we propose in this paper (i) a diffusion encoding scheme, called Slice-Interleaved Diffusion Encoding (SIDE), that interleaves each diffusion-weighted (DW) image volume with slices that are encoded with different diffusion gradients, essentially allowing the slice-undersampling of image volume associated with each diffusion gradient to significantly reduce acquisition time, and (ii) a method based on deep learning for effective reconstruction of DW images from the highly slice-undersampled data. Evaluation based on the Human Connectome Project (HCP) dataset indicates that our method can achieve a high acceleration factor of up to 6 with minimal information loss. Evaluation using dMRI data acquired with SIDE acquisition demonstrates that it is possible to accelerate the acquisition by as much as 50 folds when combined with multi-band imaging.
Objective: Multimodal measurements of the same phenomena provide complementary information and highlight different perspectives, albeit each with their own limitations. A focus on a single modality may lead to incorrect inferences, which is especially important when a studied phenomenon is a disease. In this paper, we introduce a method that takes advantage of multimodal data in addressing the hypotheses of disconnectivity and dysfunction within schizophrenia (SZ). Methods: We start with estimating and visualizing links within and among extracted multimodal data features using a Gaussian graphical model (GGM). We then propose a modularity-based method that can be applied to the GGM to identify links that are associated with mental illness across a multimodal data set. Through simulation and real data, we show our approach reveals important information about disease-related network disruptions that are missed with a focus on a single modality. We use functional MRI (fMRI), diffusion MRI (dMRI), and structural MRI (sMRI) to compute the fractional amplitude of low frequency fluctuations (fALFF), fractional anisotropy (FA), and gray matter (GM) concentration maps. These three modalities are analyzed using our modularity method. Results: Our results show missing links that are only captured by the cross-modal information that may play an important role in disconnectivity between the components. Conclusion: We identified multimodal (fALFF, FA and GM) disconnectivity in the default mode network area in patients with SZ, which would not have been detectable in a single modality. Significance: The proposed approach provides an important new tool for capturing information that is distributed among multiple imaging modalities.
Quality assessment of diffusion MRI (dMRI) data is essential prior to any analysis, so that appropriate pre-processing can be used to improve data quality and ensure that the presence of MRI artifacts do not affect the results of subsequent image analysis. Manual quality assessment of the data is subjective, possibly error-prone, and infeasible, especially considering the growing number of consortium-like studies, underlining the need for automation of the process. In this paper, we have developed a deep-learning-based automated quality control (QC) tool, QC-Automator, for dMRI data, that can handle a variety of artifacts such as motion, multiband interleaving, ghosting, susceptibility, herringbone and chemical shifts. QC-Automator uses convolutional neural networks along with transfer learning to train the automated artifact detection on a labeled dataset of ~332000 slices of dMRI data, from 155 unique subjects and 5 scanners with different dMRI acquisitions, achieving a 98% accuracy in detecting artifacts. The method is fast and paves the way for efficient and effective artifact detection in large datasets. It is also demonstrated to be replicable on other datasets with different acquisition parameters.
Diffusion magnetic resonance imaging is a noninvasive imaging technique that can indirectly infer the microstructure of tissues and provide metrics which are subject to normal variability across subjects. Potentially abnormal values or features may yield essential information to support analysis of controls and patients cohorts, but subtle confounds affecting diffusion MRI, such as those due to difference in scanning protocols or hardware, can lead to systematic errors which could be mistaken for purely biologically driven variations amongst subjects. In this work, we propose a new harmonization algorithm based on adaptive dictionary learning to mitigate the unwanted variability caused by different scanner hardware while preserving the natural biological variability present in the data. Overcomplete dictionaries, which are learned automatically from the data and do not require paired samples, are then used to reconstruct the data from a different scanner, removing variability present in the source scanner in the process. We use the publicly available database from an international challenge to evaluate the method, which was acquired on three different scanners and with two different protocols, and propose a new mapping towards a scanner-agnostic space. Results show that the effect size of the four studied diffusion metrics is preserved while removing variability attributable to the scanner. Experiments with alterations using a free water compartment, which is not simulated in the training data, shows that the effect size induced by the alterations is also preserved after harmonization. The algorithm is freely available and could help multicenter studies in pooling their data, while removing scanner specific confounds, and increase statistical power in the process.
Fitting multi-exponential models to Diffusion MRI (dMRI) data has always been challenging due to various underlying complexities. In this work, we introduce a novel and robust fitting framework for the standard two-compartment IVIM microstructural model. This framework provides a significant improvement over the existing methods and helps estimate the associated diffusion and perfusion parameters of IVIM in an automatic manner. As a part of this work we provide capabilities to switch between more advanced global optimization methods such as simplicial homology (SH) and differential evolution (DE). Our experiments show that the results obtained from this simultaneous fitting procedure disentangle the model parameters in a reduced subspace. The proposed framework extends the seminal work originated in the MIX framework, with improved procedures for multi-stage fitting. This framework has been made available as an open-source Python implementation and disseminated to the community through the DIPY project.
Tract-specific diffusion measures, as derived from brain diffusion MRI, have been linked to white matter tract structural integrity and neurodegeneration. As a consequence, there is a large interest in the automatic segmentation of white matter tract in diffusion tensor MRI data. Methods based on the tractography are popular for white matter tract segmentation. However, because of the limited consistency and long processing time, such methods may not be suitable for clinical practice. We therefore developed a novel convolutional neural network based method to directly segment white matter tract trained on a low-resolution dataset of 9149 DTI images. The method is optimized on input, loss function and network architecture selections. We evaluated both segmentation accuracy and reproducibility, and reproducibility of determining tract-specific diffusion measures. The reproducibility of the method is higher than that of the reference standard and the determined diffusion measures are consistent. Therefore, we expect our method to be applicable in clinical practice and in longitudinal analysis of white matter microstructure.
Mild Traumatic Brain Injury (mTBI) is a significant public health problem. The most troubling symptoms after mTBI are cognitive complaints. Studies show measurable differences between patients with mTBI and healthy controls with respect to tissue microstructure using diffusion MRI. However, it remains unclear which diffusion measures are the most informative with regard to cognitive functions in both the healthy state as well as after injury. In this study, we use diffusion MRI to formulate a predictive model for performance on working memory based on the most relevant MRI features. The key challenge is to identify relevant features over a large feature space with high accuracy in an efficient manner. To tackle this challenge, we propose a novel improvement of the best first search approach with crossover operators inspired by genetic algorithm. Compared against other heuristic feature selection algorithms, the proposed method achieves significantly more accurate predictions and yields clinically interpretable selected features.
Deep learning (DL) has shown great potential in medical image enhancement problems, such as super-resolution or image synthesis. However, to date, little consideration has been given to uncertainty quantification over the output image. Here we introduce methods to characterise different components of uncertainty in such problems and demonstrate the ideas using diffusion MRI super-resolution. Specifically, we propose to account for $intrinsic$ uncertainty through a heteroscedastic noise model and for $parameter$ uncertainty through approximate Bayesian inference, and integrate the two to quantify $predictive$ uncertainty over the output image. Moreover, we introduce a method to propagate the predictive uncertainty on a multi-channelled image to derived scalar parameters, and separately quantify the effects of intrinsic and parameter uncertainty therein. The methods are evaluated for super-resolution of two different signal representations of diffusion MR images---DTIs and Mean Apparent Propagator MRI---and their derived quantities such as MD and FA, on multiple datasets of both healthy and pathological human brains. Results highlight three key benefits of uncertainty modelling for improving the safety of DL-based image enhancement systems. Firstly, incorporating uncertainty improves the predictive performance even when test data departs from training data. Secondly, the predictive uncertainty highly correlates with errors, and is therefore capable of detecting predictive "failures". Results demonstrate that such an uncertainty measure enables subject-specific and voxel-wise risk assessment of the output images. Thirdly, we show that the method for decomposing predictive uncertainty into its independent sources provides high-level "explanations" for the performance by quantifying how much uncertainty arises from the inherent difficulty of the task or the limited training examples.
Purpose: To understand and characterize noise distributions in parallel imaging for diffusion MRI. Theory and Methods: Two new automated methods using the moments and the maximum likelihood equations of the Gamma distribution were developed. Simulations using stationary and spatially varying noncentral chi noise distributions were created for two diffusion weightings with SENSE or GRAPPA reconstruction and 8, 12 or 32 receiver coils. Furthermore, MRI data of a water phantom with different combinations of multiband and SENSE acceleration were acquired on a 3T scanner along with noise-only measurements. Finally, an in vivo dataset was acquired at 3T using multiband acceleration and GRAPPA reconstruction. Estimation of the noise distribution was performed with the proposed methods and compared with 3 other existing algorithms. Results: Simulations showed that assuming a Rician distribution can lead to misestimation in parallel imaging. Results on the acquired datasets showed that signal leakage in multiband can lead to a misestimation of the parameters. Noise maps are robust to these artifacts, but may misestimate parameters in some cases. The proposed algorithms herein can estimate both parameters of the noise distribution, are robust to signal leakage artifacts and perform best when used on acquired noise maps. Conclusion: Misestimation of the correct noise distribution can hamper further processing such as bias correction and denoising, especially when the measured distribution differs too much from the actual signal distribution e.g., due to artifacts. The use of noise maps can yield more robust estimates than the use of diffusion weighted images as input for algorithms.
Purpose: In the present work we describe the correction of diffusion-weighted MRI for site and scanner biases using a novel method based on invariant representation. Theory and Methods: Pooled imaging data from multiple sources are subject to variation between the sources. Correcting for these biases has become very important as imaging studies increase in size and multi-site cases become more common. We propose learning an intermediate representation invariant to site/protocol variables, a technique adapted from information theory-based algorithmic fairness; by leveraging the data processing inequality, such a representation can then be used to create an image reconstruction that is uninformative of its original source, yet still faithful to underlying structures. To implement this, we use a deep learning method based on variational auto-encoders (VAE) to construct scanner invariant encodings of the imaging data. Results: To evaluate our method, we use training data from the 2018 MICCAI Computational Diffusion MRI (CDMRI) Challenge Harmonization dataset. Our proposed method shows improvements on independent test data relative to a recently published baseline method on each subtask, mapping data from three different scanning contexts to and from one separate target scanning context. Conclusion: As imaging studies continue to grow, the use of pooled multi-site imaging will similarly increase. Invariant representation presents a strong candidate for the harmonization of these data.
Segmentation of structural and diffusion MRI (sMRI/dMRI) is usually performed independently in neuroimaging pipelines. However, some brain structures (e.g., globus pallidus, thalamus and its nuclei) can be extracted more accurately by fusing the two modalities. Following the framework of Bayesian segmentation with probabilistic atlases and unsupervised appearance modeling, we present here a novel algorithm to jointly segment multi-modal sMRI/dMRI data. We propose a hierarchical likelihood term for the dMRI defined on the unit ball, which combines the Beta and Dimroth-Scheidegger-Watson distributions to model the data at each voxel. This term is integrated with a mixture of Gaussians for the sMRI data, such that the resulting joint unsupervised likelihood enables the analysis of multi-modal scans acquired with any type of MRI contrast, b-values, or number of directions, which enables wide applicability. We also propose an inference algorithm to estimate the maximum-a-posteriori model parameters from input images, and to compute the most likely segmentation. Using a recently published atlas derived from histology, we apply our method to thalamic nuclei segmentation on two datasets: HCP (state of the art) and ADNI (legacy) - producing lower sample sizes than Bayesian segmentation with sMRI alone.
While the major white matter tracts are of great interest to numerous studies in neuroscience and medicine, their manual dissection in larger cohorts from diffusion MRI tractograms is time-consuming, requires expert knowledge and is hard to reproduce. In previous work we presented tract orientation mapping (TOM) as a novel concept for bundle-specific tractography. It is based on a learned mapping from the original fiber orientation distribution function (FOD) peaks to tract specific peaks, called tract orientation maps. Each tract orientation map represents the voxel-wise principal orientation of one tract. Here, we present an extension of this approach that combines TOM with accurate segmentations of the tract outline and its start and end region. We also introduce a custom probabilistic tracking algorithm that samples from a Gaussian distribution with fixed standard deviation centered on each peak thus enabling more complete trackings on the tract orientation maps than deterministic tracking. These extensions enable the automatic creation of bundle-specific tractograms with previously unseen accuracy. We show for 72 different bundles on high quality, low quality and phantom data that our approach runs faster and produces more accurate bundle-specific tractograms than 7 state of the art benchmark methods while avoiding cumbersome processing steps like whole brain tractography, non-linear registration, clustering or manual dissection. Moreover, we show on 17 datasets that our approach generalizes well to datasets acquired with different scanners and settings as well as with pathologies. The code of our method is openly available at https://github.com/MIC-DKFZ/TractSeg.