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Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal

Cancer is the second leading cause of death in the United States and novel methods of treating advanced malignancies are of high importance. Of these deaths, prostate cancer and breast cancer are the second most fatal carcinomas in men and women respectively, while pancreatic cancer is the fourth most fatal in both men and women. Developing new drugs for the treatment of cancer is both a slow and expensive process. It is estimated that it takes an average of 15 years and an expense of $800 million to bring a single new drug to the market. However, it is also estimated that nearly 40% of that cost could be avoided by finding alternative uses for drugs that have already been approved by the Food and Drug Administration (FDA). The research presented in this document describes the testing, identification, and mechanistic evaluation of novel methods for treating many human carcinomas using drugs previously approved by the FDA. A tissue culture plate-based screening of FDA approved drugs will identify compounds that can be used in combination with the protein TRAIL to induce apoptosis selectively in cancer cells. Identified leads will next be optimized using high-throughput microfluidic devices to determine the most effective treatment conditions. Finally, a rigorous mechanistic analysis will be conducted to understand how the FDA-approved drug mitoxantrone, sensitizes cancer cells to TRAIL-mediated apoptosis.
ContributorsTaylor, David (Author) / Rege, Kaushal (Thesis advisor) / Jayaraman, Arul (Committee member) / Nielsen, David (Committee member) / Kodibagkar, Vikram (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2013
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Compressed sensing magnetic resonance spectroscopic imaging (MRSI) is a noninvasive and in vivo potential diagnostic technique for cancer imaging. This technique undersamples the distribution of specific cancer biomarkers within an MR image as well as changes in the temporal dimension and subsequently reconstructs the missing data. This technique has been

Compressed sensing magnetic resonance spectroscopic imaging (MRSI) is a noninvasive and in vivo potential diagnostic technique for cancer imaging. This technique undersamples the distribution of specific cancer biomarkers within an MR image as well as changes in the temporal dimension and subsequently reconstructs the missing data. This technique has been shown to retain a high level of fidelity even with an acceleration factor of 5. Currently there exist several different scanner types that each have their separate analytical methods in MATLAB. A graphical user interface (GUI) was created to facilitate a single computing platform for these different scanner types in order to improve the ease and efficiency with which researchers and clinicians interact with this technique. A GUI was successfully created for both prospective and retrospective MRSI data analysis. This GUI retained the original high fidelity of the reconstruction technique and gave the user the ability to load data, load reference images, display intensity maps, display spectra mosaics, generate a mask, display the mask, display kspace and save the corresponding spectra, reconstruction, and mask files. Parallelization of the reconstruction algorithm was explored but implementation was ultimately unsuccessful. Future work could consist of integrating this parallelization method, adding intensity overlay functionality and improving aesthetics.
ContributorsLammers, Luke Michael (Author) / Kodibagkar, Vikram (Thesis director) / Hu, Harry (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Glioblastoma brain tumors are among the most lethal human cancers. Treatment efforts typically involve both surgical tumor removal, as well as ongoing therapy. In this work, we propose the use of deuterium magnetic resonance imaging (MRI) to delineate tumor boundaries based on spatial distributions of deuterated leucine, as well as

Glioblastoma brain tumors are among the most lethal human cancers. Treatment efforts typically involve both surgical tumor removal, as well as ongoing therapy. In this work, we propose the use of deuterium magnetic resonance imaging (MRI) to delineate tumor boundaries based on spatial distributions of deuterated leucine, as well as resolve the metabolism of leucine within the tumor. Accurate boundary identification contributes to effectiveness of tumor removal efforts, while amino acid metabolism information may help characterize tumor malignancy and guide ongoing treatment. So, we first examine the fundamental mechanisms of deuterium MRI. We then discuss the use of spin-echo and gradient recall echo sequences for mapping spatial distributions of deuterated leucine, and the use of single-voxel spectroscopy for imaging metabolites within a tumor.
ContributorsCostelle, Anna (Author) / Beeman, Scott (Thesis director) / Kodibagkar, Vikram (Committee member) / Barrett, The Honors College (Contributor) / Department of Physics (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2022-05
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Description
Among electrical properties of living tissues, the differentiation of tissues or organs provided by electrical conductivity is superior. The pathological condition of living tissues is inferred from the spatial distribution of conductivity. Magnetic Resonance Electrical Impedance Tomography (MREIT) is a relatively new non-invasive conductivity imaging technique. The majority of

Among electrical properties of living tissues, the differentiation of tissues or organs provided by electrical conductivity is superior. The pathological condition of living tissues is inferred from the spatial distribution of conductivity. Magnetic Resonance Electrical Impedance Tomography (MREIT) is a relatively new non-invasive conductivity imaging technique. The majority of conductivity reconstruction algorithms are suitable for isotropic conductivity distributions. However, tissues such as cardiac muscle and white matter in the brain are highly anisotropic. Until recently, the conductivity distributions of anisotropic samples were solved using isotropic conductivity reconstruction algorithms. First and second spatial derivatives of conductivity (∇σ and ∇2σ ) are integrated to obtain the conductivity distribution. Existing algorithms estimate a scalar conductivity instead of a tensor in anisotropic samples.

Accurate determination of the spatial distribution of a conductivity tensor in an anisotropic sample necessitates the development of anisotropic conductivity tensor image reconstruction techniques. Therefore, experimental studies investigating the effect of ∇2σ on degree of anisotropy is necessary. The purpose of the thesis is to compare the influence of ∇2σ on the degree of anisotropy under two different orthogonal current injection pairs.

The anisotropic property of tissues such as white matter is investigated by constructing stable TX-151 gel layer phantoms with varying degrees of anisotropy. MREIT and Diffusion Magnetic Resonance Imaging (DWI) experiments were conducted to probe the conductivity and diffusion properties of phantoms. MREIT involved current injection synchronized to a spin-echo pulse sequence. Similarities and differences in the divergence of the vector field of ∇σ (∇2σ) among anisotropic samples subjected to two different current injection pairs were studied. DWI of anisotropic phantoms involved the application of diffusion-weighted magnetic field gradients with a spin-echo pulse sequence. Eigenvalues and eigenvectors of diffusion tensors were compared to characterize diffusion properties of anisotropic phantoms.

The orientation of current injection electrode pair and degree of anisotropy influence the spatial distribution of ∇2σ. Anisotropy in conductivity is preserved in ∇2σ subjected to non-symmetric electric fields. Non-symmetry in electric field is observed in current injections parallel and perpendicular to the orientation of gel layers. The principal eigenvalue and eigenvector in the phantom with maximum anisotropy display diffusion anisotropy.
ContributorsAshok Kumar, Neeta (Author) / Sadleir, Rosalind J (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2015