<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

<p>Quality assurance (QA) is a critical component of radiation oncology medical physics for both effective treatment and patient safety, particularly as innovations in technology allow movement toward advanced treatment techniques that require increasingly higher accuracy in delivery. Comprehensive 3D dosimetry with PRESAGE® 3D dosimeters read out via optical CT has the potential to detect errors that would be missed by current systems of measurement, and thereby improve the rigor of current QA techniques through providing high-resolution, full 3D verification for a wide range of clinical applications. The broad objective of this dissertation research is to advance and strengthen the standards of QA for radiation therapy, both by driving the development and optimization of PRESAGE® 3D dosimeters for specific clinical and research applications and by applying the technique of high resolution 3D dosimetry toward addressing clinical needs in the current practice of radiation therapy. The specific applications that this dissertation focuses on address several topical concerns: (1) increasing the quality, consistency, and rigor of radiation therapy delivery through comprehensive 3D verification in remote credentialing evaluations, (2) investigating a reusable 3D dosimeter that could potentially facilitate wider implementation of 3D dosimetry through improving cost-effectiveness, and (3) validating deformable image registration (DIR) algorithms prior to clinical implementation in dose deformation and accumulation calculations.</p><p>3D Remote Dosimetry: The feasibility of remote high-resolution 3D dosimetry with the PRESAGE®/Optical-CT system was investigated using two nominally identical optical-CT scanners for 3D dosimetry were constructed and placed at the base (Duke University) and remote (IROC Houston) institutions. Two formulations of PRESAGE® (SS1, SS2) were investigated with four unirradiated PRESAGE® dosimeters imaged at the base institution, then shipped to the remote institution for planning and irradiation. After each dosimeter was irradiated with the same treatment plan and subsequently read out by optical CT at the remote institution, the dosimeters were shipped back to the base institution for remote dosimetry readout 3 days post-irradiation. Measured on-site and remote relative 3D dose distributions were registered to the Pinnacle dose calculation, which served as the reference distribution for 3D gamma calculations with passing criteria of 5%/2mm, 3%/3mm, and 3%/2mm with a 10% dose threshold. Gamma passing rates, dose profiles, and dose maps were used to assess and compare the performance of both PRESAGE® formulations for remote dosimetry. Both PRESAGE® formulations under study maintained high linearity of dose response (R2>0.996) over 14 days with response slope consistency within 4.9% (SS1) and 6.6% (SS2). Better agreements between the Pinnacle plan and dosimeter readout were observed in PRESAGE® formulation SS2, which had higher passing rates and consistency between immediate and remote results at all metrics. This formulation also demonstrated a relative dose distribution that remained stable over time. These results provide a foundation for future investigations using remote dosimetry to study the accuracy of advanced radiation treatments.</p><p>A Reusable 3D Dosimeter: New Presage-RU formulations made using a lower durometer polyurethane matrix (Shore hardness 30-50A) exhibit a response that optically clears following irradiation and opens up the potential for reirradiation and dosimeter reusability. This would have the practical benefit of improving cost-effectiveness and thereby facilitating the wider implementation of comprehensive, high resolution 3D dosimetry. Three formulations (RU-3050-1.7, RU-3050-1.5, and RU-50-1.5) were assessed with multiple irradiations of both small volume samples and larger volume dosimeters, then characterized and evaluated for dose response sensitivity, optical clearing, dose-rate independence, dosimetric accuracy, and the effects of reirradiation on dose measurement. The primary shortcoming of these dosimeters was the discovery of age-dependent gradients in dose response sensitivity, which varied dose response by as much as 30% and prevented accurate measurement. This is unprecedented in the standard formulations and presumably caused by diffusion of a desensitizing agent into the lower durometer polyurethane. The effect of prior irradiation on the dosimeters would also be a concern as it was seen that the relative amount of dose delivered to any given region of the dosimeter will affect subsequent sensitivity in that area, which would in effect create spatially-dependent variable dose sensitivities throughout the dosimeter based on the distributions of prior irradiations. While a successful reusable dosimeter may not have been realized from this work, these studies nonetheless contributed useful information that will affect future development, including in the area of deformable dosimetry, and provide a framework for future reusable dosimeter testing.</p><p>Validating Deformable Image Registration Algorithms: Deformable image registration (DIR) algorithms are used for multi-fraction dose accumulation and treatment response assessment for adaptive radiation therapy, but the accuracy of these methods must be investigated prior to clinical implementation. 12 novel deformable PRESAGE® 3D dosimeter formulations were introduced and characterized for potential use in validating DIR algorithms by providing accurate, ground-truth deformed dose measurement for comparison to DIR-predicted deformed dose distributions. Two commercial clinical DIR software algorithms were evaluated for dose deformation accuracy by comparison against a measured deformed dosimeter dose distribution. This measured distribution was obtained by irradiating a dosimeter under lateral compression, then releasing it from compression so that it could return to its original geometry. The dose distribution within the dosimeter deformed along with the dosimeter volume as it regained to its original shape, thus providing a measurable ground truth deformed dose distribution. Results showed that intensity-based DIR algorithms produce high levels of error and physically unrealistic deformations when deforming a homogeneous structure; this is expected as lack of internal structure is challenging for intensity-based DIR algorithms to deform accurately as they rely on matching fairly closely spaced heterogeneous intensity features. A biomechanical, intensity-independent DIR algorithm demonstrated substantially closer agreement to the measured deformed dose distribution with 3D gamma passing rates (3%/3mm) in the range of 90-91%. These results underscore the necessity and importance of validating DIR algorithms for specific clinical scenarios prior to clinical implementation.</p> / Dissertation

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

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.