Anatomical Modeling of Cerebral Microvascular Structures: Application to Identify Biomarkers of Microstrokes

Les réseaux microvasculaires corticaux sont responsables du transport de l’oxygène et des substrats énergétiques vers les neurones. Ces réseaux réagissent dynamiquement aux demandes énergétiques lors d’une activation neuronale par le biais du couplage neurovasculaire. Afin d’élucider le rôle de la composante microvasculaire dans ce processus de couplage, l’utilisation de la modélisation in-formatique pourrait se révéler un élément clé. Cependant, la manque de méthodologies de calcul appropriées et entièrement automatisées pour modéliser et caractériser les réseaux microvasculaires reste l’un des principaux obstacles. Le développement d’une solution entièrement automatisée est donc important pour des explorations plus avancées, notamment pour quantifier l’impact des mal-formations vasculaires associées à de nombreuses maladies cérébrovasculaires. Une observation courante dans l’ensemble des troubles neurovasculaires est la formation de micro-blocages vascu-laires cérébraux (mAVC) dans les artérioles pénétrantes de la surface piale. De récents travaux ont démontré l’impact de ces événements microscopiques sur la fonction cérébrale. Par conséquent, il est d’une importance vitale de développer une approche non invasive et comparative pour identifier leur présence dans un cadre clinique. Dans cette thèse,un pipeline de traitement entièrement automatisé est proposé pour aborder le prob-lème de la modélisation anatomique microvasculaire. La méthode de modélisation consiste en un réseau de neurones entièrement convolutif pour segmenter les capillaires sanguins, un générateur de modèle de surface 3D et un algorithme de contraction de la géométrie pour produire des mod-èles graphiques vasculaires ne comportant pas de connections multiples. Une amélioration de ce pipeline est développée plus tard pour alléger l’exigence de maillage lors de la phase de représen-tation graphique. Un nouveau schéma permettant de générer un modèle de graphe est développé avec des exigences d’entrée assouplies et permettant de retenir les informations sur les rayons des vaisseaux. Il est inspiré de graphes géométriques déformants construits en respectant les morpholo-gies vasculaires au lieu de maillages de surface. Un mécanisme pour supprimer la structure initiale du graphe à chaque exécution est implémenté avec un critère de convergence pour arrêter le pro-cessus. Une phase de raffinement est introduite pour obtenir des modèles vasculaires finaux. La modélisation informatique développée est ensuite appliquée pour simuler les signatures IRM po-tentielles de mAVC, combinant le marquage de spin artériel (ASL) et l’imagerie multidirectionnelle pondérée en diffusion (DWI). L’hypothèse est basée sur des observations récentes démontrant une réorientation radiale de la microvascularisation dans la périphérie du mAVC lors de la récupéra-tion chez la souris. Des lits capillaires synthétiques, orientés aléatoirement et radialement, et des angiogrammes de tomographie par cohérence optique (OCT), acquis dans le cortex de souris (n = 5) avant et après l’induction d’une photothrombose ciblée, sont analysés. Les graphes vasculaires informatiques sont exploités dans un simulateur 3D Monte-Carlo pour caractériser la réponse par résonance magnétique (MR), tout en considérant les effets des perturbations du champ magnétique causées par la désoxyhémoglobine, et l’advection et la diffusion des spins nucléaires. Le pipeline graphique proposé est validé sur des angiographies synthétiques et réelles acquises avec différentes modalités d’imagerie. Comparé à d’autres méthodes effectuées dans le milieu de la recherche, les expériences indiquent que le schéma proposé produit des taux d’erreur géométriques et topologiques amoindris sur divers angiogrammes. L’évaluation confirme également l’efficacité de la méthode proposée en fournissant des modèles représentatifs qui capturent tous les aspects anatomiques des structures vasculaires. Ensuite, afin de trouver des signatures de mAVC basées sur le signal IRM, la modélisation vasculaire proposée est exploitée pour quantifier le rapport de perte de signal intravoxel minimal lors de l’application de plusieurs directions de gradient, à des paramètres de séquence variables avec et sans ASL. Avec l’ASL, les résultats démontrent une dif-férence significative (p <0,05) entre le signal calculé avant et 3 semaines après la photothrombose. La puissance statistique a encore augmenté (p <0,005) en utilisant des angiogrammes capturés à la semaine suivante. Sans ASL, aucun changement de signal significatif n’est trouvé. Des rapports plus élevés sont obtenus à des intensités de champ magnétique plus faibles (par exemple, B0 = 3) et une lecture TE plus courte (<16 ms). Cette étude suggère que les mAVC pourraient être carac-térisés par des séquences ASL-DWI, et fournirait les informations nécessaires pour les validations expérimentales postérieures et les futurs essais comparatifs.----------ABSTRACT Cortical microvascular networks are responsible for carrying the necessary oxygen and energy substrates to our neurons. These networks react to the dynamic energy demands during neuronal activation through the process of neurovascular coupling. A key element in elucidating the role of the microvascular component in the brain is through computational modeling. However, the lack of fully-automated computational frameworks to model and characterize these microvascular net-works remains one of the main obstacles. Developing a fully-automated solution is thus substantial for further explorations, especially to quantify the impact of cerebrovascular malformations associ-ated with many cerebrovascular diseases. A common pathogenic outcome in a set of neurovascular disorders is the formation of microstrokes, i.e., micro occlusions in penetrating arterioles descend-ing from the pial surface. Recent experiments have demonstrated the impact of these microscopic events on brain function. Hence, it is of vital importance to develop a non-invasive and translatable approach to identify their presence in a clinical setting. In this thesis, a fully automatic processing pipeline to address the problem of microvascular anatom-ical modeling is proposed. The modeling scheme consists of a fully-convolutional neural network to segment microvessels, a 3D surface model generator and a geometry contraction algorithm to produce vascular graphical models with a single connected component. An improvement on this pipeline is developed later to alleviate the requirement of water-tight surface meshes as inputs to the graphing phase. The novel graphing scheme works with relaxed input requirements and intrin-sically captures vessel radii information, based on deforming geometric graphs constructed within vascular boundaries instead of surface meshes. A mechanism to decimate the initial graph struc-ture at each run is formulated with a convergence criterion to stop the process. A refinement phase is introduced to obtain final vascular models. The developed computational modeling is then ap-plied to simulate potential MRI signatures of microstrokes, combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). The hypothesis is driven based on recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially oriented, and op-tical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n=5) before and after inducing targeted photothrombosis, are analyzed. The computational vascular graphs are exploited within a 3D Monte-Carlo simulator to characterize the magnetic resonance (MR) re-sponse, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. The proposed graphing pipeline is validated on both synthetic and real angiograms acquired with different imaging modalities. Compared to other efficient and state-of-the-art graphing schemes, the experiments indicate that the proposed scheme produces the lowest geometric and topological error rates on various angiograms. The evaluation also confirms the efficiency of the proposed scheme in providing representative models that capture all anatomical aspects of vascular struc-tures. Next, searching for MRI-based signatures of microstokes, the proposed vascular modeling is exploited to quantify the minimal intravoxel signal loss ratio when applying multiple gradient di-rections, at varying sequence parameters with and without ASL. With ASL, the results demonstrate a significant difference (p<0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p<0.005) using angiograms captured at week 4. Without ASL, no reliable signal change is found. Higher ratios with improved significance are achieved at low magnetic field strengths (e.g., at 3 Tesla) and shorter readout TE (<16 ms). This study suggests that microstrokes might be characterized through ASL-DWI sequences, and provides necessary insights for posterior experimental validations, and ultimately, future transla-tional trials

A Low-Complexity Bayesian Estimation Scheme for Speckle Suppression in Images

Speckle noise reduction is a crucial pre-processing step for a successful interpretation of images corrupted by speckle noise, and thus, it has drawn a great deal of attention of researchers in the image processing community. The Bayesian estimation is a powerful signal estimation technique and has been widely used for speckle noise removal in images. In the Bayesian estimation based despeckling techniques, the choice of suitable signal and noise models and the development of a shrinkage function for estimation of the signal are the major concerns from the standpoint of the accuracy and computational complexity of the estimation. In this thesis, a low-complexity wavelet-based Bayesian estimation technique for despeckling of images is developed. The main idea of the proposed technique is in establishing suitable statistical models for the wavelet coefficients of additively decomposed components, namely, the reflectance image and the signal-dependant noise, of the multiplicative degradation model of the noisy image and then in using these two statistical models to develop a shrinkage function with a low-complexity realization for the estimation of the wavelet coefficients of the noise-free image. A study is undertaken to explore the effectiveness of using a two sided exponential distribution as a prior statistical model for the discrete wavelet transform (DWT) coefficients of the signal-dependant noise. This model, along with the Cauchy distribution, which is known to be a good model for the wavelet coefficients of the reflectance image, is used to develop a minimum mean square error (MMSE) Bayesian estimator for the DWT coefficients of the noise-free image. A low-cost realization of the shrinkage function resulting from the MMSE Bayesian estimation is proposed and its efficacy is verified from the standpoint of accuracy as well as computational cost. The performance of the proposed despeckling scheme is evaluated on both synthetic and real SAR images in terms of the commonly used metrics, and the results are compared to that of some other state-of-the-art despeckling schemes available in the literature. The experimental results demonstrate the validity of the proposed despeckling scheme in providing a significant reduction in the speckle noise at a very low computational cost and simultaneously in preserving the image details

AI in Education: Improving Quality for Both Centralized and Decentralized Frameworks

Education is essential for achieving many Sustainable Development Goals (SDGs). Therefore, the education system focuses on empowering more educated people and improving the quality of the education system. One of the latest technologies to enhance the quality of education is Artificial Intelligence (AI)-based Machine Learning (ML). As a result, ML has a significant influence on the education system. ML is currently widely applied in the education system for various tasks, such as creating models by monitoring student performance and activities that accurately predict student outcomes, their engagement in learning activities, decision-making, problem-solving capabilities, etc. In this research, we provide a survey of machine learning frameworks for both distributed (clusters of schools and universities) and centralized (university or school) educational institutions to predict the quality of students\u27 learning outcomes and find solutions to improve the quality of their education system. Additionally, this work explores the application of ML in teaching and learning for further improvements in the learning environment for centralized and distributed education systems

Multimodal autoencoder predicts fNIRS resting state from EEG signals

In this work, we introduce a deep learning architecture for evaluation on multimodal electroencephalographic (EEG) and functional near-infrared spectroscopy (fNIRS) recordings from 40 epileptic patients. Long short-term memory units and convolutional neural networks are integrated within a multimodal sequence-to-sequence autoencoder. The trained neural network predicts fNIRS signals from EEG, sans a priori, by hierarchically extracting deep features from EEG full spectra and specific EEG frequency bands. Results show that higher frequency EEG ranges are predictive of fNIRS signals with the gamma band inputs dominating fNIRS prediction as compared to other frequency envelopes. Seed based functional connectivity validates similar patterns between experimental fNIRS and our model’s fNIRS reconstructions. This is the first study that shows it is possible to predict brain hemodynamics (fNIRS) from encoded neural data (EEG) in the resting human epileptic brain based on power spectrum amplitude modulation of frequency oscillations in the context of specific hypotheses about how EEG frequency bands decode fNIRS signals

The performance of wearable AI in detecting stress among students : systematic review and meta-analysis

Students usually encounter stress throughout their academic path. Ongoing stressors may lead to chronic stress, adversely affecting their physical and mental well-being. Thus, early detection and monitoring of stress among students are crucial. Wearable artificial intelligence (AI) has emerged as a valuable tool for this purpose. It offers an objective, noninvasive, nonobtrusive, automated approach to continuously monitor biomarkers in real time, thereby addressing the limitations of traditional approaches such as self-reported questionnaires. This systematic review and meta-analysis aim to assess the performance of wearable AI in detecting and predicting stress among students. Search sources in this review included 7 electronic databases (MEDLINE, Embase, PsycINFO, ACM Digital Library, Scopus, IEEE Xplore, and Google Scholar). We also checked the reference lists of the included studies and checked studies that cited the included studies. The search was conducted on June 12, 2023. This review included research articles centered on the creation or application of AI algorithms for the detection or prediction of stress among students using data from wearable devices. In total, 2 independent reviewers performed study selection, data extraction, and risk-of-bias assessment. The Quality Assessment of Diagnostic Accuracy Studies-Revised tool was adapted and used to examine the risk of bias in the included studies. Evidence synthesis was conducted using narrative and statistical techniques. This review included 5.8% (19/327) of the studies retrieved from the search sources. A meta-analysis of 37 accuracy estimates derived from 32% (6/19) of the studies revealed a pooled mean accuracy of 0.856 (95% CI 0.70-0.93). Subgroup analyses demonstrated that the accuracy of wearable AI was moderated by the number of stress classes (P=.02), type of wearable device (P=.049), location of the wearable device (P=.02), data set size (P=.009), and ground truth (P=.001). The average estimates of sensitivity, specificity, and F -score were 0.755 (SD 0.181), 0.744 (SD 0.147), and 0.759 (SD 0.139), respectively. Wearable AI shows promise in detecting student stress but currently has suboptimal performance. The results of the subgroup analyses should be carefully interpreted given that many of these findings may be due to other confounding factors rather than the underlying grouping characteristics. Thus, wearable AI should be used alongside other assessments (eg, clinical questionnaires) until further evidence is available. Future research should explore the ability of wearable AI to differentiate types of stress, distinguish stress from other mental health issues, predict future occurrences of stress, consider factors such as the placement of the wearable device and the methods used to assess the ground truth, and report detailed results to facilitate the conduct of meta-analyses. PROSPERO CRD42023435051; http://tinyurl.com/3fzb5rnp. [Abstract copyright: ©Alaa Abd-alrazaq, Mohannad Alajlani, Reham Ahmad, Rawan AlSaad, Sarah Aziz, Arfan Ahmed, Mohammed Alsahli, Rafat Damseh, Javaid Sheikh. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 31.01.2024.

A simulation study investigating potential diffusion-based MRI signatures of microstrokes

ABSTRACT: Recent studies suggested that cerebrovascular micro-occlusions, i.e. microstokes, could lead to ischemic tissue infarctions and cognitive deficits. Due to their small size, identifying measurable biomarkers of these microvascular lesions remains a major challenge. This work aims to simulate potential MRI signatures combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). Driving our hypothesis are recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially-oriented, and optical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n = 5) before and after inducing targeted photothrombosis, were analyzed. Computational vascular graphs combined with a 3D Monte-Carlo simulator were used to characterize the magnetic resonance (MR) response, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. We quantified the minimal intravoxel signal loss ratio when applying multiple gradient directions, at varying sequence parameters with and without ASL. With ASL, our results demonstrate a significant difference (p < 0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p < 0.005) using angiograms measured at week 4. Without ASL, no reliable signal change was found. We found that higher ratios, and accordingly improved significance, were achieved at lower magnetic field strengths (e.g., B0 = 3T) and shorter echo time TE (< 16 ms). Our simulations suggest that microstrokes might be characterized through ASL-DWI sequence, providing necessary insights for posterior experimental validations, and ultimately, future translational trials

Compromised microvascular oxygen delivery increases brain tissue vulnerability with age

Despite the possible role of impaired cerebral tissue oxygenation in age-related cognition decline, much is still unknown about the changes in brain tissue pO2 with age. Using a detailed investigation of the age-related changes in cerebral tissue oxygenation in the barrel cortex of healthy, awake aged mice, we demonstrate decreased arteriolar and tissue pO2 with age. These changes are exacerbated after middle-age. We further uncovered evidence of the presence of hypoxic micro-pockets in the cortex of awake old mice. Our data suggests that from young to middle-age, a well-regulated capillary oxygen supply maintains the oxygen availability in cerebral tissue, despite decreased tissue pO2 next to arterioles. After middle-age, due to decreased hematocrit, reduced capillary density and higher capillary transit time heterogeneity, the capillary network fails to compensate for larger decreases in arterial pO2. The substantial decrease in brain tissue pO2, and the presence of hypoxic micro-pockets after middle-age are of significant importance, as these factors may be related to cognitive decline in elderly people