<p>Excess sodium (Na) intake is directly related to hypertension and an increased risk of developing many chronic diseases, but there is currently no method to directly quantify Na retained in the body. Because of this, the locations of Na storage and its exchange mechanisms are not well known. This information is critical for understanding the impact of increased Na intake in modern diets. In order to non-invasively quantify Na in bone and soft tissue, a compact deuterium-deuterium (DD) neutron generator-based <i>in vivo</i> neutron activation analysis (IVNAA) system was developed. MCNP was used to design a custom irradiation assembly to maximize Na activation in hand bone while minimizing dose. In order to test the system, live pigs were used. Two 100% efficient high purity germanium (HPGe) detectors collected Na-24 counts over 24 hours post irradiation. From the pig studies, a two-compartment model of exchange was developed to quantify Na in bone and in soft tissue. The right legs of four live pigs, two on a low Na diet and two on a high Na diet, both for 14 days, were irradiated inside the customized irradiation cave for 10 minutes (45 mSv dose to the leg) and then measured with the HPGe detectors. The spectra were analyzed to obtain the net Na counts at different time points. Analysis shows exponential decrease of Na in the leg during the first one hour of measurement, while the change was minimal at the second hour, and the counts were stabilized at the second and third 2 hour measurements, taken 7 and 21 hours post irradiation. Bone Na and soft tissue Na concentrations were calculated using calibration lines created with bone and soft tissue equivalent Na phantoms as well as the parameters obtained from the two-compartment model. The results show that the difference in bone and soft tissue Na between the pigs on high vs low Na diets was significant. With these results, we conclude that DD neutron generator-based IVNAA can be used to accurately quantify Na in bone and soft tissue <i>in vivo </i>and the system is a potential valuable tool for nutrition studies.</p>

<p>Proton beam therapy has shown great promise for cancer treatment due to its high precision in irradiating tumor volumes. However, due to the massive size and expense of the cyclotrons/synchrotrons needed to accelerate the protons, the widespread use of proton therapy is limited. Laser plasma accelerated (LPA) proton beams may be a potential alternative to conventional proton beams: by shooting an ultraintense, ultrashort pulsed laser at a thin target, a plasma sheath electric field may be formed with the capability of accelerating protons to potentially therapeutic energies in very short distances. In addition to accessibility, there is significant uncertainty in proton range in heterogeneous tissues. Thermoacoustic computed tomographic (TACT) imaging has the potential to provide <em>in vivo</em> dose imaging and range verification to address these uncertainties. TACT measures thermoacoustic waves generated from the absorbed dose and implements a 3D filtered backprojection to reconstruct volumetric images of the dose. The purpose of this thesis is to determine the feasibility of integrating LPA proton beams with thermoacoustic imaging into a novel image-guided small animal therapy platform as an early step towards clinical  translation to address the issues of accessibility and dosimetric spatial uncertainty. A Monte Carlo (MC) method is used to simulate an LPA proton beam with characteristics based on literature, thermoacoustic waves are simulated on a voxel-wise basis of the MC dose, and 3D filtered backprojection is used to reconstruct a volumetric image of the dose. In Specific Aim 1, the dependence of image accuracy on transducer array angular coverage is investigated; in Specific Aim 2, an iterative reconstruction algorithm is implemented to improve image accuracy through increased sampling of projection space when transducer array angular coverage is insufficient; and in Specific Aim 3, the detector sensitivity to dose is determined for several therapeutic endpoints. The work presented in this thesis not only demonstrates the feasibility of integrating LPA and thermoacoustic technologies but necessary design changes to realize a functional small animal platform.</p>

Ionization chambers (ICs) are the most commonly used detectors for radiation therapy dose measurements. Typical IC measurements use cylindrical ICs in a water phantom and therefore require initial IC alignment to the water surface. This alignment has long been ignored and only recently has a qualitative governing recommendation been made. This thesis describes a reproducible methodology for quantitative ionization chamber water surface alignment. Depth-ionization measurements are taken with twenty-eight IC designs under varying conditions including, but not limited to, changes in scan direction, speed, and resolution, radiation beam type, field size, energy, and electron contamination. Measurements are acquired using standard radiotherapy accelerators in the Virginia Commonwealth University Department of Radiation Oncology and at the National Research Council of Canada, where a customized scanning system capable of better than 0.15 mm IC positioning precision is used. Measurements are also performed with standard commercial scanning equipment on the Accuray CyberKnife, a specialized radiosurgery-class accelerator. An analytical model is developed from basic principles to test the theoretical foundations of IC response near a water surface. The theoretical foundation is further validated via Monte Carlo simulation models that fully account for all details of the ICs used to take measurements. It is determined that the dose gradient as a function of depth is maximized when a given IC reaches the water surface when moving from depth in water. This effect is unchanged under all of the measurement scenarios tested. Measurements taken at 0.1 mm resolution for several seconds per point over several millimeters near the surface will yield a gradient peak that can be used for quantitative alignment. Using developed software, multiple scans at variant resolutions can be stitched into typical clinical scans so as not to significantly affect clinical measurement workflow. The recommended measurement method is developed in a format suitable for inclusion into a clinical protocol for depth-ionization measurement acquisition.

Doctor of Philosophy / Department of Physics / Dean A. Zollman / In this study we explored students' transfer of learning in the X-ray medical imaging context, including the X-ray-based computer-assisted tomography (or CAT). For this purpose we have conducted a series of clinical and teaching interviews. The investigation was a part of a bigger research effort to design teaching-learning materials for pre-medical students who are completing their algebra-based physics course. Our students brought to the discussion pieces of knowledge transferred from very different sources such as their own X-ray experiences, previous learning and the mass media. This transfer seems to result in more or less firm mental models, although often not internally consistent or coherent. Based on our research on pre-med students' models of X-rays we designed a hands-on lab using semi-transparent Lego bricks to model CAT scans. Without "surgery" (i.e. without intrusion into the Lego "body") students determined the shape of an object, which was built out of opaque and translucent Lego bricks and hidden from view. A source of light and a detector were provided upon request. Using a learning cycle format, we introduced CAT scans after students successfully have completed this task. By comparing students' ideas before and after teaching interview with the groups of 2 or 3 participants, we have investigated transfer of learning from basic physics and everyday experience to a complex medical technology and how their peer interactions trigger and facilitate this process. During the last phase of our research we also introduced a CAT-scan simulation problem into our teaching interview routine and compared students' perception of this simulation and their perception of the hands-on activity.

In recent years, small fields have come to play a key role in advanced radiotherapy, yet protocols to perform dosimetry under small field conditions are still in their infancy. In 2008, the IAEA and AAPM published a formalism [Med. Phys. 35, 5179-5186] recommending the use of point-dose correction factors. This thesis uses Monte Carlo simulations to demonstrate that the values of these correction factors depend strongly on both detector design and field size, as well as other variables such as detector off-axis position and detector azimuthal angle. Mass density is found to be the principal determinant of detector water non-equivalence. Furthermore, it is shown that it is possible to compensate for the mass-density of a detector cavity by incorporating additional components of contrasting mass-density into that detector’s design. For small cavities, such design modifications enable the detector’s small- to large- field response ratio to be matched to that of a “point-like” water-structure: ideal detector performance can be achieved across a variety of irradiation conditions. For existing commercial detectors, a Dose Area Product (DAP) formalism is also developed and shown to be much more robust than the point-dose correction factor approach. In conclusion, correction factor values for existing detector designs depend on a host of variables and their calculation typically relies on the use of time-intensive Monte Carlo methods. This thesis indicates that future moves towards density-compensated detector designs or DAP-based protocols can simplify the methodology of small field dosimetry.

A hybrid stochastic-deterministic method, COMET-PE, is developed for dose calculation in radiotherapy. Fast, accurate dose calculation is a key component of successful radiotherapy treatment. To calculate dose, COMET-PE solves the coupled Boltzmann Transport Equations for photons and electrons. The method uses a deterministic iteration to compose response functions that are pre-computed using Monte Carlo. Thus, COMET-PE takes advantage of Monte Carlo physics without incurring the computational costs typically required for statistical convergence. This work extends the method to 3-D problems with realistic source distributions. Additionally, the performance of the deterministic solver is improved, taking advantage of both shared-memory and distributed-memory parallelism to enhance efficiency. To verify the method’s accuracy, it is compared with the DOSXYZnrc (Monte Carlo) method using three different benchmark problems: a heterogeneous slab phantom, a water phantom, and a CT-based lung phantom. For the slab phantom, all errors are less than 1.5% of the maximum dose or less than 3% of local dose. For both the water phantom and the lung phantom, over 97% of voxels receiving greater than 10% of the maximum dose pass a 2% (relative error) / 2 mm (distance-to-agreement) test. Timing comparisons show that COMET-PE is roughly 10-30 times faster than DOSXYZnrc. Thus, the new method provides a fast, accurate alternative to Monte Carlo for dose calculation in radiotherapy treatment planning.

Δεδομένης και της χρήσης της τεχνικής SPECT, ο σκοπός της παρούσας διπλωματικής εργασίας είναι η διερεύνηση του κατά πόσο μπορούν, συνδυαστικά, οι 5 αυτές τεχνικές να δείξουν μία πιο σαφή εικόνα στη διαφορική διάγνωση όγκων του ΚΝΣ. Συνδυάζοντας τα δεδομένα που θα ληφθούν από τις μετρήσεις θα δημιουργηθεί μια μικρή βάση δεδομένων η οποία ως απώτερο στόχο θα έχει τη διεύρυνσή της στο μέλλον και συνεπώς την εξαγωγή ασφαλέστερων συμπερασμάτων. / Combination and evaluation of advanced MR techniques (MRS, DWI, DTI, PWI) and Scintigraphy in the differential diagnosis of Central Nervous System tumors.

Electron beam therapy planning and custom electron bolus design were identified as areas in which improvements in equipment and techniques could lead to significant improvements in treatment delivery and patient outcomes. The electron pencil beam algorithms used in conventional Treatment Planning Systems do not accurately model the dose distribution in irregularly shaped objects, near oblique surfaces or in inhomogeneous media. For this reason, at Christchurch Oncology Centre the TPS is not relied on for planning electron beam treatments. This project is an initial study of ways to improve the design of custom electron bolus, the planning of electron beam therapy, and other radiation therapy simulation tasks, by developing a system for the accurate assessment of dose distributions under irregular contours in clinically relevant situations. A shaped water phantom system and a diode array have been developed and tested. The design and construction of this water phantom dosimetry system are described, and its capabilities and limitations discussed. An EGS/BEAM Monte Carlo simulation system has been installed, and models of the Christchurch Oncology Centre linacs in 6MeV and 9MeV electron beam modes have been built and commissioned. A test was run comparing the EGS/BEAM Monte Carlo system and the CMS Xio conventional treatment planning system with the experimental measurement technique using the water phantom and the diode array. This test was successful as a proof of the concept of the experimental technique. At the conclusion of this project, the main limitation of the diode array system was the lack of data processing software. The array produces a large volume of raw data, but not enough processed data was produced during this project to match the spatial resolution of the computer models. An automated data processing system will be needed for clinical use of the array. It has been confirmed that Monte Carlo and pencil-beam algorithms predict significantly different dose distributions for an irregularly shaped object irradiated with megavoltage electron beams. The results from the diode array were consistent with the theoretical models. This project was an initial investigation. At the time of writing, the diode array and the water phantom systems were still at an early stage of development. The work reported here was performed to build, test and commission the equipment. Additional work will be needed to produce an instrument for clinical use. Research into electron beam therapy could be continued, or the equipment used to expand research into new areas.

3T MRI provides higher signal-to-noise ratio images compared to lower field machines. However, a major drawback of 3T MRI is a higher B1 transmission-field inhomogeneity across the field-of-view compared to imaging at lower fields. B1-field mapping was performed on volunteers using a Philips 3.0T MR scanner and a typical head-first prone patient positioning technique. The B1-field transmitted in the breasts was found to be reduced towards the right side of the body. In some volunteers, the B1-field was reduced to about one-half of the nominal field in the right breast. To minimize the B1 inhomogeneity artefacts, a saturation recovery snapshot FLASH (SRSF) imaging sequence was proposed. Different saturation techniques were assessed. The best saturation efficiency was produced by Hoffmann’s saturation method. By using Hoffmann’s SRSF sequence, the error in the enhancement ratio (ER) can be reduced to about one half compared to imaging obtained using typical FLASH sequence in the presence of a 50% B1-field reduction. Other techniques i.e. bilateral power optimization and a dedicated patient support system were also tested. Both of these approaches produced substantial reductions of the B1 inhomogeneity seen with the standard technique. To address the effects of the native T1 (T10) of different tissues on DCE-MRI, novel enhancement factor indices calculated using SRSF sequence images were introduced and assessed. Computer simulations and gel phantom experiments showed that less error was observed in the indices calculated compared to the ER calculated using the conventional and widely used FLASH sequence. Furthermore, the effect of B1-field inhomogeneity on the novel indices is also reduced. One of the indices proposed is directly related to the contrast agent concentration. The theory and results presented show that the SRSF pulse sequence and the quantification techniques proposed have the potential to improve the accuracy of breast DCE-MRI at 3T.

No description available.