Dissertations / Theses on the topic 'Imaging study'

Chronic musculoskeletal pain is a leading cause of disability worldwide yet the mechanisms of chronification and neural responses to effective treatment remain elusive. Non-invasive imaging techniques are useful for investigating brain alterations associated with health and disease. Thus the overall goal of this dissertation was to investigate the white (WM) and grey matter (GM) structural differences in patients with musculoskeletal pain before and after psychotherapeutic intervention: cognitive behavioral therapy (CBT). To aid in the interpretation of clinical findings, we used a novel porcine model of low back pain-like pathophysiology and developed a post-mortem, in situ, neuroimaging approach to facilitate translational investigation. The first objective of this dissertation (Chapter 2) was to identify structural brain alterations in chronic pain patients compared to healthy controls. To achieve this, we examined GM volume and diffusivity as well as WM metrics of complexity, density, and connectivity. Consistent with the literature, we observed robust differences in GM volume across a number of brain regions in chronic pain patients, however, findings of increased GM volume in several regions are in contrast to previous reports. We also identified WM changes, with pain patients exhibiting reduced WM density in tracts that project to descending pain modulatory regions as well as increased connectivity to default mode network structures, and bidirectional alterations in complexity. These findings may reflect network level dysfunction in patients with chronic pain. The second aim (Chapter 3) was to investigate reversibility or neuroplasticity of structural alterations in the chronic pain brain following CBT compared to an active control group. Longitudinal evaluation was carried out at baseline, following 11-week intervention, and a four-month follow-up. Similarly, we conducted structural brain assessments including GM morphometry and WM complexity and connectivity. We did not observe GM volumetric or WM connectivity changes, but we did discover differences in WM complexity after therapy and at follow-up visits. To facilitate mechanistic investigation of pain related brain changes, we used a novel porcine model of low back pain-like pathophysiology (Chapter 6). This model replicates hallmarks of chronic pain, such as soft tissue injury and movement alteration. We also developed a novel protocol to perform translational post-mortem, in situ, neuroimaging in our porcine model to reproduce WM and GM findings observed in humans, followed by a unique perfusion and immersion fixation protocol to enable histological assessment (Chapter 4). In conclusion, our clinical data suggest robust structural brain alterations in patients with chronic pain as compared to healthy individuals and in response to therapeutic intervention. However, the mechanism of these brain changes remains unknown. Therefore, we propose to use a porcine model of musculoskeletal pain with a novel neuroimaging protocol to promote mechanistic investigation and expand our interpretation of clinical findings.

In MRI, it is more desirable to scan less data as possible because it reduces MRI scanning time. We want to get a clear image by reconstructing the signals we acquire from the MRI machine. Special scanning or sampling techniques are needed to overcome this issue based on various mathematical methods.

We present an improved random sampling pattern for SAKE (simultaneous autocalibrating and k-space estimation) reconstruction and an iterative GRAPPA reconstruction using Wiener filter.

In our iterative method using Wiener filter, in contrast to the conventional GRAPPA where only the auto calibration signals (ACS) are used to find the convolution weights, our proposed method iteratively updates the convolution weights using both the acquired and reconstructed data from previous iterations in the entire k-space. To avoid error propagation, the method applies adaptive Wiener filter on the reconstructed data. Experimental results demonstrate that even with a smaller number of ACS lines the proposed method improves the SNR when compared to GRAPPA.

In compressed sensing MRI, it is very important to design sampling pattern for random sampling. For example, SAKE (simultaneous auto-calibrating and k-space estimation) is a parallel MRI reconstruction method using random undersampling. It formulates image reconstruction as a structured low-rank matrix completion problem. Variable density (VD) Poisson discs are typically adopted for 2D random sampling. The basic concept of Poisson disc generation is to guarantee samples are neither too close to nor too far away from each other. However, it is difficult to meet such a condition especially in the high density region. Therefore the sampling becomes inefficient. In this paper, we present an improved random sampling pattern for SAKE reconstruction. The pattern is generated based on a conflict cost with a probability model. The conflict cost measures how many dense samples already assigned are around a target location, while the probability model adopts the generalized Gaussian distribution which includes uniform and Gaussian-like distributions as special cases. Our method preferentially assigns a sample to a k-space location with the least conflict cost on the circle of the highest probability. To evaluate the effectiveness of the proposed random pattern, we compare the performance of SAKEs using both VD Poisson discs and the proposed pattern. Experimental results for brain data show that the proposed pattern yields lower normalized mean square error (NMSE) than VD Poisson discs.

Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2009.
Committee Chair: James K. Rilling; Committee Chair: Xiaoping Hu; Committee Member: Shella Keilholz; Committee Member: Todd M. Preuss.

Aims: I investigate potential MRI markers in cerebral small vessel disease (SVD), to determine their relationship to cognitive impairment and investigate whether they are feasible for use as surrogate outcome measures in clinical trials by estimating their sensitivity to longitudinal change and calculating sample sizes for a hypothetical clinical trial. I also carry out pilot work to investigate the potential use of 7T MRI in SVD. Methods: Data from the prospective St Georges Cognition and Neuroimaging in Stroke (SCANS) study of patients with symptomatic SVD was used (n=121). Neuropsychological testing was performed annually for a period of 3 years. Multimodal MRI was also acquired annually to evaluate brain volume, T2 White Matter Hyperintensities (WMH) volume, lacunes and white matter damage on diffusion tensor imaging (DTI). Results: At baseline, lacunes and brain volume were found be important predictors of cognitive impairment on conventional MRI. There is a specific association between lacunes in the anteromedial thalamus and impaired processing speed (Chapter 3). Perivascular spaces (PvS) were not associated with cognitive impairment but were associated with other MRI markers of SVD (Chapter 4). Over 3 years, longitudinal change was detectable in MRI markers but not in cognitive measures. WMH volume and diffusion tensor imaging parameters were most sensitive to change and therefore had the smallest sample size estimates for a hypothetical clinical trial (Chapter 5). The presence of new lacunes was the only MRI marker able to predict longitudinal change in cognition over a 3 year follow-up period (Chapter 6). Conclusion: Quantitative MRI markers could significantly reduce the size of clinical trials to screen treatments for efficacy in SVD, although further validation from studies with longer follow-up is required. 7T MRI has the potential to provide new information on underlying disease mechanisms and more specific surrogate markers of SVD progression (Chapter 7).

1er objectif : Mieux caractériser les surdités neuro-sensoriellesNous avons démontré dans ce travail de thèse que nous étions capablesd’individualiser le saccule et l’utricule pour faire le diagnostic d’hydropscompartiment par compartiment. L’intérêt repose sur les propriétés biomecaniquesdifferentes de ces deux structures notamment en terme decompliance. En isolant l’hydrops sacculaire, nous avons démontré qu’ilétait lié à la présence de surdité neurosensorielle pour les patients avecune Maladie de Ménière mais également qu’il pouvait être détecté pourdes patients présentant des surdités isolées sur les basses fréquences, quine sont habituellement pas classées comme porteurs cliniquement de laMaladie de Ménière. Nous avons mis au point une séquence 3D-FLAIRutilisable en pratique clinique pour la détection d’hydrops sacculaire,utilisable quelque soit le champ magnétique et le constructeur.Pour les patients porteurs de schwannomes cochléo-vestibulaires, nousavons démontré que le degré de perte auditive était cette fois liée à laprésence d’un hydrops utriculaire. Ce diagnostic peut être porté sansinjection de produit de contraste puisque la présence d’un schwannomeobstructif entraine mécaniquement une augmentation du taux protidiquedans la périlymphe et donc une discrimination périlymphe/endolymphesur les séquences T2 en echo de gradient.En revisitant l’anatomie histologique avec la remnographie, nous avonsproposé une théorie bi-compartimentale pour les échanges endolymphe/liquidecéphalorachidien ; supposant que l’utricule et le saccule joue un rôle detampon entre le cerveau et la cochlée. En cas d’obstruction mécanique,au niveau de l’aqueduc du vestibule pour la maladie de Ménière et dunerf cochléo-vestibulaire pour les tumeurs du conduit auditif interne ; letampon ne joue plus son rôle. Surviennent alors des lésions cellulaires desstéréocils de la cochlée et la surdité attenante.2ème objectif : Mieux caractériser les altérations structurelles neuronalesrétro-cochléaires des surdités neurosensoriellesDu point de vue biophysique de l’IRM, l’étude du nerf cochléaire possèdel’avantage de posséder une structure simple essentiellement composéed’une seule population de fibre à modéliser par voxel, au prix d’une régiond’étude compliquée intricant de l’os, du liquide et de l’air dans l’ostemporal. Nous avons donc commencer par développer un algorithmede pré-traitement des données de diffusion qui utilise toutes les toolboxrécentes pour corriger les artéfacts de susceptibilité magnétique, de mouvements, de champ B0 et B1, les courants de Foucaults, les arrtéfactsde Gibbs. Nous avons utilisée une séquence de Diffusion optimisée pourêtre utilisable en pratique clinique en cas de mouvements des patients,construite par bloc de 15 directions.Nous avons ensuite appris à utiliser des biomarqueurs quantitatifs, notammentle coefficient de diffusion apparent des fibres, directement issusdu signal de Diffusion dont nous avons préalablement testé la fiabilitésur des données de diffusion multi-compartimentale de haute qualité auniveau de l’encéphale. Nous avons ensuite proposée une méthode originaled’extraction de l’information des voxels du nerf cochléaire appelée spectralclustering pour obtenir ce coefficient de densité des fibres de façon robusteau niveau de notre population témoin. Enfin, nous avons implémenté unalgorithme de Manifold Learning pour l’analyse de ce signal de diffusion,qui surpasse les biomarqueurs scalaires en confrontation à des modèlespathologiques auditifs en tenant compte de l’hétérogénité du signal dediffusion dans un cluster. Nous avons ainsi démontré que les patientsporteurs de la maladie de Ménière présentaient une augmentation de ladensité de fibre, en faisant de particulier bosn candidats à l’implantationcochléaire, en accord avec les premières études cliniques fonctionnellessur le sujet
Sensorineural hearing loss (SNHL) is a common functional disorder in humans. Besides clinical investigations, magnetic resonance imaging (MRI) is the modality of choice to explore the central auditory pathways. Indeed, new MRI sequences and postprocessing methods have revolutionized our understanding of inner ear and brain disorders.The inner ear is the organ of sound detection and balance. Within the inner ear, there are two distinct compartments filled with endolymph and perilymph.The accumulation of endolymph fluid is called “endolymphatic hydrops”. Endolymphatic hydrops may occur as a consequence of a variety of disorders, including Meniere’s Disease, immune-mediated diseases or internal auditory canal tumors.Previous classification for grading the amount of endolymph liquid using MRI has proposed a global semi-quantitative evaluation, without distinguishing the utricle from the saccule, whose biomechanical properties are different in terms of compliance.This work had two main objectives: 1°) to better characterize the role of endolymphatic hydrops in SNHL occurrence; 2°) to study secondary auditory pathways alterations.Part 1: Understanding the role and pathophysiology of endolymphatic hydrops in SNHL occurrence.Endolymphatic hydrops can be identified using MRI, acquired 4-6-hours after injection of contrast media. This work has demonstrated the feasibility and improved this technique in a clinical setting.Using optimized morphological sequences, we were able to illustrate inner ear microanatomy based on temporal bone dissection, and to distinguish the saccule and the utricle.In accordance with a multi-compartmental model, we observed that the saccular hydrops was a specific biomarker of low-tone SNHL in the context of typical or atypical forms of Meniere’s Disease. In addition, utricular hydrops was linked to the degree of hearing loss in patients with schwannomas. We raise the hypothesis that both saccule and utricle compartment play the role of a buffer in endolymph reabsorption. When their compliance is overstretched, inner ear endolymph regulation fails, subsequently leading to cochlear lesions such as loss of the shorter stereocilia of the hair cells, as suggested by experimental animal modelsThus, we were able to prove the high prevalence of endolymphatic hydrops in patients with SNHL.Part 2: Development of new imaging biomarkers to study the central auditory pathways.Diffusion-Weighted Imaging play a crucial role because it can help to assess the intracellular compartment by displaying the Brownian movements of water molecules. In the context of cochlear lesions, anterograde axonal degeneration has only been demonstrated in animal models. In the context of retrocochlear lesions, no MRI sequences have previously showed efficiency in distinguishing the cochlear from the facial nerve. This is crucial for safe surgery procedure.We have designed optimized postprocessing tools to explore SNHL patients with High-Angular Resolution DWI acquisition. We have included in the clinical setting software tools for B0 and B1 bias field artifacts’ correction, Denoising process, Gibbs artifacts’ correction, Susceptibility and Eddy Current artifacts management.The ultimate goal was to properly study the Fiber Orientation Distribution (FOD) along the auditory pathways in case-controlled studies, using top-of-the-art methods of fixels analysis and a newly developed toolbox with Machine Learning analysis of the Diffusion signal.We have studied reproducibility of these two methods on Multi-Shell Diffusion gradient scheme by test-retest procedure. We have then used the fixel method to seek for auditory pathways alterations in Meniere’s Disease and Machine Learning automatic analyses to extract Inner Auditory Canal cranial nerves.Thus, we have developed a new method for cranial nerves’ tractography using FOD spectral clustering, efficient in terms of computer requirement and in tumor condition

Thesis (Ph. D.)--University of Florida, 1999.
Title from first page of PDF file. Document formatted into pages; contains xiv, 137 p.; also contains graphics. Vita. Includes bibliographical references (p. 129-136).

Biomedical imaging is a key tool for the study of host-pathogen interactions. New techniques are enhancing the quality and flexibility of imaging systems, particularly as a result of developments in laser technologies. This work applies the combination of two advanced laser imaging methods to study the interactions between a virus and the host cells it infects. The first part of this work describes the theory and experimental implementation of coherent anti-Stokes Raman scattering microscopy. This technique-first demonstrated in its current form in 1999-permits the imaging of microscopic samples without the need for fluorescent labelling. Chemical contrast in images arises from the excitation of specific vibrations in the sample molecules themselves. A laser scanning microscope system was set up, based on an excitation source consisting of two titanium-sapphire lasers synchronized with a commercial phase-locked loop system. A custom-built microscope was constructed to provide optimal imaging performance, high detection sensitivity and straightforward adaptation to the specific requirements of biomedical experiments. The system was fully characterized to determine its performance. The second part of this work demonstrates the application of this microscope platform in virology. The microscope was configured to combine two nonlinear imaging modalities: coherent anti-Stokes Raman scattering and two-photon excitation. Mouse fibroblast cells were infected with a genetically modified cytomegalovirus. The modification causes the host cell to express the green fluorescent protein upon infection. The host cell morphology and lipid droplet distribution were recorded by imaging with coherent anti-Stokes Raman scattering, whilst the infection was monitored by imaging the viral protein expression with two-photon excitation. The cytopathic effects typical of cytomegalovirus infection were observed, including expansion of the nucleus, rounding of the cell shape, and the appearance of intracellular viral inclusions. In some cases these effects were accompanied by dense accumulations of lipid droplets at the nuclear periphery. Imaging was performed both with fixed cells and living. It was demonstrated that the lipid droplets in a single live cell could be imaged over a period of 7 hours without causing noticeable laser-induced damage. The system is shown to be a flexible and powerful tool for the investigation of virus replication and its effects on the host cell.

This thesis describes the development of three-dimensional power Doppler angiography (3D-PDA) and finally magnetic resonance imaging (MRI) perfusion techniques for the assessment of the human placental blood flow. Assessment of changes in placental blood flow may inform the clinical management of pregnancies complicated by placental dysfunction and allow modification of care with the ultimate aim of improving fetal outcome and maternal health. Ideally this should involve a non-invasive technique. I hypothesised that 3D-PDA would prove to be a reliable tool to quantify placental blood flow and demonstrate reduction in conditions associated with aberrant vascularity such as pre- eclampsia, fetal growth restriction and diabetes. I began by determining the validity of 3D-PDA and whether the 3D vascular indices would change in a predictable manner, by examining their relationship to blood flow in both the myometrium in labour and placental tissue in a phantom model. This work demonstrated that there was a relationship between the 3D vascular indices and flow rates, erythrocyte concentration and depth. The relationship was, however, complex. I then assessed within- and between-observer reliability for both data measurement and acquisition in the placenta at various gestational ages using different measurement techniques depending upon whether the entire placenta could be acquired or not. These experiments revealed variable degrees of reliability and demonstrated that the 3D-PDA whole placental technique before 21 completed weeks' gestation was most reliable. Preliminary experiments testing the reliability of an MRI perfusion technique as a tool to assess placental vascularity in the third trimester are also described in the penultimate chapter. The most reliable 3D-PDA techniques where then used to examine placental vascularity between clinical groups. Between 12 and 21 weeks whole placental FI.fmbv was Significantly higher in the diabetic compared to the normal group [54.48 (SE 0.68); 50.60 (SE 0.54) p=O.OOl] and there was a significant difference across gestation (p=0.003). Between 12 and 32 weeks the stereology within a volume technique demonstrated significant differences in FrVolBV between normal and diabetic subjects (p=0.036) and across gestation (p