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- All Subjects: MRI
- Creators: Harrington Bioengineering Program
- Creators: Braden, B. Blair
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 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.
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
Description
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
Description
Smart contrast agents allow for noninvasive study of specific events or tissue conditions inside of a patient's body using Magnetic Resonance Imaging (MRI). This research aims to develop and characterize novel smart contrast agents for MRI that respond to temperature changes in tissue microenvironments. Transmission Electron Microscopy, Nuclear Magnetic Resonance, and cell culture growth assays were used to characterize the physical, magnetic, and cytotoxic properties of candidate nanoprobes. The nanoprobes displayed thermosensitve MR properties with decreasing relaxivity with temperature. Future work will be focused on generating and characterizing photo-active analogues of the nanoprobes that could be used for both treatment of tissues and assessment of therapy.
ContributorsHussain, Khateeb Hyder (Author) / Kodibagkar, Vikram (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2014-05
Description
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
Description
In epilepsy, malformations that cause seizures often require surgery. The purpose of this research is to join forces with the Multi-Center Epilepsy Lesion Detection (MELD) project at University College London (UCL) in order to improve the process of detecting lesions in patients with drug-resistant epilepsy. This, in turn, will improve surgical outcomes via more structured surgical planning. It is a global effort, with more than 20 sites across 5 continents. The targeted populations for this study include patients whose epilepsy stems from Focal Cortical Dysplasia. Focal Cortical Dysplasia is an abnormality of cortical development, and causes most of the drug-resistant epilepsy. Currently, the creators of MELD have developed a set of protocols which wrap various
commands designed to streamline post-processing of MRI images. Using this partnership, the Applied Neuroscience and Technology Lab at PCH has been able to complete production of a post-processing pipeline which integrates locally sourced smoothing techniques to help identify lesions in patients with evidence of Focal Cortical Dysplasia. The end result is a system in which a patient with epilepsy may experience more successful post-surgical results due to the
combination of a lesion detection mechanism and the radiologist using their trained eye in the presurgical stages. As one of the main points of this work is the global aspect of it, Barrett thesis funding was dedicated for a trip to London in order to network with other MELD project collaborators. This was a successful trip for the project as a whole in addition to this particular thesis. The ability to troubleshoot problems with one another in a room full of subject matter
experts allowed for a high level of discussion and learning. Future work includes implementing machine learning approaches which consider all morphometry parameters simultaneously.
commands designed to streamline post-processing of MRI images. Using this partnership, the Applied Neuroscience and Technology Lab at PCH has been able to complete production of a post-processing pipeline which integrates locally sourced smoothing techniques to help identify lesions in patients with evidence of Focal Cortical Dysplasia. The end result is a system in which a patient with epilepsy may experience more successful post-surgical results due to the
combination of a lesion detection mechanism and the radiologist using their trained eye in the presurgical stages. As one of the main points of this work is the global aspect of it, Barrett thesis funding was dedicated for a trip to London in order to network with other MELD project collaborators. This was a successful trip for the project as a whole in addition to this particular thesis. The ability to troubleshoot problems with one another in a room full of subject matter
experts allowed for a high level of discussion and learning. Future work includes implementing machine learning approaches which consider all morphometry parameters simultaneously.
ContributorsHumphreys, Zachary William (Author) / Kodibagkar, Vikram (Thesis director) / Foldes, Stephen (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
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
Description
Background: Gait disturbance, clumsiness, and other mild movement problems are often observed in children with autism spectrum disorder (ASD) (Maurer and Damasio 1982). As the brain ages, these symptoms may persist or worsen in late adulthood in those diagnosed with ASD. This study focused on older adults with ASD to study motor behavior and underlying brain integrity. Using a finger tapping task, motor performance was measured in a cross-sectional study comparing older adults with ASD and age-matched typically developing (TD) controls. We hypothesized that older adults with ASD would show poorer motor performance (slower finger tapping speed). We also hypothesized that underlying brain differences, measured using MRI, in regions associated with motor function including the primary motor cortex, basal ganglia, and cerebellum, as well as the white matter connecting tracts would exist between groups and be associated with the proposed disparity in motor performance.
Method: A finger oscillation (Finger Tapping) test was administered to both ASD (n=21) and TD (n=20) participants aged 40-70 year old participants as a test of fine motor speed. Magnetic resonance (MR) images were collected using a Philips 3 Tesla scanner. 3D T1-weighted and diffusion tensor images (DTI) were obtained to measure gray and white matter volume and white matter integrity, respectively. FreeSurfer, an automated volumetric measurement software, was used to determine group volumetric differences. Mean, radial, and axial diffusivity, fractional anisotropy, and local diffusion homogeneity were measured from DTI images using PANDA software in order to evaluate white matter integrity.
Results: All participants were right-handed and there were no significant differences in demographic variables (ASD/TD, means) including age (51.9/49.1 years), IQ (107/112) and years education (15/16). Total brain volume was not significantly different between groups. No statistically significant group differences were observed in finger tapping speed. ASD participants compared to TDs showed a trend of slower finger tapping (taps/10 seconds) speed on the dominant hand (47.00 (±11.2) vs. (50.5 (±6.6)) and nondominant hand (44.6 (±7.6) vs. (47.2 (±6.6)). However, a large degree of variability was observed in the ASD group, and the Levene’s test for homogeneity of variance approached significance (p=0.053) on the dominant, but not the nondominant, hand. No significant group differences in gray matter regional volume were found for brain regions associated with performing motor tasks. In contrast, group differences were found on several measures of white matter including the corticospinal tract, anterior internal capsule and middle cerebellar peduncle. Brain-behavior correlations showed that dominant finger tapping speed correlated with left hemisphere white matter integrity of the corticospinal tract and right hemisphere cerebellar white matter in the ASD group.
Conclusions: No significant differences were observed between groups in finger tapping speed but the high degree of variability seen in the ASD group. Differences in motor performance appear to be associated with observed brain differences, particularly in the integrity of white matter tracts contributing to motor functioning.
Method: A finger oscillation (Finger Tapping) test was administered to both ASD (n=21) and TD (n=20) participants aged 40-70 year old participants as a test of fine motor speed. Magnetic resonance (MR) images were collected using a Philips 3 Tesla scanner. 3D T1-weighted and diffusion tensor images (DTI) were obtained to measure gray and white matter volume and white matter integrity, respectively. FreeSurfer, an automated volumetric measurement software, was used to determine group volumetric differences. Mean, radial, and axial diffusivity, fractional anisotropy, and local diffusion homogeneity were measured from DTI images using PANDA software in order to evaluate white matter integrity.
Results: All participants were right-handed and there were no significant differences in demographic variables (ASD/TD, means) including age (51.9/49.1 years), IQ (107/112) and years education (15/16). Total brain volume was not significantly different between groups. No statistically significant group differences were observed in finger tapping speed. ASD participants compared to TDs showed a trend of slower finger tapping (taps/10 seconds) speed on the dominant hand (47.00 (±11.2) vs. (50.5 (±6.6)) and nondominant hand (44.6 (±7.6) vs. (47.2 (±6.6)). However, a large degree of variability was observed in the ASD group, and the Levene’s test for homogeneity of variance approached significance (p=0.053) on the dominant, but not the nondominant, hand. No significant group differences in gray matter regional volume were found for brain regions associated with performing motor tasks. In contrast, group differences were found on several measures of white matter including the corticospinal tract, anterior internal capsule and middle cerebellar peduncle. Brain-behavior correlations showed that dominant finger tapping speed correlated with left hemisphere white matter integrity of the corticospinal tract and right hemisphere cerebellar white matter in the ASD group.
Conclusions: No significant differences were observed between groups in finger tapping speed but the high degree of variability seen in the ASD group. Differences in motor performance appear to be associated with observed brain differences, particularly in the integrity of white matter tracts contributing to motor functioning.
ContributorsDeatherage, Brandon R. (Co-author) / Braden, B. Blair (Co-author, Committee member) / Smith, Christopher J. (Co-author) / McBeath, Michael (Co-author, Thesis director) / Thompson, Aimee M. (Co-author) / Wood, Emily G. (Co-author) / McGee, Samuel C. (Co-author) / Sinha, Krishna (Co-author) / Baxter, Leslie (Co-author, Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor) / Department of Information Systems (Contributor)
Created2017-05
Description
Neurological disorders are difficult to treat with current drug delivery methods due to their inefficiency and the lack of knowledge of the mechanisms behind drug delivery across the blood brain barrier (BBB). Nanoparticles (NPs) are a promising drug delivery method due to their biocompatibility and ability to be modified by cell penetrating peptides, such as transactivating transciptor (TAT) peptide, which has been shown to increase efficiency of delivery. There are multiple proposed mechanisms of TAT-mediated delivery that also have size restrictions on the molecules that can undergo each BBB crossing mechanism. The effect of nanoparticle size on TAT-mediated delivery in vivo is an important aspect to research in order to better understand the delivery mechanisms and to create more efficient NPs. NPs called FluoSpheres are used because they come in defined diameters unlike polymeric NPs that have a broad distribution of diameters. Both modified and unmodified 100nm and 200nm NPs were able to bypass the BBB and were seen in the brain, spinal cord, liver, and spleen using confocal microscopy and a biodistribution study. Statistically significant differences in delivery rate of the different sized NPs or between TAT-modified and unmodified NPs were not found. Therefore in future work a larger range of diameter size will be evaluated. Also the unmodified NPs will be conjugated with scrambled peptide to ensure that both unmodified and TAT-modified NPs are prepared in identical fashion to better understand the role of size on TAT targeting. Although all the NPs were able to bypass the BBB, future work will hopefully provide a better representation of how NP size effects the rate of TAT-mediated delivery to the CNS.
ContributorsCeton, Ricki Ronea (Author) / Stabenfeldt, Sarah (Thesis director) / Sirianni, Rachael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Octopus arms employ a complex three dimensional array of musculature, called a
muscular hydrostat, which allows for nearly infinite degrees of freedom of movement without
the structure of a skeletal system. This study employed Magnetic Resonance Imaging with a
Gadoteridol-based contrast agent to image the octopus arm and view the internal tissues. Muscle
layering was mapped and area was measured using AMIRA image processing and the trends in
these layers at the proximal, middle, and distal portions of the arms were analyzed. A total of 39
arms from 6 specimens were scanned to give 112 total imaged sections (38 proximal, 37 middle,
37 distal), from which to ascertain and study the possible differences in musculature. The
images revealed significant increases in the internal longitudinal muscle layer percentages
between the proximal and middle, proximal and distal, and middle and distal sections of the
arms. These structural differences are hypothesized to be used for rapid retraction of the distal
segment when encountering predators or noxious stimuli. In contrast, a significant decrease in
the transverse muscle layer was found when comparing the same sections. These structural
differences are hypothesized to be a result of bending behaviors during retraction. Additionally,
the internal longitudinal layer was separately studied orally, toward the sucker, and aborally,
away from the sucker. The significant differences in oral and aboral internal longitudinal
musculature in proximal, middle, and distal sections is hypothesized to support the pseudo-joint
functionality displayed in octopus fetching behaviors. The results indicate that individual
octopus arm morphology is more unique than previously thought and supports that internal
structural differences exist to support behavioral functionality.
muscular hydrostat, which allows for nearly infinite degrees of freedom of movement without
the structure of a skeletal system. This study employed Magnetic Resonance Imaging with a
Gadoteridol-based contrast agent to image the octopus arm and view the internal tissues. Muscle
layering was mapped and area was measured using AMIRA image processing and the trends in
these layers at the proximal, middle, and distal portions of the arms were analyzed. A total of 39
arms from 6 specimens were scanned to give 112 total imaged sections (38 proximal, 37 middle,
37 distal), from which to ascertain and study the possible differences in musculature. The
images revealed significant increases in the internal longitudinal muscle layer percentages
between the proximal and middle, proximal and distal, and middle and distal sections of the
arms. These structural differences are hypothesized to be used for rapid retraction of the distal
segment when encountering predators or noxious stimuli. In contrast, a significant decrease in
the transverse muscle layer was found when comparing the same sections. These structural
differences are hypothesized to be a result of bending behaviors during retraction. Additionally,
the internal longitudinal layer was separately studied orally, toward the sucker, and aborally,
away from the sucker. The significant differences in oral and aboral internal longitudinal
musculature in proximal, middle, and distal sections is hypothesized to support the pseudo-joint
functionality displayed in octopus fetching behaviors. The results indicate that individual
octopus arm morphology is more unique than previously thought and supports that internal
structural differences exist to support behavioral functionality.
ContributorsCummings, Sheldon Daniel (Author) / Fisher, Rebecca (Thesis director) / Marvi, Hamidreza (Committee member) / Cherry, Brian (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05