Browsing by Subject "Optical-CT"

Purpose: The purpose of this work is to characterize three novel formulations of a radiochromic material Presage and identify optimal imaging procedures for accurate 3D dosimetry. The dosimetric qualities of interest were studied for each formulation of Presage dosimeter in the context of accurate 3D dosimetry. The formulation of Presage showing the most promise is compared to a clinical 3D quality assurance device to investigate the accuracy of a complex state-of-the-art brain IMRT treatment.

Methods and Materials: Three novel formulations of Presage were studied for their temporal stability, sensitivity, linearity of dose response, and feasibility of absolute dose calibration in large volume dosimeters (1 kg) with small volume cuvettes (4g). Large cylindrical dosimeters with 11 cm diameter and 10 cm height were irradiated with 5 2x2 cm fields on the upper flat surface with 3 distinct dose levels (3, 6 and 9.5 Gy, representing low, medium and high). This irradiation pattern is used to determine the dosimetric characteristics mentioned above and was chosen because of its repeatability and it lends to simple measurements of linearity and sensitivity. Measurements were taken at various time points from 0 hours to 24 hours post-irradiation using the high resolution (6.45 m pixels) Duke Medium-Sized Optical-CT Scanner (DMOS) and reconstructed with a Matlab-based reconstruction GUI created in-house. Analysis of the pertinent dosimetric characteristics was performed in the GUI. A comprehensive end-to-end QA test was performed on the optimal formulation using optimal scan timing determined from the formulation studies described above. A 5-field IMRT plan was created for head treatment. The plan was delivered both to a head phantom containing a Presage insert, and to the Delta4 QA device. Comparison of both delivered distributions together with the Eclipse predicted dose distribution enabled investigation of the accuracy of the delivery, and the consistency of independent measurement devices.

Results: The DEA-1 formulation showed up to 10% variation from 0-2 hours post-irradiation, but showed excellent temporal stability (<2% variation) between 3-7 hours post irradiation, and maintained good stability until 24 hours post-irradiation (up to 3% variation). The DEA-2 also showed up to 10% variation from 0-2 hours post-irradiation. The DEA-2 formulation then showed good stability (up to 2.1% variation) from 3-7 hours, but optical density values dropped by up to 11% after 24 hours. The DX formulation did not maintain stability of optical density for any significant time with values decreasing by ~20% by the 24-hour time point and optical density decreasing at different rates for different dose levels. Linearity of dose response was good for all formulations with an R2 value > 0.99. Gamma analysis with criteria of 3%/2mm was performed on two irradiations of the 5-field pattern on DEA-1 formulation. Voxel passing rates were 96.68% and 97.96%. Comparison of the DEA-1 formulation large dosimeter was done with small volume cuvettes of the same formulation and batch. Sensitivity of the large dosimeter was less than half the sensitivity of the cuvettes. For clinical 3D QA comparison, the DEA-1 formulation was used because it had optimal performance showed the most promise for accurate 3D dosimetry. Line dose profiles showed that Presage compared very well with the Eclipse calculation and had a much better 3D gamma passing rate for 3%/3mm criteria than the Delta4 (>99% vs 75%).

Conclusions: The DEA-1 formulation shows the most promise because of its temporal stability and linearity of dose response. The optimal imaging window for this formulation was determined to be 3-24 hours post-irradiation. The DEA-2 and DX formulation also showed potential for accurate dosimetry. The optimal imaging window for the DEA-2 formulation was determined to be 2-6 hours post-irradiation. The optimal scan time for the DX formulation was determined to be immediately post-irradiation. The amount of accuracy loss depending on the scan time is dependent on the formulation and when the dosimeter is scanned. Line dose profiles and gamma analysis results from the comparison of Presage and Eclipse calculation provide strong validation of the accuracy of the IMRT treatment delivery. Comparison of Presage to the Delta4 show the Delta4 to be somewhat lacking in its ability to calculate 3D dose in the phantom/Presage geometry.

Purpose: Radiosurgery has become a widely used procedure in the treatment of both solid tumors and secondary metastases in the brain. In cases with multiple brain lesions, isocenters are typically set up for each target, a process which can take hours and become very uncomfortable for the patient. Recently, multifocal treatments with a single isocenter have emerged as a solution. With the high doses delivered to small regions during radiosurgery, the importance of treatment verification is paramount, especially when delivering high doses to regions off isocenter.

Methods: A 5-arc RapidArc radiosurgery plan with a single isocenter and 5 targets was used to treat a dosimeter placed within a RPC-type head and neck phantom. The treatment was delivered five times at varying prescription doses, depending on the sensitivity of the PRESAGE dosimeter used. The delivered dose distribution was measured using an in-house optical-CT system and compared to the Eclipse-planned dose distribution using dose volume histograms and Gamma analysis.

Results: Reasonable dose agreement was measured between the majority of the dosimeters and the Eclipse plan (80-85% pass rate at 5%/3 mm Gamma critera). The failing voxels were located on the periphery of the dosimeter at regions of extremely high or low dose, suggesting a dose dependent stability of the PRESAGE formulation. The formulation with the best temporal stability had a much higher Gamma pass rate of 98% at 3%/2mm criteria.

Conclusions: The potential of accurate delivery of the complex radiosurgery plan was demonstrated with one of the three formulations of PRESAGE. While agreement was worse in the other formulations, the problem seemed to be an easily-fixable stability issue, resulting in improper scaling of doses. Replication of the most stable formulation would provide an excellent tool for verification of radiosurgery treatment delivery and other complex procedures.

As complex radiotherapy techniques become more readily-practiced, comprehensive 3D dosimetry is a growing necessity for advanced quality assurance. However, clinical implementation has been impeded by a wide variety of factors, including the expense of dedicated optical dosimeter readout tools, high operational costs, and the overall difficulty of use. To address these issues, a novel dry-tank optical CT scanner was designed for PRESAGE 3D dosimeter readout, relying on 3D printed components and omitting costly parts from preceding optical scanners. This work details the design, prototyping, and basic commissioning of the Duke Integrated-lens Optical Scanner (DIOS).

The convex scanning geometry was designed in ScanSim, an in-house Monte Carlo optical ray-tracing simulation. ScanSim parameters were used to build a 3D rendering of a convex ‘solid tank’ for optical-CT, which is capable of collimating a point light source into telecentric geometry without significant quantities of refractive-index matched fluid. The model was 3D printed, processed, and converted into a negative mold via rubber casting to produce a transparent polyurethane scanning tank. The DIOS was assembled with the solid tank, a 3W red LED light source, a computer-controlled rotation stage, and a 12-bit CCD camera. Initial optical phantom studies show negligible spatial inaccuracies in 2D projection images and 3D tomographic reconstructions. A PRESAGE 3D dose measurement for a 4-field box treatment plan from Eclipse shows 95% of voxels passing gamma analysis at 3%/3mm criteria. Gamma analysis between tomographic images of the same dosimeter in the DIOS and DLOS systems show 93.1% agreement at 5%/1mm criteria. From this initial study, the DIOS has demonstrated promise as an economically-viable optical-CT scanner. However, further improvements will be necessary to fully develop this system into an accurate and reliable tool for advanced QA.

Pre-clinical animal studies are used as a conventional means of translational research, as a midpoint between in-vitro cell studies and clinical implementation. However, modern small animal radiotherapy platforms are primitive in comparison with conventional linear accelerators. This work also investigates a series of 3D printed tools to expand the treatment capabilities of the X-RAD 225Cx orthovoltage irradiator, and applies them to a feasibility study of hippocampal avoidance in rodent whole-brain radiotherapy.

As an alternative material to lead, a novel 3D-printable tungsten-composite ABS plastic, GMASS, was tested to create precisely-shaped blocks. Film studies show virtually all primary radiation at 225 kVp can be attenuated by GMASS blocks of 0.5cm thickness. A state-of-the-art software, BlockGen, was used to create custom hippocampus-shaped blocks from medical image data, for any possible axial treatment field arrangement. A custom 3D printed bite block was developed to immobilize and position a supine rat for optimal hippocampal conformity. An immobilized rat CT with digitally-inserted blocks was imported into the SmART-Plan Monte-Carlo simulation software to determine the optimal beam arrangement. Protocols with 4 and 7 equally-spaced fields were considered as viable treatment options, featuring improved hippocampal conformity and whole-brain coverage when compared to prior lateral-opposed protocols. Custom rodent-morphic PRESAGE dosimeters were developed to accurately reflect these treatment scenarios, and a 3D dosimetry study was performed to confirm the SmART-Plan simulations. Measured doses indicate significant hippocampal sparing and moderate whole-brain coverage.

Micro-irradiators enable exploration of the efficacy of novel radiation treatment approaches by providing the capability to reproduce realistic treatment delivery in small animal models. An approach of current topical interest is hypofractionated stereotactic body radiation therapy (SBRT), and the study of associated tumor and normal tissue radio-biology. Rodent SBRT is extremely challenging, requiring the precise delivery of radiation beams on the order of several millimeters. At present there are no methods to comprehensively verify these delivery techniques due to the requirements for ultra-high resolution and ability to measure the dose in 3 dimensions (3D).

This work introduces a potential solution to the rodent SBRT verification challenge: radiochromic rodent-morphic 3D dosimeters compatible with ultra-high resolution optical computed tomography (optical-CT) dose read-out. Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from X-ray CT data, and using these molds to create tissue-equivalent phantoms both with and without high-Z spinal inserts for cone-beam CT targeting. Feasibility was evaluated through a series of irradiations, including a 180-degree spinal arc treatment. Dose distributions were measured in high-resolution (0.5mm isotropic voxels) with an in-house built optical-CT system, which determined dose from the change in optical density throughout the dosimeters from pre-and post-irradiation scans. Optical-CT data was calibrated to absolute dose using a calibration curve determined from irradiating small volumes of radiochromic material from the same batch as the rodent-morphic dosimeters to known doses in a 6MV beam (negligible energy response was assumed). Independent verification of absolute dose at a point was made with a novel scintillator comprised of europium and lithium doped yttrium oxide nanocrystals, with a sub-mm active length. Independent verification of the dose distribution was performed using EBT2 radiochromic film positioned in the dosimeters, which had been sliced in half. Contrast-to-noise ratio between high-Z spinal inserts and tissue-equivalent PRESAGE material was found to be ~10, sufficient for bony alignment and isocenter targeting with on-board CBCT image guidance. Absolute dose calculated at isocenter through optical-CT was found to agree with nano-detector measurement within 3%, while relative dose distributions in two orthogonal planes were found to agree with film within 4%. PRESAGE rodent-morphic dosimeters demonstrated much promise in the verification of precise radiation treatment given by the X-Rad 225Cx micro-irradiator.

Practical challenges involved in optical-CT imaging were addressed through the investigation of an in-house Fresnel-based optical-CT system with considerably less refractive index-matching fluid. The "DFOS" (Duke Fresnel-based Optical-CT System) system differed from current optical-CT systems by replacing cumbersome convex telecentric lenses with a lighter and much less expensive Fresnel system. A second major modification was the replacement of the refractive index-matching fluid bath with a solid polyurethane tank. PRESAGE radiochromic dosimeters were irradiated with orthogonal parallel-opposed treatments and a brain IMRT treatment and dose distributions were readout by the DFOS system and compared to both treatment planning software prediction and other in-house optical-CT systems. Gamma index passing rate at the 3%/3mm threshold for the two parallel-opposed and brain IMRT treatments were 89.3%, 92.1%, and 87.5%, respectively. The DFOS system showed promise for 3D dosimetry, but the performance is still substantially inferior at present to the gold-standard systems.

Purpose: Optical-CT imaging with radiochromic dosimeters is a powerful method of evaluating 3D dose distributions at high resolution and sensitivity. Current optical-CT systems require large quantities of refractively matched fluid surrounding the dosimeter in order to minimize refraction artifacts. The use of a refractively matched solid polyurethane solid-tank, in place of a fluid bath, has the potential to greatly increase practical convenience, reduce cost, and improve the efficacy of flood corrections. This thesis aims to investigate the feasibility of solid-tank optical-CT imaging for 3D dosimetry, and to use computer simulation to investigate optimal design and scanning parameters.

Methods: A Matlab based ray-tracing simulation platform, ScanSim, was used to model a parallel-source imaging system through a cubic polyurethane solid-tank containing a central cylindrical hollow into which cylindrical PRESAGE® radiochromic dosimeters can be placed. A small amount of fluid surrounds the dosimeter in the tank. ScanSim's capabilities were expanded from previous work to include the geometry and physics of dry scanning. Two imaging methods were investigated, representing a telecentric detector and an ideal detector: in the latter, all light rays are collected and used in reconstruction. In order to characterize the efficacy of these systems, and dependence on refractive index (RI) mismatches between dosimeter, solid-tank, and fluid, simulations were run for a variety of dosimeter (RI = 1.5-1.47), and fluid (RI = 1.55-1.0) combinations. Additional simulations examined the effect of increasing gap size (1-5mm) between the dosimeter and solid-tank well. For the telecentric setup, the effects of changing the lens tolerance (0.5-5.0 degrees) were also investigated. The metric for evaluation of efficacy is the usable radius, which is defined as the distance from the dosimeter center where the measured and true (known) dose differs by less than 2%.

Results: As the refractive index mismatch between the dosimeter and tank increases from 0-0.02, the telecentric system showed a significant decrease in the usable radius from 97.6% to 50.2% compared to a decrease from 97.6% to 96.4% for the ideal system. When the three media are perfectly matched, the telecentric system and ideal system perform identically. For mismatched dosimeter and solid-tank in a telecentric system, the optimal fluid match has a refractive index lower than either the tank or dosimeter, decreasing non-linearly from 1.5-1.34 as the dosimeter-tank refractive mismatch increases from 0 to 0.02. Media mismatches between the dosimeter and solid-tank also exacerbate the effects of changing the gap size, with no apparent quantifiable relationship. Generally, the optimal fluid match is closer to the dosimeter RI when the gap size is large (>3mm). Increasing the telecentric lens tolerance improves the usable radius for all refractive media combinations, and approaches the behavior of the ideal system for tolerances >5.0°.

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.

Dosimetry. 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.

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.

Biology. 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.

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.