Purpose: Diffusion weighted MRI (dMRI) and its models of neural structure provide insight into human brain organization and variations in white matter. A recent study by McMaster, et al. showed that complex graph measures of the connectome, the graphical representation of a tractogram, vary with spatial sampling changes, but biases introduced by anisotropic voxels in the process have not been well characterized. This study uses microstructural measures (fractional anisotropy and mean diffusivity) and white matter bundle properties (bundle volume, length, and surface area) to further understand the effect of anisotropic voxels on microstructure and tractography. Methods: The statistical significance of the selected measures derived from dMRI data were assessed by comparing three white matter bundles at different spatial resolutions with 44 subjects from the Human Connectome Project Young Adult dataset scan/rescan data using the Wilcoxon Signed Rank test. The original isotropic resolution (1.25 mm isotropic) was explored with six anisotropic resolutions with 0.25 mm incremental steps in the z dimension. Then, all generated resolutions were upsampled to 1.25 mm isotropic and 1 mm isotropic. Results: There were statistically significant differences between at least one microstructural and one bundle measure at every resolution (p less than or equal to 0.05, corrected for multiple comparisons). Cohen's d coefficient evaluated the effect size of anisotropic voxels on microstructure and tractography. Conclusion: Fractional anisotropy and mean diffusivity cannot be recovered with basic up sampling from low quality data with gold standard data. However, the bundle measures from tractogram become more repeatable when voxels are resampled to 1 mm isotropic.
Deformable image registration is crucial for aligning medical images in a nonlinear fashion across different modalities, allowing for precise spatial correspondence between varying anatomical structures. This paper presents NestedMorph, a novel network utilizing a Nested Attention Fusion approach to improve intra-subject deformable registration between T1-weighted (T1w) MRI and diffusion MRI (dMRI) data. NestedMorph integrates high-resolution spatial details from an encoder with semantic information from a decoder using a multi-scale framework, enhancing both local and global feature extraction. Our model notably outperforms existing methods, including CNN-based approaches like VoxelMorph, MIDIR, and CycleMorph, as well as Transformer-based models such as TransMorph and ViT-V-Net, and traditional techniques like NiftyReg and SyN. Evaluations using the HCP dataset demonstrate that NestedMorph achieves superior performance across key metrics, including SSIM, HD95, and SDlogJ, with the highest SSIM of 0.89, the lowest HD95 of 2.5 and SDlogJ of 0.22. These results highlight NestedMorph's ability to capture both local and global image features effectively, leading to superior registration performance. The promising outcomes of this study underscore NestedMorph's potential to significantly advance deformable medical image registration, providing a robust framework for future research and clinical applications. The source code and our implementation are available at: https://github.com/AS-Lab/Marthi-et-al-2024-NestedMorph-Deformable-Medical-Image-Registration
An incomplete field-of-view (FOV) in diffusion magnetic resonance imaging (dMRI) can severely hinder the volumetric and bundle analyses of whole-brain white matter connectivity. Although existing works have investigated imputing the missing regions using deep generative models, it remains unclear how to specifically utilize additional information from paired multi-modality data and whether this can enhance the imputation quality and be useful for downstream tractography. To fill this gap, we propose a novel framework for imputing dMRI scans in the incomplete part of the FOV by integrating the learned diffusion features in the acquired part of the FOV to the complete brain anatomical structure. We hypothesize that by this design the proposed framework can enhance the imputation performance of the dMRI scans and therefore be useful for repairing whole-brain tractography in corrupted dMRI scans with incomplete FOV. We tested our framework on two cohorts from different sites with a total of 96 subjects and compared it with a baseline imputation method that treats the information from T1w and dMRI scans equally. The proposed framework achieved significant improvements in imputation performance, as demonstrated by angular correlation coefficient (p < 1E-5), and in downstream tractography accuracy, as demonstrated by Dice score (p < 0.01). Results suggest that the proposed framework improved imputation performance in dMRI scans by specifically utilizing additional information from paired multi-modality data, compared with the baseline method. The imputation achieved by the proposed framework enhances whole brain tractography, and therefore reduces the uncertainty when analyzing bundles associated with neurodegenerative.
The Orientation Distribution Function (ODF) characterizes key brain microstructural properties and plays an important role in understanding brain structural connectivity. Recent works introduced Implicit Neural Representation (INR) based approaches to form a spatially aware continuous estimate of the ODF field and demonstrated promising results in key tasks of interest when compared to conventional discrete approaches. However, traditional INR methods face difficulties when scaling to large-scale images, such as modern ultra-high-resolution MRI scans, posing challenges in learning fine structures as well as inefficiencies in training and inference speed. In this work, we propose HashEnc, a grid-hash-encoding-based estimation of the ODF field and demonstrate its effectiveness in retaining structural and textural features. We show that HashEnc achieves a 10% enhancement in image quality while requiring 3x less computational resources than current methods. Our code can be found at https://github.com/MunzerDw/NODF-HashEnc.
<div><p>Diffusion MRI is a powerful tool that serves as a bridge between brain microstructure and cognition. Recent advancements in cognitive neuroscience have highlighted the persistent challenge of understanding how individual differences in brain structure influence behavior, especially in healthy people. While traditional linear models like Canonical Correlation Analysis (CCA) and Partial Least Squares (PLS) have been fundamental in this analysis, they face limitations, particularly with high-dimensional data analysis outside the training sample. To address these issues, we introduce a novel approach using deep learninga multivariate autoencoder model-to explore the complex non-linear relationships between brain microstructure and cognitive functions. The model's architecture involves separate encoder modules for brain structure and cognitive data, with a shared decoder, facilitating the analysis of multivariate patterns across these domains. Both encoders were trained simultaneously, before the decoder, to ensure a good latent representation that captures the phenomenon. Using data from the Human Connectome Project, our study centres on the insula's role in cognitive processes. Through rigorous validation, including 5 sample analyses for out-of-sample analysis, our results demonstrate that the multivariate autoencoder model outperforms traditional methods in capturing and generalizing correlations between brain and behavior beyond the training sample. These findings underscore the potential of deep learning models to enhance our understanding of brain-behavior relationships in cognitive neuroscience, offering more accurate and comprehensive insights despite the complexities inherent in neuroimaging studies.</p></div>
Diffusion-weighted MRI is increasingly used to study the normal and abnormal development of fetal brain in-utero. Recent studies have shown that dMRI can offer invaluable insights into the neurodevelopmental processes in the fetal stage. However, because of the low data quality and rapid brain development, reliable analysis of fetal dMRI data requires dedicated computational methods that are currently unavailable. The lack of automated methods for fast, accurate, and reproducible data analysis has seriously limited our ability to tap the potential of fetal brain dMRI for medical and scientific applications. In this work, we developed and validated a unified computational framework to (1) segment the brain tissue into white matter, cortical/subcortical gray matter, and cerebrospinal fluid, (2) segment 31 distinct white matter tracts, and (3) parcellate the brain's cortex and delineate the deep gray nuclei and white matter structures into 96 anatomically meaningful regions. We utilized a set of manual, semi-automatic, and automatic approaches to annotate 97 fetal brains. Using these labels, we developed and validated a multi-task deep learning method to perform the three computations. Our evaluations show that the new method can accurately carry out all three tasks, achieving a mean Dice similarity coefficient of 0.865 on tissue segmentation, 0.825 on white matter tract segmentation, and 0.819 on parcellation. The proposed method can greatly advance the field of fetal neuroimaging as it can lead to substantial improvements in fetal brain tractography, tract-specific analysis, and structural connectivity assessment.
In this study, we developed an Evidence-based Ensemble Neural Network, namely EVENet, for anatomical brain parcellation using diffusion MRI. The key innovation of EVENet is the design of an evidential deep learning framework to quantify predictive uncertainty at each voxel during a single inference. To do so, we design an evidence-based ensemble learning framework for uncertainty-aware parcellation to leverage the multiple dMRI parameters derived from diffusion MRI. Using EVENet, we obtained accurate parcellation and uncertainty estimates across different datasets from healthy and clinical populations and with different imaging acquisitions. The overall network includes five parallel subnetworks, where each is dedicated to learning the FreeSurfer parcellation for a certain diffusion MRI parameter. An evidence-based ensemble methodology is then proposed to fuse the individual outputs. We perform experimental evaluations on large-scale datasets from multiple imaging sources, including high-quality diffusion MRI data from healthy adults and clinically diffusion MRI data from participants with various brain diseases (schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, Parkinson's disease, cerebral small vessel disease, and neurosurgical patients with brain tumors). Compared to several state-of-the-art methods, our experimental results demonstrate highly improved parcellation accuracy across the multiple testing datasets despite the differences in dMRI acquisition protocols and health conditions. Furthermore, thanks to the uncertainty estimation, our EVENet approach demonstrates a good ability to detect abnormal brain regions in patients with lesions, enhancing the interpretability and reliability of the segmentation results.
Diffusion MRI (dMRI) is an advanced imaging technique characterizing tissue microstructure and white matter structural connectivity of the human brain. The demand for high-quality dMRI data is growing, driven by the need for better resolution and improved tissue contrast. However, acquiring high-quality dMRI data is expensive and time-consuming. In this context, deep generative modeling emerges as a promising solution to enhance image quality while minimizing acquisition costs and scanning time. In this study, we propose a novel generative approach to perform dMRI generation using deep diffusion models. It can generate high dimension (4D) and high resolution data preserving the gradients information and brain structure. We demonstrated our method through an image mapping task aimed at enhancing the quality of dMRI images from 3T to 7T. Our approach demonstrates highly enhanced performance in generating dMRI images when compared to the current state-of-the-art (SOTA) methods. This achievement underscores a substantial progression in enhancing dMRI quality, highlighting the potential of our novel generative approach to revolutionize dMRI imaging standards.
Quantitative magnetic resonance imaging (qMRI) is increasingly investigated for use in a variety of clinical tasks from diagnosis, through staging, to treatment monitoring. However, experiment design in qMRI, the identification of the optimal acquisition protocols, has been focused on obtaining the most precise parameter estimations, with no regard for the specific requirements of downstream tasks. Here we propose SCREENER: A general framework for task-specific experiment design in quantitative MRI. SCREENER incorporates a task-specific objective and seeks the optimal protocol with a deep-reinforcement-learning (DRL) based optimization strategy. To illustrate this framework, we employ a task of classifying the inflammation status of bone marrow using diffusion MRI data with intravoxel incoherent motion (IVIM) modelling. Results demonstrate SCREENER outperforms previous ad hoc and optimized protocols under clinical signal-to-noise ratio (SNR) conditions, achieving significant improvement, both in binary classification tasks, e.g. from 67% to 89%, and in a multi-class classification task, from 46% to 59%. Additionally, we show this improvement is robust to the SNR. Lastly, we demonstrate the advantage of DRL-based optimization strategy, enabling zero-shot discovery of near-optimal protocols for a range of SNRs not used in training. In conclusion, SCREENER has the potential to enable wider uptake of qMRI in the clinic.
There is a growing interest in using diffusion MRI to study the white matter tracts and structural connectivity of the fetal brain. Recent progress in data acquisition and processing suggests that this imaging modality has a unique role in elucidating the normal and abnormal patterns of neurodevelopment in utero. However, there have been no efforts to quantify the prevalence of crossing tracts and bottleneck regions, important issues that have been extensively researched for adult brains. In this work, we determined the brain regions with crossing tracts and bottlenecks between 23 and 36 gestational weeks. We performed probabilistic tractography on 59 fetal brain scans and extracted a set of 51 distinct white tracts, which we grouped into 10 major tract bundle groups. We analyzed the results to determine the patterns of tract crossings and bottlenecks. Our results showed that 20-25% of the white matter voxels included two or three crossing tracts. Bottlenecks were more prevalent. Between 75-80% of the voxels were characterized as bottlenecks, with more than 40% of the voxels involving four or more tracts. The results of this study highlight the challenge of fetal brain tractography and structural connectivity assessment and call for innovative image acquisition and analysis methods to mitigate these problems.
Prior work on the Image Quality Transfer on Diffusion MRI (dMRI) has shown significant improvement over traditional interpolation methods. However, the difficulty in obtaining ultra-high resolution Diffusion MRI scans poses a problem in training neural networks to obtain high-resolution dMRI scans. Here we hypothesise that the inclusion of structural MRI images, which can be acquired at much higher resolutions, can be used as a guide to obtaining a more accurate high-resolution dMRI output. To test our hypothesis, we have constructed a novel framework that incorporates structural MRI scans together with dMRI to obtain high-resolution dMRI scans. We set up tests which evaluate the validity of our claim through various configurations and compare the performance of our approach against a unimodal approach. Our results show that the inclusion of structural MRI scans do lead to an improvement in high-resolution image prediction when T1w data is incorporated into the model input.
Parcellation of human cerebellar pathways is essential for advancing our understanding of the human brain. Existing diffusion MRI tractography parcellation methods have been successful in defining major cerebellar fibre tracts, while relying solely on fibre tract structure. However, each fibre tract may relay information related to multiple cognitive and motor functions of the cerebellum. Hence, it may be beneficial for parcellation to consider the potential importance of the fibre tracts for individual motor and cognitive functional performance measures. In this work, we propose a multimodal data-driven method for cerebellar pathway parcellation, which incorporates both measures of microstructure and connectivity, and measures of individual functional performance. Our method involves first training a multitask deep network to predict various cognitive and motor measures from a set of fibre tract structural features. The importance of each structural feature for predicting each functional measure is then computed, resulting in a set of structure-function saliency values that are clustered to parcellate cerebellar pathways. We refer to our method as Deep Multimodal Saliency Parcellation (DeepMSP), as it computes the saliency of structural measures for predicting cognitive and motor functional performance, with these saliencies being applied to the task of parcellation. Applying DeepMSP we found that it was feasible to identify multiple cerebellar pathway parcels with unique structure-function saliency patterns that were stable across training folds.
The relationship between brain connections and non-imaging phenotypes is increasingly studied using deep neural networks. However, the local and global properties of the brain's white matter networks are often overlooked in convolutional network design. We introduce TractGraphFormer, a hybrid Graph CNN-Transformer deep learning framework tailored for diffusion MRI tractography. This model leverages local anatomical characteristics and global feature dependencies of white matter structures. The Graph CNN module captures white matter geometry and grey matter connectivity to aggregate local features from anatomically similar white matter connections, while the Transformer module uses self-attention to enhance global information learning. Additionally, TractGraphFormer includes an attention module for interpreting predictive white matter connections. In sex prediction tests, TractGraphFormer shows strong performance in large datasets of children (n=9345) and young adults (n=1065). Overall, our approach suggests that widespread connections in the WM are predictive of the sex of an individual, and consistent predictive anatomical tracts are identified across the two datasets. The proposed approach highlights the potential of integrating local anatomical information and global feature dependencies to improve prediction performance in machine learning with diffusion MRI tractography.
Fiber orientation distributions (FODs) is a popular model to represent the diffusion MRI (dMRI) data. However, imaging artifacts such as susceptibility-induced distortion in dMRI can cause signal loss and lead to the corrupted reconstruction of FODs, which prohibits successful fiber tracking and connectivity analysis in affected brain regions such as the brain stem. Generative models, such as the diffusion models, have been successfully applied in various image restoration tasks. However, their application on FOD images poses unique challenges since FODs are 4-dimensional data represented by spherical harmonics (SPHARM) with the 4-th dimension exhibiting order-related dependency. In this paper, we propose a novel diffusion model for FOD restoration that can recover the signal loss caused by distortion artifacts. We use volume-order encoding to enhance the ability of the diffusion model to generate individual FOD volumes at all SPHARM orders. Moreover, we add cross-attention features extracted across all SPHARM orders in generating every individual FOD volume to capture the order-related dependency across FOD volumes. We also condition the diffusion model with low-distortion FODs surrounding high-distortion areas to maintain the geometric coherence of the generated FODs. We trained and tested our model using data from the UK Biobank (n = 1315). On a test set with ground truth (n = 43), we demonstrate the high accuracy of the generated FODs in terms of root mean square errors of FOD volumes and angular errors of FOD peaks. We also apply our method to a test set with large distortion in the brain stem area (n = 1172) and demonstrate the efficacy of our method in restoring the FOD integrity and, hence, greatly improving tractography performance in affected brain regions.
Amyloid-$\beta$ (A$\beta$) plaques in conjunction with hyperphosphorylated tau proteins in the form of neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer's disease. It is well-known that the identification of individuals with A$\beta$ positivity could enable early diagnosis. In this work, we aim at capturing the A$\beta$ positivity status in an unbalanced cohort enclosing subjects at different disease stages, exploiting the underlying structural and connectivity disease-induced modulations as revealed by structural, functional, and diffusion MRI. Of note, due to the unbalanced cohort, the outcomes may be guided by those factors rather than amyloid accumulation. The partial views provided by each modality are integrated in the model allowing to take full advantage of their complementarity in encoding the effects of the A$\beta$ accumulation, leading to an accuracy of $0.762\pm0.04$. The specificity of the information brought by each modality is assessed by \textit{post-hoc} explainability analysis (guided backpropagation), highlighting the underlying structural and functional changes. Noteworthy, well-established biomarker key regions related to A$\beta$ deposition could be identified by all modalities, including the hippocampus, thalamus, precuneus, and cingulate gyrus, witnessing in favor of the reliability of the method as well as its potential in shading light on modality-specific possibly unknown A$\beta$ deposition signatures.
Diffusion MRI (dMRI) is an important neuroimaging technique with high acquisition costs. Deep learning approaches have been used to enhance dMRI and predict diffusion biomarkers through undersampled dMRI. To generate more comprehensive raw dMRI, generative adversarial network based methods are proposed to include b-values and b-vectors as conditions, but they are limited by unstable training and less desirable diversity. The emerging diffusion model (DM) promises to improve generative performance. However, it remains challenging to include essential information in conditioning DM for more relevant generation, i.e., the physical principles of dMRI and white matter tract structures. In this study, we propose a physics-guided diffusion model to generate high-quality dMRI. Our model introduces the physical principles of dMRI in the noise evolution in the diffusion process and introduce a query-based conditional mapping within the difussion model. In addition, to enhance the anatomical fine detials of the generation, we introduce the XTRACT atlas as prior of white matter tracts by adopting an adapter technique. Our experiment results show that our method outperforms other state-of-the-art methods and has the potential to advance dMRI enhancement.
Diffusion MRI (dMRI) is the primary imaging modality used to study brain microstructure in vivo. Reliable and computationally efficient parameter inference for common dMRI biophysical models is a challenging inverse problem, due to factors such as variable dimensionalities (reflecting the unknown number of distinct white matter fiber populations in a voxel), low signal-to-noise ratios, and non-linear forward models. These challenges have led many existing methods to use biologically implausible simplified models to stabilize estimation, for instance, assuming shared microstructure across all fiber populations within a voxel. In this work, we introduce a novel sequential method for multi-fiber parameter inference that decomposes the task into a series of manageable subproblems. These subproblems are solved using deep neural networks tailored to problem-specific structure and symmetry, and trained via simulation. The resulting inference procedure is largely amortized, enabling scalable parameter estimation and uncertainty quantification across all model parameters. Simulation studies and real imaging data analysis using the Human Connectome Project (HCP) demonstrate the advantages of our method over standard alternatives. In the case of the standard model of diffusion, our results show that under HCP-like acquisition schemes, estimates for extra-cellular parallel diffusivity are highly uncertain, while those for the intra-cellular volume fraction can be estimated with relatively high precision.
Modern diffusion MRI sequences commonly acquire a large number of volumes with diffusion sensitization gradients of differing strengths or directions. Such sequences rely on echo-planar imaging (EPI) to achieve reasonable scan duration. However, EPI is vulnerable to off-resonance effects, leading to tissue susceptibility and eddy-current induced distortions. The latter is particularly problematic because it causes misalignment between volumes, disrupting downstream modelling and analysis. The essential correction of eddy distortions is typically done post-acquisition, with image registration. However, this is non-trivial because correspondence between volumes can be severely disrupted due to volume-specific signal attenuations induced by varying directions and strengths of the applied gradients. This challenge has been successfully addressed by the popular FSL~Eddy tool but at considerable computational cost. We propose an alternative approach, leveraging recent advances in image processing enabled by deep learning (DL). It consists of two convolutional neural networks: 1) An image translator to restore correspondence between images; 2) A registration model to align the translated images. Results demonstrate comparable distortion estimates to FSL~Eddy, while requiring only modest training sample sizes. This work, to the best of our knowledge, is the first to tackle this problem with deep learning. Together with recently developed DL-based susceptibility correction techniques, they pave the way for real-time preprocessing of diffusion MRI, facilitating its wider uptake in the clinic.
Objective: To report imaging protocol and scheduling variance in routine care of glioblastoma patients in order to demonstrate challenges of integrating deep-learning models in glioblastoma care pathways. Additionally, to understand the most common imaging studies and image contrasts to inform the development of potentially robust deep-learning models. Methods: MR imaging data were analysed from a random sample of five patients from the prospective cohort across five participating sites of the ZGBM consortium. Reported clinical and treatment data alongside DICOM header information were analysed to understand treatment pathway imaging schedules. Results: All sites perform all structural imaging at every stage in the pathway except for the presurgical study, where in some sites only contrast-enhanced T1-weighted imaging is performed. Diffusion MRI is the most common non-structural imaging type, performed at every site. Conclusion: The imaging protocol and scheduling varies across the UK, making it challenging to develop machine-learning models that could perform robustly at other centres. Structural imaging is performed most consistently across all centres. Advances in knowledge: Successful translation of deep-learning models will likely be based on structural post-treatment imaging unless there is significant effort made to standardise non-structural or peri-operative imaging protocols and schedules.
Purpose: In diffusion MRI (dMRI), the volumetric and bundle analyses of whole-brain tissue microstructure and connectivity can be severely impeded by an incomplete field-of-view (FOV). This work aims to develop a method for imputing the missing slices directly from existing dMRI scans with an incomplete FOV. We hypothesize that the imputed image with complete FOV can improve the whole-brain tractography for corrupted data with incomplete FOV. Therefore, our approach provides a desirable alternative to discarding the valuable dMRI data, enabling subsequent tractography analyses that would otherwise be challenging or unattainable with corrupted data. Approach: We propose a framework based on a deep generative model that estimates the absent brain regions in dMRI scans with incomplete FOV. The model is capable of learning both the diffusion characteristics in diffusion-weighted images (DWI) and the anatomical features evident in the corresponding structural images for efficiently imputing missing slices of DWI outside of incomplete FOV. Results: For evaluating the imputed slices, on the WRAP dataset the proposed framework achieved PSNRb0=22.397, SSIMb0=0.905, PSNRb1300=22.479, SSIMb1300=0.893; on the NACC dataset it achieved PSNRb0=21.304, SSIMb0=0.892, PSNRb1300=21.599, SSIMb1300= 0.877. The proposed framework improved the tractography accuracy, as demonstrated by an increased average Dice score for 72 tracts (p < 0.001) on both the WRAP and NACC datasets. Conclusions: Results suggest that the proposed framework achieved sufficient imputation performance in dMRI data with incomplete FOV for improving whole-brain tractography, thereby repairing the corrupted data. Our approach achieved more accurate whole-brain tractography results with extended and complete FOV and reduced the uncertainty when analyzing bundles associated with Alzheimer's Disease.