Fiducial detection and registration for 3D IMRT QA with organ-specific dose information.

PURPOSE: Two-dimensional (2D) IMRT QA has been widely performed in Radiation Oncology clinic. However, concerns regarding its sensitivity in detecting delivery errors and its clinical meaning have been raised in publications. In this study, a robust methodology of three-dimensional (3D) IMRT QA using fiducial registration and structure-mapping was proposed to acquire organ-specific dose information. METHODS: Computed tomography (CT) markers were placed on the PRESAGE dosimeter as fiducials before CT simulation. Subsequently, the images were transferred to the treatment planning system to create a verification plan for the examined treatment plan. Patient's CT images were registered to the CT images of the dosimeter for structure mapping according to the positions of the fiducials. After irradiation, the 3D dose distribution was read-out by an optical-CT (OCT) scanner with fiducials shown on the OCT dose images. An automatic localization algorithm was developed in MATLAB to register the markers in the OCT images to those in the CT images of the dosimeter. SlicerRT was used to show and analyze the results. Fiducial registration error was acquired by measuring the discrepancies in 20 fiducial registrations, and thus the fiducial localization error and target registration error (TRE) was estimated. RESULTS: Dosimetry comparison between the calculated and measured dose distribution in various forms were presented, including 2D isodose lines comparison, 3D isodose surfaces with patient's anatomical structures, 2D and 3D gamma index, dose volume histogram and 3D view of gamma failing points. From the analysis of 20 fiducial registrations, fiducial registration error was measured to be 0.62 mm and fiducial localization error was calculated to be 0.44 mm. Target registration uncertainty of the proposed methodology was estimated to be within 0.3 mm in the area of dose measurement. CONCLUSIONS: This study proposed a robust methodology of 3D measurement-based IMRT QA for organ-specific dose comparison and demonstrated its clinical feasibility.

Temperature dependence and temporal stability of stacked radiochromic sheets for three-dimensional dose verification.

PURPOSE: Recently a novel radiochromic sheet dosimeter, termed as PRESAGE sheets, consisting of leuco crystal violet dye and radical initiator had been developed and characterized. This study examines the dosimeter's temporal stability and storage temperature dependence postirradiation, and its applicability for dose verification in three dimensions (3D) as a stack dosimeter. METHODS: PRESAGE sheets were irradiated using 6 MV photons at a dose range of 0-20 Gy with the change in optical density measured using a flatbed scanner. Following their irradiation, PRESAGE sheets were stored in different temperature environments (-18 °C, 4 °C, and 22 °C) and scanned at different time points, ranging from 1 to 168 h postirradiation, to track changes in measured signal and linearity of dose response. Multiple PRESAGE sheets were bound together to create a 12 × 13 × 8.7 cm3 film stack, with EBT3 film inserted between the sheets in the central region of the stack, that was treated using a clinical VMAT plan. Based on the results from the time and storage temperature study, two-dimensional (2D) relative dose distribution measurements in PRESAGE were acquired promptly following irradiation at selected planes in the coronal, sagittal, and axial orientation of the film stack and compared to the treatment planning system calculations in their respective axes. Dose distribution measurements on the coronal axis of the stack dosimeter were also independently verified using EBT3 film. RESULTS: The dose response was observed to be linear (R2 > 0.995) with sheets stored in colder temperatures retaining their signal and dose response sensitivity for extended periods postirradiation. Sheets stored in 22 °C environment should be measured within an hour postirradiation. Sheets stored in a 4 °C and -18 °C environment can be scanned up to 20- and 72 h postirradiation, respectively, while preserving the integrity of their dose response sensitivity and linearity of dose response within a mean absolute percent error of 2.0%. For instance, at 20 h postirradiation the dose response sensitivity for sheets stored in a -18 °C, 4 °C, and 22 °C temperature environment was measured to be 97%, 91%, and 77% of their original values measured within an hour postirradiation, respectively. The 2D gamma pass rate for central slices exceed 95% for PRESAGE film stack compared with treatment planning system on selected planes in the axial, coronal, and sagittal orientation and EBT3 film in the coronal orientation using a 2D gamma index of 2%/2mm. The gamma pass rate in comparing the calculated dose distribution with the measured dose distribution from PRESAGE-LCV was observed to decrease in sheets scanned at later elapsed times postirradiation. In one example, the gamma pass rate for 2%/2mm criteria in the coronal plane was observed to decrease from 97.7% pass rate when scanned within an hour postirradiation to 92.1% pass rate when scanned at 20 h postirradiation under room temperature conditions. CONCLUSIONS: This is the first study to demonstrate that the temporal stability of PRESAGE sheets can be enhanced through its storage in colder temperature environments postirradiation and that sheets as a film stack dosimeter hold promise for precise relative dose distribution measurements in 3D where advanced optical CT is unavailable.

Dosimetric characterization of a body-conforming radiochromic sheet.

PURPOSE: A novel radiochromic PRESAGE sheet (Heuris Inc.) with 3 mm thickness has been developed as a measurement tool for 2D dosimetry. Its inherent ability to conform to irregular surfaces makes this dosimeter advantageous for patient surface dosimetry. This study is a comprehensive investigation into the PRESAGE sheet's dosimetric characteristic, accuracy and its potential use as a dosimeter for clinical applications. METHODS: The characterization of the dosimeter included evaluation of the temporal stability of the dose linearity, reproducibility, measurement uncertainties, dose rate, energy, temperature and angular dependence, lateral response artifacts, percent depth dose curve, and 2D dose measurement. Dose distribution measurements were acquired for regular square fields on a flat and irregular surface and an irregular modulated field on the smooth surface. All measurements were performed using an Epson 11000XL high-resolution scanner. RESULTS: The examined dosimeters exhibit stable linear response, standard error of repeated measurements within 2%, negligible dose rate, energy, and angular dependence. The same linear dose response was measured while the dosimeter was in contact with a heated water surface. Gamma test and histogram analysis of the dose difference between PRESAGE and EBT3 film, PRESAGE and the treatment planning system (TPS) were used to evaluate the measured dose distributions. The PRESAGE sheet dose distributions showed good agreement with EBT3 film and TPS. A discrepancy smaller than the statistical error of the two dosimeters was reported. CONCLUSIONS: This study established a full dosimetric characterization of the PRESAGE sheets with the purpose of laying the foundation for future clinical uses. The results presented here for the comparison of this novel dosimeter with those currently in use reinforce the possibility of using this dosimeter as an alternative for irregular surface dose measurements.

3D isocentricity analysis for clinical linear accelerators.

PURPOSE: To perform a three-dimensional (3D) concurrent isocentricity measurement of a clinical linear accelerator's (linac) using a single 3D dosimeter, PRESAGE. METHODS: A 3D dosimeter, PRESAGE, set up on the treatment couch of a Varian TrueBeam LINAC using the setup lasers, was irradiated under gantry angles of 0 ∘ , 50 ∘ , 160 ∘ , and 270 ∘ with the couch fixed at 0 ∘ and subsequently, under couch angles of 10 ∘ , 330 ∘ , 300 ∘ , and 265 ∘ with the gantry fixed at 270 ∘ . The 1 cm 2 (at 100 cm SAD) square fields were delivered at 6 MV with 800 MU/field. After irradiation, the dosimeter was scanned using a single-beam optical scanner and images were reconstructed with submillimeter resolution using filtered back-projection. Postprocessing was used to extract views parallel to the star-shot planes from which beam trajectories and the smallest circles enclosing these were drawn and extracted. These circles and information from the view orthogonal to both star-shots were used to represent the rotational centers as spheroids. The linac isocenter was defined by the distribution of midpoints between any, randomly selected, points lying inside the center spheroids defined by the table and gantry rotations; isocenter location and size were defined by the average midpoint and the distribution's semi-axes. Collimator rotations were not included in this study. RESULTS: Relative to the setup center defined by lasers, the table and gantry rotation center coordinates (lat., long., vert.) were measured in units of millimeters, to be (-0.24, 0.18, -0.52) and (0.10, 0.53, -0.52), respectively. Displacements from the setup center were 0.60 and 0.75 mm for the table and gantry centers, while the distance between them measured 0.49 mm. The linac's radiation isocenter was calculated to be at (-0.07, -0.17, 0.51) relative to the setup lasers and its size was found to be most easily described by a spheroid prolate in vertical direction with semi-axis lengths of 0.13 and 0.23 mm for the lateral-longitudinal and vertical directions, respectively. CONCLUSIONS: This study demonstrates how to measure the location and sizes of rotational centers in 3D with one setup. The proposed method provides a more comprehensive view on the isocentricity of LINAC than the conventional two-dimensional film measurements. Additionally, a new definition of isocenter and its size was proposed.

An investigation of a novel reusable radiochromic sheet for 2D dose measurement.

PURPOSE: Radiochromic film remains a useful and versatile clinical dosimetry tool. Current film options are single use. Here, we introduce a novel prototype two-dimensional (2D) radiochromic sheet, which optically clears naturally at room temperature after irradiation and can be reused. We evaluate the sheets for potential as a 2D dosimeter and as a radiochromic bolus with capability for dose measurement. METHODS: A novel derivative of reusable Presage® was manufactured into thin sheets of 5 mm thickness. The sheets contained 2% cumin-leucomalachitegreen-diethylamine (LMG-DEA) and plasticizer (up to 25% by weight). Irradiation experiments were performed to characterize the response to megavoltage radiation, including dose sensitivity, temporal decay rate, consistency of repeat irradiations, intra and inter-sheet reproducibility, multi-modality response (electrons and photons), and temperature sensitivity (22°C to 36°C). The local change in optical-density (ΔOD), before and after radiation, was obtained with a flat-bed film scanner and extracting the red channel. Repeat scanning enabled investigation of the temporal decay of ΔOD. Additional studies investigated clinical utility of the sheets through application to IMRT treatment plans (prostate and a TG119 commissioning plan), and a chest wall electron boost treatment. In the latter test, the sheet performed as a radiochromic bolus. RESULTS: The radiation induced OD change in the sheets was found to be proportional to dose and to exponentially decay to baseline in ~24 h (R2 = 0.9986). The sheet could be reused and had similar sensitivity (within 1% after the first irradiation) for at least eight irradiations. Importantly, no memory of previous irradiations was observed within measurement uncertainty. The consistency of dose response from photons (6 and 15 MV) and electrons (6-20 MeV) was found to be within calibration uncertainty (~1%). The dose sensitivity of the sheets had a temperature dependence of 0.0012 ΔOD/°C. For the short (1 min) single field IMRT QA verification, good agreement was observed between the Presage sheet and EBT film (gamma pass rate 97% at 3% 3 mm dose-difference and distance-to-agreement tolerance, with a 10% threshold). For the longer (~13 min) TG-119 9-field IMRT verification the gamma agreement was lower at 93% pass rate at 5% 3 mm, 10% threshold, when compared with Eclipse. The lower rate is attributed to uncertainty arising from signal decay during irradiation and indicates a current limitation. For the electron cutout treatment, both Presage and EBT agreed well (within 2% RMS difference) but differed from the Eclipse treatment plan (~7% RMS difference) indicating some limitations to the Eclipse modeling in this case. The worst case estimates of uncertainty introduced by the signal decay for deliveries of 2, 5, and 10 min are 0.6%, 1.4%, and 2.8% respectively. CONCLUSIONS: Reusable Presage sheets show promise for 2D dose measurement and as a radiochromic bolus for in vivo dose measurement. The current prototype is suitable for deliveries of length up to 5 min, where the uncertainty introduced by signal decay is anticipated to be ~1% (worst case 1.4%), or for longer deliveries where there is no temporal modulation (e.g. physical compensators, or open beams). Additionally, spatial resolution is limited by sheet thickness and scanner resolution, resulting in a practical resolution of 0.8 mm.

Dosimetric and geometric characteristics of a small animal image-guided irradiator using 3D dosimetry/optical CT scanner.

PURPOSE: The precise dosimetric and geometric characteristics of small animal irradiators are essential to achieving reproducible dose delivery, especially in cases where image-guidance is utilized. Currently, radiochromic film is the established measurement tool used to evaluate beam characteristics for these systems. However, only 2D information can be acquired with film. This study characterized both the dosimetric and geometric properties of the small animal research radiation platform (SARRP, Xstrahl) for commissioning purposes using a 3D radiochromic dosimetry system with a submillimeter resolution optical computed tomography (OCT) scanner. METHODS: Like a modern clinical linear accelerator, the SARRP features both a beam delivery system and a cone beam computed tomography (CBCT) imaging system. Dosimetric and geometric characteristics of the SARRP were studied using EBT3 radiochromic film and 3D PRESAGE dosimeters. Dosimetric measurements included percent depth dose (PDD) curves and beam profiles. For geometric evaluation, the isocenter sizes of the treatment stage and gantry rotations as well as their coincidence were measured using star shot patterns. A commercial Epson Expression 11000XL flatbed scanner was used for readout of irradiated EBT3 films at 300 dpi resolution. Each irradiated PRESAGE dosimeter was scanned using a submillimeter resolution single laser beam OCT scanner. Acquired data were reconstructed with a resolution of 0.3 mm/pixel. RESULTS: PDD data measured from films and 3D dosimeters agree to within ±3% for depths up to 5 cm, for both 3 × 3 and 10 × 10 mm2 fixed collimation. Profiles were analyzed at 10, 20, and 30 mm depth for 3 × 3 mm2 and 10 × 10 mm2 fields. The FWHM measurements for both dosimeters agreed to within 0.01 mm, and the penumbras agreed to within 0.1 mm for 3 × 3 mm2 and 0.5 mm for 10 × 10 mm2 . Gantry and treatment stage isocenter sizes were determined to be 0.21 and 0.43 mm using EBT3 film, and 1.72 and 0.75 mm using PRESAGE dosimeters. Absolute isocenter shifts, evaluated with 3D phantoms, were 0.80 mm for the gantry rotation isocenter (treatment isocenter) with respect to the laser-defined setup isocenter, and 0.71 mm for the gantry rotation isocenter relative to treatment stage rotation isocenter (CBCT isocenter). The difference between CBCT isocenter and laser-defined setup isocenter was 0.68 mm. CONCLUSIONS: This study demonstrated that 3D PRESAGE dosimeters can be used for verification of precise targeting for the SARRP. This 3D dosimetry system can be utilized to obtain information on both geometric and dosimetric properties, as well as acquire beam data parameters for the purpose of commissioning image-guided small animal irradiator systems.

Investigating the effect of a magnetic field on dose distributions at phantom-air interfaces using PRESAGE® 3D dosimeter and Monte Carlo simulations.

Dosimetric quality assurance (QA) of the new Elekta Unity (MR-linac) will differ from the QA performed of a conventional linac due to the constant magnetic field, which creates an electron return effect (ERE). In this work we aim to validate PRESAGE® dosimetry in a transverse magnetic field, and assess its use to validate the research version of the Monaco TPS of the MR-linac. Cylindrical samples of PRESAGE® 3D dosimeter separated by an air gap were irradiated with a cobalt-60 unit, while placed between the poles of an electromagnet at 0.5 T and 1.5 T. This set-up was simulated in EGSnrc/Cavity Monte Carlo (MC) code and relative dose distributions were compared with measurements using 1D and 2D gamma criteria of 3% and 1.5 mm. The irradiation conditions were adapted for the MR-linac and compared with Monaco TPS simulations. Measured and EGSnrc/Cavity simulated profiles showed good agreement with a gamma passing rate of 99.9% for 0.5 T and 99.8% for 1.5 T. Measurements on the MR-linac also compared well with Monaco TPS simulations, with a gamma passing rate of 98.4% at 1.5 T. Results demonstrated that PRESAGE® can accurately measure dose and detect the ERE, encouraging its use as a QA tool to validate the Monaco TPS of the MR-linac for clinically relevant dose distributions at tissue-air boundaries.

Development of a 3D remote dosimetry protocol compatible with MRgIMRT.

PURPOSE: To develop a novel remote 3D dosimetry protocol to verify Magnetic Resonance-guided Radiation Therapy (MRgRT) treatments. The protocol was applied to investigate the accuracy of TG-119 IMRT irradiations delivered by the MRIdian® system (ViewRay® , Oakwood Village, OH, USA) allowing for a 48-hour delay between irradiation at a field institution and subsequent readout at a base institution. METHODS: The 3D dosimetry protocol utilizes a novel formulation of PRESAGE® radiochromic dosimeters developed for high postirradiation stability and compatibility with optical-CT readout. Optical-CT readout was performed with an in-house system utilizing telecentric lenses affording high-resolution scanning. The protocol was developed from preparatory experiments to characterize PRESAGE® response in relevant conditions. First, linearity and sensitivity of PRESAGE® dose-response in the presence of a magnetic field was evaluated in a small volume study (4 ml cuvettes) conducted under MRgRT conditions and irradiated with doses 0-15 Gy. Temporal and spatial stability of the dose-response were investigated in large volume studies utilizing large field-of-view (FOV) 2 kg cylindrical PRESAGE® dosimeters. Dosimeters were imaged at t = 1 hr and t = 48 hrs enabling the development of correction terms to model any observed spatial and temporal changes postirradiation. Polynomial correction factors for temporal and spatial changes in PRESAGE® dosimeters (CT and CR respectively) were obtained by numerical fitting to time-point data acquired in six irradiated dosimeters. A remote dosimetry protocol was developed where PRESAGE® change in optical-density (ΔOD) readings at time t = X (the irradiation to return shipment time interval) were corrected back to a convenient standard time t = 1 hr using the CT and CR corrections. This refined protocol was then applied to TG-119 (American Association of Physicists in Medicine, Task Group 119) plan deliveries on the MRIdian® system to evaluate the accuracy of MRgRT in these conditions. RESULTS: In the small volume study, in the presence of a 0.35 T magnetic field, PRESAGE® was observed to respond linearly (R2  = 0.9996) to Co-60 irradiation at t = 48 hrs postirradiation, within the dose ranges of 0 to 15 Gy, with a sensitivity of 0.0305(±0.003) ΔOD cm-1  Gy-1 . In the large volume studies, at t = 1 hr postirradiation, consistent linear response was observed, with average sensitivity of 0.0930 ± 0.002 ΔOD cm-1  Gy-1 . However, dosimeters gradually darkened with time (OD< 5% per day). A small radial dependence to the dosimeter sensitivity was measured (< 3% of maximum dose), which is attributed to a spherically symmetric dosimeter artifact arising from exothermic heating legacy in the PRESAGE® polyurethane substrate during curing. When applied to the TG-119 IMRT irradiations, the remote dosimetry protocol (including correction terms) yielded excellent line-profile and 3D gamma agreement for 3%/3 mm, 10% threshold (mean passing rate = 96.6% ± 4.0%). CONCLUSION: A novel 3D remote dosimetry protocol is introduced for validating off-site dosimetrically complex radiotherapy systems, including MRgRT. The protocol involves correcting for temporal and spatially dependent changes in PRESAGE® radiochromic dosimeters readout by optical-CT. Application of the protocol to TG-119 irradiations enabled verification of MRgRT dose distributions with high resolution.

Detection of therapeutic radiation in three-dimensions.

For over the last twenty years there has been a multitude of sophisticated three-dimensional radiation delivery procedures developed which requires a corresponding verification of the impact on patients. This article reviews the state of the art in the development of chemical detectors used to characterize the three-dimensional shape of therapeutic radiation. These detectors are composed of polyurethane, radical initiator and a leuco dye, which is radiolytically oxidized to a dye absorbing at 630 nm.

Optical-CT 3D Dosimetry Using Fresnel Lenses with Minimal Refractive-Index Matching Fluid.

Telecentric optical computed tomography (optical-CT) is a state-of-the-art method for visualizing and quantifying 3-dimensional dose distributions in radiochromic dosimeters. In this work a prototype telecentric system (DFOS-Duke Fresnel Optical-CT Scanner) is evaluated which incorporates two substantial design changes: the use of Fresnel lenses (reducing lens costs from $10-30K t0 $1-3K) and the use of a 'solid tank' (which reduces noise, and the volume of refractively matched fluid from 1 ltr to 10 cc). The efficacy of DFOS was evaluated by direct comparison against commissioned scanners in our lab. Measured dose distributions from all systems were compared against the predicted dose distributions from a commissioned treatment planning system (TPS). Three treatment plans were investigated including a simple four-field box treatment, a multiple small field delivery, and a complex IMRT treatment. Dosimeters were imaged within 2 h post irradiation, using consistent scanning techniques (360 projections acquired at 1 degree intervals, reconstruction at 2mm). DFOS efficacy was evaluated through inspection of dose line-profiles, and 2D and 3D dose and gamma maps. DFOS/TPS gamma pass rates with 3%/3mm dose difference/distance-to-agreement criteria ranged from 89.3% to 92.2%, compared to from 95.6% to 99.0% obtained with the commissioned system. The 3D gamma pass rate between the commissioned system and DFOS was 98.2%. The typical noise rates in DFOS reconstructions were up to 3%, compared to under 2% for the commissioned system. In conclusion, while the introduction of a solid tank proved advantageous with regards to cost and convenience, further work is required to improve the image quality and dose reconstruction accuracy of the new DFOS optical-CT system.

Assessment of optical CT as a future QA tool for synchrotron x-ray microbeam therapy.

Synchrotron microbeam radiation therapy (MRT) is an advanced form of radiotherapy for which it is extremely difficult to provide adequate quality assurance. This may delay or limit its clinical uptake, particularly in the paediatric patient populations for whom it could be especially suitable. This study investigates the extent to which new developments in 3D dosimetry using optical computed tomography (CT) can visualise MRT dose distributions, and assesses what further developments are necessary before fully quantitative 3D measurements can be achieved. Two experiments are reported. In the first cylindrical samples of the radiochromic polymer PRESAGE(®) were irradiated with different complex MRT geometries including multiport treatments of collimated 'pencil' beams, interlaced microplanar arrays and a multiport treatment using an anthropomorphic head phantom. Samples were scanned using transmission optical CT. In the second experiment, optical CT measurements of the biologically important peak-to-valley dose ratio (PVDR) were compared with expected values from Monte Carlo simulations. The depth-of-field (DOF) of the optical CT system was characterised using a knife-edge method and the possibility of spatial resolution improvement through deconvolution of a measured point spread function (PSF) was investigated. 3D datasets from the first experiment revealed excellent visualisation of the 50 µm beams and various discrepancies from the planned delivery dose were found. The optical CT PVDR measurements were found to be consistently 30% of the expected Monte Carlo values and deconvolution of the microbeam profiles was found to lead to increased noise. The reason for the underestimation of the PVDR by optical CT was attributed to lack of spatial resolution, supported by the results of the DOF characterisation. Solutions are suggested for the outstanding challenges and the data are shown already to be useful in identifying potential treatment anomalies.

Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters.

PURPOSE: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1-15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm(3)) optical computed tomography (optical-CT) dose read-out. METHODS: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180° continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half. RESULTS: Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ∼10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%. CONCLUSIONS: This work demonstrates the feasibility of using 3D printing technology to make anatomically accurate Presage rodent-morphic dosimeters incorporating spinal-mimicking inserts. High quality optical-CT 3D dosimetry is feasible on these dosimeters, despite the irregular surfaces and implanted inserts. The ability to measure dose distributions in anatomically accurate phantoms represents a powerful useful additional verification tool for preclinical microSBRT.

An investigation of PRESAGE® 3D dosimetry for IMRT and VMAT radiation therapy treatment verification.

The purpose of this work was to characterize three formulations of PRESAGE(®) dosimeters (DEA-1, DEA-2, and DX) and to identify optimal readout timing and procedures for accurate in-house 3D dosimetry. The optimal formulation and procedure was then applied for the verification of an intensity modulated radiation therapy (IMRT) and a volumetric modulated arc therapy (VMAT) treatment technique. PRESAGE(®) formulations were studied for their temporal stability post-irradiation, sensitivity, and linearity of dose response. Dosimeters were read out using a high-resolution optical-CT scanner. Small volumes of PRESAGE(®) were irradiated to investigate possible differences in sensitivity for large and small volumes ('volume effect'). The optimal formulation and read-out technique was applied to the verification of two patient treatments: an IMRT plan and a VMAT plan. A gradual decrease in post-irradiation optical-density was observed in all formulations with DEA-1 exhibiting the best temporal stability with less than 4% variation between 2-22 h post-irradiation. A linear dose response at the 4 h time point was observed for all formulations with an R(2) value >0.99. A large volume effect was observed for DEA-1 with sensitivity of the large dosimeter being ~63% less than the sensitivity of the cuvettes. For the IMRT and VMAT treatments, the 3D gamma passing rates for 3%/3 mm criteria using absolute measured dose were 99.6 and 94.5% for the IMRT and VMAT treatments, respectively. In summary, this work shows that accurate 3D dosimetry is possible with all three PRESAGE(®) formulations. The optimal imaging windows post-irradiation were 3-24 h, 2-6 h, and immediately for the DEA-1, DEA-2, and DX formulations, respectively. Because of the large volume effect, small volume cuvettes are not yet a reliable method for calibration of larger dosimeters to absolute dose. Finally, PRESAGE(®) is observed to be a useful method of 3D verification when careful consideration is given to the temporal stability and imaging protocols for the specific formulation used.

Issues involved in the quantitative 3D imaging of proton doses using optical CT and chemical dosimeters.

Dosimetry of proton beams using 3D imaging of chemical dosimeters is complicated by a variation with proton linear energy transfer (LET) of the dose-response (the so-called 'quenching effect'). Simple theoretical arguments lead to the conclusion that the total absorbed dose from multiple irradiations with different LETs cannot be uniquely determined from post-irradiation imaging measurements on the dosimeter. Thus, a direct inversion of the imaging data is not possible and the proposition is made to use a forward model based on appropriate output from a planning system to predict the 3D response of the dosimeter. In addition to the quenching effect, it is well known that chemical dosimeters have a non-linear response at high doses. To the best of our knowledge it has not yet been determined how this phenomenon is affected by LET. The implications for dosimetry of a number of potential scenarios are examined.Dosimeter response as a function of depth (and hence LET) was measured for four samples of the radiochromic plastic PRESAGE(®), using an optical computed tomography readout and entrance doses of 2.0 Gy, 4.0 Gy, 7.8 Gy and 14.7 Gy, respectively. The dosimeter response was separated into two components, a single-exponential low-LET response and a LET-dependent quenching. For the particular formulation of PRESAGE(®) used, deviations from linearity of the dosimeter response became significant for doses above approximately 16 Gy. In a second experiment, three samples were each irradiated with two separate beams of 4 Gy in various different configurations. On the basis of the previous characterizations, two different models were tested for the calculation of the combined quenching effect from two contributions with different LETs. It was concluded that a linear superposition model with separate calculation of the quenching for each irradiation did not match the measured result where two beams overlapped. A second model, which used the concept of an 'effective dose' matched the experimental results more closely. An attempt was made to measure directly the quench function for two proton beams as a function of all four variables of interest (two physical doses and two LET values). However, this approach was not successful because of limitations in the response of the scanner.

PRESAGE 3D dosimetry accurately measures Gamma Knife output factors.

Small-field output factor measurements are traditionally very difficult because of steep dose gradients, loss of lateral electronic equilibrium, and dose volume averaging in finitely sized detectors. Three-dimensional (3D) dosimetry is ideal for measuring small output factors and avoids many of these potential challenges of point and 2D detectors. PRESAGE 3D polymer dosimeters were used to measure the output factors for the 4 mm and 8 mm collimators of the Leksell Perfexion Gamma Knife radiosurgery treatment system. Discrepancies between the planned and measured distance between shot centers were also investigated. A Gamma Knife head frame was mounted onto an anthropomorphic head phantom. Special inserts were machined to hold 60 mm diameter, 70 mm tall cylindrical PRESAGE dosimeters. The phantom was irradiated with one 16 mm shot and either one 4 mm or one 8 mm shot, to a prescribed dose of either 3 Gy or 4 Gy to the 50% isodose line. The two shots were spaced between 30 mm and 60 mm apart and aligned along the central axis of the cylinder. The Presage dosimeters were measured using the DMOS-RPC optical CT scanning system. Five independent 4 mm output factor measurements fell within 2% of the manufacturer's Monte Carlo simulation-derived nominal value, as did two independent 8 mm output factor measurements. The measured distances between shot centers varied by ± 0.8 mm with respect to the planned shot displacements. On the basis of these results, we conclude that PRESAGE dosimetry is excellently suited to quantify the difficult-to-measure Gamma Knife output factors.

On the feasibility of polyurethane based 3D dosimeters with optical CT for dosimetric verification of low energy photon brachytherapy seeds.

PURPOSE: To investigate the feasibility of and challenges yet to be addressed to measure dose from low energy (effective energy <50 keV) brachytherapy sources (Pd-103, Cs-131, and I-125) using polyurethane based 3D dosimeters with optical CT. METHODS: The authors' evaluation used the following sources: models 200 (Pd-103), CS-1 Rev2 (Cs-131), and 6711 (I-125). The authors used the Monte Carlo radiation transport code MCNP5, simulations with the ScanSim optical tomography simulation software, and experimental measurements with PRESAGE(®) dosimeters/optical CT to investigate the following: (1) the water equivalency of conventional (density = 1.065 g/cm(3)) and deformable (density = 1.02 g/cm(3)) formulations of polyurethane dosimeters, (2) the scatter conditions necessary to achieve accurate dosimetry for low energy photon seeds, (3) the change in photon energy spectrum within the dosimeter as a function of distance from the source in order to determine potential energy sensitivity effects, (4) the optimal delivered dose to balance optical transmission (per projection) with signal to noise ratio in the reconstructed dose distribution, and (5) the magnitude and characteristics of artifacts due to the presence of a channel in the dosimeter. Monte Carlo simulations were performed using both conventional and deformable dosimeter formulations. For verification, 2.8 Gy at 1 cm was delivered in 92 h using an I-125 source to a PRESAGE(®) dosimeter with conventional formulation and a central channel with 0.0425 cm radius for source placement. The dose distribution was reconstructed with 0.02 and 0.04 cm(3) voxel size using the Duke midsized optical CT scanner (DMOS). RESULTS: While the conventional formulation overattenuates dose from all three sources compared to water, the current deformable formulation has nearly water equivalent attenuation properties for Cs-131 and I-125, while underattenuating for Pd-103. The energy spectrum of each source is relatively stable within the first 5 cm especially for I-125. The inherent assumption of radial symmetry in the TG43 geometry leads to a linear increase in sample points within the 3D dosimeter as a function of distance away from the source, which partially offsets the decreasing signal. Simulations of dose reconstruction using optical CT showed the feasibility of reconstructing dose out to a radius of 10 cm without saturating projection images using an optimal dose and high dynamic range scanning; the simulations also predicted that reconstruction artifacts at the channel surface due to a small discrepancy in refractive index should be negligible. Agreement of the measured with calculated radial dose function for I-125 was within 5% between 0.3 and 2.5 cm from the source, and the median difference of measured from calculated anisotropy function was within 5% between 0.3 and 2.0 cm from the source. CONCLUSIONS: 3D dosimetry using polyurethane dosimeters with optical CT looks to be a promising application to verify dosimetric distributions surrounding low energy brachytherapy sources.

On the feasibility of comprehensive high-resolution 3D remote dosimetry.

PURPOSE: This study investigates the feasibility of remote high-resolution 3D dosimetry with the PRESAGE®/Optical-CT system. In remote dosimetry, dosimeters are shipped out from a central base institution to a remote institution for irradiation, then shipped back to the base institution for subsequent readout and analysis. METHODS: Two nominally identical optical-CT scanners for 3D dosimetry were constructed and placed at the base (Duke University) and remote (Radiological Physics Center) institutions. Two formulations of PRESAGE® (SS1, SS2) radiochromic dosimeters were investigated. Higher sensitivity was expected in SS1, which had higher initiator content (0.25% bromotrichloromethane), while greater temporal stability was expected in SS2. Four unirradiated PRESAGE® dosimeters (two per formulation, cylindrical dimensions 11 cm diameter, 8.5-9.5 cm length) were imaged at the base institution, then shipped to the remote institution for planning and irradiation. Each dosimeter was irradiated with the same simple treatment plan: an isocentric 3-field "cross" arrangement of 4 × 4 cm open 6 MV beams configured as parallel opposed laterals with an anterior beam. This simple plan was amenable to accurate and repeatable setup, as well as accurate dose modeling by a commissioned treatment planning system (Pinnacle). After irradiation and subsequent (within 1 h) optical-CT readout at the remote institution, the dosimeters were shipped back to the base institution for remote dosimetry readout 3 days postirradiation. 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%/2 mm, 3%/3 mm, and 3%/2 mm with a 10% dose threshold. Gamma passing rates, dose profiles, and color-maps were all used to assess and compare the performance of both PRESAGE® formulations for remote dosimetry. RESULTS: The best agreements between the Pinnacle plan and dosimeter readout were observed in PRESAGE® formulation SS2. Under 3%/3 mm 3D gamma passing criteria, passing rates were 91.5% ± 3.6% (SS1) and 97.4% ± 2.2% (SS2) for immediate on-site dosimetry, 96.7% ± 2.4% (SS1) and 97.6% ± 0.6% (SS2) for remote dosimetry. These passing rates are well within TG119 recommendations (88%-90% passing). Under the more stringent criteria of 3%/2 mm, there is a pronounced difference [8.0 percentage points (pp)] between SS1 formulation passing rates for immediate and remote dosimetry while the SS2 formulation maintains both higher passing rates and consistency between immediate and remote results (differences ≤ 1.2 pp) at all metrics. Both PRESAGE® formulations under study maintained high linearity of dose response (R(2) > 0.996) for 1-8 Gy over 14 days with response slope consistency within 4.9% (SS1) and 6.6% (SS2), and a relative dose distribution that remained stable over time was demonstrated in the SS2 dosimeters. CONCLUSIONS: Remote 3D dosimetry was shown to be feasible with a PRESAGE® dosimeter formulation (SS2) that exhibited relative temporal stability and high accuracy when read off-site 3 days postirradiation. Characterization of the SS2 dose response demonstrated linearity (R(2) > 0.998) over 14 days and suggests accurate readout over longer periods of time would be possible. This result provides a foundation for future investigations using remote dosimetry to study the accuracy of advanced radiation treatments. Further work is planned to characterize dosimeter reproducibility and dose response over longer periods of time.

Performance of an improved first generation optical CT scanner for 3D dosimetry.

Performance analysis of a modified 3D dosimetry optical scanner based on the first generation optical CT scanner OCTOPUS is presented. The system consists of PRESAGE dosimeters, the modified 3D scanner, and a new developed in-house user control panel written in Labview program which provides more flexibility to optimize mechanical control and data acquisition technique. The total scanning time has been significantly reduced from initial 8 h to ∼2 h by using the modified scanner. The functional performance of the modified scanner has been evaluated in terms of the mechanical integrity uncertainty of the data acquisition process. Optical density distribution comparison between the modified scanner, OCTOPUS and the treatment plan system has been studied. It has been demonstrated that the agreement between the modified scanner and treatment plans is comparable with that between the OCTOPUS and treatment plans.

Establishing the suitability of quantitative optical CT microscopy of PRESAGE® radiochromic dosimeters for the verification of synchrotron microbeam therapy.

Previous research on optical computed tomography (CT) microscopy in the context of the synchrotron microbeam has shown the potential of the technique and demonstrated high quality images, but has left two questions unanswered: (i) are the images suitably quantitative for 3D dosimetry? and (ii) what is the impact on the spatial resolution of the system of the limited depth-of-field of the microscope optics? Cuvette and imaging studies are reported here that address these issues. Two sets of cuvettes containing the radiochromic plastic PRESAGE® were irradiated at the ID17 biomedical beamline of the European Synchrotron Radiation facility over the ranges 0-20 and 0-35 Gy and a third set of cuvettes was irradiated over the range 0-20 Gy using a standard medical linac. In parallel, three cylindrical PRESAGE® samples of diameter 9.7 mm were irradiated with test patterns that allowed the quantitative capabilities of the optical CT microscope to be verified, and independent measurements of the imaging modulation transfer function (MTF) to be made via two different methods. Both spectrophotometric analysis and imaging gave a linear dose response, with gradients ranging from 0.036-0.041 cm(-1) Gy(-1) in the three sets of cuvettes and 0.037 (optical CT units) Gy(-1) for the imaging. High-quality, quantitative imaging results were obtained throughout the 3D volume, as illustrated by depth-dose profiles. These profiles are shown to be monoexponential, and the linear attention coefficient of PRESAGE® for the synchrotron-generated x-ray beam is measured to be (0.185 ± 0.02) cm(-1) in excellent agreement with expectations. Low-level (<5%) residual image artefacts are discussed in detail. It was possible to resolve easily slit patterns of width 37 µm (which are smaller than many of the microbeams used on ID-17), but some uncertainty remains as to whether the low values of MTF for the higher spatial frequencies are scanner related or a result of genuine (but non-ideal) dose distributions. We conclude that microscopy images from our scanner do indeed have intensities that are proportional to spectrophotometric optical density and can thus be used as the basis for accurate dosimetry. However, further investigations are necessary before the microscopy images can be used to make the quantitative measures of peak-to-valley ratios for small-diameter microbeams. We suggest various strategies for moving forward and are optimistic about the future potential of this system.

On the need for comprehensive validation of deformable image registration, investigated with a novel 3-dimensional deformable dosimeter.

PURPOSE: To introduce and evaluate a novel deformable 3-dimensional (3D) dosimetry system (Presage-Def/Optical-CT) and its application toward investigating the accuracy of dose deformation in a commercial deformable image registration (DIR) package. METHODS AND MATERIALS: Presage-Def is a new dosimetry material consisting of an elastic polyurethane matrix doped with radiochromic leuco dye. Radiologic and mechanical properties were characterized using standard techniques. Dose-tracking feasibility was evaluated by comparing dose distributions between dosimeters irradiated with and without 27% lateral compression. A checkerboard plan of 5-mm square fields enabled precise measurement of true deformation using 3D dosimetry. Predicted deformation was determined from a commercial DIR algorithm. RESULTS: Presage-Def exhibited a linear dose response with sensitivity of 0.0032 ΔOD/(Gy∙cm). Mass density is 1.02 g/cm(3), and effective atomic number is within 1.5% of water over a broad (0.03-10 MeV) energy range, indicating good water-equivalence. Elastic characteristics were close to that of liver tissue, with Young's modulus of 13.5-887 kPa over a stress range of 0.233-303 kPa, and Poisson's ratio of 0.475 (SE, 0.036). The Presage-Def/Optical-CT system successfully imaged the nondeformed and deformed dose distributions, with isotropic resolution of 1 mm. Comparison with the predicted deformed 3D dose distribution identified inaccuracies in the commercial DIR algorithm. Although external contours were accurately deformed (submillimeter accuracy), volumetric dose deformation was poor. Checkerboard field positioning and dimension errors of up to 9 and 14 mm, respectively, were identified, and the 3D DIR-deformed dose γ passing rate was only γ(3%/3 mm) = 60.0%. CONCLUSIONS: The Presage-Def/Optical-CT system shows strong potential for comprehensive investigation of DIR algorithm accuracy. Substantial errors in a commercial DIR were found in the conditions evaluated. This work highlights the critical importance of careful validation of DIR algorithms before clinical implementation.