Browsing by Subject "Nuclear physics and radiation"

Purpose: Current Monte Carlo simulations modeling space radiation exposure typically use simplistic human phantoms with low anatomical detail and minimal variability in physical characteristics. This thesis describes the development of a GEANT4-based simulation framework (EVEREST – Evaluation of Variable-Environment Radiation Exposure during Space Travel) that incorporates highly realistic and diverse 4D extended cardiac-torso (XCAT) digital phantoms, combined with advanced NASA models of planetary atmospheres, spaceflight trajectories, and space radiation spectra, to evaluate radiation exposure in interplanetary missions and on planetary habitats.

Methods: Galactic cosmic radiation spectra as a function of time and radial distance from the Sun were modeled using the Badhwar-O’Neill 2020 model, while the Van Allen belt spectra were modeled using the AE-8/AP-8 models, and solar particle event spectra could be selected from historical data. The magnetic field input to the AE-8/AP-8 model was generated using the 13th generation International Geomagnetic Reference Field. Planetary atmospheres were modeled using NASA Global Reference Atmospheric Models, which provide mean atmospheric data for any altitude, latitude, longitude, and time, and the effect of Earth’s magnetic field was accounted for using a geomagnetic cutoff rigidity algorithm. Planetary orbits, trajectories, and relative positions of objects in the Solar System were determined using the NAIF SPICE observation geometry information system. Finally, highly detailed extended cardiac-torso (XCAT) digital phantoms were integrated into EVEREST in order to accurately model radiation exposure to individual organs. XCAT phantoms model over 100 segmented structures, range in age from neonate to 78 years, and cover various combinations of height, weight, and BMI. The EVEREST framework itself was designed using a novel lookup table method, in which different stages of particle propagation were divided into separate simulations, which are then convolved in post-processing.

Results: EVEREST was validated against personal radiation dosimeter data collected by the lunar module pilot on the Apollo 15 mission and also flux data from the Mars Science Laboratory Radiation Assessment Detector (RAD). Simulation results were found to agree very well with dosimeter readings by the Apollo 15 command module pilot. Comparison of Martian surface particle fluxes simulated by EVEREST to RAD data demonstrated an agreement to within an order of magnitude, with the best agreement seen for protons, He4, Z=6-8, Z=14-24, and Z>24. Finally, as a proof of concept, EVEREST was used to evaluate radiation exposure to a population of eight XCAT phantoms (3 adult and 1 pediatric, male and female) under three different nominal shielding configurations on the surface of Mars (unshielded, 50 cm thick ice, and 50 cm thick Martian regolith) at four different timepoints during the day (12 am, 6 am, 12 pm, and 6 pm). Using the federal yearly occupational dose limit of 50 mSv (effective dose) as a metric, it was found that the phantoms evaluated would reach this limit within 70.9 – 83.8 days unshielded, 139.2 – 161.2 days with 50 cm ice shielding, and 188.1 – 235.7 days with 50 cm Martian regolith shielding, if terrestrial radiation protection standards were to be applied. The results revealed that the brain receives one of the highest organ doses in the body and that unshielded radiation exposure is lowest at midnight when analyzed across all phantoms. Based on these findings, it is recommended that extra care be taken to provide additional radiation shielding in astronauts’ helmets and that extended forays outside of the habitat be planned for late evening to reduce the biological impact of radiation exposure.

Conclusion: EVEREST is a tested and validated framework for accurate estimation of total body and organ dose in space. EVEREST’s geometric versatility makes it ideal for evaluating doses to diverse populations of XCAT phantoms within different types of planetary habitats and spacecraft, enabling optimization of mission planning with respect to radiation exposure in the near future. The model has currently been validated for Lunar and Martian missions, and the framework can be applied to any space travel mission or planetary mission where the atmospheric models for that planet are available.

The $\eta$ meson is an interesting tool to study fundamental symmetries in Quantum Chromodynamics (QCD). In particular, its radiative decay width, $\Gamma\left(\eta\rightarrow\gamma\gamma\right)$, is an important quantity that can be predicted in the framework of Chiral Perturbation Theory. A precision measurement of this quantity would provide critical inputs to understanding the mixing of the $\eta$ and $\eta'$ mesons and extracting constants with wide-ranging applications in low-energy QCD. This decay width has been measured in the past using two different experimental techniques. The more popular technique utilized $e^{+}e^{-}$ collisions to produce $\eta$ mesons through electromagnetic interactions. Today, the Particle Data Group (PDG) averages the results of five such experiments to obtain their currently-accepted value of the decay width as: 0.515$\pm$0.018~keV. However the first measurement of this quantity was obtained from a fixed-target experiment that measured the cross section for photoproduction of $\eta$ mesons on a nuclear target via the Primakoff effect. Their result of 0.324$\pm$0.046~keV shows strong tension with the average of the collider measurements, motivating a new, high precision measurement using the Primakoff method.

For this purpose, the PrimEx-\textit{eta} experiment was conducted in Hall D of the Thomas Jefferson National Accelerator Facility (Jefferson Lab or JLab). The data is currently being analyzed to measure the differential cross section for the photoproduction of $\eta$ mesons on a liquid, $^{4}$He target. Preliminary results obtained from the analysis of the first phase of the PrimEx-\textit{eta} experiment show reasonable agreement with the currently-accepted PDG value of the radiative decay width. However, as will be discussed, there are many challenges to this precision measurement which must be studied before any results can be finalized and compared with previous measurements.

In parallel to the $\eta$ decay width measurement, the PrimEx-\textit{eta} experiment measured the total cross section for the fundamental, Quantum Electrodynamics (QED) process of Compton scattering from the atomic electrons inside the target. The results obtained from this measurement are in strong agreement with the next-to-leading order QED calculations, and the total combined uncertainties are below 3\% for incident photon energies between 7-10~GeV. In addition to providing the first precision measurement of the total Compton scattering cross section within this beam energy range, this measurement verifies the capability of the PrimEx-\textit{eta} experimental setup to perform absolute cross section measurements at forward angles, and serves as a reference process for the calibration of systematic uncertainties.

In external beam radiation therapy (EBRT) for cancer patients, it is highly desirable to completely eradicate the cancerous cells for the purpose of improving the patient’s quality of life and increasing the patient’s likelihood of survival. However, there can be significant side effects when large regions of healthy cells are irradiated during EBRT, particularly for organs-at-risk (OARs). Due to the juxtaposition of the cancerous and non-cancerous tissue, trade-offs need to be made between target coverage and OAR sparing during treatment planning. For this reason, the treatment planning process can be posed as a multi-criterial optimization (MCO) problem, which has previously been studied extensively with several exact solutions existing specifically for radiation therapy. Typical MCO implementations for EBRT involve creating, optimizing, and calculating many treatment plans to infer the set of feasible best radiation doses, or the Pareto surface. However, each optimization and calculation can take 10-30 minutes per plan. As a result, generating enough plans to attain an accurate representation of the Pareto surface can be very time-consuming, particularly in higher-dimensions with many possible trade-offs.

The purpose of this study is to streamline the MCO workflow by using a machine-learning model to quickly predict the Pareto surface plan doses, rather than exactly computing them. The primary focus of this study focuses on the development and analysis of the dose prediction model. The secondary focus of this study is to develop new metrics for analyzing the similarity between different Pareto surface interpolations. The tertiary focus of this study is to investigate the feasibility of deliberately irradiating the epidural space in spine stereotactic radiosurgery (SRS), as well as estimate its potential effect on preventing tumor recurrence.

For the primary focus of this study, the model’s architecture proceeds as follows. The model begins by creating an initial dose distribution via an inverse fit of inter-slice and intra-slice PTV distance maps on a voxel-wise basis. The model proceeds by extracting three sets of transverse patches from all structure maps and the initialized dose map at each voxel. The model then uses the patch vectors as inputs for a neural network which updates and refines the dose initialization to achieve a final dose prediction. The primary motivation behind our model is to use our understanding of the general shape of dose distributions to remove much of the nonlinearity of the dose prediction problem, decreasing the difficulty of subsequent network predictions. Our model is able to take the optimization priorities into account during dose prediction and infer feasible dose distributions across a range of optimization priority combinations, allowing for indirect Pareto surface inference.

The model’s performance was analyzed on conventional prostate volumetric modulated arc therapy (VMAT), pancreas stereotactic body radiation therapy (SBRT), and spine stereotactic radiosurgery (SRS) with epidural space irradiation. For each of these treatment paradigms, the Pareto surfaces of many patients were thoroughly sampled to train and test the model. On all of these cases, our model achieved good performance in terms of speed and accuracy. Overfitting was shown to be minimal in all cases, and dose distribution slices and dose-volume histograms (DVHs) were shown for comparison, confirming the proficiency of our model. This model is relatively fast (0.05-0.20 seconds per plan), and it is capable of sampling the entire Pareto surface much faster than commercial dose optimization and calculation engines.

While these results were generally promising, the model achieved lower error on the prostate VMAT treatment plans compared to the pancreas SBRT and spine SRS treatment plans. This is likely due to the existence of heavier beam streaks in the stereotactic treatment plans which are generated by a sharper control of the delivered dose distribution. However, the Pareto surface errors were similar across all three cases, so these dose distribution errors did not propagate to the Pareto objective space.

The secondary focus of this study is the development and analysis of Pareto surface similarity metrics. The dose prediction model can be used to rapidly estimate many Pareto-optimal plans for quick Pareto surface inference. This could allow for a potentially significant increase in the speed at which Pareto surfaces are inferenced to provide treatment planning assistance and acceleration. However, previous investigations into Pareto surface analysis typically do not compare a ground truth Pareto surface with a Pareto surface prediction. Therefore, there is a need to develop a Pareto surface metric in order to evaluate the ability of the model to generate accurate Pareto surfaces in addition to accurate dose distributions.

To address these needs, we developed four Pareto surface similarity metrics, emphasizing the ability to represent distances between the interpolations rather than the sampled points. The most straightforward metric is the root-mean-square error (RMSE) evaluated between matched, sampled points on the Pareto surfaces, augmented by intra-simplex upsampling of the barycentric dimensions of each simplex. The second metric is the Hausdorff distance, which evaluates the maximum closest distance between the sets of sampled points. The third metric is the average projected distance (APD), which evaluates the displacements between the sampled points and evaluates their projections along the mean displacement. The fourth metric is the average nearest-point distance (ANPD), which numerically integrates point-to-simplex distances over the upsampled simplices of the Pareto surfaces. These metrics are compared by their convergence rates as a function of intra-simplex upsampling, the calculation times required to achieve convergence, and their qualitative meaningfulness in representing the underlying interpolated surfaces. For testing, several simplex pairs were constructed abstractly, and Pareto surfaces were constructed using inverse optimization and our dose prediction model applied to conventional prostate VMAT, pancreas SBRT, and spine SRS with epidural irradiation.

For the abstract simplex pairs, convergence within 1% was typically achieved at approximately 50 and 100 samples per barycentric dimension for the ANPD and the RMSE, respectively. The RMSE and the ANPD required approximately 50 milliseconds and 3 seconds to calculate to these sampling rates, respectively, while the APD and HD required much less than 1 millisecond. Additionally, the APD values closely resembled the ANPD limits, while the RMSE limits and HD tended to be more different. The ANPD is likely more meaningful than the RMSE and APD, as the ANPD’s point-to-simplex distance functions more closely represent the dissimilarity between the underlying interpolated surfaces rather than the sampling points on the surfaces. However, in situations requiring high-speed evaluations, the APD may be more desirable due to its speed, lack of subjective specification of intra-simplex upsampling rates, and similarity to the ANPD limits.

The tertiary focus of this study is the analysis of the feasibility of epidural space irradiation in spine SRS. The epidural space is a frequent site of cancer recurrence after spine SRS. This may be due to microscopic disease in the epidural space which is under-dosed to obey strict spinal cord dose constraints. We hypothesized that the epidural space could be purposefully irradiated to prescription dose levels, potentially reducing the risk of recurrence in the epidural space without increasing toxicity. To address this, we sought to analyze the feasibility of irradiating the epidural space in spine SRS. Analyzing the data associated with this study is synergistic to our MCO acceleration study, since the range of trade-offs between epidural space irradiation and spinal cord sparing represents an MCO problem which our dose prediction model may quickly solve.

Spine SRS clinical treatment plans with associated spinal PTV (PTVspine) and spinal cord contours, and prior delivered dose distributions were identified retrospectively. An epidural space PTV (PTVepidural) was contoured to avoid the spinal cord and focus on regions near the PTVspine. Clinical plan constraints included PTVspine constraints (D95% = 1800 cGy, D5% < 1950 cGy) and spinal cord constraints (Dmax < 1300 cGy, D10% < 1000 cGy). Prior clinical plan doses were mapped onto the new PTVepidural contour for analysis. Plans were copied and revised to additionally target the PTVepidural, optimizing PTVepidural D95% after meeting clinical plan constraints. Tumor control probabilities (TCPs) were estimated for the PTVepidural using a radiobiological linear-quadratic model of cell survival for both clinical and revised plans. Clinical and revised plans were compared according to their PTVepidural DVH distributions, D95% distributions, and TCPs.

Seventeen SSRS plans were identified and included in this study. Revised plan DVHs demonstrated higher doses to the epidural low-dose regions, with D95% improving from 10.96 Gy ± 1.76 Gy to 16.84 Gy ± 0.87 Gy (p < 10-5). Our TCP modeling set the clinical plan TCP average to 85%, while revised plan TCPs were all greater than 99.99%. Therefore, irradiating the epidural space in spine SRS is likely feasible, and purposefully targeting the epidural space in SSRS should increase control in the epidural space without significantly increasing the risk of spinal cord toxicity.

As complex radiotherapy techniques become more readily-practiced, comprehensive 3D dosimetry is a growing necessity for advanced quality assurance. However, clinical implementation has been impeded by a wide variety of factors, including the expense of dedicated optical dosimeter readout tools, high operational costs, and the overall difficulty of use. To address these issues, a novel dry-tank optical CT scanner was designed for PRESAGE 3D dosimeter readout, relying on 3D printed components and omitting costly parts from preceding optical scanners. This work details the design, prototyping, and basic commissioning of the Duke Integrated-lens Optical Scanner (DIOS).

The convex scanning geometry was designed in ScanSim, an in-house Monte Carlo optical ray-tracing simulation. ScanSim parameters were used to build a 3D rendering of a convex ‘solid tank’ for optical-CT, which is capable of collimating a point light source into telecentric geometry without significant quantities of refractive-index matched fluid. The model was 3D printed, processed, and converted into a negative mold via rubber casting to produce a transparent polyurethane scanning tank. The DIOS was assembled with the solid tank, a 3W red LED light source, a computer-controlled rotation stage, and a 12-bit CCD camera. Initial optical phantom studies show negligible spatial inaccuracies in 2D projection images and 3D tomographic reconstructions. A PRESAGE 3D dose measurement for a 4-field box treatment plan from Eclipse shows 95% of voxels passing gamma analysis at 3%/3mm criteria. Gamma analysis between tomographic images of the same dosimeter in the DIOS and DLOS systems show 93.1% agreement at 5%/1mm criteria. From this initial study, the DIOS has demonstrated promise as an economically-viable optical-CT scanner. However, further improvements will be necessary to fully develop this system into an accurate and reliable tool for advanced QA.

Pre-clinical animal studies are used as a conventional means of translational research, as a midpoint between in-vitro cell studies and clinical implementation. However, modern small animal radiotherapy platforms are primitive in comparison with conventional linear accelerators. This work also investigates a series of 3D printed tools to expand the treatment capabilities of the X-RAD 225Cx orthovoltage irradiator, and applies them to a feasibility study of hippocampal avoidance in rodent whole-brain radiotherapy.

As an alternative material to lead, a novel 3D-printable tungsten-composite ABS plastic, GMASS, was tested to create precisely-shaped blocks. Film studies show virtually all primary radiation at 225 kVp can be attenuated by GMASS blocks of 0.5cm thickness. A state-of-the-art software, BlockGen, was used to create custom hippocampus-shaped blocks from medical image data, for any possible axial treatment field arrangement. A custom 3D printed bite block was developed to immobilize and position a supine rat for optimal hippocampal conformity. An immobilized rat CT with digitally-inserted blocks was imported into the SmART-Plan Monte-Carlo simulation software to determine the optimal beam arrangement. Protocols with 4 and 7 equally-spaced fields were considered as viable treatment options, featuring improved hippocampal conformity and whole-brain coverage when compared to prior lateral-opposed protocols. Custom rodent-morphic PRESAGE dosimeters were developed to accurately reflect these treatment scenarios, and a 3D dosimetry study was performed to confirm the SmART-Plan simulations. Measured doses indicate significant hippocampal sparing and moderate whole-brain coverage.

The production of heavy quarkonium in heavy ion collisions has been used as an important probe of the quark-gluon plasma (QGP). Due to the plasma screening effect, the color attraction between the heavy quark antiquark pair inside a quarkonium is significantly suppressed at high temperature and thus no bound states can exist, i.e., they ``melt". In addition, a bound heavy quark antiquark pair can dissociate if enough energy is transferred to it in a dynamical process inside the plasma. So one would expect the production of quarkonium to be considerably suppressed in heavy ion collisions. However, experimental measurements have shown that a large amount of quarkonia survive the evolution inside the high temperature plasma. It is realized that the in-medium recombination of unbound heavy quark pairs into quarkonium is as crucial as the melting and dissociation. Thus, phenomenological studies have to account for static screening, dissociation and recombination in a consistent way. But recombination is less understood theoretically than the melting and dissociation. Many studies using semi-classical transport equations model the recombination effect from the consideration of detailed balance at thermal equilibrium. However, these studies cannot explain how the system of quarkonium reaches equilibrium and estimate the time scale of the thermalization. Recently, another approach based on the open quantum system formalism started being used. In this framework, one solves a quantum evolution for in-medium quarkonium. Dissociation and recombination are accounted for consistently. However, the connection between the semi-classical transport equation and the quantum evolution is not clear.

In this dissertation, I will try to address the issues raised above. As a warm-up project, I will first study a similar problem: $\alpha$-$\alpha$ scattering at the $^8$Be resonance inside an $e^-e^+\gamma$ plasma. By applying pionless effective field theory and thermal field theory, I will show how the plasma screening effect modifies the $^8$Be resonance energy and width. I will discuss the need to use the open quantum system formalism when studying the time evolution of a system embedded inside a plasma. Then I will use effective field theory of QCD and the open quantum system formalism to derive a Lindblad equation for bound and unbound heavy quark antiquark pairs inside a weakly-coupled QGP. Under the Markovian approximation and the assumption of weak coupling between the system and the environment, the Lindblad equation will be shown to turn to a Boltzmann transport equation if a Wigner transform is applied to the open system density matrix. These assumptions will be justified by using the separation of scales, which is assumed in the construction of effective field theory. I will show the scattering amplitudes that contribute to the collision terms in the Boltzmann equation are gauge invariant and infrared safe. By coupling the transport equation of quarkonium with those of open heavy flavors and solving them using Monte Carlo simulations, I will demonstrate how the system of bound and unbound heavy quark antiquark pairs reaches detailed balance and equilibrium inside the QGP. Phenomenologically, my calculations can describe the experimental data on bottomonium production. Finally I will extend the framework to study the in-medium evolution of heavy diquarks and estimate the production rate of the doubly charmed baryon $\Xi_{cc}^{++}$ in heavy ion collisions.

Purpose: To investigate the inter-patient and inter-sequence variation in liver tumor contrast in MRI and the feasibility of improving the liver tumor contrast by using an in-house developed multi-source adaptive fusion method for use in MRI-based treatment planning.

Methods and Materials: MR-images from 29 patients were retrospectively reviewed in this study. The imaging sequences acquired by a 1.5T GE and 3T Siemens MR scanner consisted of T1-w, T1-w, Post C, T2-w, T2/T1-w, and DWI. Using an in-house developed MSAF algorithm, we created fused images for a smaller subset of 12 patients using T1-w, T2-w, T2/T1-w, and DWI as inputs. Two fusion-images were obtained for each patient by implementing either an input-driven or output-driven fusion optimization method. Once a fusion-image was obtained an analysis was performed on each original image, and the fusion-image for each patient to calculate the tumor-to-tissue contrast-to-noise ratio(CNR) by contouring the tumor and a liver background-region(BG) in a homogeneous region of the liver using this in-house algorithm. CNR was calculated by (Itum-IBG)/SDBG, where Itum and IBG are the mean values of the tumor and the BG respectively, and SDBG is the standard deviation of the BG. To assess variation in tumor to tissue CNR for each image type an inter-patient coefficient-of-variation(CV) was calculated across all patients, as well as an inter-sequence CV. CV was calculated using the following: CV = σ/µ, where σ and µ are the standard deviation, and mean CNR for a single image sequence, respectively. These values were calculated for the original sequence types and fusion-images and compared.

Results: Our results from the 29 patients showed large inter-patient and inter-sequence variability, ranging from 86.90% to 67.03%, and 134.67% to 1.22% respectively. The T1-w, T1-w, Post Contrast, T2-w, T2/T1-w, DWI, and CT CV was 85.25%, 84.11%, 67.03%, 81.78%, 86.90%, and 74.30% respectively. Tumor CNR ranged from 0.95 to 4.47 with mean (± SD) CNR for T1-w, T1-w, Post Contrast, T2-w, T2/T1-w, DWI, and CT of 1.90 (±1.60), 2.12 (±1.42), 3.59 (±2.94), 1.95 (±1.70), 4.47 (±3.32), and 0.95 (±0.81) respectively. In the smaller subset of 12 patients, our results show a reduction in the inter-patient CV when using the in-house algorithm to obtain a tumor enhanced – fusion image. The inter-patient CV for T1-w, T2-w, T2/T1-w, DWI, Balanced Anatomy – Fusion, and Tumor Enhanced – Fusion was 94.16%, 112.73%, 105.69%, 124.23%, and 67.94% respectively. Tumor-CNR was significantly enhanced for each patient when using the in-house algorithm to obtain a tumor-enhanced image. The mean (± SD) CNR for T1-w, T2-w, T2/T1-w, Balanced Anatomy – Fusion, and Tumor Enhanced – Fusion was 2.11 (±1.99), 3.89 (±4.38), 3.71 (±3.92), 5.73 (±7.12), and 17.01 (±11.55) respectively.

Conclusion: The in-house multi-source adaptive fusion algorithm has the potential to increase the liver tumor contrast, as well as, improve the consistency for use in MRI based radiation therapy treatment planning.

I develop and apply a Bayesian method for quantitatively estimating properties of the quark-gluon plasma (QGP), an extremely hot and dense state of fluid-like matter created in relativistic heavy-ion collisions.

The QGP cannot be directly observed---it is extraordinarily tiny and ephemeral, about 10^(-14) meters in size and living 10^(-23) seconds before freezing into discrete particles---but it can be indirectly characterized by matching the output of a computational collision model to experimental observations.

The model, which takes the QGP properties of interest as input parameters, is calibrated to fit the experimental data, thereby extracting a posterior probability distribution for the parameters.

In this dissertation, I construct a specific computational model of heavy-ion collisions and formulate the Bayesian parameter estimation method, which is based on general statistical techniques.

I then apply these tools to estimate fundamental QGP properties, including its key transport coefficients and characteristics of the initial state of heavy-ion collisions.

Perhaps most notably, I report the most precise estimate to date of the temperature-dependent specific shear viscosity eta/s, the measurement of which is a primary goal of heavy-ion physics.

The estimated minimum value is eta/s = 0.085(-0.025)(+0.026) (posterior median and 90% uncertainty), remarkably close to the conjectured lower bound of 1/4pi =~ 0.08.

The analysis also shows that eta/s likely increases slowly as a function of temperature.

Other estimated quantities include the temperature-dependent bulk viscosity zeta/s, the scaling of initial state entropy deposition, and the duration of the pre-equilibrium stage that precedes QGP formation.

Coherent Elastic Neutrino-Nucleus Scattering (CEvNS) was first measured by COHERENT in 2017 nearly 40 years after it was first proposed. The process involved measuring tiny nuclear recoils that result from a neutrino scattering off of atomic nuclei. COHERENT made the first two measurements of CEvNS at the Spallation Neutron Source (SNS) and is working toward additional measurements there with the goal of observing the dependence of the cross section on detector material. The SNS, as the name implies, is an intense neutron source. These neutrons must be fully accounted for as a background for CEvNS because they are coincident with the neutrinos and because they can leave a similar recoil signature in detectors.\\ \indent The Multiplicity And Recoil Spectrometer (MARS) was deployed at the SNS to measure neutrons. MARS takes advantage of capture-gating to identify neutrons separate from other environmental backgrounds. In order to measure neutrons at the SNS, MARS must be characterized there to assess detection efficiencies and performance. The detection efficiency for MARS was determined to be 3.9$\%$ for 14 MeV neutrons and is a function of cuts on the variables characteristic to the capture-gating method.\\ \indent In this work, other characterization measurements are detailed including trigger efficiency, light yield and resolution as a function of position, and neutron detection efficiency. A first measurement of the neutron fluence with MARS is described for its original location in Neutrino Alley. After determining cuts on the relevant variables, 179 $\pm$ 27 neutrons are used to measure a fluence of 415 neutrons/m$^2$/10$^{12}$J $\pm$15$\%_{stat}$ + $\pm$54$\%_{sys}$ of protons on target. This fluence is expectedly lower than previous measurements with other detectors as MARS was in a more neutron-quiet location. A first look at the deposited energy spectrum from these neutrons is also shown.

Project 1: Chest Phantom Development for Chest X-ray Radiation Protection Surveys

Purpose: Develop an acrylic phantom to accurately represent an average adult’s chest for use in radiographic chest unit radiation protection surveys.

Materials and Methods: 6 sheets of 3.81 cm thick acrylic were cut and assembled to form a 30.5 x 30.5 x 20.3 cm hollow box phantom. The acrylic served as tissue equivalent material and the hollow center simulated lungs in a human patient. Six sheets of 1 mm thick aluminum were cut to line the inner walls of the acrylic phantom to potentially boost scatter radiation. Three phantoms underwent posterior-anterior (PA) and lateral chest protocol radiographic scans: the acrylic phantom (with and without the aluminum lining), a 3 gallon water bottle filled with water, and an adult male anthropomorphic phantom. The phantoms were set up as though they were adult patients and scanned with automatic exposure control. Scatter radiation was measured with ion chamber survey meters at 4 points within the room for each phantom and protocol. The scatter data from the acrylic phantom and water bottle were compared to the anthropomorphic phantom to determine which one more accurately represented an adult patient.

Results: For the PA protocol, the average percent difference in measurements between the acrylic phantom and anthropomorphic phantom was 33.3±28.8% with the aluminum lining and 33.0±21.2% without the lining. The percent difference between the water bottle and anthropomorphic phantom was 66.5±42.0%. For the lateral protocol, the average percent difference in measurements between the acrylic phantom and anthropomorphic phantom was 157.6±5.6% with the aluminum lining and 143.0±17.6% without the lining. The percent difference between the water bottle and anthropomorphic phantom was 78.3±22.8%.

Conclusions: The acrylic phantom provided a more accurate comparison to the anthropomorphic phantom than the water bottle for the PA protocol. For the lateral protocol, neither the acrylic phantom nor water bottle provided an adequate comparison to the anthropomorphic phantom.

Project 2: Internal Beta Dosimetry of an Iodine-131 Labelled Elastin-Like Polypeptide

Purpose: Develop a model and simulation to better understand the dosimetry of an I-131 labeled elastin-like polypeptide (ELP) brachytherapy technique.

Materials and Methods: To develop the model, an average scenario based on mouse trials was explored. A 125 mg tumor was approximated as a sphere, with the I-131 ELP injected into its center. The ELP solidifies into a spherical depot – approximately 1/3 the volume of the tumor – and becomes a permanent brachytherapy source. The injected activity of I-131 was 1.25 mCi. I-131 primarily emits β radiation with an average energy of 182 keV, therefore it was determined that all such emissions were confined within the bounds of the tumor. Gamma emissions associated with I-131 were ignored as they were determined to have enough energy to escape the bounds of the tumor without any interaction. This model was implemented into a simulation using the Monte Carlo program FLUKA. From this simulation, the absorbed dose to the tumor and ELP depot, along with the dose profile, was calculated.

Results: The tumor received an absorbed dose of 72.3 Gy while the ELP received 1.14×10^3 Gy. From the dose profile, it was determined that 99% of the absorbed dose to the tumor was highly localized to a 0.3 mm region surrounding the ELP depot.

Conclusions: The model and simulation provided a better understanding of the dosimetry underlying the novel ELP brachytherapy technique. Results obtained demonstrated that the ELP method delivers doses that are comparable to current conventional brachytherapy techniques.

Project 3: I-131 Beta Detection Using a Scintillating Nanoparticle Detector

Purpose: Determine if a scintillating nanocrystal fiber optic detector (nano-FOD) could detect β emissions from I-131.

Materials and Methods: The nano-FOD’s β response was tested using a source vial containing 101 mCi of I-131 in 2 mL of stabilizing solution. A glass vial containing the I-131 was placed inside a lead pig for shielding. A 1 mm diameter hole was drilled through the tops of the vial and pig to allow insertion of the nano-FOD. Measurements were taken every day over a 17 day period by repeatedly submerging the nano-FOD in the I-131 solution and recording the voltage signal it produced. The activity at the time of measurement was calculated based on the time and date of data acquisition. The net signal and signal-to-noise ratio (SNR) were then calculated and plotted as functions of I-131 concentration.

Results: The nano-FOD produced a measurable response when exposed to the β emissions of I-131. The net signal and SNR both demonstrated a linear correlation with the concentration of I-131.

Conclusions: The nano-FOD was demonstrated to be capable of β detection with a linear correlation to activity. If the signals measured can be calibrated to radiation exposure, then the nano-FOD has promising applications as a novel β detector.

The growth in the neutrino sector over the last several decades has offered interesting answers to questions about the neutrino's fundamental nature and the essential role it plays in astrophysical processes. The field's success allows a trend towards bolder and more precise observations of the oft-eluding particle, and concrete cross section measurements are possible like never before. Coherent elastic neutrino-nucleus scattering (CEvNS) is a neutral-current process in which a neutrino scatters off a nucleus as a cohesive unit, depositing a tiny recoil energy (few-to-tens-of-keV). Observed for the first time by the COHERENT experiment in 2017, the clean theoretical cross section prediction allows CEvNS to function as not only a probe for non-standard interactions and nuclear form factors, but also as a predictable flavor-blind signature from all manner of sources. The process is important in core-collapse supernovae and also presents an opportunity for detection of a burst of core-collapse neutrinos in low-threshold detectors designed for solar neutrino and dark matter detection. Often partnered with neutrino beam facilities, a second trend in the field has been leveraging new technologies and techniques to scale up to the ton-scale and beyond.

The work presented here will cover the ability of ton-scale scintillators to measure CEvNS interactions with neutrinos from two sources. The first covers the prospects for flavor-blind supernova neutrino burst detection via CEvNS (E$\nu$=10s of MeV) in existing and future large scintillating detectors. This study will present an analytic method for obtaining the expected photon spectra and provide predictions on the CEvNS observation power during the exceedingly neutrino-luminous burst. The second undertaking details the deployment of COHERENT's new multi-ton NaI[Tl] subsystem, a scintillating detector designed to observe CEvNS from pulsed, stopped-pion neutrinos at the Spallation Neutron Source (also 10s of MeV). Analysis of the in-situ backgrounds of the first half-ton module is conducted to lay the foundation for a long-term CEvNS measurement on sodium.

Purpose: To validate commissioning results associated with the Xstrahl Small Animal Radiation Research Platform (SARRP) installed at Duke University in October 2021, verify the accuracy of the Xstrahl Point Dose Calculator (PDC) and MuriPlan dose calculation in simple geometries, and design and characterize a novel in-house kV mini-GRID capability on the SARRP.Methods: After installation at Duke University, Xstrahl SARRP TG-61 output was measured for independent verification using a Farmer ion chamber at reference conditions (33 cm SSD, 2 cm depth, open field, 220 kVp, 13 mA). Half-value layer was measured using the same ion chamber, with copper sheets to vary thickness. The accuracy of the PDC was investigated in simple water and bolus stack phantoms using EBT3 film. A range of field sizes (10x10, 20x20, 30x30, 40x40, 10x20, 20x10, 15x40, 10x40, 30x70 mm2) and depths (1 cm, 2 cm) were spot-checked. MuriPlan simulations of treatment delivery to the bolus phantom and water phantom were compared to results of EBT3 film measurements. Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detectors were also used for independent verification, with detectors being embedded within a tissue-equivalent mouse phantom at 1 cm depth. GRID irradiations were performed with the SARRP, using a 220 kVp beam, 13 mA, and a 40 mm x 40 mm field size. Pencil and bar GRIDs with beamlet spacings of 1 mm and 1.25 mm were characterized by first inserting GRID into a 3D-printed mount and positioning the mount on top of a PLA plastic block, surrounded by distilled water. EBT3 films were infixed to the top level of the PLA block and positioned at isocenter. PDC was utilized to determine irradiation time. The beam was turned on for 102 seconds—sufficient time to administer 6 Gy with a 40 mm x 40 mm field size to the surface film at isocenter with no GRID blocking the beam. EBT3 film results were analyzed to determine the output factors, peak-to-valley ratios, integral dose relative to open field, relative dose maps, as well as to produce dose volume histograms for each GRID. Results were compared to GRID characterizations in Johnson et al [18]. GRID characterizations were used to inform experimental plan for pre-clinical trial evaluating treatment efficacy of GRID therapy with PD-L1 checkpoint inhibition compared to conventional radiation therapy. Results: TG-61 dose rate and half-value layer measured during on-site commissioning showed excellent agreement with Xstrahl factory commissioning results (≈1% difference). The PDC and MuriPlan dose calculation predicted results for field sizes and depths demonstrated acceptable agreement with actual results measured by EBT3 film (.2% to 12%), with exception of several outliers. Using EBT3 film dosimetry for verification (tissue-equivalent bolus medium), MuriPlan simulations were within 2% and 12% difference from the film measured dose for 5/7 field sizes in the bolus phantom and within 3% and 13% for 4/5 field sizes in the water phantom. MOSFET detector measurements using the mouse phantom demonstrated improved agreement with the PDC-predicted dose, with percent errors ranging from .12% to 5.97% (with a single outlier at 18.3%). Measured output factors using the SARRP for the 20 mm x 20 mm pencil GRIDs were .77 ± .03 and .74 ± .02 (1 mm and 1.25 mm beamlet spacing, respectively). For the bar GRIDs, these values were evaluated to be .83 ± .03 and .80 ± .03 (1 mm and 1.25 mm beamlet spacing, respectively). Peak:valley ratios for the 1 mm and 1.25 mm beamlet spacing pencil GRIDs were determined to be 24.5 ± 0.6 and 25.1 ± 1.3, respectively. Peak:valley ratios for the 1 mm and 1.25 mm beamlet spacing bar GRIDs were found to be lower than for pencil GRIDs with equivalent beamlet spacing, being evaluated to be 13.2 ± 1.1 and 18.5 ± 1.2, respectively. Output factors, peak:valley ratios, integral dose relative to open field, and dose volume histograms for the pencil and bar GRIDs using the SARRP largely corroborated the results of Johnson et al in terms of experimental trends (peak:valley ratios being higher for pencil GRIDs and increasing with increasing beamlet spacing, output factors decreasing with increasing beamlet spacing for both GRID types, and decreasing integral dose with increasing beamlet spacing for pencil GRIDs and increasing integral dose with increasing beamlet spacing for bar GRIDs). 4.67% to 30.5% difference was observed for experimentally measured peak:valley ratios relative to the results for the same GRIDs in Johnson et al.. Better agreement was demonstrated in GRID output factor measurements (≈0% to 14%). Integral dose experimental measurements demonstrated exceptional agreement with Johnson et al.., with percent differences ranging from 1% to 2.1%. These measured differences are likely a result of using the SARRP versus the XRAD 225Cx used in Johnson et al, but lend significant credence to reproducibility of results found using the XRAD 225Cx. Conclusions: The PDC and MuriPlan computations provide an effective estimate of the exposure time necessary to deliver dose for corresponding MVC field sizes and depths (within 6% error using the MOSFET for verification). EBT3 film was determined to be an unreliable measure of SARRP dose delivery; MOSFET detectors demonstrated more consistency and effectiveness for treatment planning verification. Xstrahl’s SARRP was able to replicate the kV mini-GRID capabilities of the XRAD 225Cx used in Johnson et al. and can be used for mini-GRID characterizations and preclinical mouse trials.

Purpose: To develop a comprehensive method to measure the radiation uncertainty and coincidence with the kV-CBCT imaging coordinate system using NIPAM kV-CBCT dosimetry.

Methods: An N-isopropylacrylamide (NIPAM) dosimeter is irradiated at eight gantry/couch combinations which enter the dosimeter at unique orientations such that the beams do not overlap except at the isocenter. 1-3 CBCT images are acquired before and immediately after irradiation, radiation profile is detected per beam, and the displacement from the imaging isocenter is quantified. This test has been performed on SRS cone sizes ranging from 4 mm to 15 mm diameter and a 5 mm diameter MLC field, delivering approximately 16 Gy per beam. Matlab code was developed in house to detect each beam’s geometry and to quantify relevant parameters, including radiation isocenter and coincidence with the CBCT origin and the actual gantry and couch angles per beam. The dose profile of each beam was detected in the CBCT using the contrast-to-noise ratio (CNR) of the irradiated high dose regions relative to the surrounding background signal of the dosimeter. Reproducibility was demonstrated by repeating the test on two separate NIPAM dosimeters using the 6 mm cone. To determine the robustness of our test, our results were compared to the results of the traditional Winston-Lutz test, film based “star shots,” and the Varian Machine Performance Check (MPC). The ability of our Matlab code to detect alignment errors was demonstrated by applying a 0.5 mm shift to the MLCs in the direction of leaf travel.

Results: Setup, irradiation, and imaging can be completed in under 40 minutes. The minimum radius to encompass all beams calculated by automated analysis for the MLCs, 4 mm cone, 6 mm cone, 7.5 mm cone, 12.5 mm cone, and 15 mm cone was 0.38 mm, 0.44 mm, 0.53 mm, 0.48 mm, 0.75 mm, 0.5 mm, and 0.57 mm, respectively. When determined manually, these values slightly decreased to 0.28 mm, 0.40 mm, 0.33 mm, 0.41 mm, 0.61 mm, 0.48, and 0.34 mm, respectively. The isocenter verification test was repeated using the 6 mm cone; in both tests, the smallest radius to encompass all beams was found to be 0.53 mm, indicating that the test is reproducible. For comparison, the 3D isocenter radius was 0.24 mm, 0.25 mm, and 0.28 mm for the traditional Winston-Lutz test with MLCs, the Varian MPC, and a “star shot” QA sample. Lastly, when a 0.5 mm shift was applied to the MLCs, the smallest radius to encompass all beams increased from 0.38 mm to 0.90 mm.

Conclusion: The results of this project demonstrate the feasibility of a comprehensive isocenter verification test using NIPAM kV-CBCT dosimetry which incorporates the evaluation of radiation coincidence with the imaging coordinate system, and is capable of producing sub-mm results. This test is applicable to all SRS cone sizes as well as MLCs and can be performed in a typical QA time slot.

The fields of medical health physics, imaging, and radiotherapy have pushed the development and implementation of numerous radiation monitoring systems. Furthermore, detection and measurement of ionizing radiation is essential for many industrial processes. Various detection systems including ion chambers, thermoluminescent detectors, electronic portal imaging devices, semiconductor detectors, and scintillation-based systems have been developed to suit this need. Diagnostic imaging systems most often make use of large arrays of inorganic scintillation crystals. These crystals must be grown using specialized equipment in a laboratory environment. Furthermore, the crystal geometry is limited to relatively small volumes, and production time is on the order of months. Plastic scintillation materials have also been extensively studied for dosimetry applications. These detectors offer high sensitivity with lower production cost and a production timeline on the order of days. Plastic scintillators are most often created by extrusion, casting, and injection molding. These techniques allow for larger volume detectors, but their geometry is still limited in most cases to regular geometric shapes. In recent years, advancements in 3D printing technology have been proposed as alternative manufacturing methods for radiation detectors. These techniques offer the ability for rapid prototyping and allow for at-will creation of complex detector geometries that would otherwise be prohibitively time consuming and expensive using current scintillator manufacturing methods. Furthermore, the wide availability of affordable off-the-shelf consumer 3D printers allows detector manufacturing outside of laboratory environments. The primary focus of this dissertation is the development and characterization of 3D printed radiation detectors using [Y1.903; Eu0.1, Li0.16] scintillating nanoparticles suspended in a printable glycol-modified polyethylene terephthalate (PETG) filament. We assess this technology for use in two applications: (1) as a real-time x-ray imaging screen, and (2) as an inorganic scintillation detector element in a fiber-optic probe dosimeter. (1) The imaging screen was characterized by investigating the accuracy of the scintillation image vs incident exposure patterns, the radiation stability of the detectors, and their ability to differentiate tissue thickness and material density in biologically relevant samples. Scintillation images were captured using a smartphone camera situated outside of the primary x-ray field. A housing apparatus was designed to hold the detector plane perpendicular to the field, and above an optical grade mirror angled 45° relative to the camera. Accuracy of the scintillation image was investigated using cutout-patterned lead masks to attenuate portions of the incident x-ray field. Localization of photons generated in the detector volume was quantified for 5 printed samples using local contrast between adjacent areas of the scintillation image corresponding to shielded and unshielded regions of the detector surface. We calculated the difference in scintillation intensity between these regions of the scintillation image were 7.97 ± 5.4% times higher than measured for the baseline shielded areas. Radiation damage effects on scintillation light output due to prolonged exposures was assessed using 6 detector samples. One detector was used as a control group, while the remaining 5 accumulated absorbed dose using a Cs-137 Irradiator to provide lifetime doses ranging from 1.3 – 14 kGy. The average surface scintillation intensity for each detector was measured relative to the control detector prior to and post irradiation. Relative scintillation intensity showed no discernable change due to the lifetime accumulated dose values investigated. Performance of the detector screen imaging biologically relevant samples was assessed in three stages. Firstly, the ability of the scintillation image to show increased attenuation due to material thickness was demonstrated by imaging a mouse femur. The image showed clear signal difference in thicker portions of the bone, allowing for a pseudo-topological reconstruction of the femur based on pixel gray values in the smartphone camera image. The second stage was demonstrating signal differentiation from attenuation differences due to material density in the range of biological tissues. Tissue-equivalent phantoms representative of lung, breast, soft tissue, brain, 1 year-old bone, and adult bone were used in this study. The phantoms were imaged in groups at various x-ray fields of tube potential from 40-120 kVp. Minimal differences in tissue differentiation were seen across this energy range. Our results suggest the material density threshold for differentiation lies between 0.08 and 0.15 g/cm3. The third stage of the printed detector screen assessment focused on imaging anatomical features of a complete biological sample using a plasticized mouse. Scintillation images were captured corresponding to 120 kVp x-ray projections of 4 regions of the mouse. Specifically, regions centered on the head, neck, torso, and hindquarters were imaged. Radiochromic film was placed on top of the detector plane to provide a comparison x-ray projection image. These scintillation images demonstrated the presence of prominent skeletal structures, and the torso image showed clearly defined lung volumes, a region of increased attenuation representative of the mouse liver, and hints of a gradient of attenuation for overlapping organs of the digestive track. These investigations provide proof-of-principle for the use of 3D printed real-time imaging screens. (2) A fiber-optic probe detector was developed using an aluminum brace to couple 3D printed detector chips to an acrylic light guide in order to funnel scintillation photons into the terminal end of a 0.6 mm diameter optical fiber. The probe detector was fitted with 1 mm thick and 2mm thick detector chips printed at maximum scintillation nanomaterial concentration. Fluorescence spectrometer measurements of these two configurations showed comparable scintillation intensity under 130 kVp x-ray excitation, suggesting that the observed scintillation photons are primarily generated on the surface of the printed detector chip. The probe detector light output was then measured with 1 mm thick chips printed at scintillator loading concentrations of 1, 5, 10, 25, and 35% by weight. Fluorescence spectrometer measurements showed monotonic increase in scintillation intensity vs detector chip concentration. Dose response curves for probe detector fitted with 35% printed chips under 80, 160, and 240 kVp excitation were plotted using a NIST-traceable ion chamber as a gold standard for dose measurement. The detector signal was shown to have a strongly linear relationship to incident dose rate for all three energy x-ray fields. The lower detection limit for 80, 160, and 240 kVp exposures was calculated to be 3.55 ± 0.16 cGy/min, 4.09 ± 0.18 cGy/min, and 4.93 ± 0.22 cGy/min respectively. We conclude that 3D printed scintillation detectors are viable for use in optical fiber dosimetry systems, In addition to investigations into 3D printed radiation detectors, this dissertation also serves to extend the applications and physical characterization of the novel Nano-FOD detection system. This detector makes use of inorganic scintillating nanomaterials coupled with an optical fiber and photodiode to provide real-time dose rate measurements. This work builds on previous characterization studies by implementing a methodology for determining lower detection limits using signal vs dose rate calibration curves. Lower detection limits for 5 Nano-FOD detectors were calculated for 60, 80, 100, 120, 150, 200, and 250 kVp x-ray fields. We observed roughly 30% standard deviation in detection limits among the five sampled Nano-FODs at each energy level measured. In addition to this measurement, we quantified sensitivity variations using dose rate calibration factors for all fibers at each energy level. We also explored the capacity of the Nano-FOD system for in vivo measurement of I-131 in small animal applications. This proof-of-concept study focused on in vitro measurement of 103 mCi of I-131 mixed with 2ml of stabilizing solution inside of a lead shielded glass vial. Two Nano-FOD detectors were used in the investigation, one of which was shielded from β particles via an acrylic sheath. Measurements for each detector were taken over a period of 20 days in order to observe the decay behavior of the Nano-FOD signals. The signal of the shielded fiber was subtracted from the unshielded fiber signal after accounting for differences in diode sensitivity, detector sensitivity, and γ attenuation due to the acrylic sheath. The first two of these correction factors were calculated using data from lower detection limit investigations. The difference in incident γ dose rate on the two detectors due to attenuation was derived computationally using the FLUKA Monte Carlo simulation package to model our experimental geometry. Nano-FOD signal from β- emissions was isolated using this two-fiber subtraction method and shown to decay with a half-life of 7.73 ± 0.31 days. These results demonstrate the viability of the two-fiber subtraction method for I-131 β- dose measurement using the Nano-FOD system.

Translational cancer research has been around for many years and has resulted

in many advancements in cancer treatment. Preclinical radiation therapy is an important

tool used in some studies to better understand the biological effects due to radiation.

Current preclinical radiation treatment techniques do not emulate the advanced

techniques used in cancer clinics, such as intensity modulated radiation therapy (IMRT).

In this work we explore the possibility of developing and implementing an IMRT

treatment capability for an orthovoltage micro irradiator used for small animal research.

In order to implement IMRT to the micro irradiator, every step of the radiation

therapy treatment process had to be evaluated, developed, and tested. The first step was

to develop and treatment planning software that can be used for small animal studies.

Using the open source Computational Environment for Radiotherapy Research (CERR)

and adapting it for use with an orthovoltage irradiator, monte carlo dose calculations

could be performed for small animal data sets. CERR does not have the ability to

optimize dose calculations, so a Matlab script was developed and written for inverse

optimization for treatment planning. Treatment plans were designed and optimized for

several small animal cases to evaluate the optimization algorithm. Following successful

simulation development, treatment delivery techniques needed to be developed. 3D

printing was used as a tool to create physical compensators that could be used as an

add-on device to the micro irradiator. With the capability of submillimeter printing

resolution, 3D printing has the capability to handle the high resolution required for very

small structures inside of small animals. Using the simulation data, another Matlab

script was developed to create both compensator and inverse compensator 3D models.

Many materials and techniques were evaluated to determine the best method for

compensator production. Materials were tested for attenuation properties, printing

capabilities, and ease of use until a satisfactory result was achieved.

Once the simulation and delivery techniques were developed to a satisfactory

level, an end to end test was designed to verify the IMRT capability. Using a 2.2 cm

diameter cylindrical Presage® dosimeter as the quality assurance (QA) device/patient, a

treatment plan was created based on the geometry of the Radiologic Physics Center

(RPC) Head and Neck phantom design. The dose tolerances used for the inverse

optimization were the same as the RPC Head and Neck protocol with a stricter tolerance

for the organ at risk (OAR). Compensators were produced for the plan and both 2D and

3D analysis was performed. Radiochromic film was used for 2D dose map analysis.

Gamma analysis was performed using 2D film data with varying criteria for distance to

agreement and dose difference. 3D analysis was done by delivering the treatment plan

to the Presage® dosimeter. Using optical-CT for dose readout of the dosimeter,

qualitative analysis was performed to show the 3D delivered dose data.

The end to end test showed strong evidence that IMRT could be implemented on

the small animal irradiator. The 9 field treatment plan was delivered in under 30

minutes with no mechanical or collisional issues. The 2D dose analysis showed 7 out of 9

treatment fields had a passing rate greater than 90% for a gamma analysis using 10%/0.5

mm tolerances. 3D dose analysis showed promising spatial resolution of the dose

modulation. As a feasibility and an initial testing study for a new treatment technique on

the small animal irradiator, these results showed the capability of the 3D printed

compensators to modulate dose with high spatial precision and moderately accurate

dose delivery.

Kinematically complete measurements of three-body photodisintegration of $^3$He were performed at the High Intensity $\gamma$-ray Source (HI$\gamma$S) with nearly monoenergetic 15 MeV photons. The experiment relied on two-nucleon coincidence measurements in which the nucleons are emitted on opposite sides of the incident $\gamma$-ray beam axis. The setup consisted of seven 10 cm long cylindrical gas targets pressurized near 4 atm with thin windows to allow low-energy charged particles to exit with acceptable energy loss. Charged particles were detected in silicon strip detectors with angular acceptance constrained by a collimator system. Neutrons were detected in arrays of liquid organic scintillator cells. Data for neutron-proton (np) coincidences were acquired in configurations which selectively include or exclude the np final state interaction. Measurements of proton-proton (pp) coincidences along the same kinematic locus containing the np final state interaction (FSI) were also taken in-situ. Products from the two-body reaction were used as a luminosity monitor. Theory predictions were propagated through a GEANT4 simulation of the experimental setup. There was good agreement between predictions and measurements in the vicinity of the collinear point in which a proton remains at rest as measured by np coincidences. The measured np FSI peak included additional low-energy neutrons not anticipated by the simulation, which are likely associated with intermediate neutron scattering. The np FSI peak was found to be underpredicted by about 20$\%$. The pp coincidence data were consistently about 39$\%$ above predictions.

Purpose: An interest in FLASH radiotherapy has been reawakened due to its noted ability to spare normal tissue, equal tumor control compared to conventional irradiation methods and technological advancement allowing for ultra-high dose rates required for FLASH radiotherapy to be more accessible compared to previous decades. The underlying biological mechanism of the FLASH effect are unknown and developing an in vitro model to study it has proven difficult. This work aims to combine two unique technologies, an organotypic rat brain slice model which models the in-vivo micro-environment in an in vitro setting and a linear accelerator capable of delivering variable FLASH pulses to design experiments which will facility the study of the FLASH effect.Methods: The experiments utilize a 35 MeV electron beam provided by Triangle Universities Nuclear Laboratory’s (TUNL) High Intensity Gamma-ray Source linac (HIGS). The beam can supply electron pulses with a temporal width of 1.2 s or 100 ns and work was performed with Gafchromic EBT3 and EBT-XD film to accurately determine the dose and dose rates of each pulse. Experiments were performed over 5 sessions to establish the use and effectiveness of the HIGS linac and biological rat brain model. A 2D translational stage was developed and targeting procedures were developed to ensure accurate targeting of each well containing an organotypic rat brain slice in a 12 well plate. Each rat brain was shot with a yellow fluorescent protein marker and seeded with 4T1 cancer cells tagged with mCherry and firefly luciferase. An imaging analysis workflow was developed to effectively capture and segment mCherry signal and determine the 4T1 proliferation four to five days after irradiation. These were compared to a final firefly luciferase readout. Each experiment was followed by a conventional irradiation as a control group. Monte Carlo model using TOPAS was created to simulate the HIGS linac dose profiles. Results: The HIGS linac can provide a mean dose rate up to 100 Gy/s and an instantaneous dose rate up to 100 MGy/s. The repeatability of the pulse dose was found to be within 4-5% of the average dose for a given experiment. Targeting was repeatable and dose superposition was confirmed. Well targeting quality assurance procedures of the translational stage allowed for consistent targeting of the pulse to each well. Yellow fluorescent protein bleed through in the mCherry signal was effectively filtered out and mCherry analysis reflects the end readout of firefly Luciferase. A gamma analysis between simulated and measured dose demonstrates a passing rate of 99.4% when using a criteria of 2%/2mm and threshold of 10%. Conclusions: FLASH capable dose rates can be supplied by the HIGS linac and is amongst the highest instantaneous dose rates currently available. The HIGS linac and organotypic rat brain model can be combined to irradiate and measure radiation effects to 4T1 cancer cell growth. There is qualitative data to support the observation of the FLASH effect in the rat brain model and the mCherry and firefly luciferase analysis agreement demonstrates the capabilities of the model to measure radiation effects to cancer cells in the 1-10 Gy range. Future work will be to quantitively measure the neuron health of the brain slices and DNA damage differences between FLASH and conventional irradiation.

Project 1 (Chapter 2): X-Strahl CIX3 CharacterizationPurpose: In Fall 2021 Duke University purchased an Xstrahl CIX3 Cabinet Xray Irradiator. A characterization of this machine was performed to determine its dosimetry characteristics and best practices for radiobiological studies at Duke. Basic irradiator acceptance tests were expanded on to fully characterize this new machine. Two unique aspects of this machine were of particular interest. First a unique (non-uniform) filter design was investigated to determine if it has unintended side effects on field conformity. Second the lack of accessible cable ports made thermoluminescent dosimeters (TLDs) the primary dosimeters for experiments. For this reason additional investigations were conducted characterizing TLDs. Materials and Methods: To assess the dosimetric properties of this new machine the following parameters were investigated: output consistency, beam quality, field uniformity, and exposure rates. Output consistency was measured by comparing expected and observed max energy in kVp using a Piranha X-ray multimeter. Beam quality was measured as half value layer of aluminum and compared to expected results from Spekcalc. Spekcalc was used to determine energy fluence and mean energy of the spectrum. Field uniformity was assessed using Gafchromic ™ EBT3 film on an Epson Expression 10000 XL scanner with lateral response artifact correction factors and film calibrated using a NIST traceable 0.18 cc ion chamber. Exposure rates were characterized using a NIST traceable 0.18cc ion chamber and varying filtration, tube energy (kVp), and tray position for all available configurations. TLD energy response, positional response, and batch correction factor techniques were characterized on this machine. Energy response was determined by irradiating TLD’s to a range of energies (70-300 kVp) and the charge response reliv ative to the exposure (50 R) received was determined. Positional response in the field was investigated using the Duke Radiation Dosimetry Laboratory (DRDL) TLD holder and Gafchromic ™ EBT3 film. The relative exposure each TLD received was determined and compared to the ion chamber exposure. Results: The CIX3 had consistent energy output as measured by max energy conformance. The average difference from input voltage to output voltage was 0.84 % with the worst being 1.6 % (150 kVp, 1 mm copper Filtration). Theoretical estimations (Spekcalc) of the beam quality had good agreement with measured half value layers (using Piranha) with an average difference of 1.36 % and worst error of 2.99 % across the energy ranges sampled (50-150 kVp). Field uniformity results indicated general conformance to machine data (90 % within 25.9 cm diameter field) but some non-uniformities were identified. Areas of higher dose (105-110%) relative to the center were observed in the upper right quadrant of the field (from beam eye perspective). TLD energy response followed expected over-response in lower energy ranges, reducing to a normal response as energy increases. The highest over response was at 70 kVp, a 15 % over response compared to 300 kVp (the max energy of the CIX3). The film study to determine TLD positional response determined there were unequal exposures to the 50 TLDs. The trend observed an increase in exposure consistent with the field uniformity results in which the dose relative to the center of the field increased by 5-10 % towards the upper right quadrant. This effect was more pronounced at the lower energy level sampled (90 kVp). Conclusions: The full characterization of the CIX3 was very important to understand the nuances of the new machine. Conformance in beam quality results gave good indications that the machine is operating as designed and radiobiological studies expect to have consistent results between experiments under like conditions. The unique field uniformity results observed could help inform future experimental planning. More importantly it is an extremely important finding for TLD dose calibration. Since TLDs experience at most 6-7 % over exposure compared to the ion chamber it is important to use these findings in future calibrations. Project 2 (Chapter 3): Dose Depth of Small AnimalWater Phantom Purpose: Much is understood about the midpoint dose estimation of small animal phantoms and it has been the focus of DRDL to conduct dosimetry using this value. However, little data was available on the dose depth profile of small animal phantoms. This investigation sought to fill in that dose depth data, compare doses under varying experimental conditions in order to fully understand how the dose is distributed along the beam axis for small animal phantoms. Materials and Methods: A small animal water phantom (50 cc water vial) was characterized on the CIX3 using Gafchromic ™ EBT3 film. Film was calibrated using a NIST traceable 0.18 cc ion chamber. The phantom was irradiated with strips of film (15 total) varying filtration and whether a backscatter plate (uniform piece of acrylic) was included. The film was scanned and analyzed using Film QA software and aggregated dose depth profiles were determined using R Studio and Excel. Results: The dose depth of the phantom was characterized with a coefficient of variation of about 2-3 % across all depths and configurations. The inclusion of the backscatter plate improved the dose uniformity by an average of 2.14 % with most improvements coming from the bottom half of the phantom (closest to the backscatter plate). Average dose rates under each configuration were determined. The midpoint dose rate was found to have good conformance (within 0.5%) to the averaged dose rate across the depth. The dose rate increased by 33 % when using the backscatter plate due to the increased backscatter spectrum and the inverse square law effects. Conclusions: This data gave increased certainty in using the midpoint dose as a surrogate measure for whole body dose averages in small animal phantoms. The improvement in dose uniformity when using the backscatter plate seems like a promising addition to future experimental configurations. However in application the size of the backscatter plate makes it unusable for large experiment samples and it should be implemented only in specific studies as determined during the dosimetry consult with DRDL. Project 3 (Chapter 4): Novel Mouse Phantom Investigation Purpose: In recent years DRDL developed a novel mouse phantom based on feedback from researchers. This novel phantom flattened the mouse to mimic a mouse laying on an irradiation platform, especially when sedated. This investigation sought to determine if the novel ’flat’ phantom made of polymethyl methacrylate (acrylic) (PMMA) had a significant difference in dosimetry when compared with a standard cylindrical phantom made of soft tissue equivalent material. Materials and Methods: To compare the dosimetric differences each phantom a FLUKA Monte Carlo simulation was compared with experimental results from TLDs on the CIX3. In the simulation the dose was compared using a midpoint dose volume. In the experimental design TLDs were used to determine the dose at the midpoint of each phantom. The dose rates were analyzed and compared to determine if there was a significant difference. Results: The Monte Carlo results indicated there were very slight differences between phantom rates. The cylinder phantom had a dose rate of 1.83±0.038 Gy/min while the flat phantom had a midpoint dose of 1.81 ± 0.045 Gy/min, 1.1 percent lower than the cylindrical phantom. An unpaired t-test was performed to determine if the samples were different and was found to give a p-value of 0.71 which gives a high probability that the sampled data are not significantly different. The experimental results were found to be similar. The cylinder phantom had a dose rate of 1.77 ± 0.05 Gy/min while the flat phantom had a midpoint dose of 1.81 ± 0.045 Gy/min, 2.25 percent higher than the cylindrical phantom. Again a t-test was performed and these were determined to not be significantly different (p = 0.31). Conclusions: The flat phantom therefore is very similar to the dosimetry found in the cylinder phantom. Small variations due to material properties, height of phantom, scatter material, and attenuating material all balanced out to provide dosimetry properties that are similar. This means that the cheaper to manufacture flat phantom is just as good as the much more expensive cylinder phantom and both can be used for small animal dosimetry. Project 4 (Chapter 5): Shepherd Mk I - 68A Dose Uniformity Purpose: In 2009 a study was conducted to determine the dose uniformity in a Shepherd Mk I-68A Cs-137 irradiator. Since then vast improvements have been made on film design and software to analyze scanned film with improved accuracy. A follow up study was designed to revisit this previous characterization and update the dose uniformity of the irradiator cavity using these new dosimeters and techniques. Materials and Methods: Gafchromic ™ EBT3 film was calibrated using a NIST traceable 0.18 cc ion chamber on the Shepherd irradiator in each of the three positions available. Large film sheets were then irradiated in a 2 mm acrylic holder in all positions under rotating and non-rotating configurations. The scanned film was analyzed using FilmQA software, R studio, and Excel to determine the dose uniformity relative to the dose in the center. Results: An ion chamber sample was compared to the film results and found to be in good agreement (within 1 %) which indicated the film was appropriately irradiated, scanned, and calibrated. Rotating dose distributions in positions 2 and 3 were nearly equivalent to manufacturer predicted isodose distributions with noted discrepancies at the edges of the field. At a height of 15 cm to achieve dose uniformity of 100 % ± 5 % the rotating tray has a usable radius of 7 cm from the center in position 2 and 8 cm in position 3. Stationary dose distributions were compared to previous uniformity and found to be in general agreement in the center. However the isodose mapping previously characterized did not include a scanner lateral response artifact correction factor which indicated a better uniformity than what was found in this experiment. Position 1 results were similar to previous dose distributions and most importantly confirmed the positioning of the source in the chamber. Conclusions: The updated dose uniformity data provides QA feedback as part of a larger dosimetry program for Duke University. These results indicated that this irradiator was and still is performing as expected and no mechanical failures have caused a source to become misaligned or any major changes to the expected dosimetry.

Problem: PET system performance, particularly the count rate-related effects, depends on a variety of effects including the patient size and the amount and distribution of radioactivity in the patient. The performance also depends on the particular PET system. This is primarily due to differences in detector material and detector size. This leads to a difference in image quality for the same activity level for different detectors. The current activity dosing protocol in Duke University’s Cancer Center is weight-based and system-independent, even though the systems vary greatly in count rate capability. This protocol might not be the most optimal protocol given that patients of the same weight are given the same dose but would produce different image qualities depending on the system they were scanned on. The work done in this thesis explores the components of the dosing protocol in an effort to reconsider the patient- and system- specific dosing needs for optimal image quality. This study uses Noise Equivalent Count (NEC) curves to simulate image quality for data that has been acquired using different systems, body sizes and shapes, and activity levels.Methods: This study investigates the behavior of three different hybrid PET/CT systems: the GE Discovery 690 (D690), the GE Discovery IQ (DIQ), and the GE Discovery MI (DMI). Phantom data were used to understand the performance of the three systems, and existing patient data were used to further evaluate the effects that different body characteristics have on each system. Two phantoms were used in this study: a whole-body phantom that simulates a medium- large patient and a smaller cylindrical phantom that simulates an extreme case of a small object. Both phantoms were filled with a large amount of activity (about 18 mCi for the whole-body phantom and about 12 mCi for the smaller cylindrical phantom) and thoroughly mixed before being scanned repeatedly for a long duration on all three systems to test each system’s behavior with different-sized phantoms. A Bash script was run to collect information from the phantoms’ DICOM headers so that NEC formulas could be calculated, and NEC curves could be analyzed. The dead-time model was adjusted to best fit the simulated data to the actual data to potentially improve accuracy with patient data. The phantoms were used to analyze the systems’ general behaviors without any human factors such as different uptakes for different organs, a larger variety of shapes and sizes, and different compositions. Once the general behaviors were understood and the models were adjusted, a large selection of patient data (500 for the DIQ and 500 for the DMI) was obtained. This was accomplished through the creation of multiple Bash and Python scripts that ran through patient data, retrieved the desired patients and patient scans based on specific criteria determined by the scripts, and collected anonymized data used to form NEC curves and experiment with body metrics. A few anonymized CT and PET images were saved for each patient as well so that body diameter measurements could be made. Results: It was determined that the NEC curves produced by the two different detector materials (BGO and LYSO) peaked at different activity levels for the same phantom. Also, to obtain the same NEC rate, the smaller cylindrical phantom required less activity than the whole- body phantom for each of the three systems. Dead-time data found in the image header was analyzed using Stearns’ NEC model, and his model appeared to consistently deviate from actual measurements. To improve the model, adjustments were made to parameters in the dead-time model to create a best fit to the phantom data, considering the three different systems and two phantom sizes. It was determined that a single dosing protocol may not be optimal for all systems since the NEC curves peaked at very different activities for each system and peaked at different counts per second for each system. Furthermore, the dosing protocol may not be benefiting patients of all sizes, as heavier patients may be receiving higher doses than needed for good image quality. Various body metrics were tested to compare which is the best to implement into an improved dosing protocol. These included body weight, BMI, and a pseudodiameter calculated from a cylindrical body approximation. This pseudodiameter was formed as an effort to approximate body diameters from patient weights and heights. The relationship between optimal dose (the dose at which peak image quality occurs) and the three body metrics was tested to determine whether a new dosing protocol can be formed based off of optimal doses depending on a certain body metric. It was determined that there is no correlation between optimal dose and the three body metrics. Conclusion: Body weight was concluded to be the most meaningful metric for calculating patient doses due to the ease of the measurement and the consistent relationship between image quality and patient weight for each system. Since patients with similar weights tend to produce similar image qualities, body weight can be used as a fairly reliable predictor of image quality when injected with a specific dose. Due to the differences in detection between the Discovery IQ and Discovery MI, the NEC curves produced by either system are very different, so the current dosing protocol would work best if it were system-dependent. Patients scanned on the DIQ could especially be receiving lower doses while still producing near-optimal image quality. If the goal of scanning patients is to produce the same image quality for every patient, then the dose for some patients could be significantly decreased. This can be concluded due to the NEC curves of patients at different body weights peaking at different count rates (where the lightest patients peak at higher count rates, and the heaviest patients peak at lower count rates). In this case, the current system-independent dosing calculation may not be optimal. A new dosing protocol was proposed. For the DIQ, patients would all be injected with 5.84 mCi. For the DMI, patients would be injected with a dose calculated by multiplying patients’ body weights by 0.06 mCi/kg, with a maximum injected dose of 11 mCi.

There are few existing measurements of low energy neutrino-nucleus interactions. The COHERENT collaboration is seeking to measure several of these processes using the intense pulsed neutrinos produced at the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory (ORNL).

The primary process of interest to COHERENT is coherent elastic neutrino-nucleus scattering (CEvNS), a process predicted in 1974 but only first measured by COHERENT in 2017. In a CEvNS interaction, a neutrino elastically scatters off a nucleus, causing its nucleons to recoil in phase, leading to a large increase in the scattering cross section. The large cross section provides several potential applications of CEvNS, however the signature of interaction, a keV-scale nuclear recoil, can be difficult to detect.

This thesis highlights experimental work to develop and measure neutrino-nucleus interactions on a variety of targets, including both CEvNS interactions and inelastic neutrino-nucleus interactions. This includes the development a ton-scale sodium-iodide scintillator array, a 185-kg prototype NaI detector, and analysis of neutrino-induced neutron detectors seeking to study unobserved neutrino-nucleus interactions on lead and iron. In addition, supporting measurements carried out at the Triangle Universities Nuclear Laboratory (TUNL) to measure quenching factors in NaI[Tl] are discussed.

A first measurement of $\nu_{e} + {}^{16}\text{O} \to e^{-} + {}^{16}\text{F}^{*}$ cross section from 45 MeV to 125 MeV was performed using the atmospheric neutrinos incident to the Super-Kamiokande detector over 24 years. This corresponds to an exposure of 485 kTon$\cdot$years, and 125 (after cuts) expected $\nu_{e} - {}^{16}\text{O}$ events between 45 and 125 MeV. An event generator to simulate $\nu_{e} - {}^{16}\text{O}$ interactions, a multivariate method to separate events with de-excitation gammas, and an unbinned likelihood fitter to extract the flux-weighted cross section are developed. Using these tools, a scaling factor of $1.87^{+0.35\text{(stat)}+0.62\text{(syst)}}_{-0.36\text{(stat)}-0.34\text{(syst)}}$ to the Haxton prediction was measured, corresponding to $233^{+89}_{-62}$ observed events and an atmospheric $\nu_{e}$ flux-weighted cross section of $10.8^{+4.1}_{-3.0} \times 10^{-40} \text{cm}^{2}$. This is $1.7\sigma$ larger than the Haxton prediction of $5.8 \times 10^{-40} \text{cm}^{2}$, and $3.6\sigma$ away from the null hypothesis. The measured ratio can be used to rescale the $\nu_{e} - {}^{16}\text{O}$ cross section in supernova burst studies and diffuse supernova neutrino background searches. Finally, atmospheric neutrinos at this energy range will be a background for the future WIMP dark matter searches via coherent elastic neutrino-nucleus scattering. Combined with an independent $\nu_{e} - {}^{16}\text{O}$ cross section measurement, this measurement can be used to constrain the uncertainties in the low energy atmospheric neutrino flux, which is relevant for the estimation of the WIMP neutrino floor.