Monte Carlo Analysis and Physics Characterization of a Novel Nanoparticle Detector for Medical and Micro-dosimetry Applications

The outcomes for both (i) radiation therapy and (ii) preclinical small animal radio- biology studies are dependent on the delivery of a known quantity of radiation to a specific and intentional location. Adverse effects can result from these procedures if the dose to the target is too high or low, and can also result from an incorrect spatial distribution in which nearby normal healthy tissue can be undesirably damaged by poor radiation delivery techniques. Thus, in mice and humans alike, the spatial dose distributions from radiation sources should be well characterized in terms of the absolute dose quantity, and with pin-point accuracy. When dealing with the steep spatial dose gradients consequential to either (i) high dose rate (HDR) brachytherapy or (ii) within the small organs and tissue inhomogeneities of mice, obtaining accurate and highly precise dose results can be very challenging, considering commercially available radiation detection tools, such as ion chambers, are often too large for in-vivo use.

In this dissertation two tools are developed and applied for both clinical and preclinical radiation measurement. The first tool is a novel radiation detector for acquiring physical measurements, fabricated from an inorganic nano-crystalline scintillator that has been fixed on an optical fiber terminus. This dosimeter allows for the measurement of point doses to sub-millimeter resolution, and has the ability to be placed in-vivo in humans and small animals. Real-time data is displayed to the user to provide instant quality assurance and dose-rate information. The second tool utilizes an open source Monte Carlo particle transport code, and was applied for small animal dosimetry studies to calculate organ doses and recommend new techniques of dose prescription in mice, as well as to characterize dose to the murine bone marrow compartment with micron-scale resolution.

Hardware design changes were implemented to reduce the overall fiber diameter to <0.9 mm for the nano-crystalline scintillator based fiber optic detector (NanoFOD) system. Lower limits of device sensitivity were found to be approximately 0.05 cGy/s. Herein, this detector was demonstrated to perform quality assurance of clinical 192Ir HDR brachytherapy procedures, providing comparable dose measurements as thermo-luminescent dosimeters and accuracy within 20% of the treatment planning software (TPS) for 27 treatments conducted, with an inter-quartile range ratio to the TPS dose value of (1.02-0.94=0.08). After removing contaminant signals (Cerenkov and diode background), calibration of the detector enabled accurate dose measurements for vaginal applicator brachytherapy procedures. For 192Ir use, energy response changed by a factor of 2.25 over the SDD values of 3 to 9 cm; however a cap made of 0.2 mm thickness silver reduced energy dependence to a factor of 1.25 over the same SDD range, but had the consequence of reducing overall sensitivity by 33%.

For preclinical measurements, dose accuracy of the NanoFOD was within 1.3% of MOSFET measured dose values in a cylindrical mouse phantom at 225 kV for x-ray irradiation at angles of 0, 90, 180, and 270˝. The NanoFOD exhibited small changes in angular sensitivity, with a coefficient of variation (COV) of 3.6% at 120 kV and 1% at 225 kV. When the NanoFOD was placed alongside a MOSFET in the liver of a sacrificed mouse and treatment was delivered at 225 kV with 0.3 mm Cu filter, the dose difference was only 1.09% with use of the 4x4 cm collimator, and -0.03% with no collimation. Additionally, the NanoFOD utilized a scintillator of 11 µm thickness to measure small x-ray fields for microbeam radiation therapy (MRT) applications, and achieved 2.7% dose accuracy of the microbeam peak in comparison to radiochromic film. Modest differences between the full-width at half maximum measured lateral dimension of the MRT system were observed between the NanoFOD (420 µm) and radiochromic film (320 µm), but these differences have been explained mostly as an artifact due to the geometry used and volumetric effects in the scintillator material. Characterization of the energy dependence for the yttrium-oxide based scintillator material was performed in the range of 40-320 kV (2 mm Al filtration), and the maximum device sensitivity was achieved at 100 kV. Tissue maximum ratio data measurements were carried out on a small animal x-ray irradiator system at 320 kV and demonstrated an average difference of 0.9% as compared to a MOSFET dosimeter in the range of 2.5 to 33 cm depth in tissue equivalent plastic blocks. Irradiation of the NanoFOD fiber and scintillator material on a 137Cs gamma irradiator to 1600 Gy did not produce any measurable change in light output, suggesting that the NanoFOD system may be re-used without the need for replacement or recalibration over its lifetime.

For small animal irradiator systems, researchers can deliver a given dose to a target organ by controlling exposure time. Currently, researchers calculate this exposure time by dividing the total dose that they wish to deliver by a single provided dose rate value. This method is independent of the target organ. Studies conducted here used Monte Carlo particle transport codes to justify a new method of dose prescription in mice, that considers organ specific doses. Monte Carlo simulations were performed in the Geant4 Application for Tomographic Emission (GATE) toolkit using a MOBY mouse whole-body phantom. The non-homogeneous phantom was comprised of 256x256x800 voxels of size 0.145x0.145x0.145 mm3. Differences of up to 20-30% in dose to soft-tissue target organs was demonstrated, and methods for alleviating these errors were suggested during whole body radiation of mice by utilizing organ specific and x-ray tube filter specific dose rates for all irradiations.

Monte Carlo analysis was used on 1 µm resolution CT images of a mouse femur and a mouse vertebra to calculate the dose gradients within the bone marrow (BM) compartment of mice based on different radiation beam qualities relevant to x-ray and isotope type irradiators. Results and findings indicated that soft x-ray beams (160 kV at 0.62 mm Cu HVL and 320 kV at 1 mm Cu HVL) lead to substantially higher dose to BM within close proximity to mineral bone (within about 60 µm) as compared to hard x-ray beams (320 kV at 4 mm Cu HVL) and isotope based gamma irradiators (137Cs). The average dose increases to the BM in the vertebra for these four aforementioned radiation beam qualities were found to be 31%, 17%, 8%, and 1%, respectively. Both in-vitro and in-vivo experimental studies confirmed these simulation results, demonstrating that the 320 kV, 1 mm Cu HVL beam caused statistically significant increased killing to the BM cells at 6 Gy dose levels in comparison to both the 320 kV, 4 mm Cu HVL and the 662 keV, 137Cs beams.

Collimation of a D-D Neutron Generator for Clinical Implementation of Neutron Stimulated Emission Computed Tomography: a Monte Carlo Study

This work is an investigation into collimator designs for a deuterium-deuterium (DD) neutron generator for an inexpensive and compact neutron imaging system that can be implemented in a hospital. The envisioned application is for a spectroscopic imaging technique called neutron stimulated emission computed tomography (NSECT).

Previous NSECT studies have been performed using a Van-de-Graaff accelerator at the Triangle Universities Nuclear Laboratory (TUNL) in Duke University. This facility has provided invaluable research into the development of NSECT. To transition the current imaging method into a clinically feasible system, there is a need for a high-intensity fast neutron source that can produce collimated beams. The DD neutron generator from Adelphi Technologies Inc. is being explored as a possible candidate to provide the uncollimated neutrons. This DD generator is a compact source that produces 2.5 MeV fast neutrons with intensities of 1012 n/s (4π). The neutron energy is sufficient to excite most isotopes of interest in the body with the exception of carbon and oxygen. However, a special collimator is needed to collimate the 4π neutron emission into a narrow beam. This work describes the development and evaluation of a series of collimator designs to collimate the DD generator for narrow beams suitable for NSECT imaging.

A neutron collimator made of high-density polyethylene (HDPE) and lead was modeled and simulated using the GEANT4 toolkit. The collimator was designed as a 52 x 52 x 52 cm3 HDPE block coupled with 1 cm lead shielding. Non-tapering (cylindrical) and tapering (conical) opening designs were modeled into the collimator to permit passage of neutrons. The shape, size, and geometry of the aperture were varied to assess the effects on the collimated neutron beam. Parameters varied were: inlet diameter (1-5 cm), outlet diameter (1-5 cm), aperture diameter (0.5-1.5 cm), and aperture placement (13-39 cm). For each combination of collimator parameters, the spatial and energy distributions of neutrons and gammas were tracked and analyzed to determine three performance parameters: neutron beam-width, primary neutron flux, and the output quality. To evaluate these parameters, the simulated neutron beams are then regenerated for a NSECT breast scan. Scan involved a realistic breast lesion implanted into an anthropomorphic female phantom.

This work indicates potential for collimating and shielding a DD neutron generator for use in a clinical NSECT system. The proposed collimator designs produced a well-collimated neutron beam that can be used for NSECT breast imaging. The aperture diameter showed a strong correlation to the beam-width, where the collimated neutron beam-width was about 10% larger than the physical aperture diameter. In addition, a collimator opening consisting of a tapering inlet and cylindrical outlet allowed greater neutron throughput when compared to a simple cylindrical opening. The tapering inlet design can allow additional neutron throughput when the neck is placed farther from the source. On the other hand, the tapering designs also decrease output quality (i.e. increase in stray neutrons outside the primary collimated beam). All collimators are cataloged in measures of beam-width, neutron flux, and output quality. For a particular NSECT application, an optimal choice should be based on the collimator specifications listed in this work.