Ai-Driven Segmentation And Volumetric Response Modeling Of Liver Regions To Radiotherapy, Aashish Chandra Gupta

Dissertations and Theses (Open Access)

In liver-directed radiotherapy (RT), liver regions receiving higher doses typically undergo atrophy while contralateral/adjacent lower-dose regions may exhibit compensatory hypertrophy through regeneration of healthy tissue. Optimizing the RT plan to promote regional hypertrophy while minimizing the risk of developing atrophy has the potential to enhance post-RT liver function and long-term survivorship. However, current clinical practice largely relies on global liver dose-volume metrics during RT-planning, which may obscure favorable dose-response correlation and limit actionable guidance for clinicians. Therefore, we hypothesized that post-RT regional liver response is governed by a combination of region-specific dose-volume and patient clinical features, and that these responses …

Membrane Organization Of Rheb And Rhoa: Roles In Function And Allosteric Druggability, Chase M. Hutchins

Dissertations and Theses (Open Access)

Small GTPases of the Ras superfamily are membrane-bound molecular switches that regulate nearly all major cellular processes, and their dysregulation drives cancers, neurological disorders, and metabolic diseases. While anchored to cellular membranes, the catalytic domains of small GTPases undergo orientation dynamics, adopting distinct configurations that can occlude or expose effector-binding surfaces and modulate signaling output. These dynamics have been characterized in the Ras oncoproteins, but whether they extend across the superfamily and influence allosteric druggability has remained unknown.

In this dissertation, I address these questions through Rheb and RhoA, two small GTPases with complementary differences in subfamily lineage, membrane localization, …

Facilitating The Clinical Translation Of Flash Radiotherapy Through Dosimetry Development And Beam Parameter Optimization, Kevin Liu

Dissertations and Theses (Open Access)

Advisory Professor: Emil Schüler, PhD

Radiation therapy (RT) is a crucial component of curative cancer therapy, with a majority of cancer patients in the United States receiving RT as part of treatment. The goal of RT is to maximize the therapeutic index in curing disease while minimizing any associated normal-tissue complications¹. Recently, ultra-high dose-rate (UHDR) RT (mean dose rates ≥40 Gy/s for a total duration of ≤200 ms) has been reported to selectively spare normal tissues and organs while maintaining an isoeffective tumoricidal effect compared to conventional (CONV) dose rate RT in a variety of in vivo preclinical …

Uncertainty In The Physical Basis Of Estimates Of Relative Biological Effectiveness In Carbon Radiotherapy, Shannon Hartzell, Shannon Hartzell Ph.D.

Dissertations and Theses (Open Access)

Carbon ion radiotherapy is a novel modality used for the treatment of tumors that are unresectable, close to critical structures, or resistant to standard radiotherapy. A unique benefit of this therapy is the relative biological effectiveness (RBE) of the beam (i.e., how biologically potent carbon ions are as compared to x-rays), which is significantly elevated. This RBE also varies as a function of many parameters, and there are currently several models implemented in clinical and research-based treatment planning systems with which to predict RBE. These algorithms are computationally expensive and there are currently no means of validating their implementation within …

Advancement Of A 3d Computational Phantom And Its Age Scaling Methodologies For Retrospective Dose Reconstruction Studies, Aashish Gupta

Dissertations and Theses (Open Access)

We have used a 3D age-scalable computational phantom for over two decades for retrospective dose reconstruction studies of childhood cancer survivors (CCS) treated with 2D historic radiotherapy (RT). However, our phantom and its age scaling functions (ASF) must be updated so that it can be used in studies that include survivors treated with contemporary RT. We aimed to implement our phantom and its age scaling functions in DICOM format and determine the feasibility of applying our ASFs to accurately scale the whole-body CT-based anatomies.

In the implementation study, we developed Python scripts that model the phantom and ASFs in a …

Hyperpolarized Carbon-13 Magnetic Resonance Measurements Of Tissue Perfusion And Metabolism, Keith Michel

Dissertations and Theses (Open Access)

Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime.

In …

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations and Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

Commissioning Of Micro-Cube Thermoluminescent Dosimeters For Small Field Dosimetry Quality Assurance In Radiotherapy, Brandon Luckett

Dissertations and Theses (Open Access)

Small field dosimetry presents complications and uncertainties that could be circumvented by using detectors which are smaller than the radiation field. This study evaluates the reproducibility and accuracy of TLD micro-cubes for use in stereotactic radiosurgery (SRS) remote auditing quality assurance (QA) for treatment centers participating in clinical trials. This study tested the hypothesis that TLD micro-cubes could be commissioned to evaluate small field dosimetry, and provide reproducibility within 3%, as well as assure agreement between measured dose and calculated doses to within 5%.

The aims of this thesis were to characterize and commission TLD micro-cubes as well as to …

Modeling Proton Relative Biological Effectiveness Using Monte Carlo Simulations Of Microdosimetry, Mark A. Newpower

Dissertations and Theses (Open Access)

Proton therapy is a radiotherapy modality that can offer a better physical dose distribution when compared to photon radiotherapy by taking advantage of the Bragg peak, a narrow region of rapid energy loss. Proton therapy is also known to offer an enhanced relative biological effectiveness (RBE) compared to photons. In the current clinical standard, RBE is fixed at 1.1 at all points along the proton beam, meaning protons are assumed to require 10% less dose than photons to achieve target coverage and organ at risk (OAR) sparing. However, there is mounting clinical evidence, and a significant number of in vitro …

Quantifying Uncertainty In A Measurement-Based Assessment Of Relative Biological Effectiveness In Carbon Ion Radiotherapy, Shannon Hartzell

Dissertations and Theses (Open Access)

One of the largest inconsistencies in dose delivered during carbon ion therapy is due to uncertainties in relative biological effectiveness (RBE), a value that is calculated via one of several clinically implemented algorithms. This study investigates the uncertainty in measured microdosimetric parameters for RBE calculation by the Microdosimetric Kinetic Model (MKM), Repair Misrepair Fixation model (RMF), and Local Effect Model I (LEM) using a Tissue Equivalent Proportional Counter (TEPC).

Microdosimetric spectra, kinetic energy spectra, and dose fragment contributions were calculated using Monte Carlo (GEANT IV) for monoenergetic and SOBP carbon beams of clinical energy. From microdosimetric spectra, lineal energy values …

Evaluation Of Presage® As A 3d Dose Verification To Ol In Proton Beams, Mitchell Carroll

Dissertations and Theses (Open Access)

Radiotherapy techniques have advanced and radiation dose plans have become much more complex over the last decade. This is especially true in proton therapy, which involves extremely steep dose gradients as a result of positioning the Bragg peak to cover the volumes to be treated. The Bragg peak can be shifted significantly in the patient as a result of nonuniformities in the tissue composition in its path, which can result in treatment complications. Some traditional dose verification tools used in proton beam commissioning and treatment plan verification are film, TLD, and ionization chambers. Such 0D and 2D dosimeters are incapable …

Volumetric, Magnetic Resonance-Visible, And Radiation-Sensitive Detectors For Magnetic Resonance Image-Guided Radiation Therapy, Hannah J. Lee

Dissertations and Theses (Open Access)

VOLUMETRIC, MAGNETIC RESONANCE-VISIBLE, AND RADIATION-SENSITIVE DETECTORS FOR MAGNETIC RESONANCE IMAGE-GUIDED RADIATION THERAPY

Hannah Jungeun Lee

Advisory Professor: Geoffrey S. Ibbott, Ph.D.

Due to the superior soft-tissue contrast of magnetic resonance imaging (MRI) compared to conventional computed tomography (CT) and other on-board imaging techniques, several groups have integrated MRI and radiation treatment machine systems. The advent of MR image-guided radiation therapy (MR-IGRT) using systems, such as the 1.5 MRI – 7 MV linear accelerator (MR-Linac), now allow for improved soft-tissue on-board imaging for patient position and tumor target localization verification and the ability to assess functional biological tissue characteristics with MRI, …

An Automated Syringe Pump System For Improving The Reproducibility Of Dynamic Hyperpolarized Mri Phantoms, Harlee G. Harrison

Dissertations and Theses (Open Access)

AN AUTOMATED SYRINGE PUMP SYSTEM FOR IMPROVING THE REPRODUCIBILITY OF DYNAMIC HYPERPOLARIZED MRI PHANTOMS

Harlee Grace Harrison, B.S.

Advisory Professor: James Bankson, Ph.D.

Magnetic Resonance Imaging (MRI) is a powerful tool in the diagnosis of cancer due to its ability to provide good soft tissue contrast and image resolution without the use of ionizing radiation. The use of hyperpolarized pyruvate as a contrast agent for tumor metabolism during MR scans has the potential to provide information about tumor metabolism in vivo that is not available from traditional imaging measurements or any other method. Hyperpolarization is achieved through dynamic nuclear polarization. …

Characterization Of Low Density Intracranial Lesions Using Dual-Energy Computed To Mography, Jessica L. Nute

Dissertations and Theses (Open Access)

Calcific and hemorrhagic foci of susceptibility are frequently encountered on routine brain MR studies. Both etiologies cause variations in local magnetic field strength, leading to dark regions on the MR images that cannot be classified. Single-energy CT (SECT) can be used to identify lesions with attenuation over 100 HU as calcific, however lesions with lower attenuation cannot be reliably identified. While calcific lesions are unlikely to cause harm, hemorrhagic lesions carry a risk of subsequent intracranial bleeding; as such, identification of hemorrhage is vital in preventing the inappropriate use of anticoagulant medications in patients with hemorrhagic lesions.

Given there currently …

Radiogenic Second Cancer Risk Differences In Female Hodgkin Lymphoma Patients Treated With Proton Versus Photon Radiotherapies, Kenneth L. Homann

Dissertations and Theses (Open Access)

Hodgkin Lymphoma (HL) is the most common cancer diagnosis of young adults in the United States. Advances in curative treatments for HL, including the use of photon radiation therapy (RT) techniques, have increased 10 year survival rates to approximately 90% among young patients. These RT treatments, however, contribute to an increased incidence of radiogenic second cancer (RSC) formation to the healthy tissue surrounding the tumor volume relative to the general population. These RSCs are the leading cause of death among long-term HL survivors. Proton therapy has been shown to reduce the therapeutic dose, and therefore, the risk of developing a …

Clinical Impact Of Couch To P And Rails On Imrt And Arc Therapy, Kiley B. Pulliam

Dissertations and Theses (Open Access)

Purpose: To evaluate the clinical impact of the Varian Exact Couch on dose and volume coverage to targets and critical structures and tumor control probability (TCP) for 6-MV IMRT and Arc Therapy.

Methods: Five clinical prostate patients were planned with both, 6-MV 8-field IMRT and 6-MV 2-field RapidArc using the Eclipse treatment planning system (TPS). These plans neglected treatment couch attenuation, as is standard clinical practice. Dose distributions were then recalculated in Eclipse with the inclusion of the Varian Exact Couch (imaging couch top) and the rails in varying configurations. The changes in dose and coverage were evaluated using the …

The Development And Implementation Of An Anthropomorphic Head Phantom For The Assessment Of Proton Therapy Treatment Procedures, Paige A. Summers

Dissertations and Theses (Open Access)

Proton therapy has become an increasingly more common method of radiation therapy, with the dose sparing to distal tissue making it an appealing option, particularly for treatment of brain tumors. This study sought to develop a head phantom for the Radiological Physics Center (RPC), the first to be used for credentialing of institutions wishing to participate in clinical trials involving brain tumor treatment of proton therapy. It was hypothesized that a head phantom could be created for the evaluation of proton therapy treatment procedures (treatment simulation, planning, and delivery) to assure agreement between the measured dose and calculated dose within …

New To Ols For Monitoring Gamma Camera Uniformity, Brad K. Lofton

Dissertations and Theses (Open Access)

Detector uniformity is a fundamental performance characteristic of all modern gamma camera systems, and ensuring a stable, uniform detector response is critical for maintaining clinical images that are free of artifact. For these reasons, the assessment of detector uniformity is one of the most common activities associated with a successful clinical quality assurance program in gamma camera imaging. The evaluation of this parameter, however, is often unclear because it is highly dependent upon acquisition conditions, reviewer expertise, and the application of somewhat arbitrary limits that do not characterize the spatial location of the non-uniformities. Furthermore, as the goal of any …