Brain age estimation at tract group level and its association with daily life measures, cardiac risk factors and genetic variants

Abstract Brain age can be estimated using different Magnetic Resonance Imaging (MRI) modalities including diffusion MRI. Recent studies demonstrated that white matter (WM) tracts that share the same function might experience similar alterations. Therefore, in this work, we sought to investigate such issue focusing on five WM bundles holding that feature that is Association, Brainstem, Commissural, Limbic and Projection fibers, respectively. For each tract group, we estimated brain age for 15,335 healthy participants from United Kingdom Biobank relying on diffusion MRI data derived endophenotypes, Bayesian ridge regression modeling and 10 fold-cross validation. Furthermore, we estimated brain age for an Ensemble model that gathers all the considered WM bundles. Association analysis was subsequently performed between the estimated brain age delta as resulting from the six models, that is for each tract group as well as for the Ensemble model, and 38 daily life style measures, 14 cardiac risk factors and cardiovascular magnetic resonance imaging features and genetic variants. The Ensemble model that used all tracts from all fiber groups (FG) performed better than other models to estimate brain age. Limbic tracts based model reached the highest accuracy with a Mean Absolute Error (MAE) of 5.08, followed by the Commissural ( $$\hbox {MAE}=5.23$$ MAE = 5.23 ), Association ( $$\hbox {MAE}=5.24$$ MAE = 5.24 ), and Projection ( $$\hbox {MAE}=5.28$$ MAE = 5.28 ) ones. The Brainstem tracts based model was the less accurate achieving a MAE of 5.86. Accordingly, our study suggests that the Limbic tracts experience less brain aging or allows for more accurate estimates compared to other tract groups. Moreover, the results suggest that Limbic tract leads to the largest number of significant associations with daily lifestyle factors than the other tract groups. Lastly, two SNPs were significantly (p value $$< 5\hbox {E}{-}8$$ < 5 E - 8 ) associated with brain age delta in the Projection fibers. Those SNPs are mapped to HIST1H1A and SLC17A3 genes

Brain age estimation at tract group level and its association with daily life measures, cardiac risk factors and genetic variants

Brain age can be estimated using different Magnetic Resonance Imaging (MRI) modalities including diffusion MRI. Recent studies demonstrated that white matter (WM) tracts that share the same function might experience similar alterations. Therefore, in this work, we sought to investigate such issue focusing on five WM bundles holding that feature that is Association, Brainstem, Commissural, Limbic and Projection fibers, respectively. For each tract group, we estimated brain age for 15,335 healthy participants from United Kingdom Biobank relying on diffusion MRI data derived endophenotypes, Bayesian ridge regression modeling and 10 fold-cross validation. Furthermore, we estimated brain age for an Ensemble model that gathers all the considered WM bundles. Association analysis was subsequently performed between the estimated brain age delta as resulting from the six models, that is for each tract group as well as for the Ensemble model, and 38 daily life style measures, 14 cardiac risk factors and cardiovascular magnetic resonance imaging features and genetic variants. The Ensemble model that used all tracts from all fiber groups (FG) performed better than other models to estimate brain age. Limbic tracts based model reached the highest accuracy with a Mean Absolute Error (MAE) of 5.08, followed by the Commissural ([Formula: see text]), Association ([Formula: see text]), and Projection ([Formula: see text]) ones. The Brainstem tracts based model was the less accurate achieving a MAE of 5.86. Accordingly, our study suggests that the Limbic tracts experience less brain aging or allows for more accurate estimates compared to other tract groups. Moreover, the results suggest that Limbic tract leads to the largest number of significant associations with daily lifestyle factors than the other tract groups. Lastly, two SNPs were significantly (p value [Formula: see text]) associated with brain age delta in the Projection fibers. Those SNPs are mapped to HIST1H1A and SLC17A3 genes

Imaging Genetics through Brain Age Estimation and Image Derived Phenotypes

In this thesis, we investigated brain aging using different simple and complex models through brain age estimation using IDPs extracted from brain MRI.We have also applied simple methods and machine learning explainability models to identify the most informative features to model brain age. We further estimated brain age for fiber groups within brain white matter tracts. In addition, we revealed the effects of daily life style, cardiac risk factors and morbidity in brain aging. Finally, we used causal models to explore the role of TL in healthy aging and Alzheimer’s disease in unhealthy aging to cause alterations within brain structures and functions

Multimodal neuroimaging computing: the workflows, methods, and platforms

The last two decades have witnessed the explosive growth in the development and use of noninvasive neuroimaging technologies that advance the research on human brain under normal and pathological conditions. Multimodal neuroimaging has become a major driver of current neuroimaging research due to the recognition of the clinical benefits of multimodal data, and the better access to hybrid devices. Multimodal neuroimaging computing is very challenging, and requires sophisticated computing to address the variations in spatiotemporal resolution and merge the biophysical/biochemical information. We review the current workflows and methods for multimodal neuroimaging computing, and also demonstrate how to conduct research using the established neuroimaging computing packages and platforms

Spatially Regularized Spherical Reconstruction: A Cross-Domain Filtering Approach for HARDI Signals

Despite the immense advances of science and medicine in recent years, several aspects regarding the physiology and the anatomy of the human brain are yet to be discovered and understood. A particularly challenging area in the study of human brain anatomy is that of brain connectivity, which describes the intricate means by which different regions of the brain interact with each other. The study of brain connectivity is deeply dependent on understanding the organization of white matter. The latter is predominantly comprised of bundles of myelinated axons, which serve as connecting pathways between approximately 10¹¹ neurons in the brain. Consequently, the delineation of fine anatomical details of white matter represents a highly challenging objective, and it is still an active area of research in the fields of neuroimaging and neuroscience, in general. Recent advances in medical imaging have resulted in a quantum leap in our understanding of brain anatomy and functionality. In particular, the advent of diffusion magnetic resonance imaging (dMRI) has provided researchers with a non-invasive means to infer information about the connectivity of the human brain. In a nutshell, dMRI is a set of imaging tools which aim at quantifying the process of water diffusion within the human brain to delineate the complex structural configurations of the white matter. Among the existing tools of dMRI high angular resolution diffusion imaging (HARDI) offers a desirable trade-off between its reconstruction accuracy and practical feasibility. In particular, HARDI excels in its ability to delineate complex directional patterns of the neural pathways throughout the brain, while remaining feasible for many clinical applications. Unfortunately, HARDI presents a fundamental trade-off between its ability to discriminate crossings of neural fiber tracts (i.e., its angular resolution) and the signal-to-noise ratio (SNR) of its associated images. Consequently, given that the angular resolution is of fundamental importance in the context of dMRI reconstruction, there is a need for effective algorithms for de-noising HARDI data. In this regard, the most effective de-noising approaches have been observed to be those which exploit both the angular and the spatial-domain regularity of HARDI signals. Accordingly, in this thesis, we propose a formulation of the problem of reconstruction of HARDI signals which incorporates regularization assumptions on both their angular and their spatial domains, while leading to a particularly simple numerical implementation. Experimental evidence suggests that the resulting cross-domain regularization procedure outperforms many other state of the art HARDI de-noising methods. Moreover, the proposed implementation of the algorithm supersedes the original reconstruction problem by a sequence of efficient filters which can be executed in parallel, suggesting its computational advantages over alternative implementations

Realistic numerical simulations of diffusion tensor cardiovascular magnetic resonance: the effects of perfusion and membrane permeability

Purpose To study the sensitivity of diffusion tensor cardiovascular magnetic resonance (DT-CMR) to microvascular perfusion and changes in cell permeability. Methods Monte Carlo (MC) random walk simulations in the myocardium have been performed to simulate self-diffusion of water molecules in histology-based media with varying extracellular volume fraction (ECV) and permeable membranes. The effect of microvascular perfusion on simulations of the DT-CMR signal has been incorporated by adding the contribution of particles traveling through an anisotropic capillary network to the diffusion signal. The simulations have been performed considering three pulse sequences with clinical gradient strengths: monopolar stimulated echo acquisition mode (STEAM), monopolar pulsed-gradient spin echo (PGSE), and second-order motion-compensated spin echo (MCSE). Results Reducing ECV intensifies the diffusion restriction and incorporating membrane permeability reduces the anisotropy of the diffusion tensor. Widening the intercapillary velocity distribution results in increased measured diffusion along the cardiomyocytes long axis when the capillary networks are anisotropic. Perfusion amplifies the mean diffusivity for STEAM while the opposite is observed for short diffusion encoding time sequences (PGSE and MCSE). Conclusion The effect of perfusion on the measured diffusion tensor is reduced using an increased reference b-value. Our results pave the way for characterization of the response of DT-CMR to microstructural changes underlying cardiac pathology and highlight the higher sensitivity of STEAM to permeability and microvascular circulation due to its longer diffusion encoding time

Imagerie de diffusion en temps-réel (correction du bruit et inférence de la connectivité cérébrale)

La plupart des constructeurs de systèmes d'imagerie par résonance magnétique (IRM) proposent un large choix d'applications de post-traitement sur les données IRM reconstruites a posteriori, mais très peu de ces applications peuvent être exécutées en temps réel pendant l'examen. Mises à part certaines solutions dédiées à l'IRM fonctionnelle permettant des expériences relativement simples ainsi que d'autres solutions pour l'IRM interventionnelle produisant des scans anatomiques pendant un acte de chirurgie, aucun outil n'a été développé pour l'IRM pondérée en diffusion (IRMd). Cependant, comme les examens d'IRMd sont extrêmement sensibles à des perturbations du système hardware ou à des perturbations provoquées par le sujet et qui induisent des données corrompues, il peut être intéressant d'investiguer la possibilité de reconstruire les données d'IRMd directement lors de l'examen. Cette thèse est dédiée à ce projet innovant. La contribution majeure de cette thèse a consisté en des solutions de débruitage des données d'IRMd en temps réel. En effet, le signal pondéré en diffusion peut être corrompu par un niveau élevé de bruit qui n'est plus gaussien, mais ricien ou chi non centré. Après avoir réalisé un état de l'art détaillé de la littérature sur le bruit en IRM, nous avons étendu l'estimateur linéaire qui minimise l'erreur quadratique moyenne (LMMSE) et nous l'avons adapté à notre cadre de temps réel réalisé avec un filtre de Kalman. Nous avons comparé les performances de cette solution à celles d'un filtrage gaussien standard, difficile à implémenter car il nécessite une modification de la chaîne de reconstruction pour y être inséré immédiatement après la démodulation du signal acquis dans l'espace de Fourier. Nous avons aussi développé un filtre de Kalman parallèle qui permet d'appréhender toute distribution de bruit et nous avons montré que ses performances étaient comparables à celles de notre méthode précédente utilisant un filtre de Kalman non parallèle. Enfin, nous avons investigué la faisabilité de réaliser une tractographie en temps-réel pour déterminer la connectivité structurelle en direct, pendant l'examen. Nous espérons que ce panel de développements méthodologiques permettra d'améliorer et d'accélérer le diagnostic en cas d'urgence pour vérifier l'état des faisceaux de fibres de la substance blanche.Most magnetic resonance imaging (MRI) system manufacturers propose a huge set of software applications to post-process the reconstructed MRI data a posteriori, but few of them can run in real-time during the ongoing scan. To our knowledge, apart from solutions dedicated to functional MRI allowing relatively simple experiments or for interventional MRI to perform anatomical scans during surgery, no tool has been developed in the field of diffusion-weighted MRI (dMRI). However, because dMRI scans are extremely sensitive to lots of hardware or subject-based perturbations inducing corrupted data, it can be interesting to investigate the possibility of processing dMRI data directly during the ongoing scan and this thesis is dedicated to this challenging topic. The major contribution of this thesis aimed at providing solutions to denoise dMRI data in real-time. Indeed, the diffusion-weighted signal may be corrupted by a significant level of noise which is not Gaussian anymore, but Rician or noncentral chi. After making a detailed review of the literature, we extended the linear minimum mean square error (LMMSE) estimator and adapted it to our real-time framework with a Kalman filter. We compared its efficiency to the standard Gaussian filtering, difficult to implement, as it requires a modification of the reconstruction pipeline to insert the filter immediately after the demodulation of the acquired signal in the Fourier space. We also developed a parallel Kalman filter to deal with any noise distribution and we showed that its efficiency was quite comparable to the non parallel Kalman filter approach. Last, we addressed the feasibility of performing tractography in real-time in order to infer the structural connectivity online. We hope that this set of methodological developments will help improving and accelerating a diagnosis in case of emergency to check the integrity of white matter fiber bundles.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Super Resolution of HARDI images Using Compressed Sensing Techniques

Effective techniques of inferring the condition of neural tracts in the brain is invaluable for clinicians and researchers towards investigation of neurological disorders in patients. It was not until the advent of diffusion Magnetic Resonance Imaging (dMRI), a noninvasive imaging method used to detect the diffusion of water molecules, that scientists have been able to assess the characteristics of cerebral diffusion in vivo. Among different dMRI methods, High Angular Resolution Diffusion Imaging (HARDI) is well known for striking a balance between ability to distinguish crossing neural fibre tracts while requiring a modest number of diffusion measurements (which is directly related to acquisition time). HARDI data provides insight into the directional properties of water diffusion in cerebral matter as a function of spatial coordinates. Ideally, one would be interested in having this information available at fine spatial resolution while minimizing the probing along different spatial orientations (so as to minimize the acquisition time). Unfortunately, availability of such datasets in reasonable acquisition times are hindered by limitations in current hardware and scanner protocols. On the other hand, post processing techniques prove promising in increasing the effective spatial resolution, allowing more detailed depictions of cerebral matter, while keeping the number of diffusion measurements within a feasible range. In light of the preceding developments, the main purpose of this research is to look into super resolution of HARDI data, using the modern theory of compressed sensing. The method proposed in this thesis allows an accurate approximation of HARDI signals at a higher spatial resolution compared to data obtained with a typical scanner. At the same time, ideas for reducing the number of diffusion measurements in the angular domain to improve the acquisition time are explored. Accordingly, the novel method of applying two distinct compressed sensing approaches in both spatial and angular domain, and combining them into a single framework for performing super resolution forms the main contribution provided by this thesis