Matching Items (68)
Description
Intracranial aneurysms, which form in the blood vessels of the brain, are particularly dangerous because of the importance and fragility of the human brain. When an intracranial aneurysm gets large it poses a significant risk of bursting and causing subarachnoid hemorrhaging (SAH), a possibly fatal condition. One possible treatment involves placing a stent in the vessel to act as a flow diverter. In this study we look at the hemodynamics of two geometries of idealized basilar tip aneurysms, at 2,3, and 4 ml/s pulsatile flow, at three different points in the cardiac cycle. The smaller model had neck and dome diameters of 2.67 mm and 4 mm respectively, while the larger aneurysm had neck and dome diameters of 3 mm and 6 mm respectively. Both diameters and the dome to neck ratio increased in the second model, representing growth over time. Flow was analyzed using stereoscopic particle image velocimetry (PIV) for both geometries in untreated models, as well as after treatment with a high porosity Enterprise stent (Codman and Shurtleff Inc.). Flow in the models was characterized by root mean square velocity in the aneurysm and neck plane, cross neck flow, max aneurysm vorticity, and total aneurysm kinetic energy. It was found that in the smaller aneurysm model (model 1), Enterprise stent treatment reduced all flow parameters substantially. The smallest reduction was in max vorticity, at 42.48%, and the largest in total kinetic energy, at 75.69%. In the larger model (model 2) there was a 52.18% reduction in cross neck flow, but a 167.28% increase in aneurysm vorticity. The other three parameters experienced little change. These results, along with observed velocity vector fields, indicate a noticeable diversion of flow away from the aneurysm in the stent treated model 1. Treatment in model 2 had a small flow diversion effect, but also altered flow in unpredictable ways, in some cases having a detrimental effect on aneurysm hemodynamics. The results of this study indicate that Enterprise stent treatment is only effective in small, relatively undeveloped aneurysm geometries, and waiting until an aneurysm has grown too large can eliminate this treatment option altogether.
ContributorsLindsay, James Bryan (Author) / Frakes, David (Thesis director) / LaBelle, Jeffrey (Committee member) / Nair, Priya (Committee member) / Barrett, The Honors College (Contributor) / School of Humanities, Arts, and Cultural Studies (Contributor)
Created2013-05
Description
Development of a rapid and label-free Electrochemical Impedance Spectroscopy (EIS) biosensor for Cardiovascular Disease (CVD) detection based on Inerluekin-18 (IL-18) sensitivity was proposed to fill the technology gap between rapid and portable CVD point-of-care diagnosis. IL-18 was chosen for this CVD biosensor due to its ability to detect plaque vulnerability of the heart. Custom (hand) made sensors, which utilized a three electrode configuration with a gold disk working electrode, were created to run EIS using both IL-18 and anti-IL-18 molecules in both purified and blood solutions. The EIS results for IL-18 indicated the optimal detection frequency to be 371Hz. Blood interaction on the working electrode increased the dynamic range of impedance values for the biosensor. Future work includes Developing and testing prototypes of the biosensor along with determining if a Nafion based coating on the working electrode will reduce the dynamic range of impedance values caused by blood interference.
ContributorsJha, Amit (Author) / LaBelle, Jeffrey (Thesis director) / Mossman, Kenneth (Committee member) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / Department of Management (Contributor)
Created2013-05
Description
In 1937 Canadian neurosurgeon Wilder Penfield made the first to attempt to map the sensorimotor cortex of the human brain in his paper entitled Somatic Motor and Sensory Representation in the Cerebral Cortex of Man as Studied by Electrical Stimulation. While analogous experimentation had been carried out previously using animal subjects, Penfield sought to understand the delicate and complex neuronal pathways that served as the hidden control mechanisms for human activity. The motor homunculus that followed from his findings has been widely accepted as the standard model for the relative spatial representation of the functionality of the motor cortex, and has been virtually unaltered since its inception. While Penfield took measures to collect cortical data in a manner as accurately as scientifically possible for the time period, his original model is deserving of further analysis using modern techniques. This study uses functional magnetic resonance imaging (fMRI) to quantitatively determine motor function volumes and spatial relationships for four motor tasks: toe, finger, eyebrow, and tongue. Although Penfield's general representation of the superior-to-inferior spatial distribution of the motor cortex was replicated with reasonable accuracy, relative mean task volumes seem to differ from Penfield's original model. The data was first analyzed in each individual patient's native anatomical space for task comparison within a single subject. The volumes of the motor cortex devoted to the eyebrow and toe tasks, which comprise only small portions of the Penfield homunculus, are shown to be relatively large in their fMRI representation compared to finger and tongue. However, these tasks have large deviation values, indicating a lack of consistency in task volume size among patients. Behaviorally, toe movement may include whole foot movement in some individuals, and eyebrows may include face movement, causing distributions that are more widespread. The data was then analyzed in the Montreal Neurological Institute (MNI) space, which is mathematically normalized for task comparison between different subjects. Tongue and finger tasks were the largest in volume, much like Penfield's model. However, they also had substantial deviation, again indicating task volume size inconsistencies. Since the Penfield model is only a qualitative spatial evaluation of motor function along the precentral gyrus, numerical deviation from the model cannot necessarily be quantified. Hence, the results of this study can be interpreted standalone without a current comparison. While future research will serve to further validate these distances and volumes, this quantitative model of the functionality of the motor cortex will be of great utility for future neurological research and during preoperative evaluations of neurosurgical patients.
ContributorsOland, Gabriel Lee (Author) / Frakes, David (Thesis director) / Santello, Marco (Committee member) / Baxter, Leslie (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Description
Electroencephalogram (EEG) used simultaneously with video monitoring can record detailed patient physiology during a seizure to aid diagnosis. However, current patient monitoring systems typically require a patient to stay in view of a fixed camera limiting their freedom of movement. The goal of this project is to design an automatic patient monitoring system with software to track patient movement in order to increase a patient's mobility. This report discusses the impact of an automatic patient monitoring system and the design steps used to create and test a functional prototype.
ContributorsBui, Robert Truong (Author) / Frakes, David (Thesis director) / Helms Tillery, Stephen (Committee member) / Barrett, The Honors College (Contributor) / Electrical Engineering Program (Contributor)
Created2014-05
Description
Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm3 to 62 mm3, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.
ContributorsRutter, Erica (Author) / Stepien, Tracy (Author) / Anderies, Barrett (Author) / Plasencia, Jonathan (Author) / Woolf, Eric C. (Author) / Scheck, Adrienne C. (Author) / Turner, Gregory H. (Author) / Liu, Qingwei (Author) / Frakes, David (Author) / Kodibagkar, Vikram (Author) / Kuang, Yang (Author) / Preul, Mark C. (Author) / Kostelich, Eric (Author) / College of Liberal Arts and Sciences (Contributor)
Created2017-05-31
Description
The ability of cochlear implants (CI) to restore auditory function has advanced significantly in the past decade. Approximately 96,000 people in the United States benefit from these devices, which by the generation and transmission of electrical impulses, enable the brain to perceive sound. But due to the predominantly Western cochlear implant market, current CI characterization primarily focuses on improving the quality of American English. Only recently has research begun to evaluate CI performance using other languages such as Mandarin Chinese, which rely on distinct spectral characteristics not present in English. Mandarin, a tonal language utilizes four, distinct pitch patterns, which when voiced a syllable, conveys different meanings for the same word. This presents a challenge to hearing research as spectral, or frequency based information like pitch is readily acknowledged to be significantly reduced by CI processing algorithms. Thus the present study sought to identify the intelligibility differences for English and Mandarin when processed using current CI strategies. The objective of the study was to pinpoint any notable discrepancies in speech recognition, using voice-coded (vocoded) audio that simulates a CI generated stimuli. This approach allowed 12 normal hearing English speakers, and 9 normal hearing Mandarin listeners to participate in the experiment. The number of frequency channels available and the carrier type of excitation were varied in order to compare their effects on two cases of Mandarin intelligibility: Case 1) word recognition and Case 2) combined word and tone recognition. The results indicated a statistically significant difference between English and Mandarin intelligibility for Condition 1 (8Ch-Sinewave Carrier, p=0.022) given Case 1 and Condition 1 (8Ch-Sinewave Carrier, p=0.001) and Condition 3 (16Ch-Sinewave Carrier, p=0.001) given Case 2. The data suggests that the nature of the carrier type does have an effect on tonal language intelligibility and warrants further research as a design consideration for future cochlear implants.
ContributorsSchiltz, Jessica Hammitt (Author) / Berisha, Visar (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
Background
Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.
Methodology
We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.
Principal Findings
We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.
Conclusions
Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.
Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.
Methodology
We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.
Principal Findings
We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.
Conclusions
Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.
ContributorsNandakumar, Vivek (Author) / Kelbauskas, Laimonas (Author) / Hernandez, Kathryn (Author) / Lintecum, Kelly (Author) / Senechal, Patti (Author) / Bussey, Kimberly (Author) / Davies, Paul (Author) / Johnson, Roger (Author) / Meldrum, Deirdre (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School of Electrical, Computer and Energy Engineering (Contributor) / Biodesign Institute (Contributor) / Center for Biosignatures Discovery Automation (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / Department of Physics (Contributor)
Created2012-01-05
Customized Endovascular Treatment Fixture Construction for Patient-Specific Cerebral Aneurysm Repair
Description
Cerebral aneurysms are pathological bulges in blood vessels of the brain that can rupture and cause brain damage or death. Treating aneurysms by isolating them from circulation can prevent aneurysm rupture. Endovascular techniques for cerebral aneurysm treatment are preferred because they are minimally invasive and have a shorter recovery time, and endovascular coiling is considered the gold standard as a result. The coils used in endovascular treatment come in standard shapes and sizes, mass-manufactured by medical device companies. Clinicians select the coils for treatment based on the aneurysm volume. However, cerebral aneurysms have unique shapes and dimensions, and vary on a patient-specific basis. Therefore, customizing the coils to fit a unique aneurysm morphology by using shape memory alloys could potentially improve endovascular treatment outcomes. In order to shape set a shape memory alloy into a customized coil configuration a fixture based on the aneurysm morphology must first be developed. Digital surface models of aneurysm patient cases were collected from an online repository and isolated from surrounding vasculature. Anchors used to assist in winding coils around these models were then added to create a computational fixture model. These fixtures were 3D printed in stainless steel, and tested on their ability to maintain their shape after being exposed to high temperatures needed in shape setting processes. The study demonstrated that customized fixtures can be created from patient-specific images or models, and manufactured with high levels of accuracy without deformation at high temperatures. The results suggest that 3D printed stainless steel fixtures could be used to develop customized endovascular coils for cerebral aneurysm treatment.
ContributorsHess, Ryan Ambrose (Author) / Kleim, Jeff (Thesis director) / Nair, Priya (Committee member) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Introduction: There are 350 to 400 pediatric heart transplants annually according to the Pediatric Heart Transplant Database (Dipchand et al. 2014). Finding appropriate donors can be challenging especially for the pediatric population. The current standard of care is a donor-to-recipient weight ratio. This ratio is not necessarily a parameter directly indicative of the size of a heart, potentially leading to ill-fitting allografts (Tang et al. 2010). In this paper, a regression model is presented - developed by correlating total cardiac volume to non-invasive imaging parameters and patient characteristics – for use in determining ideal allograft fit with respect to total cardiac volume.
Methods: A virtual, 3D library of clinically-defined normal hearts was compiled from reconstructed CT and MR scans. Non-invasive imaging parameters and patient characteristics were collected and subjected to backward elimination linear regression to define a model relating patient parameters to the total cardiac volume. This regression model was then used to retrospectively accept or reject an ‘ideal’ donor graft from the library for 3 patients that had undergone heart transplantation. Oversized and undersized grafts were also transplanted to qualitatively analyze virtual transplantation specificity.
Results: The backward elimination approach of the data for the 20 patients rejected the factors of BMI, BSA, sex and both end-systolic and end-diastolic left ventricular measurements from echocardiography. Height and weight were included in the linear regression model yielding an adjusted R-squared of 82.5%. Height and weight showed statistical significance with p-values of 0.005 and 0.02 respectively. The final equation for the linear regression model was TCV = -169.320+ 2.874h + 3.578w ± 73 (h=height, w=weight, TCV= total cardiac volume).
Discussion: With the current regression model, height and weight significantly correlate to total cardiac volume. This regression model and virtual normal heart library provide for the possibility of virtual transplant and size-matching for transplantation. The study and regression model is, however, limited due to a small sample size. Additionally, the lack of volumetric resolution from the MR datasets is a potentially limiting factor. Despite these limitations the virtual library has the potential to be a critical tool for clinical care that will continue to grow as normal hearts are added to the virtual library.
Methods: A virtual, 3D library of clinically-defined normal hearts was compiled from reconstructed CT and MR scans. Non-invasive imaging parameters and patient characteristics were collected and subjected to backward elimination linear regression to define a model relating patient parameters to the total cardiac volume. This regression model was then used to retrospectively accept or reject an ‘ideal’ donor graft from the library for 3 patients that had undergone heart transplantation. Oversized and undersized grafts were also transplanted to qualitatively analyze virtual transplantation specificity.
Results: The backward elimination approach of the data for the 20 patients rejected the factors of BMI, BSA, sex and both end-systolic and end-diastolic left ventricular measurements from echocardiography. Height and weight were included in the linear regression model yielding an adjusted R-squared of 82.5%. Height and weight showed statistical significance with p-values of 0.005 and 0.02 respectively. The final equation for the linear regression model was TCV = -169.320+ 2.874h + 3.578w ± 73 (h=height, w=weight, TCV= total cardiac volume).
Discussion: With the current regression model, height and weight significantly correlate to total cardiac volume. This regression model and virtual normal heart library provide for the possibility of virtual transplant and size-matching for transplantation. The study and regression model is, however, limited due to a small sample size. Additionally, the lack of volumetric resolution from the MR datasets is a potentially limiting factor. Despite these limitations the virtual library has the potential to be a critical tool for clinical care that will continue to grow as normal hearts are added to the virtual library.
ContributorsSajadi, Susan (Co-author) / Lindquist, Jacob (Co-author) / Frakes, David (Thesis director) / Ryan, Justin (Committee member) / Harrington Bioengineering Program (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Owing to the surge in development of endovascular devices such as coils and flow diverter stents, doctors are inclined to approach surgical cases non-invasively more often than before. Treating brain aneurysms as a bulging of a weakened area of a blood vessel is no exception. Therefore, promoting techniques that can help surgeons have a better idea of treatment outcomes are of invaluable importance.
In order to investigate the effects of these devices on intra-aneurysmal hemodynamics, the conventional computational fluid dynamics (CFD) approach uses the explicit geometry of the device within an aneurysm and discretizes the fluid domain to solve the Navier-Stokes equations. However, since the devices are made of small struts, the number of mesh elements in the boundary layer region would be considerable. This cumbersome task led to the implementation of the porous medium assumption. In this approach, the explicit geometry of the device is eliminated, and relevant porous medium assumptions are applied. Unfortunately, as it will be shown in this research, some of the porous medium approaches used in the literature are over-simplified. For example, considering the porous domain to be homogeneous is one major drawback which leads to significant errors in capturing the intra-aneurysmal flow features. Specifically, since the devices must comply with the complex geometry of an aneurysm, the homogeneity assumption is not valid.
In this research, a novel heterogeneous porous medium approach is introduced. This results in a substantial reduction in the total number of mesh elements required to discretize the flow domain while not sacrificing the accuracy of the method by over-simplifying the utilized assumptions.
In order to investigate the effects of these devices on intra-aneurysmal hemodynamics, the conventional computational fluid dynamics (CFD) approach uses the explicit geometry of the device within an aneurysm and discretizes the fluid domain to solve the Navier-Stokes equations. However, since the devices are made of small struts, the number of mesh elements in the boundary layer region would be considerable. This cumbersome task led to the implementation of the porous medium assumption. In this approach, the explicit geometry of the device is eliminated, and relevant porous medium assumptions are applied. Unfortunately, as it will be shown in this research, some of the porous medium approaches used in the literature are over-simplified. For example, considering the porous domain to be homogeneous is one major drawback which leads to significant errors in capturing the intra-aneurysmal flow features. Specifically, since the devices must comply with the complex geometry of an aneurysm, the homogeneity assumption is not valid.
In this research, a novel heterogeneous porous medium approach is introduced. This results in a substantial reduction in the total number of mesh elements required to discretize the flow domain while not sacrificing the accuracy of the method by over-simplifying the utilized assumptions.
ContributorsYadollahi Farsani, Hooman (Author) / Herrmann, Marcus (Thesis advisor) / Frakes, David (Thesis advisor) / Chong, Brian (Committee member) / Peet, Yulia (Committee member) / Oswald, Jay (Committee member) / Arizona State University (Publisher)
Created2018