Typescript (Photocopy) Includes copies of 5 published papers co-authored by the author in back Bibliography: leaves 214-230

<p>The technique of ESR-dosimetry and strategies for investigation of new materials as in regard to their applicability as ESR-dosimeters for radiotherapy has been reviewed. As an example six salts of formic and lactic acid has been evaluated. The applicability of the dosimeter has been judged by evaluating the tissue equivalence, radical yield, radical stability, spectral suitability, optimal readout parameters, dose response and sensitivity of the dosimetric system. Dependence of material characteristics and influence parameters has been analysed.</p><p>The reviewed methods have been successfully used for evaluation of the new materials. Lithium formate has been shown to be a good candidate relative to the state of the art dosimeter of alanine. Using optimal readout parameters lithium formate has been shown to be nine times as sensitive but even at moderate settings lithium formate is more sensitive. The results for lithium formate are in accordance to those of previous studies. The signal intensity of sodium formate has also proved to be high but unfortunately the signal fades rapidly.</p><p>Two new methods have been proposed as synthesis of the reviewed methods. The first allows flexible, effective and objective baseline correction of the ESR-spectrum. The second deals with dose response measurement by linear regression of the entire spectrum and was found to be successful in separating the spectral peaks of the induced radicals from the background signal.</p>

A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophagus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents. Each wall was divided into many small regions so that the histologic and radiosensitive variations of the tissues across the wall could be distinguished. The characteristic parameters were determined based on the newest information available in the literature. Each of these sections except the stomach was subdivided into multiple subsections to include the spatiotemporal variations in the shape and characteristic parameters. This new GIT was integrated into an anthropomorphic phantom representing both an adult male and a larger-than-average adult female. The current phantom contains 14 different types of tissue. This phantom was coupled with the MCNP 4C Monte Carlo simulation package. The initial design and coding of the phantom and the Monte Carlo treatment employed in this study were validated using the results obtained by Cristy and Eckerman (1987). The code was used for calculating specific absorbed fractions (SAFs) in various organs and radiosensitive tissues from uniformly distributed sources of fifteen monoenergetic photons and electrons, 10 keV - 4 MeV, in the lumenal contents of the five sections of the GIT. The present studies showed that the average photon SAFs to the walls were significantly different from that to the radiosensitive cells (stem cells) for the energies below 50 keV. Above 50 keV, the photon SAFs were found to be almost constant across the walls. The electron SAF at the depth of the stem cells was a small fraction of the SAF routinely estimated at the contents-mucus interface. Electron studies showed that the “self-dose” for the energies below 300 keV and the “cross-dose” below 2 MeV were only from bremsstrahlung and fluorescent radiations at the depth of the stem cells and were not important.

The technique of ESR-dosimetry and strategies for investigation of new materials as in regard to their applicability as ESR-dosimeters for radiotherapy has been reviewed. As an example six salts of formic and lactic acid has been evaluated. The applicability of the dosimeter has been judged by evaluating the tissue equivalence, radical yield, radical stability, spectral suitability, optimal readout parameters, dose response and sensitivity of the dosimetric system. Dependence of material characteristics and influence parameters has been analysed. The reviewed methods have been successfully used for evaluation of the new materials. Lithium formate has been shown to be a good candidate relative to the state of the art dosimeter of alanine. Using optimal readout parameters lithium formate has been shown to be nine times as sensitive but even at moderate settings lithium formate is more sensitive. The results for lithium formate are in accordance to those of previous studies. The signal intensity of sodium formate has also proved to be high but unfortunately the signal fades rapidly. Two new methods have been proposed as synthesis of the reviewed methods. The first allows flexible, effective and objective baseline correction of the ESR-spectrum. The second deals with dose response measurement by linear regression of the entire spectrum and was found to be successful in separating the spectral peaks of the induced radicals from the background signal.

Absorbed dose distributions in lineal energy for neutrons and gamma rays were measured by using both a tissue-equivalent walled counter (TEPC) and a graphite-walled low pressure proportional counter (GPC) in the Am-Be neutron source facility at UOIT. A series of measurements were performed with the counters filled with propane-based TE gas (55.1% C3H8, 39.5% CO2 and 5.4% N2) at operating gas pressures corresponding to tissue spheres 2.0 , 4.0 and 8.0 μm in diameter. The results of these measurements indicated satisfactory performance of counters to measure microdosimetric spectra extending down to event-sizes that cover the gamma component of a mixed field. The spectra and the related mean values ̅y F and ̅y D are compared with other similar work but with monoenergetic neutrons of different energy range, the agreement between them is good. An assessment of the performance of different size TEPC has been done. An excellent agreement between their event size spectra was found and the proton edge appears at the same position on the lineal energy scale and differences in microdosimetric parameters ̅ and ̅ is not exceeding 3%, which is in the region of counting statistics. In Am-Be neutron field, the efficiency of the TEPCs was measured to have an average value of 250 counts per μSv or equivalently about 4.17 counts per minutes per μSv/hr. This efficiency is reasonable for dose equivalent measurements but needs a long integration period. The measurements showed that the dose equivalent which depends on the measurement of energy deposition by the secondary charged particles was originated mainly from elastic collisions of the incident neutrons with hydrogen atoms. Moreover the number of events in the sensitive gas is dominated by proton recoils. A non- negligible fraction of the dose equivalent resulted from gamma interactions, alpha and recoil nuclei. The energy deposition patterns in these micro-scale targets are strongly dependent on radiation quality, so differences of linear energy transfer (LET) of the components in a mixed radiation field are significant. Accordingly, in a radiation field with an unknown gamma ray energy spectrum, absorbed dose for neutrons can be obtained by the separation of neutron induced events from gamma events using their distribution in lineal energy. To separate neutron dose from gamma dose a simple lineal energy threshold technique has been used in addition to a more sophisticated methods using γ-fitting and the graphite-walled counter measurements. The results of this study will establish the degree of error introduced by using a lineal energy threshold, which is likely to be used in any hand-held neutron monitor based on TEPCs. / UOIT

In this dissertation work, a computer simulation model based on the Geant4 simulation package has been designed and developed to study the energy deposition and track structures of cosmic muons and their secondary electrons in tissue-like materials. The particle interactions in a cubic water volume were first simulated. To analyze the energy deposition and tracks in small structures, with the intention of studying the energy localization in nanometric structures such as DNA, the chamber was sliced in three dimentions. Validation studies have been performed by comparing the results with experimental, theoretical, and other simulation results to test the accuracy of the simulation model. A human body phantom in sea-level muon environment was modeled to measure the yearly dose to a human from cosmic muons. The yearly dose in this phantom is about 22 millirems. This is close to the accepted value for the yearly dose from cosmic radiation at sea level. Shielding cosmic muons with a concrete slab from 0 to 2 meters increased the dose received by the body. This dissertation presents an extensive study on the interactions of secondary electrons created by muons in water.

Microbeam Radiation Therapy (MRT) is an experimental form of radiation treatment which has the potential to improve the treatment of many types of cancer. In MRT, the radiation is applied as a grid by passing the collimated X-ray beam from a synchrotron through a microplane collimator, which is a stack of parallel plates of two materials with dramatically different X-ray transparencies. The peak-to-valley dose ratio (PVDR) is the difference between the dose in the microbeams and the dose delivered between the beams. It is the PVDR that is of biological importance in MRT. Therefore a dosimeter for MRT requires a combination of a large dynamic range for dose response into the kilo-Gray regime, and high spatial resolution on the micron scale. This project characterizes fluorophosphate glasses doped with trivalent samarium ions as a potential valency conversion dosimeter for MRT using the conversion of Sm3+→Sm2+ to measure the delivered dose. Samples irradiated at the Canadian Light Source synchrotron showed X-ray induced conversion that could be optically characterized by changes in the photoluminescence emission spectra to obtain irradiation dose. The conversion efficiency depends almost linearly on the irradiation dose up to 150 Gy and saturates at doses exceeding 1500 Gy. The conversion shows a strong correlation with an observed increase in absorbance of the glass in the range of 200-750 nm. The absorbance increases with X-ray dose and is related to the formation of phosphorous-oxygen hole centers (POHC) and POn electron centers. The presence of these defects within the irradiated glass was determined by examination of the induced optical absorbance and electron paramagnetic resonance (EPR) spectra. The formation of these hole centers along with the conversion of Sm3+→Sm2+ under X-ray irradiation suggests that the X-rays cause the formation of electron-hole pairs in the glass. The electrons are then primarily captured by the Sm3+ ions, becoming Sm2+ ions, with some of the electrons being captured by POn electron centers. The holes are captured by the POHCs. This process can be represented chemically as Sm3+ + e-→ Sm2+ and PO + h+→POHC. The stability of the Sm conversion under illumination was examined using photoluminescence spectra and the stability of the X-ray induced defects was examined via the induced optical absorbance and EPR spectra.

<p>Optical-CT has been shown to be a potentially useful imaging tool for for the two very different spheres of biologists and radiation therapy physicists, but it has yet to live up to that potential. In radiation therapy, researchers have used optical-CT for the readout of 3D dosimeters, but it is yet to be a clinically relevant tool as the technology is too slow to be considered practical. Biologists have used the technique for structural imaging, but have struggled with emission tomography as the reality of photon attenuation for both excitation and emission have made the images quantitatively irrelevant. </p><p><bold>Dosimetry.</bold> The DLOS (Duke Large field of view Optical-CT Scanner) was designed and constructed to make 3D dosimetry utilizing optical-CT a fast and practical tool while maintaining the accuracy of readout of the previous, slower readout technologies. Upon construction/optimization/implementation of several components including a diffuser, band pass filter, registration mount & fluid filtration system the dosimetry system provides high quality data comparable to or exceeding that of commercial products. In addition, a stray light correction algorithm was tested and implemented. The DLOS in combination with the 3D dosimeter it was designed for, PREAGETM, then underwent rigorous commissioning and benchmarking tests validating its performance against gold standard data including a set of 6 irradiations. </p><p>DLOS commissioning tests resulted in sub-mm isotropic spatial resolution (MTF >0.5 for frequencies of 1.5lp/mm) and a dynamic range of ~60dB . Flood field uniformity was 10% and stable after 45minutes. Stray light proved to be small, due to telecentricity, but even the residual can be removed through deconvolution. Benchmarking tests showed the mean 3D passing gamma rate (3%, 3mm, 5% dose threshold) over the 6 benchmark data sets was 97.3% ± 0.6% (range 96%-98%) scans totaling ~10 minutes, indicating excellent ability to perform 3D dosimetry while improving the speed of readout. Noise was low at ~2% for 2mm reconstructions. The DLOS/PRESAGE® benchmark tests show consistently excellent performance, with very good agreement to simple known distributions. The telecentric design was critical to enabling fast (~15mins) imaging with minimal stray light artifacts. The system produces accurate isotropic 2mm3 dose data over clinical volumes (e.g. 16cm diameter phantoms, 12 cm height), and represents a uniquely useful and versatile new tool for commissioning complex radiotherapy techniques. The system also has wide versatility, and has successfully been used in preliminary tests with protons and with kV irradiations.</p><p><bold>Biology.</bold> Attenuation corrections for optical-emission-CT were done by modeling physical parameters in the imaging setup within the framework of an ordered subset expectation maximum (OSEM) iterative reconstruction algorithm. This process has a well documented history in single photon emission computed tomography (SPECT), but is inherently simpler due to the lack of excitation photons to account for. Excitation source strength distribution, excitation and emission attenuation were modeled. The accuracy of the correction was investigated by imaging phantoms containing known distributions of attenuation and fluorophores. The correction was validated on a manufactured phantom designed to give uniform emission in a central cuboidal region and later applied to a cleared mouse brain with GFP (green-fluorescent-protein) labeled vasculature and a cleared 4T1 xenograft flank tumor with constitutive RFP (red-fluorescent-protein). Reconstructions were compared to corresponding slices imaged with a fluorescent dissection microscope. </p><p>Significant optical-ECT attenuation artifacts were observed in the uncorrected phantom images and appeared up to 80% less intense than the verification image in the central region. The corrected phantom images showed excellent agreement with the verification image with only slight variations. The corrected tissue sample reconstructions showed general agreement between the verification images. Comprehensive modeling in optical-ECT imaging was successfully implemented, creating quantitatively accurate 3D fluorophore distributions. This work represents the 1st successful attempt encompassing such a complete set of corrections. This method provides a means to accurately obtain 3D fluorophore distributions with the potential to better understand tumor biology and treatment responses.</p> / Dissertation

As radiation specialists, one of our primary objectives in the Navy is protecting people and the environment from the effects of ionizing and non-ionizing radiation. Focusing on radiological dispersal devices (RDD) will provide increased personnel protection as well as optimize emergency response assets for the general public. An attack involving an RDD has been of particular concern because it is intended to spread contamination over a wide area and cause massive panic within the general population. A rapid method of triage will be necessary to segregate the unexposed and slightly exposed from those needing immediate medical treatment. Because of the aerosol dispersal of the radioactive material, inhalation of the radioactive material may be the primary exposure route. The primary radionuclides likely to be used in a RDD attack are Co-60, Cs-137, Ir-192, Sr-90 and Am-241. Through the use of a MAX phantom along with a few Simulink MATLAB programs, a good anthropomorphic phantom was created for use in MCNPX simulations that would provide organ doses from internally deposited radionuclides. Ludlum model 44-9 and 44-2 detectors were used to verify the simulated dose from the MCNPX code. Based on the results, acute dose rate limits were developed for emergency response personnel that would assist in patient triage.

A novel Y-90 liquid brachytherapy strategy is currently being studied for the treatment of osteosarcoma using a preclinical translational model in dogs to assess its potential efficacy and toxicity. In this study, dosimetry calculations are performed for Y-90 liquid brachytherapy in a dog with osteosarcoma using the Geant4 Monte Carlo code. A total of 611.83 MBq Y-90 radiopharmaceutical is administered via direct injections, and the in vivo distribution of Y-90 is assessed using a time-of-flight (TOF) PET/CT scanner. A patient-specific geometry is built using anatomical data obtained from CT images. The material properties of tumor and surrounding tissues are calculated based on a CT number - electron density calibration. The Y-90 distribution is sampled in Geant4 from PET images using a collapsing 3-D rejection technique to determine the decay sites. Dose distributions in the tumor bed and surrounding tissues are calculated demonstrating significant heterogeneity with multiple hot spots at the injection sites. Dose volume histograms show about 33.9 percent of bone and tumor and 70.2 percent of bone marrow and trabecular bone receive a total dose over 200 Gy; about 3.2 percent of bone and tumor and 31.0 percent of bone marrow and trabecular bone receive a total dose of over 1000 Gy. Y-90 liquid brachytherapy has the potential to be used as an adjuvant therapy or for palliation purposes. Future work includes evaluation of pharmacokinetics of the Y-90 radiopharmaceutical, calibration of PET/CT scanners for the direct quantitative assessment of Y-90 activity concentration, and assessment of efficacy of the Y-90 liquid brachytherapy strategy.