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Description
The apolipoprotein E (APOE) e4 genotype is the most prevalent known genetic risk factor for Alzheimer's disease (AD). In this paper, we examined the longitudinal effect of APOE e4 on hippocampal morphometry in Alzheimer's Disease Neuroimaging Initiative (ADNI). Generally, atrophy of hippocampus has more chance occurs in AD patients who carrying the APOE e4 allele than those who are APOE e4 noncarriers. Also, brain structure and function depend on APOE genotype not just for Alzheimer's disease patients but also in health elderly individuals, so APOE genotyping is considered critical in clinical trials of Alzheimer's disease. We used a large sample of elderly participants, with the help of a new automated surface registration system based on surface conformal parameterization with holomorphic 1-forms and surface fluid registration. In this system, we automatically segmented and constructed hippocampal surfaces from MR images at many different time points, such as 6 months, 1- and 2-year follow up. Between the two different hippocampal surfaces, we did the high-order correspondences, using a novel inverse consistent surface fluid registration method. At each time point, using Hotelling's T^2 test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the non-demented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes.
ContributorsLi, Bolun (Author) / Wang, Yalin (Thesis advisor) / Maciejewski, Ross (Committee member) / Liang, Jianming (Committee member) / Arizona State University (Publisher)
Created2015
Description
While techniques for reading DNA in some capacity has been possible for decades,
the ability to accurately edit genomes at scale has remained elusive. Novel techniques
have been introduced recently to aid in the writing of DNA sequences. While writing
DNA is more accessible, it still remains expensive, justifying the increased interest in
in silico predictions of cell behavior. In order to accurately predict the behavior of
cells it is necessary to extensively model the cell environment, including gene-to-gene
interactions as completely as possible.
Significant algorithmic advances have been made for identifying these interactions,
but despite these improvements current techniques fail to infer some edges, and
fail to capture some complexities in the network. Much of this limitation is due to
heavily underdetermined problems, whereby tens of thousands of variables are to be
inferred using datasets with the power to resolve only a small fraction of the variables.
Additionally, failure to correctly resolve gene isoforms using short reads contributes
significantly to noise in gene quantification measures.
This dissertation introduces novel mathematical models, machine learning techniques,
and biological techniques to solve the problems described above. Mathematical
models are proposed for simulation of gene network motifs, and raw read simulation.
Machine learning techniques are shown for DNA sequence matching, and DNA
sequence correction.
Results provide novel insights into the low level functionality of gene networks. Also
shown is the ability to use normalization techniques to aggregate data for gene network
inference leading to larger data sets while minimizing increases in inter-experimental
noise. Results also demonstrate that high error rates experienced by third generation
sequencing are significantly different than previous error profiles, and that these errors can be modeled, simulated, and rectified. Finally, techniques are provided for amending this DNA error that preserve the benefits of third generation sequencing.
the ability to accurately edit genomes at scale has remained elusive. Novel techniques
have been introduced recently to aid in the writing of DNA sequences. While writing
DNA is more accessible, it still remains expensive, justifying the increased interest in
in silico predictions of cell behavior. In order to accurately predict the behavior of
cells it is necessary to extensively model the cell environment, including gene-to-gene
interactions as completely as possible.
Significant algorithmic advances have been made for identifying these interactions,
but despite these improvements current techniques fail to infer some edges, and
fail to capture some complexities in the network. Much of this limitation is due to
heavily underdetermined problems, whereby tens of thousands of variables are to be
inferred using datasets with the power to resolve only a small fraction of the variables.
Additionally, failure to correctly resolve gene isoforms using short reads contributes
significantly to noise in gene quantification measures.
This dissertation introduces novel mathematical models, machine learning techniques,
and biological techniques to solve the problems described above. Mathematical
models are proposed for simulation of gene network motifs, and raw read simulation.
Machine learning techniques are shown for DNA sequence matching, and DNA
sequence correction.
Results provide novel insights into the low level functionality of gene networks. Also
shown is the ability to use normalization techniques to aggregate data for gene network
inference leading to larger data sets while minimizing increases in inter-experimental
noise. Results also demonstrate that high error rates experienced by third generation
sequencing are significantly different than previous error profiles, and that these errors can be modeled, simulated, and rectified. Finally, techniques are provided for amending this DNA error that preserve the benefits of third generation sequencing.
ContributorsFaucon, Philippe Christophe (Author) / Liu, Huan (Thesis advisor) / Wang, Xiao (Committee member) / Crook, Sharon M (Committee member) / Wang, Yalin (Committee member) / Sarjoughian, Hessam S. (Committee member) / Arizona State University (Publisher)
Created2017
Description
Neural tissue is a delicate system comprised of neurons and their synapses, glial cells for support, and vasculature for oxygen and nutrient delivery. This complexity ultimately gives rise to the human brain, a system researchers have become increasingly interested in replicating for artificial intelligence purposes. Some have even gone so far as to use neuronal cultures as computing hardware, but utilizing an environment closer to a living brain means having to grapple with the same issues faced by clinicians and researchers trying to treat brain disorders. Most outstanding among these are the problems that arise with invasive interfaces. Optical techniques that use fluorescent dyes and proteins have emerged as a solution for noninvasive imaging with single-cell resolution in vitro and in vivo, but feeding in information in the form of neuromodulation still requires implanted electrodes. The implantation process of these electrodes damages nearby neurons and their connections, causes hemorrhaging, and leads to scarring and gliosis that diminish efficacy. Here, a new approach for noninvasive neuromodulation with high spatial precision is described. It makes use of a combination of ultrasound, high frequency acoustic energy that can be focused to submillimeter regions at significant depths, and electric fields, an effective tool for neuromodulation that lacks spatial precision when used in a noninvasive manner. The hypothesis is that, when combined in a specific manner, these will lead to nonlinear effects at neuronal membranes that cause cells only in the region of overlap to be stimulated. Computational modeling confirmed this combination to be uniquely stimulating, contingent on certain physical effects of ultrasound on cell membranes. Subsequent in vitro experiments led to inconclusive results, however, leaving the door open for future experimentation with modified configurations and approaches. The specific combination explored here is also not the only untested technique that may achieve a similar goal.
ContributorsNester, Elliot (Author) / Wang, Yalin (Thesis advisor) / Muthuswamy, Jitendran (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2022
Description
Functional magnetic resonance imaging (fMRI) has been widely used to measure the retinotopic organization of early visual cortex in the human brain. Previous studies have identified multiple visual field maps (VFMs) based on statistical analysis of fMRI signals, but the resulting geometry has not been fully characterized with mathematical models. This thesis explores using concepts from computational conformal geometry to create a custom software framework for examining and generating quantitative mathematical models for characterizing the geometry of early visual areas in the human brain. The software framework includes a graphical user interface built on top of a selected core conformal flattening algorithm and various software tools compiled specifically for processing and examining retinotopic data. Three conformal flattening algorithms were implemented and evaluated for speed and how well they preserve the conformal metric. All three algorithms performed well in preserving the conformal metric but the speed and stability of the algorithms varied. The software framework performed correctly on actual retinotopic data collected using the standard travelling-wave experiment. Preliminary analysis of the Beltrami coefficient for the early data set shows that selected regions of V1 that contain reasonably smooth eccentricity and polar angle gradients do show significant local conformality, warranting further investigation of this approach for analysis of early and higher visual cortex.
ContributorsTa, Duyan (Author) / Wang, Yalin (Thesis advisor) / Maciejewski, Ross (Committee member) / Wonka, Peter (Committee member) / Arizona State University (Publisher)
Created2013
Description
In brain imaging study, 3D surface-based algorithms may provide more advantages over volume-based methods, due to their sub-voxel accuracy to represent subtle subregional changes and solid mathematical foundations on which global shape analyses can be achieved on complicated topological structures, such as the convoluted cortical surfaces. On the other hand, given the enormous amount of data being generated daily, it is still challenging to develop effective and efficient surface-based methods to analyze brain shape morphometry. There are two major problems in surface-based shape analysis research: correspondence and similarity. This dissertation covers both topics by proposing novel surface registration and indexing algorithms based on conformal geometry for brain morphometry analysis.
First, I propose a surface fluid registration system, which extends the traditional image fluid registration to surfaces. With surface conformal parameterization, the complexity of the proposed registration formula has been greatly reduced, compared to prior methods. Inverse consistency is also incorporated to drive a symmetric correspondence between surfaces. After registration, the multivariate tensor-based morphometry (mTBM) is computed to measure local shape deformations. The algorithm was applied to study hippocampal atrophy associated with Alzheimer's disease (AD).
Next, I propose a ventricular surface registration algorithm based on hyperbolic Ricci flow, which computes a global conformal parameterization for each ventricular surface without introducing any singularity. Furthermore, in the parameter space, unique hyperbolic geodesic curves are introduced to guide consistent correspondences across subjects, a technique called geodesic curve lifting. Tensor-based morphometry (TBM) statistic is computed from the registration to measure shape changes. This algorithm was applied to study ventricular enlargement in mild cognitive impatient (MCI) converters.
Finally, a new shape index, the hyperbolic Wasserstein distance, is introduced. This algorithm computes the Wasserstein distance between general topological surfaces as a shape similarity measure of different surfaces. It is based on hyperbolic Ricci flow, hyperbolic harmonic map, and optimal mass transportation map, which is extended to hyperbolic space. This method fills a gap in the Wasserstein distance study, where prior work only dealt with images or genus-0 closed surfaces. The algorithm was applied in an AD vs. control cortical shape classification study and achieved promising accuracy rate.
First, I propose a surface fluid registration system, which extends the traditional image fluid registration to surfaces. With surface conformal parameterization, the complexity of the proposed registration formula has been greatly reduced, compared to prior methods. Inverse consistency is also incorporated to drive a symmetric correspondence between surfaces. After registration, the multivariate tensor-based morphometry (mTBM) is computed to measure local shape deformations. The algorithm was applied to study hippocampal atrophy associated with Alzheimer's disease (AD).
Next, I propose a ventricular surface registration algorithm based on hyperbolic Ricci flow, which computes a global conformal parameterization for each ventricular surface without introducing any singularity. Furthermore, in the parameter space, unique hyperbolic geodesic curves are introduced to guide consistent correspondences across subjects, a technique called geodesic curve lifting. Tensor-based morphometry (TBM) statistic is computed from the registration to measure shape changes. This algorithm was applied to study ventricular enlargement in mild cognitive impatient (MCI) converters.
Finally, a new shape index, the hyperbolic Wasserstein distance, is introduced. This algorithm computes the Wasserstein distance between general topological surfaces as a shape similarity measure of different surfaces. It is based on hyperbolic Ricci flow, hyperbolic harmonic map, and optimal mass transportation map, which is extended to hyperbolic space. This method fills a gap in the Wasserstein distance study, where prior work only dealt with images or genus-0 closed surfaces. The algorithm was applied in an AD vs. control cortical shape classification study and achieved promising accuracy rate.
ContributorsShi, Jie, Ph.D (Author) / Wang, Yalin (Thesis advisor) / Caselli, Richard (Committee member) / Li, Baoxin (Committee member) / Xue, Guoliang (Committee member) / Arizona State University (Publisher)
Created2016