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Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique

Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
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The objective of the research presented here was to validate the use of kinetic models for the analysis of the dynamic behavior of a contrast agent in tumor tissue and evaluate the utility of such models in determining kinetic properties - in particular perfusion and molecular binding uptake associated with

The objective of the research presented here was to validate the use of kinetic models for the analysis of the dynamic behavior of a contrast agent in tumor tissue and evaluate the utility of such models in determining kinetic properties - in particular perfusion and molecular binding uptake associated with tissue hypoxia - of the imaged tissue, from concentration data acquired with dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) procedure. Data from two separate DCE-MRI experiments, performed in the past, using a standard contrast agent and a hypoxia-binding agent respectively, were analyzed. The results of the analysis demonstrated that the models used may provide novel characterization of the tumor tissue properties. Future research will work to further characterize the physical significance of the estimated parameters, particularly to provide quantitative oxygenation data for the imaged tissue.
ContributorsMartin, Jonathan Michael (Author) / Kodibagkar, Vikram (Thesis director) / Rege, Kaushal (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2013-12
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The International Dyslexia Association defines dyslexia as a learning disorder that is characterized by poor spelling, decoding, and word recognition abilities. There is still no known cause of dyslexia, although it is a very common disability that affects 1 in 10 people. Previous fMRI and MRI research in dyslexia has

The International Dyslexia Association defines dyslexia as a learning disorder that is characterized by poor spelling, decoding, and word recognition abilities. There is still no known cause of dyslexia, although it is a very common disability that affects 1 in 10 people. Previous fMRI and MRI research in dyslexia has explored the neural correlations of hemispheric lateralization and phonemic awareness in dyslexia. The present study investigated the underlying neurobiology of five adults with dyslexia compared to age- and sex-matched control subjects using structural and functional magnetic resonance imaging. All subjects completed a large battery of behavioral tasks as part of a larger study and underwent functional and structural MRI acquisition. This data was collected and preprocessed at the University of Washington. Analyses focused on examining the neural correlates of hemispheric lateralization, letter reversal mistakes, reduced processing speed, and phonemic awareness. There were no significant findings of hemispheric differences between subjects with dyslexia and controls. The subject making the largest amount of letter reversal errors had deactivation in their cerebellum during the fMRI language task. Cerebellar white matter volume and surface area of the premotor cortex was the largest in the individual with the slowest reaction time to tapping. Phonemic decoding efficiency had a high correlation with neural activation in the primary motor cortex during the fMRI motor task (r=0.6). Findings from the present study suggest that brain regions utilized during motor control, such as the cerebellum, premotor cortex, and primary motor cortex, may have a larger role in dyslexia then previously considered. Future studies are needed to further distinguish the role of the cerebellum and other motor regions in relation to motor control and language processing deficits related to dyslexia.
ContributorsHoulihan, Chloe Carissa Prince (Author) / Rogalsky, Corianne (Thesis director) / Peter, Beate (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and

Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Repetitive practice of functional movement patterns during motor rehabilitation are known to drive learning (or relearning) of novel motor skills, but the learning process is highly variable between individuals such that responsiveness to task-specific training is often patient-specific. A number of neuroimaging and neurophysiological methods have been proposed to better

Repetitive practice of functional movement patterns during motor rehabilitation are known to drive learning (or relearning) of novel motor skills, but the learning process is highly variable between individuals such that responsiveness to task-specific training is often patient-specific. A number of neuroimaging and neurophysiological methods have been proposed to better predict a patient’s responsiveness to a given type or dose of motor therapy. However, these methods are often time- and resource-intensive, and yield results that are not readily interpretable by clinicians. In contrast, standardized visuospatial tests may offer a more feasible solution. The work presented in this dissertation demonstrate that a clinical paper-and-pencil test of visuospatial function may improve predictive models of motor skill learning in older adults and individuals with stroke pathology. To further our understanding of the neuroanatomical correlates underlying this behavioral relationship, I collected diffusion-weighted magnetic resonance images from 19 nondemented older adults to determine if diffusion characteristics of white matter tracts explain shared variance in delayed visuospatial memory test scores and motor skill learning. Consistent with previous work, results indicated that the structural integrity of regions with the bilateral anterior thalamic radiations, corticospinal tracts, and superior longitudinal fasciculi are related to delayed visuospatial memory performance and one-week skill retention. Overall, results of this dissertation suggest that incorporating a clinical paper-and-pencil test of delayed visuospatial memory may prognose motor rehabilitation outcomes and support that personalized variables should be considered in standards of care. Moreover, regions within specific white matter tracts may underlie this behavioral relationship and future work should investigate these regions as potential targets for therapeutic intervention.
ContributorsLingo VanGilder, Jennapher (Author) / Schaefer, Sydney Y (Thesis advisor) / Santello, Marco (Committee member) / Buneo, Christopher (Committee member) / Rogalsky, Corianne (Committee member) / Duff, Kevin (Committee member) / Arizona State University (Publisher)
Created2021
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Description
This dissertation develops a second order accurate approximation to the magnetic resonance (MR) signal model used in the PARSE (Parameter Assessment by Retrieval from Single Encoding) method to recover information about the reciprocal of the spin-spin relaxation time function (R2*) and frequency offset function (w) in addition to the typical

This dissertation develops a second order accurate approximation to the magnetic resonance (MR) signal model used in the PARSE (Parameter Assessment by Retrieval from Single Encoding) method to recover information about the reciprocal of the spin-spin relaxation time function (R2*) and frequency offset function (w) in addition to the typical steady-state transverse magnetization (M) from single-shot magnetic resonance imaging (MRI) scans. Sparse regularization on an approximation to the edge map is used to solve the associated inverse problem. Several studies are carried out for both one- and two-dimensional test problems, including comparisons to the first order approximation method, as well as the first order approximation method with joint sparsity across multiple time windows enforced. The second order accurate model provides increased accuracy while reducing the amount of data required to reconstruct an image when compared to piecewise constant in time models. A key component of the proposed technique is the use of fast transforms for the forward evaluation. It is determined that the second order model is capable of providing accurate single-shot MRI reconstructions, but requires an adequate coverage of k-space to do so. Alternative data sampling schemes are investigated in an attempt to improve reconstruction with single-shot data, as current trajectories do not provide ideal k-space coverage for the proposed method.
ContributorsJesse, Aaron Mitchel (Author) / Platte, Rodrigo (Thesis advisor) / Gelb, Anne (Committee member) / Kostelich, Eric (Committee member) / Mittelmann, Hans (Committee member) / Moustaoui, Mohamed (Committee member) / Arizona State University (Publisher)
Created2019
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Description
Cognitive deficits often accompany language impairments post-stroke. Past research has focused on working memory in aphasia, but attention is largely underexplored. Therefore, this dissertation will first quantify attention deficits post-stroke before investigating whether preserved cognitive abilities, including attention, can improve auditory sentence comprehension post-stroke. In Experiment 1a, three components of

Cognitive deficits often accompany language impairments post-stroke. Past research has focused on working memory in aphasia, but attention is largely underexplored. Therefore, this dissertation will first quantify attention deficits post-stroke before investigating whether preserved cognitive abilities, including attention, can improve auditory sentence comprehension post-stroke. In Experiment 1a, three components of attention (alerting, orienting, executive control) were measured in persons with aphasia and matched-controls using visual and auditory versions of the well-studied Attention Network Test. Experiment 1b then explored the neural resources supporting each component of attention in the visual and auditory modalities in chronic stroke participants. The results from Experiment 1a indicate that alerting, orienting, and executive control are uniquely affected by presentation modality. The lesion-symptom mapping results from Experiment 1b associated the left angular gyrus with visual executive control, the left supramarginal gyrus with auditory alerting, and Broca’s area (pars opercularis) with auditory orienting attention post-stroke. Overall, these findings indicate that perceptual modality may impact the lateralization of some aspects of attention, thus auditory attention may be more susceptible to impairment after a left hemisphere stroke.

Prosody, rhythm and pitch changes associated with spoken language may improve spoken language comprehension in persons with aphasia by recruiting intact cognitive abilities (e.g., attention and working memory) and their associated non-lesioned brain regions post-stroke. Therefore, Experiment 2 explored the relationship between cognition, two unique prosody manipulations, lesion location, and auditory sentence comprehension in persons with chronic stroke and matched-controls. The combined results from Experiment 2a and 2b indicate that stroke participants with better auditory orienting attention and a specific left fronto-parietal network intact had greater comprehension of sentences spoken with sentence prosody. For list prosody, participants with deficits in auditory executive control and/or short-term memory and the left angular gyrus and globus pallidus relatively intact, demonstrated better comprehension of sentences spoken with list prosody. Overall, the results from Experiment 2 indicate that following a left hemisphere stroke, individuals need good auditory attention and an intact left fronto-parietal network to benefit from typical sentence prosody, yet when cognitive deficits are present and this fronto-parietal network is damaged, list prosody may be more beneficial.
ContributorsLaCroix, Arianna (Author) / Rogalsky, Corianne (Thesis advisor) / Azuma, Tamiko (Committee member) / Braden, B. Blair (Committee member) / Liss, Julie (Committee member) / Arizona State University (Publisher)
Created2019