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- Creators: Harrington Bioengineering Program
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
The global population over the age of 60 is estimated to rise to 23% by 2050 only increase the prevalence of functional neurological disorders and stroke. Increase in cases of functional neurological disorders and strokes will place a greater burden on the healthcare industry, specifically physical therapy. Physical therapy is vital for a patient’s recovery of motor function which is time demanding and taxing on the physical therapist. Wearable robotics have been proven to improve functional outcomes in gait rehabilitation by providing controlled high dosage and high-intensity training. Accurate control strategies for assistive robotic exoskeletons are vital for repetitive high precisions assistance for cerebral plasticity to occur.
This thesis presents a preliminary determination and design of a control algorithm for an assistive ankle device developed by the ASU RISE Laboratory. The assistive ankle device functions by compressing a spring upon heel strike during gait, remaining compressed during mid-stance and then releasing upon initiation of heel-off. The relationship between surface electromyography and ground reactions forces were used for identification of user-initiated heel-off. The muscle activation of the tibialis anterior combined with the ground reaction forces of the heel pressure sensor generated potential features that will be utilized in the revised control algorithm for the assistive ankle device. Work on this project must proceed in order to test and validate the revised control algorithm to determine its accuracy and precision.
This thesis presents a preliminary determination and design of a control algorithm for an assistive ankle device developed by the ASU RISE Laboratory. The assistive ankle device functions by compressing a spring upon heel strike during gait, remaining compressed during mid-stance and then releasing upon initiation of heel-off. The relationship between surface electromyography and ground reactions forces were used for identification of user-initiated heel-off. The muscle activation of the tibialis anterior combined with the ground reaction forces of the heel pressure sensor generated potential features that will be utilized in the revised control algorithm for the assistive ankle device. Work on this project must proceed in order to test and validate the revised control algorithm to determine its accuracy and precision.
ContributorsGaytan-Jenkins, Daniel Rinaldo (Author) / Zhang, Wenlong (Thesis director) / Tyler, Jamie (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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
With dwindling water resources due to drought and other pressures, water utilities are seeking to tap into alternative water sources as a means to improve water sustainability. Reclaimed water consists of treated wastewater and is widely used for non-potable purposes, such as irrigation, both agricultural and recreational. However, the reclaimed water distribution system can be subject to substantial regrowth of microorganisms, including opportunistic pathogens, even following rigorous disinfection. Factors that can influence regrowth include temperature, organic carbon levels, disinfectant type, and the time transported (i.e., water age) in the system. One opportunistic pathogen (OP) that is critical to understanding microbial activity in both reclaimed and drinking water distribution systems is Acanthamoeba. In order to better understand the potential for this amoeba to proliferate in reclaimed water systems and influence other OPs, a simulated reclaimed water distribution system was studied. The objective of this study was to compare the prevalence of Acanthamoeba and one of its endosymbionts, Legionella, across varying assimilable organic carbon (AOC) levels, temperatures, disinfectants, and water ages in a simulated reclaimed water distribution system. The results of the study showed that cooler temperatures, larger water age, and chlorine conditions yielded the lowest detection of Acanthamoeba gene copies per mL or cm2 for bulk water and biofilm samples, respectively.
ContributorsDonaldson, Kandace (Author) / Ankeny, Casey (Thesis director) / Edwards, Marc (Committee member) / Pruden, Amy (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The effect of conflicting sensorimotor memories on optimal force strategies was explored. Subjects operated a virtual object controlled by a physical handle to complete a simple straight-line task. Perturbations applied to the handle induced a period of increased error in subject accuracy. After two blocks of 33 trials, perturbations switched direction, inducing increased error from the previous trials. Subjects returned after a 24-hour period to complete a similar protocol, but beginning with the second context and ending with the first. Interference from the first context on each day caused an increase in initial error for the second (P < 0.05). Following the rest period, subjects showed retention of the sensorimotor memory from the previous day through significantly decreased initial error (P = 3x10-6). However, subjects showed an increase in forces for each new context resulting from a sub-optimal motor strategy. Higher levels of total effort (P < 0.05) and a lack of separation between force values for opposing and non-opposing digits (P > 0.05) indicated a strategy that used more energy to complete the task, even when rates of learning appeared identical or improved. Two possible mechanisms for this lack of energy conservation have been proposed.
ContributorsSmith, Michael David (Author) / Santello, Marco (Thesis director) / Kleim, Jeffrey (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Medial compartment knee osteoarthritis (OA) is a disease whose severity has been associated with the peak adduction moment during walking (pKAM). Unfortunately, measuring patients' pKAM to track their therapy progress involves the use of a gait laboratory which is expensive and time intensive. This study aimed to develop and assess a regression method to predict the pKAM using only plantar pressure measurements. This approach could greatly reduce the burden of evaluating pKAM.
ContributorsThomas, Kevin Andrew (Author) / Hinrichs, Richard (Thesis director) / Harper, Erin (Committee member) / Favre, Julien (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
Human walking is a complex and rhythmical activity that comprises of the brain, nerves and muscles. Neuromuscular disorder (NMD) is a broad term that refers to conditions that affect the proper use of muscles and nervous system, thus also impairing the walking or gait cycle of an individual. The improper gait cycle might be attributed to the lack of force produced at the toe-off stage. This project addresses if it is possible to create an OpenSim model to find the ideal time and force magnitude needed of an assistive force ankle device to improve gait patterns in individuals with NMD.
ContributorsRivera, Jose Luis (Author) / Zhang, Wenlong (Thesis director) / Lockhart, Thurmon (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05