In recent years there has been a considerable research effort in improving the specificity of magnetic resonance imaging (MRI) techniques by employing quantitative methods. These methods offer greater reproducibility over traditional acquisitions, and hold the potential for obtaining improved information at the microstructural level. However, they typically require a longer duration for the experiments as the quantitative information is often obtained from multiple acquisitions. Here, a multi-echo extension of the MP2RAGE pulse sequence for the simultaneous mapping of T1, T2* (and magnetic susceptibility) is introduced, optimized and validated. This acquisition technique can be faster than the separate acquisition of T1 and T2*, and has the advantage of producing intrinsically co-localized maps. This is helpful in reducing the preprocessing complexity, but most importantly it removes the need for image alignment (registration) which is shown to introduce significant bias in quantitative MRI maps. One of the reasons why the knowledge of T1 and T2* is of relevance in neuroscience is because their reciprocal, R1 and R2*, have been shown to predict quantitatively myelin and iron content in ex vivo experiments using a linear model of relaxation. However, the post-mortem results cannot be applied directly to the in vivo case. Therefore, an adaptation of the linear relaxation model to the in vivo case is proposed. This is capable of predicting (with some limitations) the myelin and iron contents of the brain under in vivo conditions, by using prior knowledge from the literature to calibrate the linear coefficients. The dependence of the relaxation parameters from the biochemical composition in brain tissues is further explored with ex vivo experiments. In particular, the hyaluronan component of the extracellular matrix is investigated. The contribution to T1 and T2* is measured with a sophisticated experiments that allow for a greater control over experimental conditions compared to a typical MRI experiment. The result indicate a small but appreciable contribution of hyaluronan to the relaxation parameters. In conclusion, this work develops a method for measuring T1 and T2* maps simultaneously. These are then used to quantify myelin and iron under in vivo conditions using a linear model of relaxation. In parallel, the hyaluronan-based extracellular matrix was shown to be a marginal but measurable component in T1 and T2* relaxation maps in ex vivo experiments.

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Image segmentation and image registration are two fundamental problems in computer vision and medical image processing. In image segmentation, one seeks to partition an image into meaningful segments by assigning a label to each pixel indicating which segment it belongs to. In image registration, one seeks to recover a spatial transformation that geometrically aligns two or more images, which allows downstream image analyses in which the registered images share a coordinate system. Image processing pipelines typically apply these procedures sequentially even though the segmentation of an image could improve its registration and registration of an image could improve its segmentation. With an appropriate parametrization, one can view these two tasks as an inference problem in which the spatial transformation and segmentation are latent variables. In this work, registration and segmentation are integrated through a hierarchical Bayesian generative framework. The framework models the data generating process of a set of magnetic resonance (MR) images of ischemic stroke lesioned brains. Under this framework, we simultaneously estimate a lesion tissue segmentation along with a spatial diffeomorphic transformation that maps a subject image into spatial correspondence with a healthy template image. The framework is evaluated on two-dimensional images both real and synthetic. Experimental results on real MR images show that simultaneous segmentation and registration can significantly improve the accuracy of lesion segmentation as well as the accuracy of registration near the lesion.

L’observation du système nerveux, de son métabolisme et de certaines de ses structures est possible grâce à la neuroimagerie. Une littérature importante issue du « neurodroit » véhicule des imaginaires et des fantasmes relatifs aux possibilités judiciaires qu’offriraient ces technologies. Qu’il s’agisse de détection du mensonge, d’identification cérébrale des individus dangereux ou encore de prédiction de comportements déviants, la neuroimagerie, en l’état actuel des technologies, ne peut pourtant être sérieusement conçue comme pouvant faire l’objet de telles applications. L’utilisation de la neuroimagerie dans le cadre d’expertises est néanmoins une réalité, dans les tribunaux canadiens comme dans la loi française. Cette thèse souligne que les conceptions des technologies dont témoignent les deux systèmes juridiques étudiés s’avèrent lacunaires, ce qui engendre des risques. Elle évoque les conditions du recours à une normativité extra-juridique, la normalisation technique, qui pourrait s’élaborer dans ce contexte controversé, et esquisse les traits d’un dialogue amélioré entre les normativités juridique et technologique. / Neuroimaging allows the observation of the nervous system, of both its metabolism and some of its structures. An important literature in “neurolaw” conveys illusions and fantaisies about the judicial possibilities that imaging technologies would contain. Whether it is about lies detection, cerebral identifications of dangerous individuals through their neurobiology or predictions of criminal behaviors, neuroimaging, in the current state of technologies, can not be seriously conceived as being able to offer such applications. Judicial uses of neuroimaging through expertise are a reality nonetheless, in Canadian courts as in French law. This thesis emphasizes that the conceptions of imaging technologies integrated in the two legal systems studied are incomplete, which creates an important amount of risks. It discusses the conditions for the use of an extra-legal normativity, the international technical standardization, which could be elaborated in this particular and controversial context, and outlines several features of an increased dialogue between legal and technological norms

The traditional diagnosis of patients with disorders of consciousness relies solely on behavioral responses. In 1996 it was estimated that 43% of patients diagnosed with unresponsive wakefulness syndrome (vegetative state) receive the wrong diagnosis. Assessing consciousness is perhaps the most crucial part of the diagnostic process. The challenging task of identifying covert consciousness in this patient group seems to be the biggest issue. In 2006 willful modulation of brain activity in response to a mental imagery task was discovered in a patient with unresponsive wakefulness syndrome. The brain activity was measured with functional magnetic resonance imaging. It was concluded that consciousness was preserved in this patient and new research investigating this novel method began to take place. The aim of this thesis was to conduct a systematic review of the literature and thereby arrive at the best current estimate of the proportion of patients who receive a diagnosis that wrongfully defines them as “unconscious” although they in fact are “covertly conscious”. In this review, 11 studies were examined. The results showed that patients with unresponsive wakefulness syndrome, who still receive the wrong diagnosis, decreased to 22-28% by the use of neuroimaging. This improvement points to the possible use of neuroimaging methods in the diagnosis of disorders of consciousness. However, this result cannot be taken without reservations. The limitations of the studies have to be taken into consideration. For example, most studies included a limited sample size and healthy controls did not always give the expected response to mental imagery tasks.

Adolescence is an exceptional period of life, not least in terms of social and brain development. Friends become increasingly important, susceptibility to peer rejection increases, and brain regions involved in social cognition are predicted to go through major changes. Adolescents’ social lives today may, to different extents, take place on social-media platforms online. This systematic review investigates how social-media use (SMU) affects adolescents’ brains. Out of 626 studies from the initial search, seven met the inclusion criteria. Out of these, five studies used functional magnetic resonance imaging, one study used diffusion tensor imaging, and one study used diffusion-weighted imaging. Functional findings suggest the reward circuit of the brain, as well as brain regions implicated in social cognition, to be involved in SMU. Activity in the nucleus accumbens was elicited by both giving and getting likes on posted pictures, whereas more SMU related to increased activity in the medial prefrontal cortex during physical self-judgement. Structural findings indicate frequent SMU to be associated with more reward sensitivity in terms of increased white matter in reward-processing pathways. These studies provide an initial understanding of the neural mechanisms of adolescents’ SMU. Future research is needed to draw inferences about how SMU affects the brains of adolescents.

Indiana University-Purdue University Indianapolis (IUPUI) / Over 5 million older adults have Alzheimer's disease (AD) in the US, and this number is projected to double by 2050. Clinical trials of potential pharmacological treatments for AD have largely shown that once cognitive decline has occurred, targeting AD pathology in the brain does not improve cognition. Therefore, it is likely that the most effective treatments for AD will need to be administered before cognitive symptoms occur, necessitating a biomarker for the early, preclinical stages of AD. Cerebral blood flow (CBF) is a promising early biomarker for AD. CBF is decreased in individuals with AD compared to their normally aging counterparts, and it has been shown that CBF is altered in mild cognitive impairment (MCI) and earlier stages and may occur prior to amyloid or tau aggregation. In addition, CBF can be measured using arterial spin labeled (ASL) MRI, a noninvasive imaging technique that can be safely repeated over time to track prognosis or treatment efficacy. The complex temporal and spatial patterns of altered CBF over the course of AD, as well as the relationships between CBF and AD-specific and -nonspecific factors, will be critical to elucidate in order for CBF to be an effective early biomarker of AD. Here, we begin to characterize the relationships between CBF and risk factors, pathologies, and symptoms of AD. Chapter 1 is a systematic review of published literature that compares CBF in individuals with AD and MCI to CBF in cognitively normal (CN) controls and assesses the relationship between CBF and cognitive function. Chapter 2 reports our original research assessing the relationships between CBF, hypertension, and race/ethnicity in older adults without dementia from the the Indiana Alzheimer’s Disease Research Center (IADRC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Chapter 3 reports our original research assessing the relationships between CBF and amyloid beta and tau aggregation measured with PET, as well as whether hypertension or APOEε4 positivity affects these relationships, in older adults without dementia from the IADRC. Chapter 4 reports our original research assessing the relationship between the spatial distribution of tau and subjective memory concerns. / 2023-05-24

The neuronal substrates underlying aspects of comorbidity in brain disease states may be described over psychiatric and neurologic conditions that include affective disorders, cognitive disorders, schizophrenia, obsessive-compulsive disorder, substance abuse disorders as well as the neurodegenerative disorders. Regional and circuitry analyses of biogenic amine systems that are implicated in neural and behavioural pathologies are elucidated using neuroimaging, electrophysiological, neurochemical, neuropharmacological and neurobehavioural methods that present demonstrations of the neuropathological phenomena, such as behavioural sensitisation, cognitive impairments, maladaptive reactions to environmental stress and serious motor deficits. Considerations of neuronal alterations that may or may not be associated with behavioural abnormalities examine differentially the implications of discrete areas within brains that have been assigned functional significance; in the case of the frontal lobes, differential deficits of ventromedial and dorsolateral prefrontal cortex may be associated with different aspects of cognition, affect, remission or response to medication thereby imparting a varying aspect to any investigation of comorbidity.

Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive neuroimaging technique that utilizes spontaneous low-frequency fluctuations of blood-oxygenation-level dependent (BOLD) signals to examine resting-state functional connectivity in the brain. In the past two decades, this technique has been increasingly utilized to investigate properties of large-scale functional neural networks as well as their alterations in various cognitive and disease states. However, much less is known about large-scale functional neural networks of the rodent brain, particularly in the awake state. Therefore, we attempted to unveil local and global functional connectivity in awake rat through a combination of seed-based analysis, independent component analysis and graph-theory analysis. In the current studies, we revealed elementary local networks and their global organization in the awake rat brain. We further systematically compared the functional neural networks in awake and anesthetized states, revealing that the rat brain was locally reorganized while maintaining global topological properties from awake to anesthetized states. Furthermore, specific neural circuitries of the rat brain were examined using resting-state fMRI. First anticorrelated functional connectivity between infralimbic cortex and amygdala were found to be evident with different preprocessing methods (global signal regression, regression of ventricular and white matter signal and no signal regression). Secondly the thalamocortical connectivity was mapped for individual thalamic groups, revealing group-specific functional cortical connections that were generally consistent with known anatomical connections in rat. In conclusion, large-scale neural networks can be robustly and reliably studied using rs-fMRI in awake rat, and with this technique we established a baseline of local and global neural networks in the awake rat brain as well as their alterations in the anesthetized condition.