A key challenge in the imaging of spinal cord injury (SCI) patients is the ability to accurately determine structural or functional abnormality as well as level and severity of injury. Over the years a substantial number of studies have addressed this issue, however most of them utilized qualitative analysis of the acquired imaging data. Quantitative analysis of patients with SCI is an important issue in both diagnostic and treatment planning. Hence in this work new multispectral magnetic resonance (MR) image based approaches were developed for high-throughput extraction of quantitative features from pediatric spinal cord MR images and subsequent analysis using decision support algorithms. This may potentially improve diagnostic, prognostic, and predictive accuracy between typically developing (TD) pediatric spinal cord subjects and patients with SCI. The technique extracts information from both axial structural MRI images (such as T2-weighted gradient echo images) and functional MRI images (such as diffusion tensor images). The extracted data contains first order statistics (diffusion tensor tractography and histogram based texture descriptors), second order (co-occurrence indices) and high order (wavelet primitives) statistics. MRI data from total of 43 subjects that includes 23 healthy TD subjects with the age range of 6-16 (11.94±3.26 (mean ±standard deviation)) who had no evidence of SCI or pathology and 20 SCI subjects with the age range of 7-16 (11.28±3.00 (mean ±standard deviation)) were recruited and scanned using 3.0T Siemens Verio MR scanner. Standard 4-channel neck matrix and 8-channel spine array RF coils were used for data collection. After data collection various post processing methods were used to improve the data quality. A novel ghost artifact suppression technique was implemented and tested. Initially, 168 quantitative measures of multi-spectral images (functional and structural) were calculated by using regions of interest (ROIs) manually drawn on the whole cord along the entire spinal cord being anatomically localized by an independent board certified neuroradiologist. These measures were then statistically compared between TD and SCI groups using standard least squared linear regression model based on restricted maximum likelihood (REML) method. Statistically, significant changes have been shown in 44 features: 30 features obtained from functional images and 14 features selected from structural images. Also, it has been shown that the quantitative measures of the spinal cord in DTI and T2W-GRE images above and below injury level were altered significantly. Finally, tractography measures were also obtained on a subset of the patients to demonstrate quantitative analysis of the extracted white matter structures. Overall the results show that the proposed techniques may have potential to be used as surrogate biomarkers for detection of the injured spinal cord. These measures enable us to quantify the functional and structural plasticity in chronic SCI and consequently has the potential to improve our understanding of damage and recovery in diseased states of the spinal cord. / Bioengineering

Borderline personality disorder (BPD) and schizotypal personality disorder (SPD) are both characterized by inflexible and pervasive behavioral patterns that frequently lead to significant functional impairment. Although considerable research has been conducted on the biological and phenotypic aspects of these disorders, researching, diagnosing, and treating them remains a challenge, primarily due to the difficulties associated with the categorical nature of current diagnostic methods (Skodol and Bender, 2009) which, in turn, results in significant within-group heterogeneity and between-group co-occurrence. Given the relative paucity of research comparing aspects of these disorders with one another, the current study aimed to evaluate overlapping and differentiating aspects of BPD and SPD by examining the integrity of a brain region frequently implicated in both disorders, the cingulum. The current study used a 3T Siemens scanner to acquire structural and diffusion tensor imaging in age-, sex-, and education-matched groups of 28 adults with BPD, 32 adults with SPD, and 36 healthy control participants (HC). The anterior and posterior cingulate were manually traced on all participants and then volume and fractional anisotropy (FA) comparisons were conducted across the groups for the left and right anterior and posterior cingulate. Compared with HC, SPD patients had smaller relative cingulate white matter volume and BPD patients had marginally significantly smaller relative cingulate white matter volume, and the two patient groups did not differ from one another. With regard to FA findings, a spectrum pattern emerged, such that the BPD group had significantly lower FA in the posterior cingulum relative to controls, whereas the SPD group also had lower FA in this region but did not differ from HC. The BPD group had marginally lower FA in dorsal aspects of the anterior cingulum when compared with HC, and the SPD patients did not differ from HC or BPD individuals. In summary, the current study provides evidence of aberrant connectivity of the cingulum in BPD patients, but not SPD patients, compared with HC individuals. Consistent with prior work, overall results suggest potential involvement of cingulum in BPD symptomatology. / Psychology

Background: Given the growing aging population, it is crucial to better understand the neurobiological underpinnings of healthy aging and how changes in structure relate to changes in function. The current study derived diffusion tensor imaging (DTI) metrics of white matter microstructure in younger and older adults to simulate the healthy aging process. Methods: The DTI metrics of fractional anisotropy (FA) and mean diffusivity (MD) as well as the cognitive domains of memory and executive function were examined in 34 healthy participants divided into older adults (17; Mean = 70.9, SD = 5.4) and younger adults (17; Mean = 28.1, SD = 2.8). Cognitive performance on the California Verbal Learning Test 2nd Edition (CVLT-II) and the trails making test (Trails-A & Trails-B) were used to evaluate memory and executive function, respectively. The differences in white matter microstructure between older and younger adults were analyzed using tract based spatial statistics (TBSS; p < 0.05, corrected for multiple comparisons) in FSL. Associations between the DTI metrics and cognition were then evaluated for each group. Results: Older adults had lower FA and higher MD in diffuse brain regions, including major tracts such as the corticospinal tract, corpus callosum and superior and inferior longitudinal fasciculi. There was a significant negative correlation between executive function and MD in the right superior and anterior corona radiata and the body of the corpus callosum of older adults. No significant relationship was detected between memory performance and DTI metrics in older adults. Furthermore, no significant relationships were detected between memory or executive function performance and FA or MD in younger adults. Conclusions: The differences in DTI metrics between groups as well as the association between MD and executive function support further examinations into the healthy aging process. Future studies should use longitudinal designs with large sample sizes to better understand changes and trajectories during healthy aging. / Graduate / 2023-08-19

Since its inception, Magnetic Resonance Imaging (MRI) has largely been used for qualitative diagnosis. Radiologists and physicians are increasingly becoming interested in quantitative assessments. The American College of Radiology (ACR) developed an accreditation program that incorporates tests pertaining to quantitative and qualitative analyses. As a result, sites often use the ACR procedure for daily quality assurance (QA) testing. The ACR accreditation program uses information obtained from clinical and phantom images to assess overall image quality of a scanner. For the phantom assessment, a human observer performs manual tests on T1 and T2-weighted volumes of the provided phantom. As these tests are tedious and time consuming, the primary goal of this research was to fully automate the procedure for QA purposes. The performance of the automated procedure was assessed by comparing the test results with the decisions made by human observers. The test results of the automated ACR QA procedure were well correlated with that of human observers. The automated ACR QA procedure takes approximately 5 minutes to complete. Upon program completion, the test results are logged in multiple text files. To this date, no QA procedure has been reported for Diffusion Tensor Imaging (DTI). Therefore, the secondary goal of this thesis was to develop a DTI QA procedure that assess two of the associated features used most in diagnosis, namely, diffusion anisotropy and the direction of primary diffusion. To this end, a physical phantom was constructed to model restricted diffusion, relative to axon size, using water-filled polytetrafluoroethylene (PTFE) microbore capillary tubes. Automated procedures were developed to test fractional anisotropy (FA) map contrast and capillary bundle (axon) orientation accuracy. / Master of Science

Diffusion Tensor Magnetic Resonance Imaging (DT-MRI), also known as Diffusion Tensor Imaging (DTI), is a unique medical imaging modality that provides non-invasive estimates of White Matter (WM) connectivity based on local principal directions of anisotropic water diffusion. DTI tractography estimates are a macroscopically sampled description of underlying microscopic structure, and are therefore of limited validity. The under-sampling of underlying white matter structure in DTI data gives rise to Intra-Voxel Orientational Heterogeneity (IVOH), a condition in which white matter structures of multiple different orientations are averaged into a single DTI voxel sample, causing a loss of validity in the diffusion tensor model. Fast Marching Tractography (FMT) algorithms based on fast marching level set methods have been proposed to better handle the presence of IVOH in DTI data when compared to older Streamline Tractography (SLT) methods. However, the actual performance advantage of any tractography algorithm over another cannot be conclusively stated until a ground truth standard of comparison is developed. This work develops an optimized version of the FMT algorithm that is dubbed the Front Propagation Tractography (FPT) algorithm. The FPT algorithm includes unique approaches to the speed function, connectivity estimation, and likelihood estimation components of the FMT framework. The performance of the FPT algorithm is compared against the SLT algorithm using ground truth software phantom data and human brain data. Software phantom ground truth experiments compare the performance of each algorithm in single tract and crossing tract structures for varying levels of diffusion tensor field perturbation. Human brain estimates in the corpus callosum yield qualitative comparisons from inspection of 3D visualizations. A final area of exploration is the construction and analysis of a ground truth physical DTI phantom manifesting IVOH. / Master of Science

Yes / Objectives: To assess the test-retest variability of both diffusion parameters and fat fraction (FF) estimates in normal muscle, and to assess differences in normal values between muscles in the thigh. Methods: 29 healthy volunteers (mean age 37 years, range 20-60 years, 17/29 males) completed the study. Magnetic resonance images of the mid-thigh were acquired using a stimulated echo acquisition mode-echoplanar imaging (STEAM-EPI) imaging sequence, to assess diffusion, and 2-point Dixon imaging, to assess FF. Imaging was repeated in 19 participants after a 30 min interval in order to assess test-retest variability of the measurements. Results: Intraclass correlation coefficients (ICCs) for test-retest variability were 0.99 [95% confidence interval, (CI): 0.98, 1] for FF, 0.94 (95% CI: 0.84, 0.97) for mean diffusivity and 0.89 (95% CI: 0.74, 0.96) for fractional anisotropy (FA). FF was higher in the hamstrings than the quadriceps by a mean difference of 1.81% (95% CI:1.63, 2.00)%, p < 0.001. Mean diffusivity was significantly lower in the hamstrings than the quadriceps (0.26 (0.13, 0.39) x10-3 mm2s-1, p < 0.001) whereas fractional anisotropy was significantly higher in the hamstrings relative to the quadriceps with a mean difference of 0.063 (0.05, 0.07), p < 0.001. Conclusions: This study has shown excellent test-retest, variability in MR-based FF and diffusion measurements and demonstrated significant differences in these measures between hamstrings and quadriceps in the healthy thigh. Advances in knowledge: Test-retest variability is excellent for STEAM-EPI diffusion and 2-point Dixon-based FF measurements in the healthy muscle. Inter- and intraobserver variability were excellent for region of interest placement for STEAM-EPI diffusion and 2-point Dixon-based FF measurements in the healthy muscle. There are significant differences in FF and diffusion measurements between the hamstrings and quadriceps in the normal muscle. / ICA-CL-2016-02-017/DH_/Department of Health/United Kingdom; NIHR

Following peripheral nerve transection and microsurgical repair (PNIr) most patients retain significant sensorimotor impairments, a proportion of which also develop chronic neuropathic pain. Individual psychological factors may contribute to the development, intensity and duration of chronic pain. Furthermore, a large body of evidence has indentified beneficial and maladaptive cortical plasticity following disease or injury. The general aim of this thesis was to determine the extent of sensory and motor recovery, functional and structural brain changes, and the impact of chronic neuropathic pain on sensorimotor outcomes following upper limb PNIr. Towards this main aim a sensorimotor psychophysical assessment (that included psychological assessments), nerve conduction testing, and an MRI session that examined brain function and structure was performed in patients with peripipheral nerve injury induced neuropathic pain (PNI-P) and those with no neuropathic pain (PNI-NP). Nerve conduction testing demonstrated that all patients had incomplete peripheral nerve regeneration, and that PNI-P patients had worse sensory nerve regeneration. Psychophysical assessment confirmed that all PNIr patients had significant sensorimotor deficits. Additionally, deficits on tests of vibration detection, sensorimotor integration, and fine dexterity were significantly greater in PNI-P patients. Psychological measures clearly distinguished PNI-P from PNI-NP and healthy controls (HC). Vibrotactile stimulation of the deafferented territory in PNI-NP patients results in reduced BOLD activation within the primary and secondary somatosensory cortices. Interestingly, the regions of reduced BOLD corresponded with gray matter thinning which was negatively correlated with behavioural measures of sensory recovery. Structural abnormalities were also identified in the right insula. PNI-P patients had thinning within the right middle insula and a corresponding decrease in white matter pathways projecting into/out of that region. PNI-P patients also had white matter abnormalities in pathways feeding into/out of the contralesional primary somatosensory cortex and thalamus. In conclusion, PNIr is clearly associated with sensorimotor impairments and brain plasticity. Furthermore, neuropathic pain is associated with worse peripheral nerve regeneration, sensorimotor deficits, different psychological profiles, and structural alterations in brain regions involved in pain perception and somatosensation. These results provide insight into peripheral regeneration, the development of chronic pain, brain plasticity and structure-function-behavioural relationships following nerve injury and have important therapeutic implications.

Following peripheral nerve transection and microsurgical repair (PNIr) most patients retain significant sensorimotor impairments, a proportion of which also develop chronic neuropathic pain. Individual psychological factors may contribute to the development, intensity and duration of chronic pain. Furthermore, a large body of evidence has indentified beneficial and maladaptive cortical plasticity following disease or injury. The general aim of this thesis was to determine the extent of sensory and motor recovery, functional and structural brain changes, and the impact of chronic neuropathic pain on sensorimotor outcomes following upper limb PNIr. Towards this main aim a sensorimotor psychophysical assessment (that included psychological assessments), nerve conduction testing, and an MRI session that examined brain function and structure was performed in patients with peripipheral nerve injury induced neuropathic pain (PNI-P) and those with no neuropathic pain (PNI-NP). Nerve conduction testing demonstrated that all patients had incomplete peripheral nerve regeneration, and that PNI-P patients had worse sensory nerve regeneration. Psychophysical assessment confirmed that all PNIr patients had significant sensorimotor deficits. Additionally, deficits on tests of vibration detection, sensorimotor integration, and fine dexterity were significantly greater in PNI-P patients. Psychological measures clearly distinguished PNI-P from PNI-NP and healthy controls (HC). Vibrotactile stimulation of the deafferented territory in PNI-NP patients results in reduced BOLD activation within the primary and secondary somatosensory cortices. Interestingly, the regions of reduced BOLD corresponded with gray matter thinning which was negatively correlated with behavioural measures of sensory recovery. Structural abnormalities were also identified in the right insula. PNI-P patients had thinning within the right middle insula and a corresponding decrease in white matter pathways projecting into/out of that region. PNI-P patients also had white matter abnormalities in pathways feeding into/out of the contralesional primary somatosensory cortex and thalamus. In conclusion, PNIr is clearly associated with sensorimotor impairments and brain plasticity. Furthermore, neuropathic pain is associated with worse peripheral nerve regeneration, sensorimotor deficits, different psychological profiles, and structural alterations in brain regions involved in pain perception and somatosensation. These results provide insight into peripheral regeneration, the development of chronic pain, brain plasticity and structure-function-behavioural relationships following nerve injury and have important therapeutic implications.

Background: Adolescence and young adulthood are particularly vulnerable periods for the development of mental health disorders, including bipolar disorder (BD). Mental health screening at universities could aid in the early identification of particularly at- risk individuals, with the long-term aim of providing early treatment interventions to improve clinical outcomes. However, further research into the identification of appropriate behavioral and biological markers for vulnerability to psychiatric disorders – as well as into the acceptability and efficacy of mental health screening - is warranted. Methods: Young adults were recruited via an already existing Internet-based mental health screening survey of undergraduate students at the University of Oxford. In Study 1, qualitative interviews of young adults with and without previous mental health problems were conducted to assess the acceptability and efficacy of mental health screening within a university setting. In Studies 2-5 we explored the hypotheses of altered emotional decision-making, reward processing and neurostructural integrity as behavioral and neurobiological markers for vulnerability to bipolar disorder via the study of young adults with a common bipolar phenotype (BPP) - some of whom meet diagnostic criteria for bipolar II or not-otherwise-specified disorder (BD II/NOS). To that end, we employed a diverse range of methodologies: alcohol challenge (Study 2); neuropsychological task performance (Study 3); functional magnetic resonance imaging (fMRI; Study 4); diffusion tensor imaging (DTI) and voxel-based morphometry (VBM; Study 5). Results: Findings from Study 1 suggest that young adults are willing to participate in mental health screening within a university setting, and that such screening may be used to offer subsequent treatment interventions. Taken together, findings from Studies 2 and 4 suggest a general blunted reward response among unmedicated young adults at increased risk for BD during euthymia, and additionally suggest pathophysiological similarities between BD and alcohol use disorders (AUDs) that may provide a causal link between the elevated co-occurrence rates of the two disorders. Finally, findings from Study 5 suggest widespread white matter microstructural alterations – which are likely to be neurodevelopmental in origin – among antipsychotic- and mood-stabilizer naïve young adults with BD II/NOS. Conclusions: These data support the hypothesis of neurodevelopmental alterations identifiable prior to significant clinical impairment among young adults at increased risk of – or already meeting DSM-IV criteria for – bipolar disorder. They also suggest that young adults in higher education are willing to participate in mental health screening. Future studies should aim to identify more specific markers for individual disorders such as BD.

Le trouble bipolaire est un trouble de l’humeur chronique marqué par l'alternance de dépressions, d'épisodes maniaques et de rémissions. La neuroimagerie permet l'étude de l'anatomie et du fonctionnement cérébral des patients bipolaires. Des études existantes avaient ainsi retrouvé des anomalies dans les aires du traitement des émotions chez les patients bipolaires. L'IRM anatomique avait permis de mettre en évidence certaines modifications morphométriques des régions associées (amygdale, gyrus cingulaire, thalamus) ainsi que des hypersignaux de la substance blanche. En imagerie fonctionnelle, lors du traitement d'informations émotionnelles, les patients bipolaires présentaient une hyperactivation d'un réseau ventro-limbique et une hypoactivation d'un réseau dorsal cognitif. Nous avons tout d’abord utilisé l'IRM de diffusion pour étudier la connectivité anatomique dans le trouble bipolaire. Dans une première étude, nous avons reconstruit le faisceau uncine, reliant le réseau dorsal cognitif au réseau ventro-limbique, chez 16 patients bipolaires et 16 contrôles en utilisant les techniques de suivi de fibres dites de tractographie exploitant les données d'IRM de diffusion. Les patients bipolaires avaient plus de fibres reconstruites dans le faisceau uncine gauche. Dans le même échantillon, en étudiant l'anisotropie du processus de diffusion dans tout le cerveau, nous avons également identifié une augmentation diffuse de la connectivité anatomique chez les patients. Enfin, nous avons réalisé une étude multicentrique internationale d’IRM de diffusion incluant 118 patients 10 bipolaires et 86 contrôles. Nous avons alors montré une diminution significative de l'anisotropie le long du corps calleux, du cingulum gauche et du faisceau arqué gauche chez les patients. Les patients bipolaires avec caractéristiques psychotiques avaient une anisotropie du corps calleux plus basse que les patients sans caractéristiques psychotiques. Dans une seconde partie de notre travail, nous avons étudié l'interférence produite par une information émotionnelle sur un traitement cognitif chez les patients. Nous avons comparé 17 patients bipolaires euthymiques à 17 sujets contrôles en IRM fonctionnelle lors d'un paradigme de type go/no-go émotionnel. Notre étude apporte des arguments tendant à démontrer l'existence d'une altération de la modulation par une information émotionnelle d’un traitement cognitif chez les patients avec une hyperactivation d’un réseau fronto-cingulo-striatal. Enfin, nous avons réalisé une synthèse quantitative de la littérature s'intéressant à l'imagerie anatomique, fonctionnelle et de diffusion dans le trouble bipolaire. Nous avons retrouvé chez les patients une diminution d’activation dans les tâches émotionnelles et une diminution du volume de substance grise dans des régions frontales et dorsales, tandis que sont présentes des hyperactivations dans des régions limbiques. L'ensemble de ces résultats a permis de préciser le modèle neural du trouble bipolaire avec les anomalies les plus importantes au niveau des zones impliquées dans la régulation automatique des émotions. Nos travaux ont significativement contribué à faire envisager le trouble bipolaire comme lié à des anomalies de la connectivité préfronto-limbique. Ils ouvrent aussi des perspectives de travail pour progresser dans la compréhension de sa physiopathologie. En particulier, le suivi prospectif d'une cohorte de patients permettra d'évaluer l'influence de l'évolution de la maladie bipolaire sur la structure cérébrale. Les techniques récentes d'IRM de diffusion permettront de mieux comprendre la signification physiopathologique des anomalies identifiées. Enfin, la reconceptualisation dimensionnelle proposée par le DSM-5 et le NIMH permettra probablement d'identifier des dimensions plus pertinentes que les catégories diagnostiques actuelles. / [Summary made by the web site Reverso] The bipolar disorder is a confusion of the chronic humor marked by the alternation of depressions, manic episodes and forgiveness. The neuroimaging allows the study of the anatomy and the cerebral functioning of the bipolar patients. Existing studies had so found anomalies in the areas of the treatment of the feelings at the bipolar patients. The anatomical MRI had allowed to highlight certain morphométriques modifications of the regions associated (tonsil, gyrus cingulaire, thalamus) as well as hypersignals of the white material. In functional imaging, during the processing of emotional information, the bipolar patients presented a hyperactivation of a network ventro-limbique and a hypoactivation of a cognitive dorsal network. We used first of all the MRI of distribution to study the anatomical connectivity in the bipolar disorder. In a first study, we reconstructed the beam uncine, connecting(binding) the cognitive dorsal network with the ventro-limbique network, at 16 bipolar patients and 16 controls by using the techniques of follow-up of said fibers of tractographie exploiting the data of MRI of distribution. The bipolar patients had more fibers reconstructed in the beam left uncine. In the same sample, by studying the anisotropie of the process of distribution in all the brain, we also identified a diffuse increase of the anatomical connectivity at the patients. In the same sample, by studying the anisotropie of the process of distribution in all the brain, we also identified a diffuse increase of the anatomical connectivity at the patients. Finally, we realized a study international multicentrique of MRI of distribution including 118 bipolar patients 10 and 86 controls. We then showed a significant decrease of the anisotropie along the corpus callusum, along the left(awkward) cingulum and along the left hooked beam at the patients. The bipolar patients with psychotic characteristics had an anisotropie of the corpus callusum lower than the patients without psychotic characteristics. In a second part of our work, we studied the interference produced by an emotional information about a cognitive treatment at the patients. We compared 17 bipolar patients euthymiques on 17 subjects controls in functional MRI during one paradigm of type emotional go / no-go. Our study brings arguments tending to demonstrate the existence of a change of the modulation by an emotional information of a cognitive treatment at the patients with a hyperactivation of a fronto-cingulo-striatal network. Finally, we realized a quantitative synthesis of the literature being interested in the anatomical, functional imaging and of distribution in the bipolar disorder. We found at the patient's a decrease of activation in the emotional tasks and a decrease of the volume of grey matter in frontal and dorsal regions, whereas are present hyperactivations in limbiques regions. All these results allowed to specify the neural model of the bipolar disorder with the most important anomalies at the level of zones implied in the self-regulation of the feelings. Our works significantly contributed to make envisage the bipolar disorder as bound to anomalies of the préfronto-limbique connectivity. They also open working perspectives to progress in the understanding of its physiopathology. In particular, the forward-looking follow-up of patients' troop will allow to estimate the influence of the evolution of the bipolar disease on the intellectual structure. The recent techniques of MRI of distribution will allow to understand better the physiopathological meaning of the identified anomalies. Finally, the dimensional reconceptualisation proposed by the DSM-5 and the NIMH will probably allow to identify dimensions more relevant than the current diagnostic categories.