An AI-based universal phantom analysis method based on XML-SVG wireframes with novel functional object identifiers.

Objective.Quality assurance (QA) testing must be performed at regular intervals to ensure that medical devices are operating within designed specifications. Numerous QA phantoms and software packages have been developed to facilitate measurements of machine performance. However, due to the hard-coded nature of geometric phantom definition in analysis software, users are typically limited to the use of a small subset of compatible QA phantoms. In this work, we present a novel AI-based universal Phantom (UniPhan) algorithm that is not phantom specific and can be easily adapted to any pre-existing image-based QA phantom.Approach.Extensible Markup Language Scalable Vector Graphics (XML-SVG) was modified to include several new tags describing the function of embedded phantom objects for use in QA analysis. Functional tags include contrast and density plugs, spatial linearity markers, resolution bars and edges, uniformity regions, and light-radiation field coincidence areas. Machine learning was used to develop an image classification model for automatic phantom type detection. After AI phantom identification, UniPhan imported the corresponding XML-SVG wireframe, registered it to the image taken during the QA process, performed analysis on the functional tags, and exported results for comparison to expected device specifications. Analysis results were compared to those generated by manual image analysis.Main results.XML-SVG wireframes were generated for several commercial phantoms including ones specific to CT, CBCT, kV planar imaging, and MV imaging. Several functional objects were developed and assigned to the graphical elements of the phantoms. The AI classification model was tested for training and validation accuracy and loss, along with phantom type prediction accuracy and speed. The results reported training and validation accuracies of 99%, phantom type prediction confidence scores of around 100%, and prediction speeds of around 0.1 s. Compared to manual image analysis, Uniphan results were consistent across all metrics including contrast-to-noise ratio, modulation-transfer function, HU accuracy, and uniformity.Significance.The UniPhan method can identify phantom type and use its corresponding wireframe to perform QA analysis. As these wireframes can be generated in a variety of ways this represents an accessible automated method of analyzing image-based QA phantoms that is flexible in scope and implementation.

Radiation-Chemical Oxygen Depletion Depends on Chemical Environment and Dose Rate: Implications for the FLASH Effect.

PURPOSE: FLASH (dose rates >40 Gy/s) radiation therapy protects normal tissues from radiation damage, compared with conventional radiation therapy (∼Gy/m). Radiation-chemical oxygen depletion (ROD) occurs when oxygen reacts with radiation-induced free radicals, so a possible mechanism for FLASH involves radioprotection by the decreased oxygen as ROD occurs. High ROD rates would favor this mechanism, but prior studies have reported low ROD values (∼0.35 µM/Gy) in chemical environments such as water and protein/nutrient solutions. We proposed that intracellular ROD might be much larger, possibly promoted by its strongly reducing chemical environment. METHODS AND MATERIALS: ROD was measured, using precision polarographic sensors, from ∼100 µM to zero in solutions containing intracellular reducing agents ± glycerol (1M), to simulate intracellular reducing and hydroxyl-radical-scavenging capacity. Cs irradiators and a research proton beamline allowed dose rates from 0.0085 to 100 Gy/s. RESULTS: Reducing agents significantly altered ROD values. Most greatly increased ROD but some (eg, ascorbate) actually decreased ROD and additionally imposed an oxygen dependence of ROD at low oxygen concentrations. The highest values of ROD were found at low dose rates, but these montonically decreased with increasing dose rate. CONCLUSIONS: ROD was greatly augmented by some intracellular reducing agents but others (eg, ascorbate) effectively reversed this effect. Ascorbate had its greatest effect at low oxygen concentrations. ROD decreased with increasing dose rate in most cases.

A phenomenological model of proton FLASH oxygen depletion effects depending on tissue vasculature and oxygen supply.

Introduction: Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning. Methods: The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries. Results: Dynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radio-resistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 µm vasculature spacing and 18.9 µM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect. Conclusion: We developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments.

Oxygen Monitoring in Model Solutions and In Vivo in Mice During Proton Irradiation at Conventional and FLASH Dose Rates.

FLASH is a high-dose-rate form of radiation therapy that has the reported ability, compared with conventional dose rates, to spare normal tissues while being equipotent in tumor control, thereby increasing the therapeutic ratio. The mechanism underlying this normal tissue sparing effect is currently unknown, however one possibility is radiochemical oxygen depletion (ROD) during dose delivery in tissue at FLASH dose rates. In order to investigate this possibility, we used the phosphorescence quenching method to measure oxygen partial pressure before, during and after proton radiation delivery in model solutions and in normal muscle and sarcoma tumors in mice, at both conventional (Conv) (∼0.5 Gy/s) and FLASH (∼100 Gy/s) dose rates. Radiation dosimetry was determined by Advanced Markus Chamber and EBT-XL film. For solutions contained in sealed glass vials, phosphorescent probe Oxyphor PtG4 (1 µM) was dissolved in a buffer (10 mM HEPES) containing glycerol (1 M), glucose (5 mM) and glutathione (5 mM), designed to mimic the reducing and free radical-scavenging nature of the intracellular environment. In vivo oxygen measurements were performed 24 h after injection of PtG4 into the interstitial space of either normal thigh muscle or subcutaneous sarcoma tumors in mice. The "g-value" for ROD is reported in mmHg/Gy, which represents a slight modification of the more standard chemical definition (µM/Gy). In solutions, proton irradiation at conventional dose rates resulted in a g-value for ROD of up to 0.55 mmHg/Gy, consistent with earlier studies using X or gamma rays. At FLASH dose rates, the g-value for ROD was ∼25% lower, 0.37 mmHg/Gy. pO2 levels were stable after each dose delivery. For normal muscle in vivo, oxygen depletion during irradiation was counterbalanced by resupply from the vasculature. This process was fast enough to maintain tissue pO2 virtually unchanged at Conv dose rates. However, during FLASH irradiation there was a stepwise decrease in pO2 (g-value ∼0.28 mmHg/Gy), followed by a rebound to the initial level after ∼8 s. The g-values were smaller and recovery times longer in tumor tissue when compared to muscle and may be related to the lower initial endogenous pO2 levels in the former. Considering that the FLASH effect is seen in vivo even at doses as low as 10 Gy, it is difficult to reconcile the amount of protection seen by oxygen depletion alone. However, the phosphorescence probe in our experiments was confined to the extracellular space, and it remains possible that intracellular oxygen depletion was greater than observed herein. In cell-mimicking solutions the oxygen depletion g-vales were indeed significantly higher than observed in vivo.

Improving the efficiency of small animal 3D-printed compensator IMRT with beamlet intensity total variation regularization.

PURPOSE: There is growing interest in the use of modern 3D printing technology to implement intensity-modulated radiation therapy (IMRT) on the preclinical scale that is analogous to clinical IMRT. However, current 3D-printed IMRT methods suffer from complex modulation patterns leading to long delivery times, excess filament usage, and less accurate compensator fabrication. In this work, we have developed a total variation regularization (TVR) approach to address these issues. METHODS: TVR-IMRT was used to optimize the beamlet intensity map, which was then converted to a thickness of the corresponding compensator attenuation region in copper-doped polylactic acid (PLA) filament. IMRT and TVR-IMRT heart and lung plans were generated for two different mice using three, five, or seven gantry angles. The total compensator thickness, total variation of compensator beamlet thicknesses, total variation of beamlet intensities, and exposure time were compared. The individual field doses and composite dose were delivered to film for one plan and gamma analysis was performed. RESULTS: In total, 12 mice heart and lung plans were generated for both IMRT and TVR-IMRT cases. Across all cases, it was found that TVR-IMRT reduced the total variation of compensator beamlet thicknesses and beamlet intensities by 54 ± 4 % $54\pm 4\%$ and 50 ± 3 % $50\pm 3\%$ on average when compared to standard 3D-printed compensator IMRT. On average, the total mass of compensator material consumed and radiation beam-on time were reduced by 45 ± 6 % $45\pm 6\%$ and 24 ± 4 % $24\pm 4\%$ , respectively, whereas dose metrics remained comparable. Heart plan compensators were printed and delivered to film and subsequent gamma analysis performed for each of the single fields as well as the composite dose. For the composite delivery, a passing rate of 89.1% for IMRT and 95.4% for TVR-IMRT was achieved for a 3 % / 0.3 $3\%/0.3$ mm criterion. CONCLUSIONS: TVR can be applied to small animal IMRT beamlet intensities to produce fluence maps and subsequent 3D-printed compensator patterns with significantly less complexity while still maintaining similar dose conformity to traditional IMRT. This can simplify/accelerate the 3D printing process, reduce the amount of filament required, and reduce overall beam-on time to deliver a plan.

Ultrafast Tracking of Oxygen Dynamics During Proton FLASH.

PURPOSE: Radiation therapy delivered at ultrafast dose rates, known as FLASH RT, has been shown to provide a therapeutic advantage compared with conventional radiation therapy by selectively protecting normal tissues. Radiochemical depletion of oxygen has been proposed to underpin the FLASH effect; however, experimental validation of this hypothesis has been lacking, in part owing to the inability to measure oxygenation at rates compatible with FLASH. METHODS AND MATERIALS: We present a new variant of the phosphorescence quenching method for tracking oxygen dynamics with rates reaching up to ∼3.3 kHz. Using soluble Oxyphor probes we were able to resolve, both in vitro and in vivo, oxygen dynamics during the time of delivery of proton FLASH. RESULTS: In vitro in solutions containing bovine serum albumin the O2 depletion g values (moles/L of O2 depleted per radiation dose, eg, µM/Gy) are higher for conventional irradiation (by ∼13% at 75 µM [O2]) than for FLASH, and in the low-oxygen region (<25 µM [O2]) they decrease with oxygen concentration. In vivo, depletion of oxygen by a single FLASH is insufficient to achieve severe hypoxia in initially well-oxygenated tissue, and the g values measured appear to correlate with baseline oxygen levels. CONCLUSIONS: The developed method should be instrumental in radiobiological studies, such as studies aimed at unraveling the mechanism of the FLASH effect. The FLASH effect could in part originate from the difference in the oxygen dependencies of the oxygen consumption g values for conventional versus FLASH RT.

Characterization of a high-resolution 2D transmission ion chamber for independent validation of proton pencil beam scanning of conventional and FLASH dose delivery.

INTRODUCTION: Ultra-high dose rate (FLASH) radiotherapy has become a popular research topic with the potential to reduce normal tissue toxicities without losing the benefit of tumor control. The development of FLASH proton pencil beam scanning (PBS) delivery requires accurate dosimetry despite high beam currents with correspondingly high ionization densities in the monitoring chamber. In this study, we characterized a newly designed high-resolution position sensing transmission ionization chamber with a purpose-built multichannel electrometer for both conventional and FLASH dose rate proton radiotherapy. METHODS: The dosimetry and positioning accuracies of the ion chamber were fully characterized with a clinical scanning beam. On the FLASH proton beamline, the cyclotron output current reached up to 350 nA with a maximum energy of 226.2 MeV, with 210 ± 3 nA nozzle pencil beam current. The ion recombination effect was characterized under various bias voltages up to 1000 V and different beam intensities. The charge collected by the transmission ion chamber was compared with the measurements from a Faraday cup. RESULTS: Cross-calibrated with an Advanced Markus chamber (PTW, Freiburg, Germany) in a uniform PBS proton beam field at clinical beam setting, the ion chamber calibration was 38.0 and 36.7 GyE·mm2 /nC at 100 and 226.2 MeV, respectively. The ion recombination effect increased with larger cyclotron current at lower bias voltage while remaining ≤0.5 ± 0.5% with ≥200 V of bias voltage. Above 200 V, the normalized ion chamber readings demonstrated good linearity with the mass stopping power in air for both clinical and FLASH beam intensities. The spot positioning accuracy was measured to be 0.10 ± 0.08 mm in two orthogonal directions. CONCLUSION: We characterized a transmission ion chamber system under both conventional and FLASH beam current densities and demonstrated its suitability for use as a proton pencil beam dose and spot position delivery monitor under FLASH dose rate conditions.

Small Animal IMRT Using 3D-Printed Compensators.

PURPOSE: Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. METHODS AND MATERIALS: Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx1) with boost (Rx2) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. RESULTS: Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V95% = 95%) with organ sparing (organs at risk Dmax < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V95%,Rx2 = 91.6%, normoxic tumor V95%,Rx1 = 95.7%, normal tissue V100%,Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V95%,Rx2 = 90.9%, hypoxic tumor V95%,Rx1 = 62.7%, and normal tissue V100%,Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. CONCLUSIONS: This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.

Current delivery limitations of proton PBS for FLASH.

PURPOSE: Proton Pencil Beam Scanning (PBS) is an attractive solution to realize the advantageous normal tissue sparing elucidated from FLASH high dose rates. The mechanics of PBS spot delivery will impose limitations on the effective field dose rate for PBS. METHODS: This study incorporates measurements from clinical and FLASH research beams on uniform single energy and the spread-out Bragg Peak PBS fields to extrapolate the PBS dose rate to high cyclotron beam currents 350, 500, and 800 nA. The impact of the effective field dose rate from cyclotron current, spot spacing, slew time and field size were studied. RESULTS: When scanning magnet slew time and energy switching time are not considered, single energy effective field FLASH dose rate (≥40 Gy/s) can only be achieved with less than 4 × 4 cm2 fields when the cyclotron output current is above 500 nA. Slew time and energy switching time remain the limiting factors for achieving high effective dose rate of the field. The dose rate-time structures were obtained. The amount of the total dose delivered at the FLASH dose rate in single energy layer and volumetric field was also studied. CONCLUSION: It is demonstrated that while it is difficult to achieve FLASH dose rate for a large field or in a volume, local FLASH delivery to certain percentage of the total dose is possible. With further understanding of the FLASH radiobiological mechanism, this study could provide guidance to adapt current clinical multi-field proton PBS delivery practice for FLASH proton radiotherapy.

Mechanism and Model of a Soft Robot for Head Stabilization in Cancer Radiation Therapy.

We present a parallel robot mechanism and the constitutive laws that govern the deformation of its constituent soft actuators. Our ultimate goal is the real-time motion-correction of a patient's head deviation from a target pose where the soft actuators control the position of the patient's cranial region on a treatment machine. We describe the mechanism, derive the stress-strain constitutive laws for the individual actuators and the inverse kinematics that prescribes a given deformation, and then present simulation results that validate our mathematical formulation. Our results demonstrate deformations consistent with our radially symmetric displacement formulation under a finite elastic deformation framework.

Optimization based trajectory planning for real-time 6DoF robotic patient motion compensation systems.

PURPOSE: Robotic stabilization of a therapeutic radiation beam with respect to a dynamically moving tumor target can be accomplished either by moving the radiation source, the patient, or both. As the treatment beam is on during this process, the primary goal is to minimize exposure of normal tissue to radiation as much as possible when moving the target back to the desired position. Due to the complex mechanical structure of 6 degree-of-freedom (6DoF) robots, it is not intuitive as to what 6 dimensional (6D) correction trajectory is optimal in achieving such a goal. With proportional-integrative-derivative (PID) and other controls, the potential exists that the controller may generate a trajectory that is highly curved, slow, or suboptimal in that it leads to unnecessary exposure of healthy tissue to radiation. This work investigates a novel feedback planning method that takes into account a robot's mechanical joint structure, patient safety tolerances, and other system constraints, and performs real-time optimization to search the entire 6D trajectory space in each time cycle so it can respond with an optimal 6D correction trajectory. METHODS: Computer simulations were created for two 6DoF robotic patient support systems: a Stewart-Gough platform for moving a patient's head in frameless maskless stereotactic radiosurgery, and a linear accelerator treatment table for moving a patient in prostate cancer radiation therapy. Motion planning was formulated as an optimization problem and solved at real-time speeds using the L-BFGS algorithm. Three planning methods were investigated, moving the platform as fast as possible (platform-D), moving the target along a straight-line (target-S), and moving the target based on the fastest descent of position error (target-D). Both synthetic motion and prior recorded human motion were used as input data and output results were analyzed. RESULTS: For randomly generated 6D step-like and sinusoidal synthetic input motion, target-D planning demonstrated the smallest net trajectory error in all cases. On average, optimal planning was found to have a 45% smaller target trajectory error than platform-D control, and a 44% smaller target trajectory error than target-S planning. For patient head motion compensation, only target-D planning was able to maintain a ≤0.5mm and ≤0.5deg clinical tolerance objective for 100% of the treatment time. For prostate motion, both target-S planning and target-D planning outperformed platform-D control. CONCLUSIONS: A general 6D target trajectory optimization framework for robotic patient motion compensation systems was investigated. The method was found to be flexible as it allows control over various performance requirements such as mechanical limits, velocities, acceleration, or other system control objectives.

A conceptual study on real-time adaptive radiation therapy optimization through ultra-fast beamlet control.

A central problem in the field of radiation therapy (RT) is how to optimally deliver dose to a patient in a way that fully accounts for anatomical position changes over time. As current RT is a static process, where beam intensities are calculated before the start of treatment, anatomical deviations can result in poor dose conformity. To overcome these limitations, we present a simulation study on a fully dynamic real-time adaptive radiation therapy (RT-ART) optimization approach that uses ultra-fast beamlet control to dynamically adapt to patient motion in real-time. A virtual RT-ART machine was simulated with a rapidly rotating linear accelerator (LINAC) source (60 RPM) and a binary 1D multi-leaf collimator (MLC) operating at 100 Hz. If the real-time tracked target motion exceeded a predefined threshold, a time dependent objective function was solved using fast optimization methods to calculate new beamlet intensities that were then delivered to the patient. To evaluate the approach, system response was analyzed for patient derived continuous drift, step-like, and periodic intra-fractional motion. For each motion type investigated, the RT-ART method was compared against the ideal case with no patient motion (static case) as well as to the case without the use RT-ART. In all cases, isodose lines and dose-volume-histograms (DVH) showed that RT-ART plan quality was approximately the same as the static case, and considerably better than the no RT-ART case. Based on tests using several different motion types, RT-ART was able to recover dose conformity to the level that it was similar to an ideal RT delivery with no anatomical changes. With continued advances in real-time patient motion tracking and fast computational processes, there is significant potential for the RT-ART optimization process to be realized on next generation RT machines.

Use of a laser-guided collimation system to perform direct kilovoltage x-ray spectra measurements on a linear accelerator onboard imager.

PURPOSE: The increased use of image-guided radiation therapy (IGRT) has led to increased use of kV on board imaging (OBI) devices. At present, directly measured OBI beam quality data have only been reported in terms of half-value layers (HVL). However, the HVL metric alone does not give the full OBI energy spectra as needed for accurate beam modeling. Although direct kV spectrometer devices exist they typically suffer from detector pile-up when used with OBI sources. We therefore present, for the first time, a novel laser-guided collimation system that allows direct measurement of the full energy spectrum for clinical OBI systems. METHODS: Several clinically relevant spectra (80, 100, and 125 kVp), with and without the half bow-tie filter, were measured using a thermoelectric cooled cadmium telluride (CdTe) detector paired with a multichannel analyzer. To prevent detector saturation, the photon flux at the detector was reduced by use of an in-house designed laser-guided collimation system. After applying energy bin corrections, direct spectroscopic measurements were compared to Monte Carlo (MC) simulated spectra in order to verify accuracy of collected data. Both percent depth dose (PDD) curves and digitally reconstructed radiographs (DRR) were compared using the measured vs MC spectra. RESULTS: Measured and MC spectra agree with RMSD between 1.96% and 3.29%. PDD curves generated from the measured and MC spectra were found to match except for in the small buildup region, with an overall match for the six beams ranging between 0.3% and 2.7% RMSD. DRRs matched well with a maximum difference in contrast of 1.1% and RMSD of 0.46% contrast for various materials in DRRs. CONCLUSIONS: The use of a laser-guided collimation system provided a method for quickly obtaining highly accurate kV spectrum data from OBI sources. For kV dose or DRR calculation, it was found that both spectra produced similar results.

Towards frameless maskless SRS through real-time 6DoF robotic motion compensation.

Stereotactic radiosurgery (SRS) uses precise dose placement to treat conditions of the CNS. Frame-based SRS uses a metal head ring fixed to the patient's skull to provide high treatment accuracy, but patient comfort and clinical workflow may suffer. Frameless SRS, while potentially more convenient, may increase uncertainty of treatment accuracy and be physiologically confining to some patients. By incorporating highly precise robotics and advanced software algorithms into frameless treatments, we present a novel frameless and maskless SRS system where a robot provides real-time 6DoF head motion stabilization allowing positional accuracies to match or exceed those of traditional frame-based SRS. A 6DoF parallel kinematics robot was developed and integrated with a real-time infrared camera in a closed loop configuration. A novel compensation algorithm was developed based on an iterative closest-path correction approach. The robotic SRS system was tested on six volunteers, whose motion was monitored and compensated for in real-time over 15 min simulated treatments. The system's effectiveness in maintaining the target's 6DoF position within preset thresholds was determined by comparing volunteer head motion with and without compensation. Comparing corrected and uncorrected motion, the 6DoF robotic system showed an overall improvement factor of 21 in terms of maintaining target position within 0.5 mm and 0.5 degree thresholds. Although the system's effectiveness varied among the volunteers examined, for all volunteers tested the target position remained within the preset tolerances 99.0% of the time when robotic stabilization was used, compared to 4.7% without robotic stabilization. The pre-clinical robotic SRS compensation system was found to be effective at responding to sub-millimeter and sub-degree cranial motions for all volunteers examined. The system's success with volunteers has demonstrated its capability for implementation with frameless and maskless SRS treatments, potentially able to achieve the same or better treatment accuracies compared to traditional frame-based approaches.

Sensitivity evaluation and selective plane imaging geometry for x-ray-induced luminescence imaging.

PURPOSE: X-ray-induced luminescence (XIL) is a hybrid x-ray/optical imaging modality that employs nanophosphors that luminescence in response to x-ray irradiation. X-ray-activated phosphorescent nanoparticles have potential applications in radiation therapy as theranostics, nanodosimeters, or radiosensitizers. Extracting clinically relevant information from the luminescent signal requires the development of a robust imaging model that can determine nanophosphor distributions at depth in an optically scattering environment from surface radiance measurements. The applications of XIL in radiotherapy will be limited by the dose-dependent sensitivity at depth in tissue. We propose a novel geometry called selective plane XIL (SPXIL), and apply it to experimental measurements in optical gel phantoms and sensitivity simulations. METHODS: An imaging model is presented based on the selective plane geometry which can determine the detected diffuse optical signal for a given x-ray dose and nanophosphor distribution at depth in a semi-infinite, optically homogenous material. The surface radiance in the model is calculated using an analytical solution to the extrapolated boundary condition. Y2 O3 :Eu3+ nanoparticles are synthesized and inserted into various optical phantom in order to measure the luminescent output per unit dose for a given concentration of nanophosphors and calibrate an imaging model for XIL sensitivity simulations. SPXIL imaging with a dual-source optical gel phantom is performed, and an iterative Richardson-Lucy deconvolution using a shifted Poisson noise model is applied to the measurements in order to reconstruct the nanophosphor distribution. RESULTS: Nanophosphor characterizations showed a peak emission at 611 nm, a linear luminescent response to tube current and nanoparticle concentration, and a quadratic luminescent response to tube voltage. The luminescent efficiency calculation accomplished with calibrated bioluminescence mouse phantoms determines 1.06 photons were emitted per keV of x-ray radiation absorbed per g/mL of nanophosphor concentration. Sensitivity simulations determined that XIL could detect a concentration of 1 mg/mL of nanophosphors with a dose of 1 cGy at a depth ranging from 2 to 4 cm, depending on the optical parameters of the homogeneous diffuse optical environment. The deconvolution applied to the SPXIL measurements could resolve two sources 1 cm apart up to a depth of 1.75 cm in the diffuse phantom. CONCLUSIONS: We present a novel imaging geometry for XIL in a homogenous, diffuse optical environment. Basic characterization of Y2 O3 :Eu3+ nanophosphors are presented along with XIL/SPXIL measurements in optical gel phantoms. The diffuse optical imaging model is validated using these measurements and then calibrated in order to execute initial sensitivity simulations for the dose-depth limitations of XIL imaging. The SPXIL imaging model is used to perform a deconvolution on a dual-source phantom, which successfully reconstructs the nanophosphor distributions.

Use of proximal operator graph solver for radiation therapy inverse treatment planning.

PURPOSE: Most radiation therapy optimization problems can be formulated as an unconstrained problem and solved efficiently by quasi-Newton methods such as the Limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm. However, several next generation planning techniques such as total variation regularization- based optimization and MV+kV optimization, involve constrained or mixed-norm optimization, and cannot be solved by quasi-Newton methods. Using standard optimization algorithms on such problems often leads to prohibitively long optimization times and large memory requirements. This work investigates the use of a recently developed proximal operator graph solver (POGS) in solving such radiation therapy optimization problems. METHODS: Radiation therapy inverse treatment planning was formulated as a graph form problem, and the proximal operators of POGS for quadratic optimization were derived. POGS was exploited for the first time to impose hard dose constraints along with soft constraints in the objective function. The solver was applied to several clinical treatment sites (TG119, liver, prostate, and head&neck), and the results were compared to the solutions obtained by other commercial and non-commercial optimizers. RESULTS: For inverse planning optimization with nonnegativity box constraints on beamlet intensity, the speed of POGS can compete with that of LBFGSB in some situations. For constrained and mixed-norm optimization, POGS is about one or two orders of magnitude faster than the other solvers while requiring less computer memory. CONCLUSIONS: POGS was used for solving inverse treatment planning problems involving constrained or mixed-norm formulation on several example sites. This approach was found to improve upon standard solvers in terms of computation speed and memory usage, and is capable of solving traditionally difficult problems, such as total variation regularization-based optimization and combined MV+kV optimization.

Spatial and rotational quality assurance of 6DOF patient tracking systems.

PURPOSE: External tracking systems used for patient positioning and motion monitoring during radiotherapy are now capable of detecting both translations and rotations. In this work, the authors develop a novel technique to evaluate the 6 degree of freedom 6(DOF) (translations and rotations) performance of external motion tracking systems. The authors apply this methodology to an infrared marker tracking system and two 3D optical surface mapping systems in a common tumor 6DOF workspace. METHODS: An in-house designed and built 6DOF parallel kinematics robotic motion phantom was used to perform motions with sub-millimeter and subdegree accuracy in a 6DOF workspace. An infrared marker tracking system was first used to validate a calibration algorithm which associates the motion phantom coordinate frame to the camera frame. The 6DOF positions of the mobile robotic system in this space were then tracked and recorded independently by an optical surface tracking system after a cranial phantom was rigidly fixed to the moveable platform of the robotic stage. The calibration methodology was first employed, followed by a comprehensive 6DOF trajectory evaluation, which spanned a full range of positions and orientations in a 20 × 20 × 16 mm and 5° × 5° × 5° workspace. The intended input motions were compared to the calibrated 6DOF measured points. RESULTS: The technique found the accuracy of the infrared (IR) marker tracking system to have maximal root-mean square error (RMSE) values of 0.18, 0.25, 0.07 mm, 0.05°, 0.05°, and 0.09° in left-right (LR), superior-inferior (SI), anterior-posterior (AP), pitch, roll, and yaw, respectively, comparing the intended 6DOF position and the measured position by the IR camera. Similarly, the 6DOF RSME discrepancy for the HD optical surface tracker yielded maximal values of 0.46, 0.60, 0.54 mm, 0.06°, 0.11°, and 0.08° in LR, SI, AP, pitch, roll, and yaw, respectively, over the same 6DOF evaluative workspace. An earlier generation 3D optical surface tracking unit was observed to have worse tracking capabilities than both the IR camera unit and the newer 3D surface tracking system with maximal RMSE of 0.69, 0.74, 0.47 mm, 0.28°, 0.19°, and 0.18°, in LR, SI, AP, pitch, roll, and yaw, respectively, in the same 6DOF evaluation space. CONCLUSIONS: The proposed technique was found to be effective at evaluating the performance of 6DOF patient tracking systems. All observed optical tracking systems were found to exhibit tracking capabilities at the sub-millimeter and subdegree level within a 6DOF workspace.

Technical Note: High temporal resolution characterization of gating response time.

PURPOSE: Low temporal latency between a gating ON/OFF signal and the LINAC beam ON/OFF during respiratory gating is critical for patient safety. Here the authors describe a novel method to precisely measure gating lag times at high temporal resolutions. METHODS: A respiratory gating simulator with an oscillating platform was modified to include a linear potentiometer for position measurement. A photon diode was placed at linear accelerator isocenter for beam output measurement. The output signals of the potentiometer and diode were recorded simultaneously at 2500 Hz with an analog to digital converter for four different commercial respiratory gating systems. The ON and OFF of the beam signal were located and compared to the expected gating window for both phase and position based gating and the temporal lag times extracted. RESULTS: For phase based gating, a real-time position management (RPM) infrared marker tracking system with a single camera and a RPM system with a stereoscopic camera were measured to have mean gate ON/OFF lag times of 98/90 and 86/44 ms, respectively. For position based gating, an AlignRT 3D surface system and a Calypso magnetic fiducial tracking system were measured to have mean gate ON/OFF lag times of 356/529 and 209/60 ms, respectively. CONCLUSIONS: Temporal resolution of the method was high enough to allow characterization of individual gate cycles and was primary limited by the sampling speed of the data recording device. Significant variation of mean gate ON/OFF lag time was found between different gating systems. For certain gating devices, individual gating cycle lag times can vary significantly.

Robotic real-time translational and rotational head motion correction during frameless stereotactic radiosurgery.

PURPOSE: To develop a control system to correct both translational and rotational head motion deviations in real-time during frameless stereotactic radiosurgery (SRS). METHODS: A novel feedback control with a feed-forward algorithm was utilized to correct for the coupling of translation and rotation present in serial kinematic robotic systems. Input parameters for the algorithm include the real-time 6DOF target position, the frame pitch pivot point to target distance constant, and the translational and angular Linac beam off (gating) tolerance constants for patient safety. Testing of the algorithm was done using a 4D (XY Z + pitch) robotic stage, an infrared head position sensing unit and a control computer. The measured head position signal was processed and a resulting command was sent to the interface of a four-axis motor controller, through which four stepper motors were driven to perform motion compensation. RESULTS: The control of the translation of a brain target was decoupled with the control of the rotation. For a phantom study, the corrected position was within a translational displacement of 0.35 mm and a pitch displacement of 0.15° 100% of the time. For a volunteer study, the corrected position was within displacements of 0.4 mm and 0.2° over 98.5% of the time, while it was 10.7% without correction. CONCLUSIONS: The authors report a control design approach for both translational and rotational head motion correction. The experiments demonstrated that control performance of the 4D robotic stage meets the submillimeter and subdegree accuracy required by SRS.

Development of a 6DOF robotic motion phantom for radiation therapy.

PURPOSE: The use of medical technology capable of tracking patient motion or positioning patients along 6 degree-of-freedom (6DOF) has steadily increased in the field of radiation therapy. However, due to the complex nature of tracking and performing 6DOF motion, it is critical that such technology is properly verified to be operating within specifications in order to ensure patient safety. In this study, a robotic motion phantom is presented that can be programmed to perform highly accurate motion along any X (left-right), Y (superior-inferior), Z (anterior-posterior), pitch (around X), roll (around Y), and yaw (around Z) axes. In addition, highly synchronized motion along all axes can be performed in order to simulate the dynamic motion of a tumor in 6D. The accuracy and reproducibility of this 6D motion were characterized. METHODS: An in-house designed and built 6D robotic motion phantom was constructed following the Stewart-Gough parallel kinematics platform archetype. The device was controlled using an inverse kinematics formulation, and precise movements in all 6 degrees-of-freedom (X, Y, Z, pitch, roll, and yaw) were performed, both simultaneously and separately for each degree-of-freedom. Additionally, previously recorded 6D cranial and prostate motions were effectively executed. The robotic phantom movements were verified using a 15 fps 6D infrared marker tracking system and the measured trajectories were compared quantitatively to the intended input trajectories. The workspace, maximum 6D velocity, backlash, and weight load capabilities of the system were also established. RESULTS: Evaluation of the 6D platform demonstrated translational root mean square error (RMSE) values of 0.14, 0.22, and 0.08 mm over 20 mm in X and Y and 10 mm in Z, respectively, and rotational RMSE values of 0.16°, 0.06°, and 0.08° over 10° of pitch, roll, and yaw, respectively. The robotic stage also effectively performed controlled 6D motions, as well as reproduced cranial trajectories over 15 min, with a maximal RMSE of 0.04 mm translationally and 0.04° rotationally, and a prostate trajectory over 2 min, with a maximal RMSE of 0.06 mm translationally and 0.04° rotationally. CONCLUSIONS: This 6D robotic phantom has proven to be accurate under clinical standards and capable of reproducing tumor motion in 6D. Such functionality makes the robotic phantom usable for either quality assurance or research purposes.