Physical Sciences and Mathematics Commons^™

Evaluation Of An End-To-End Radiotherapy Treatment Planning Pipeline For Prostate Cancer, Mohammad Daniel El Basha, Court Laurence, Carlos Eduardo Cardenas, Julianne Pollard-Larkin, Steven Frank, David T. Fuentes, Falk Poenisch, Zhiqian H. Yu

Dissertations & Theses (Open Access)

Radiation treatment planning is a crucial and time-intensive process in radiation therapy. This planning involves carefully designing a treatment regimen tailored to a patient’s specific condition, including the type, location, and size of the tumor with reference to surrounding healthy tissues. For prostate cancer, this tumor may be either local, locally advanced with extracapsular involvement, or extend into the pelvic lymph node chain. Automating essential parts of this process would allow for the rapid development of effective treatment plans and better plan optimization to enhance tumor control for better outcomes.

The first objective of this work, to automate the treatment …

Proof-Of-Concept For Converging Beam Small Animal Irradiator, Benjamin Insley

Dissertations & Theses (Open Access)

The Monte Carlo particle simulator TOPAS, the multiphysics solver COMSOL., and

several analytical radiation transport methods were employed to perform an in-depth proof-ofconcept

for a high dose rate, high precision converging beam small animal irradiation platform.

In the first aim of this work, a novel carbon nanotube-based compact X-ray tube optimized for

high output and high directionality was designed and characterized. In the second aim, an

optimization algorithm was developed to customize a collimator geometry for this unique Xray

source to simultaneously maximize the irradiator’s intensity and precision. Then, a full

converging beam irradiator apparatus was fit with a multitude …

The Development Of Artificial Intelligence-Based Tools For Expert Peer Review Of Radiotherapy Treatment Plans, Mary Gronberg

Dissertations & Theses (Open Access)

Creating a patient-specific radiation treatment plan is a time-consuming and operator-dependent manual process. The treatment planner adjusts the planning parameters in a trial-and-error fashion in an effort to balance the competing clinical objectives of tumor coverage and normal tissue sparing. Often, a plan is selected because it meets basic organ at risk dose thresholds for severe toxicity; however, it is evident that a plan with a decreased risk of normal tissue complication probability could be achieved. This discrepancy between “acceptable” and “best possible” plan is magnified if either the physician or treatment planner lacks focal expertise in the disease site. …

Multiparametric Magnetic Resonance Imaging Artificial Intelligence Pipeline For Oropharyngeal Cancer Radiotherapy Treatment Guidance, Kareem Wahid

Dissertations & Theses (Open Access)

Oropharyngeal cancer (OPC) is a widespread disease and one of the few domestic cancers that is rising in incidence. Radiographic images are crucial for assessment of OPC and aid in radiotherapy (RT) treatment. However, RT planning with conventional imaging approaches requires operator-dependent tumor segmentation, which is the primary source of treatment error. Further, OPC expresses differential tumor/node mid-RT response (rapid response) rates, resulting in significant differences between planned and delivered RT dose. Finally, clinical outcomes for OPC patients can also be variable, which warrants the investigation of prognostic models. Multiparametric MRI (mpMRI) techniques that incorporate simultaneous anatomical and functional information …

The Safe And Effective Clinical Deployment Of Artificial Intelligence Tools, Kelly Nealon

Dissertations & Theses (Open Access)

18 million new cancer cases are diagnosed each year. Roughly half of these patients will be treated with radiation therapy, a complex technique that requires an interdisciplinary team of clinical staff and expensive equipment to be delivered safely. Cancer centers in Low- and Middle-Income Countries (LMIC) have an especially difficult time meeting the demands of radiation therapy as the complexity of treatment techniques increase, with only 37% of patients in these regions having access to the care they need. Artificial Intelligence (AI) based tools are being developed to simplify the treatment planning and quality assurance processes to increase the number …

Automating The Radiation Therapy Treatment Planning Process For Pediatric Patients With Medulloblastoma, Soleil Hernandez

Dissertations & Theses (Open Access)

Over the past 50 years, pediatric cancer 5-year survival rates increased from 20% to 80% in high-income countries, however, these trends have not been mirrored in low-and-middle-income countries (LMICs). This is due in part to delayed diagnosis, higher rates of advanced disease at presentation and a growing lack of access to high quality medical personnel and technology necessary to deliver complex treatments.

The long-term goal of this study was to alleviate demanding workflows and increase global access to high-quality pediatric radiation therapy by harnessing the power of artificial intelligence to automate the radiation therapy treatment planning process for pediatric patients …

Quantifying The Magnitude Of Total Dose Deviation Caused By Various Sources Of Error Among Iroc Phantom Irradiation Results, Sharbacha S. Edward

Dissertations & Theses (Open Access)

The Imaging and Radiation Oncology Core (IROC) phantoms are used as an end-to-end test of an institution’s radiotherapy processes, and for clinical trial credentialing. Phantoms are treated like patients, and evaluation of the doses received by the thermoluminescent dosimeters (TLDs) inside the phantom, reflects the accuracy with which an institution can image, plan and irradiate a phantom or patient. Recent phantom results show that among the hundreds of various IROC phantoms irradiated annually, 8-17% of institutions fail this test. The purpose of this work was to investigate the various types of errors that may occur during the treatment process and …

Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez

Dissertations & Theses (Open Access)

Molecular breast imaging (MBI) uses two dedicated-breast semiconductor detectors to visualize the preferential uptake of technetium-99m-sestamibi (^99mTc-sestamibi) by breast cancer cells relative to surrounding benign breast tissues. Clinically, MBI is used primarily as a supplementary tool to standard-of-care mammography because of its improved detection of breast cancers, especially in women with mammographically-dense breasts. Because of a lack of image corrections, MBI applications are currently limited to qualitative evaluations of relative pixel intensities between image regions with suspected lesions and normal tissue.

The objective of this dissertation was to use Monte Carlo simulations to better characterize the MBI imaging …

Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg

Dissertations & Theses (Open Access)

Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …

Hepatocellular Carcinoma Image-Guided Intervention: Quantitative Characterization Of Reagents For Thermochemical Ablation, Emily A. Thompson

Dissertations & Theses (Open Access)

Thermochemical ablation (TCA) is a minimally invasive therapy under development for hepatocellular carcinoma, a leading cause of cancer death worldwide. TCA utilizes acid-base chemistry delivered simultaneously to induce local ablation when administered. When delivered via a mixing catheter placed directly into the tumor, acid (e.g., AcOH) and base (e.g., NaOH) react to completion at the catheter tip, producing the acetate salt, water, and releasing heat (Δ>50°C) in sufficient quantities to induce lethal osmotic and thermal stress in tumor cells. However, these two reagents are not distinguishable from tissues with noninvasive imaging modalities, which makes monitoring the delivery of TCA …

Modeling Of Cns Cancer With A Focus On The Immune Component, Daniel Zamler

Dissertations & Theses (Open Access)

The knowledge surrounding cancers of the central nervous system remains poorly developed, in particular with regard to the immune component. The works contained in this thesis look at craniopharyngioma, glioblastoma, and several forms of brain metastasis. While some attention is given to the tumor cells themselves, as well as the patient setting which these studies model, the immune component of disease progression and treatment plays a strong role in each and is the primary focus of the works contained.

Craniopharyngioma is a relatively rare tumor in adults. Although histologically benign, it can be locally aggressive and may require additional therapeutic …

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

Dissertations & 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 …

Automation Of Radiation Treatment Planning For Cervical Cancer, Dong Joo Rhee

Dissertations & Theses (Open Access)

Cervical cancer is one of the most common cancer in low- and middle-income countries (LMICs). The mortality rate can be reduced if radiation treatment becomes widely available. However, due to the lack of radiation treatment facilities and human resources, many cervical cancer patients in Africa are not able to receive timely treatments or advanced therapies. To increase the availability of radiation treatment in low-and middle-income countries (LMICs) including African countries, many attempts have been made to reduce the cost of medical linear accelerators. However, increasing the number of treatment machines would not instantly resolve the issues, as there would be …

Quantitative Magnetic Resonance Imaging For The Early Prediction Of Treatment Response In Triple Negative Breast Cancer, Benjamin C. Musall

Dissertations & Theses (Open Access)

Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer which lacks upregulated hormone receptors. Because of this, it is not vulnerable to clinically available targeted therapies. When treated with standard of care neoadjuvant systemic therapy (NAST), TNBC only shows approximately a 40% rate of pathologic complete response (pCR). A biomarker which could predict TNBC response to NAST early during treatment would be useful, as it would allow for non-responders to be triaged to alternative therapies and potentially allow for the treatment of responders to be de-escalated.

Quantitative Magnetic Resonance Imaging (MRI) may be used to probe and …

Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede

Dissertations & Theses (Open Access)

Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of …

A Fully-Automated, Deep Learning-Based Framework For Ct-Based Localization, Segmentation, Verification And Planning Of Metastatic Vertebrae, Tucker Netherton, Tucker James Netherton

Dissertations & Theses (Open Access)

Palliative radiotherapy is an effective treatment for the palliation of symptoms caused by vertebral metastases. Visible evidence of disease is localized on medical images as part of the treatment planning process. However, complicating factors such as time pressures, anatomic variants in the spine, and similarities in adjacent vertebrae are associated with wrong level treatments of the spine. In addition, erroneous manual contouring of anatomic structures is a major failure mode in radiotherapy treatment planning.

The purpose of this study is to mitigate the challenges associated with treatment planning of the spine by automating the treatment planning process for three-dimensional conformal …

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

Dissertations & 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, …

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

Dissertations & 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 …

Development Of Fully Balanced Ssfp And Computer Vision Applications For Mri-Assisted Radiosurgery (Mars), Jeremiah Sanders

Dissertations & Theses (Open Access)

Prostate cancer is the second most common cancer in men and the second-leading cause of cancer death in men. Brachytherapy is a highly effective treatment option for prostate cancer, and is the most cost-effective initial treatment among all other therapeutic options for low to intermediate risk patients of prostate cancer. In low-dose-rate (LDR) brachytherapy, verifying the location of the radioactive seeds within the prostate and in relation to critical normal structures after seed implantation is essential to ensuring positive treatment outcomes.

One current gap in knowledge is how to simultaneously image the prostate, surrounding anatomy, and radioactive seeds within the …

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

Dissertations & 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 …

Development And Commissioning Of An Independent Peer Review System For A Small Animal Irradiator, Mary Peters

Dissertations & Theses (Open Access)

Dosimetry for small animal irradiators lacks the standardization of clinical radiotherapy practice, yet plays a central translational role in human trial design. The purpose of this work was to improve the dosimetric accuracy and consistency of animal studies by developing an independent peer review system to verify dose delivery from animal irradiators. This study focused on the development of a mouse phantom and characterization of the thermoluminescent dosimetry system for a commonly used small animal irradiator.

First, a mouse model and irradiation stand were designed with the purpose of being used in a mailable audit. Two mouse phantoms were machined …

Development Of 3d-Printed Patient Specific Bolus For Clinical Use In Total Scalp Irradiation, Garrett Baltz

Dissertations & Theses (Open Access)

Total scalp irradiation (TSI) is a specialized radiation therapy technique that aims to deliver a uniform dose to the entire scalp. Original electron-based TSI techniques had limited homogeneity due to hot and cold spots created at field junctions due to the multiple matched fields that were required to treat the entire scalp. The transition to photon volumetric-modulated arc therapy based TSI techniques has improved homogeneity, to the point where non-conformal bolus is now a limiting factor. Bolus is required to build-up full dose to the scalp surface in total scalp irradiation. Creating bolus that is conformal to the scalp is …

Improvements In Four-Dimensional And Dual Energy Computed Tomography, Rachael M. Martin

Dissertations & Theses (Open Access)

Dual energy and 4D computed tomography (CT) seek to address some of the limitations in traditional CT imaging. Dual energy CT, among other purposes, allows for the quantification and improved visualization of contrast materials, and 4D CT is often used in radiation therapy applications as it allows for the visualization and quantification of object motion. While much research has been done with these technologies, areas remain for potential improvement, both in preclinical and clinical settings, which will be explored in this dissertation. Preclinical dual energy cone-beam CT (CBCT) can benefit from wider separation between the peak energy of the two …

Identifying Treatment Planning System Errors In Iroc-Houston Head And Neck Phantom Irradiations, James Kerns

Dissertations & Theses (Open Access)

Treatment Planning System (TPS) errors can affect large numbers of cancer patients receiving radiation therapy. Using an independent recalculation system, the Imaging and Radiation Oncology Core-Houston (IROC-H) can identify institutions that have not sufficiently modelled their linear accelerators in their TPS model. Linear accelerator point measurement data from IROC-H’s site visits was aggregated and analyzed from over 30 linear accelerator models. Dosimetrically similar models were combined to create “classes”. The class data was used to construct customized beam models in an independent treatment dose verification system (TVS). Approximately 200 head and neck phantom plans from 2012 to 2015 were recalculated …

Voxel-Level Absorbed Dose Calculations With A Deterministic Grid-Based Boltzmann Solver For Nuclear Medicine And The Clinical Value Of Voxel-Level Calculations, Justin Mikell

Dissertations & Theses (Open Access)

Voxel-level absorbed dose (VLAD) is rarely calculated for nuclear medicine (NM) procedures involving unsealed sources or 90Y microspheres (YM). The current standard of practice for absorbed dose calculations in NM utilizes MIRD S-values, which 1) assume a uniform distribution in organs, 2) do not use patient specific geometry, and 3) lack a tumor model. VLADs overcome these limitations. One reason VLADs are not routinely performed is the difficulty in obtaining accurate absorbed doses in a clinically acceptable time. The deterministic grid-based Boltzmann solver (GBBS) was recently applied to radiation oncology where it was reported as fast and accurate for both …

Quantification Of Imrt Severity Scores For Improvement Of Fmea Results, Jacqueline T. Faught

Dissertations & Theses (Open Access)

Accurate delivery of intensity modulation radiation therapy (IMRT) requires perfect execution of a long, complicated chain of events; failure of any component of this process may contribute to dose delivery errors, compromising treatment quality and, more importantly, patient safety. Prospective, process-wide risk mitigation techniques are becoming more prevalent in radiotherapy to establish comprehensive quality management (QM) programs, such as failure modes and effects analysis (FMEA). The subjective nature of the ordinal scores used for FMEA leads questionable reliability and validity of the results. Additionally, physics components are commonly grouped together, leaving out valuable details important to physics QM. While the …

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

Dissertations & 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 …

Use Of Positron Emission Tomography For Proton Therapy Verification, Jongmin Cho

Dissertations & Theses (Open Access)

Positron emission tomography (PET), a tool commonly used for cancer staging and response monitoring, has recently been used for proton therapy verification. By imaging tissue activation following proton treatment, attempts have been made to verify proton dose and range. In this dissertation, two novel approaches were developed and tested for the purpose of help improve the proton dose and range estimation as well as verification.

Although there are still some challenges, attempts for proton dose verification using PET has been made by comparing Monte Carlo dose and PET simulations with treatment planned dose and measured PET. In this approach, …

Performance Evaluation Of Material Decomposition Using Rapid Kvp-Switching Dual-Energy Ct For Assessing Bone Mineral Density, John M. Wait

Dissertations & Theses (Open Access)

Osteoporosis is diagnosed by assessing the bone mineral density (BMD) of the trabecular bone, and has previously been characterized with dual-energy x-ray absorptiometry (DXA) or single-energy computed tomography (SECT). Dual-energy computed tomography (DECT) is able to create two three-dimensional sets of images representing the densities of two materials in a given basis pair. DECT is theoretically capable of providing a true density measurement of trabecular bone material with the proper material basis pair.

Using the rapid kVp-switching GE HD750 scanner, the concentrations of various solutes were assessed in two-material syringe-phantoms in different experimental conditions with DECT material density images, SECT …

Image-Guided Proton Therapy For Online Dose-Evaluation And Adaptive Planning, Joey P. Cheung

Dissertations & Theses (Open Access)

The main advantage for using protons in radiotherapy is their finite range in patients, allowing for potential improved sparing of normal tissues. However, this comes at a cost of increased sensitivity to range uncertainties. Density changes along the beam path will affect the proton range and the resultant dose distribution, making it difficult to estimate the impact of visible anatomic changes to the patient dose distribution. In order to better understand the effect of anatomy change on proton dose, some form of treatment-time verification is required and methods to correct for observed changes would be beneficial. Therefore, this project aims …