<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

Radiation therapy, one of the most common forms of cancer treatment, is continually evolving with the introduction of new technology, more complex treatments and more advanced radiation dose calculations. To ensure the effectiveness and safety of modern radiation therapy, dose measurement tools must improve to accommodate these advances. X-ray computed tomography (CT) polymer gel dosimetry is a unique type of dosimeter that has many advantages and the potential to address some of the challenges in the verification of dose delivery and calculation in radiation therapy. This dissertation investigates the advancement of an x-ray CT polymer gel dosimetry system for use in clinical applications and in particular for deformable dose verification. The first part of this work consists of a reproducibility study of an established x-ray CT polymer gel dosimetry system in an effort to determine the accuracy and precision of dose measurements made with this system and the feasibility of interbatch and generic calibration. Gel measurements were found to have excellent agreement with Monte Carlo dose calculation when using a generic calibration curve. The excellent dosimetric and spatial accuracy established in this study suggest that this dosimetry system is ideally suited for the measurement of high-dose fractionation treatments such as stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT). The second stage was the development and characterization of the first deformable x-ray CT polymer gel dosimetry system. This study established the setup reproducibility, deformation characteristics and dose response of the new deformable system. The dose response was found to be similar to that of the non-deformable system with similar dosimetric and spatial accuracy when compared to Monte Carlo dose calculation. The system was also found to have sub-millimetre setup reproducibility and the deformable dosimeter was found to reproducibly deform and relax for external compression of up to 30 mm and over 100 consecutive compressions. This work established several important characteristics of the new deformable dosimetry system and it shows excellent potential for use in the evaluation of deformable dose accumulation algorithms. The final component of this dissertation was the use of the newly developed deformable dosimetry system in the evaluation of a novel deformable dose accumulation algorithm, defDOSXYZ. Gel measurements and defDOSXYZ showed excellent agreement in the case of a static control case and this set a benchmark for deformable dose measurements. Measurements of deformed dose by the gel dosimeter showed significant disagreement with dose deformed by defDOSXYZ and the dosimetric differences were well outside the uncertainties established in the first two studies of this dissertation. The results from this study provided some insight into potential avenues of improvement for both the deformable dose calculation and deformable dose measurements. These results were also the first example of deforming dose measured by an x-ray CT read out gel dosimetry system. Overall, the results in this dissertation represent a significant advancement in x-ray CT polymer gel dosimetry and establish its suitability for several clinical applications. / Graduate / 2019-12-06

New radiation therapy (RT) techniques for treating cancer are continually under development. Our ability to demonstrate the safe and accurate implementation of new RT treatment techniques is dependent on the information provided by current dosimetric tools. Advanced dosimetric tools will become increasingly necessary as treatments become more complex. This work examines the readout of an advanced dosimeter --- the polyacrylamide, gelatin, and tetrakis (hydroxymethyl) phosphonium chloride (PAGAT) dosimeter --- using a prototype fan-beam optical computed tomography (CT) scanner. A number of developments sought to improve the performance of the optical CT device. A new fan-creation method (laser diode module) and new matching tank were introduced. Artefact removal techniques were developed to remove flask seam artefacts and ring artefacts via sinogram space. A flask registration technique was established to achieve reproducible placement of flasks in the optical CT scanner. A timing-correction technique was implemented to allow for the scanning of continuously rotating samples. A number of experiments examined factors related to the PAGAT dosimeter. Comparisons of post-irradiation scans to pre-irradiation scans improved dosimeter readout quality. Changes to the PAGAT dosimeter cooling/scanning routine provided further improvements to dosimeter readout. Evaluations of calibration curves showed that a linear calibration curve was less capable of describing PAGAT dose response than a quadratic calibration curve. Intra-gel calibration using another dose distribution was shown to be no less accurate than self calibration, but inter-gel calibrations saw a statistically significant increase in absolute readout errors. A set of investigations examined how optical CT scanning protocols affected readout quality for PAGAT dosimeters. Doubling the dose delivered to the dosimeter doubled the signal-to-noise ratio. Acquiring and averaging additional light profiles at each projection angle provided only slight reductions in readout noise. Sampling a higher number of projection angles provided substantial reductions in readout noise. Those reductions in readout noise were not lost when sinograms with many projections were encapsulated into sinograms of fewer projection angles. Detector element binning (sinogram space) and pixel binning (image space) also provided substantial reductions in readout noise. None of these elements of the scanning protocol had statistically significant effects on readout errors. Finally, distinct imaging artefacts seen throughout this work were shown to be caused by radiation-induced refractive index changes in PAGAT dosimeters. Radiation-induced refraction (RIR) artefacts result when dose gradients caused the refraction of fan-beam raylines towards high dose regions. A filtering technique was developed to remove RIR artefacts in sinogram space, but this technique caused substantial blurring to the measured dose distribution. / Graduate / 0760 / 0756 / 0752 / warreng1983@gmail.com

A dynamic mathematical model was developed to simulate the response of polyacrylamide gel (PAG) dosimeters to a single spherical radioactive brachytherapy seed. Simulations were conducted for a high dose-rate (HDR) seed using 192Ir and a low dose-rate (LDR) seed using 125I. The model is able to predict the amount of polymer formed, the crosslink density, and the volume fraction of aqueous phase as a function of radial distance and time. Results show that PAG dosimeters can provide accurate HDR brachytherapy dosimetry at distances larger than 4 mm from the centre of the seed but will give poor results for LDR due to monomer diffusion. Experiments were conducted to evaluate the potential for using pentacosa-10,12-diynoic acid (PCDA) as the reporter molecule in micelle gel dosimeters for optical computed tomography (CT) readout. Several gels containing PCDA that was solubilized using sodium dodecyl sulfate (SDS) responded to radiation by changing from colourless to blue. Unfortunately, all phantoms that showed colour changes were turbid, making them unsuitable for optical CT scanning. Several techniques were used to produce transparent gels containing PCDA but none of these gels responded noticeably to radiation. Only turbid gels with precipitated PCDA responded, indicating that the colour change was due to oligomerization within PCDA crystals and that PCDA molecules solubilized in micelles did not undergo oligomerization. As a result, PCDA is not suitable for use in radiochromic micelle gel dosimeters. A new recipe for a radiochromic leuco crystal violet (LCV) micelle gel dosimeters with enhanced dose sensitivity was developed for optical CT readout. The recipe contains LCV, trichloro acetic acid (TCAA), Cetyl Trimethyl Ammonium Bromide (CTAB), 2,2,2-Trichloroethanol (TCE), and gelatin. Experiments were conducted to improve understanding about interactions between the different components of LCV micelle gel, highlighting the importance of pH on dose sensitivity and transparency. Results also showed the effectiveness of chlorinated compounds in improving dose sensitivity. Statistical techniques were used to build empirical models that were used to optimize the gel recipe. Additional testing in larger phantoms will be required to assess the effectiveness of the proposed gel for clinical dosimetry. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2014-03-27 11:11:47.655

The current state of a prototype fan-beam optical computed tomography scanner for three-dimensional radiation dosimetry has been presented. The system uses a helium-neon laser and a line-generating lens for fan-beam creation. Five photodiode arrays form an approximate arc detector array of 320-elements. Two options of physical collimators provide two levels of scatter-rejection: single-slot (SS) and multi-hole (MH). A pair of linear polarizers has been introduced as a means of light intensity modulation. This work examined: (i) the characterization of system components, (ii) data acquisition & imaging protocols, and (iii) the scanning of an nPAG dosimeter. (i): The polarizer-pair method of light intensity modulation has been calibrated and the polarization sensitivity of the detector array was evaluated. The relationship between detected values and both light intensity and photodiode integration time was examined. This examination indicated the need for an offset correction to treat all data acquired by the system. Data corruption near the edges of each photodiode array was found to cause ring artefacts in image reconstructions. Two methods of extending the dynamic range of the system---via integration time and light intensity---were presented. The use of master absorbent solutions and spectrophotometric data allowed for the preparation of absorption-based and scatter-based samples of known opacities. This ability allowed for the evaluation of the relative scatter-rejection capabilities of the system's two collimators. The MH collimator accurately measured highly-attenuating solutions of both absorption-based and scatter-based agents. The SS collimator experienced some contamination by scattered light with absorption-based agents, and significant contamination with scatter-based agents. Also, using the SS collimator, a `spiking' artefact was observed in highly-attenuating samples of both solution types. (ii): A change in imaging protocol has been described that greatly reduces ring artefacts that plagued the system previously. Scanning parameters related to the reference scan (Io) and data acquisition were evaluated with respect to image noise. Variations in flask imperfections were found to be a significant source of noise. (iii): An nPAG dosimeter was prepared, planned for, irradiated, and imaged using the fan-beam system. In addition to ring artefacts caused by data-corruption, refractive inhomogeneities and particulates in the gelatin were found to cause errors in image reconstructions. Otherwise, contour and percent depth dose comparisons between measured and expected values showed good agreement. Findings have indicated that significant imaging gains may be achieved by performing pre-irradiation and post-irradiation scans of dosimeters.