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 …

Treatment Planning Automation For Rectal Cancer Radiotherapy, Kai Huang

Dissertations & Theses (Open Access)

Background

Rectal cancer is a common type of cancer. There is an acute health disparity across the globe where a significant population of the world lack adequate access to radiotherapy treatments which is a part of the standard of care for rectal cancers. Safe radiotherapy treatments require specialized planning expertise and are time-consuming and labor-intensive to produce.

Purpose:

To alleviate the health disparity and promote the safe and quality use of radiotherapy in treating rectal cancers, the entire treatment planning process needs to be automated. The purpose of this project is to develop automated solutions for the treatment planning process …

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 …

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 …

Development Of Graphical Models And Statistical Physics Motivated Approaches To Genomic Investigations, Yashwanth Lagisetty

Dissertations & Theses (Open Access)

Identifying genes involved in disease pathology has been a goal of genomic research since the early days of the field. However, as technology improves and the body of research grows, we are faced with more questions than answers. Among these is the pressing matter of our incomplete understanding of the genetic underpinnings of complex diseases. Many hypotheses offer explanations as to why direct and independent analyses of variants, as done in genome-wide association studies (GWAS), may not fully elucidate disease genetics. These range from pointing out flaws in statistical testing to invoking the complex dynamics of epigenetic processes. In the …

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 …

The Importance Of Dna Repair Capacity To (And A Model To Predict) Cell Radiosensitivity To Ions, David B. Flint, David B. Flint

Dissertations & Theses (Open Access)

Radiation therapy with ions has a number of advantages over conventional radiation therapy with photons, including favorable depth-dose distributions, greater relative biological effectiveness (RBE) and a lesser dependence on a number of biological factors known to affect radiosensitivity to photons, including DNA repair capacity. Thus, it is expected that an additional benefit of using ions is that they mitigate the great heterogeneities in treatment responses commonly observed in photon therapies.

However, by analyzing the cell survival of human cancer cell lines exposed to clinically relevant photon, proton, and carbon ion beams, we show there is not significantly less relative variability …

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 …

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 …

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 …

Development Of Quantitative Ultrasound-Mediated Molecular Imaging Of The Tumor Microenvironment, Trevor Mitcham

Dissertations & Theses (Open Access)

While conventional diagnostic imaging modalities provide anatomical information to clinicians, these techniques are not sensitive to critical physiological processes. In order to properly classify cancer, it is necessary to investigate noninvasive methods which can provide insight into these processes, allowing clinicians to determine personalized therapeutic options. Therefore, molecular imaging is focused on visualization and characterization of biomarkers within the tumor microenvironment (TME), which can then be combined with the anatomical information provided from diagnostic imaging.

Two such biomarkers of interest are blood oxygen saturation (SO₂) and cell receptor expression. SO₂ is a measure of the fraction of …

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 …

Characterization Of Treatment Planning System Photon Beam Modeling Errors In Iroc Houston Phantom Irradiations, Mallory Glenn

Dissertations & Theses (Open Access)

In radiation therapy, proper commissioning of the treatment planning system’s (TPS) dose calculation algorithm is critical because any errors in this process impact all treatment plans prepared in the system. Previously, TPS errors have been identified as a major cause for poor phantom irradiation performance, which may also mean that patients are treated suboptimally. The purpose of this work was to investigate the TPS beam modeling developed by the radiotherapy community to understand where inconsistencies may arise, which variables are most susceptible to variations, and in what way changing these variables can alter dose calculations.

Using the Imaging and Radiation …

Active Magnetic Radiation Shielding For Long-Duration Human Spaceflight, Kristine Ferrone

Dissertations & Theses (Open Access)

Exploration of interplanetary space presents dramatic hazards to human survival.

Space radiation hazards outside the protection of the Earth’s magnetosphere can

produce both acute and chronic health risks and thus become limiting factors for

NASA’s planned mission to Mars by the 2030s. Radiation exposure on a Mars mission

is delivered primarily by high energy ions from galactic cosmic rays and moderate

energy protons from solar particle events. The chronic radiation dose due to galactic

cosmic rays on a typical Mars mission is on the order of 1 Sv, and additional acute

radiation dose from solar flares can reach over 4 …

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 …

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

Dissertations & 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 …

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

Dissertations & 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 …

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

Dissertations & 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 …

3d Scintillator Detector Quenching Characterization For Scanning Proton Beams, Fahed Alsanea

Dissertations & Theses (Open Access)

Proton pencil beam scanning is becoming the standard treatment delivery technique for proton therapy centers. Scanned proton pencil beams provide a highly conformal dose distribution. The complex dose distribution poses challenges for quality assurance measurements leading to sophisticated detector setups and time consuming measurements. Fast 3D measurements are therefore desirable to verify the complex dose distribution and to enable the utilization of the full potential of proton therapy. The overall objective of this project is to improve volumetric scintillators detectors to provide 3D measurements for applications for beam commissioning, quality assurance program, and patient-specific treatment delivery verification.

Detectors based on …

Identification Of Intracranial Lesions With Dual-Energy Computed Tomography And Magnetic Resonance Phase Imaging, Megan C. Jacobsen

Dissertations & Theses (Open Access)

On conventional Single-energy Computed Tomography (SECT), lesions with an attenuation greater than 100 Hounsfield Units (HU) can be definitively diagnosed as calcification. However, low-density calcifications and hemorrhage may have overlapping attenuation ranges between 40 and 100 HU and, therefore, cannot be differentiated with SECT alone. On T2*-weighted Gradient Recalled Echo (GRE) MRI, these lesions appear as “foci of susceptibility” in which their signal is hypointense due to the magnetic susceptibility of the lesions differing from that of the background tissue.

Dual-energy Computed Tomography (DECT) and Phase-Sensitive Magnetic Resonance Imaging (PS-MRI) represent two new imaging paradigms which both have the potential …

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 …

Improved Target Coverage Of Spinal Metastases Through The Use Of Flattening Filter Free Beams, Laura Bennett

Dissertations & Theses (Open Access)

Of the patients that are diagnosed with metastatic disease, up to 40% will develop vertebral osseous metastases. These metastases tend to be located in close proximity to the spinal cord itself, making it difficult to achieve the recommended minimum dose of 14 Gy for single fraction SBRT or 21 Gy¹ for three fraction SBRT while maintaining acceptable doses to the cord and cauda equina. This proximity of the target to critical structures has the potential to compromise the efficacy of the radiation treatment plan in favor of reducing normal tissue dose, resulting in poor local control and tumor recurrence …

Development And Implementation Of A Homogeneous And A Heterogeneous Anthropomorphic End To End Quality Assurance Audit System Phantom For Magnetic Resonance Guided Radiotherapy Modalities Ranging From 0.35 T To 1.50 T, Angela Steinmann

Dissertations & Theses (Open Access)

Introduction: Magnetic resonance (MR) guided radiation therapy (MRgRT) is an emerging field that integrates an MR imager with either a linear accelerator or three radioactive cobalt-60 sources. Before institutions participate in multi-institutional NCI-sponsored clinical trials, they are required to perform a credentialing test provided by IROC-Houston. During the credentialing test, end-to-end phantoms are used to evaluate the institution’s ability to perform consistent and accurate radiation treatments. IROC-Houston’s conventional anthropomorphic phantoms are not visible in MR, thus they are insufficient for MRgRT systems. The purpose of this work was to create an anthropomorphic thorax and a head and neck (H&N) phantom …

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 …

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

Dissertations & 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, …

Detecting And Evaluating Therapy Induced Changes In Radiomics Features Measured From Non-Small Cell Lung Cancer To Predict Patient Outcomes, Xenia J. Fave

Dissertations & Theses (Open Access)

The purpose of this study was to investigate whether radiomics features measured from weekly 4-dimensional computed tomography (4DCT) images of non-small cell lung cancers (NSCLC) change during treatment and if those changes are prognostic for patient outcomes or dependent on treatment modality. Radiomics features are quantitative metrics designed to evaluate tumor heterogeneity from routine medical imaging. Features that are prognostic for patient outcome could be used to monitor tumor response and identify high-risk patients for adaptive treatment. This would be especially valuable for NSCLC due to the high prevalence and mortality of this disease.

A novel process was designed to …