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PURPOSE Although volumetric modulated arc therapy (VMAT) is a well-accepted treatment technique in radiotherapy using a coplanar delivery approach, VMAT might be further improved by including dynamic table and collimator rotations leading to dynamic trajectory radiotherapy (DTRT). In this work, an optimization procedure for DTRT was developed and the potential benefit of DTRT was investigated for different treatment sites. METHODS For this purpose, a dedicated optimization framework for DTRT was developed using the Eclipse Scripting Research Application Programming Interface (ESRAPI). The contours of the target and organs at risk (OARs) structures were exported by applying the ESRAPI and were used to determine the fractional volume-overlap of the OARs with the target from several potential beam directions. Thereby, an additional weighting was applied taking into account the relative position of the OAR with respect to the target and radiation beam, that is, penalizing directions where the OAR is proximal to the target. The resulting two-dimensional gantry-table map was used as input for an A* path finding algorithm returning an optimized gantry-table path. Thereby, the process is also taking into account CT scan length and collision restrictions. The A* algorithm was used again to determine the dynamic collimator angle path by optimizing the area between the MLC leaves and the target contour for each gantry-table path leading to gantry-collimator paths. The resulting gantry-table and gantry-collimator paths are combined and serve as input for the intensity modulation optimization using a research VMAT optimizer and the ESRAPI resulting in dynamic trajectories. This procedure was evaluated for five clinically motivated cases: two head and neck, one lung, one esophagus, and one prostate. Final dose calculations were performed using the Swiss Monte Carlo Plan (SMCP). Resulting dose distributions for the DTRT treatment plans and for the standard VMAT plans were compared based on dose distributions and dose volume histogram (DVH) parameters. For this comparison, the dose distribution for the VMAT plans were recalculated using the SMCP. In addition, the suitability of the delivery of a DTRT treatment plan was demonstrated by means of gafchromic film measurements on a TrueBeam linear accelerator. RESULTS DVHs for the target volumes showed similar or improved coverage and dose homogeneity for DTRT compared with VMAT using equal or less number of dynamic trajectories for DTRT than arcs for VMAT for all cases studied. Depending on the case, improvements in mean and maximum dose for the DTRT plans were achieved for almost all OARs compared with the VMAT plans. Improvements in DTRT treatment plans for mean and maximum dose compared to VMAT plans were up to 16% and 38% relative to the prescribed dose, respectively. The measured and calculated dose values resulted in a passing rate of more than 99.5% for the two-dimensional gamma analysis using 2% and 2 mm criteria and a threshold of 10%. CONCLUSIONS DTRT plans for different treatment sites were generated and compared with VMAT plans. The delivery is suitable and dose comparisons demonstrate a high potential of DTRT to reduce dose to OARs using less dynamic trajectories than arcs, while target coverage is preserved.

Purpose: In this experimental study, the authors explored the possibility to deliver the dose for proton therapy with fast uniform scanning on a gantry primarily designed for the delivery of conformal beam scanning and IMPT. The uniform scanning submode has been realized without equipment modifications by using the same small pencil beam used for conformal scanning, resulting in reduced realization costs. Uniform scanning has recently been adopted in a few proton therapy centers, as a basic beam delivery solution, and as an alternative to the use of scattering foils. The option to use such a mode to mimic scattering on a full-fledged scanning gantry could be of interest for treating some specific indications and as a possible solution for treating moving targets. Methods: Uniform iso-energy dose layers were painted by fast magnetic scanning alternated with fast energy changes with the gantry beam line. The layers were stacked and repainted appropriately to produce homogeneous three-dimensional dose distributions. A collimator/compensator was used to adjust the dose to coincide laterally/distally with the target volume. In addition, they applied volumetric repainting, since they are confident that this will further mitigate the effects of organ motion as compared with the presently used clinical scanning solutions.more » With the approach presented in this paper, they can profit from the higher flexibility of the scanning system to obtain additional advantages. For instance the shape of the energy layers can be adjusted to the projected target shape in order to reduce treatment time and neutrons produced in the collimator. The shape of the proximal layers can be shrunk, according to the cross section of the target at the corresponding range. This provides variable range modulation (proximal conformity) while standard scattering only provides fixed range modulation with unnecessary 100% dose proximal to the target. The field-specific hardware for a spherical target volume was mounted on the Gantry 2 nozzle. One field with proximal field size shrinking and one without, each of 1 Gy, were delivered. The dose distributions at different depths were recorded as CCD images of a scintillating screen. Results: The time to scan the volume once was about 4 s and the total delivery time was approximately 30 s. For the field with proximal conformity, dose sparing of up to 25% was measured in the region proximal to the target. A repainting capability of 48 times was achieved on the most distal layer. The proximal layers were repainted more due to the contribution of the plateau dose from the deeper layers. Conclusions: The flexibility of a fast scanning gantry with very fast energy changes can easily provide beam delivery by uniform layer stacking with a significant degree of volumetric repainting and with the benefit of a dose reduction proximal to the target volume.« less

This article reports on a 4D-treatment planning workshop (4DTPW), held on 7–8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to discuss current approaches, challenges, and future research directions in 4D-treatment planning in the context of actively scanned particle radiotherapy. Key aspects were addressed in plenary sessions, in which leaders of the field summarized the state-of-the-art. Each plenary session was followed by an extensive discussion. As a result, this article presents a summary of recommendations for the treatment of mobile targets (intrafractional changes) with actively scanned particles and a list of requirements to elaborate and apply these guidelines clinically.

To assess whether air scintillation produced during standard radiation treatments can be visualized and used to monitor a beam in a nonperturbing manner.Air scintillation is caused by the excitation of nitrogen gas by ionizing radiation. This weak emission occurs predominantly in the 300-430 nm range. An electron-multiplication charge-coupled device camera, outfitted with an f/0.95 lens, was used to capture air scintillation produced by kilovoltage photon beams and megavoltage electron beams used in radiation therapy. The treatment rooms were prepared to block background light and a short-pass filter was utilized to block light above 440 nm.Air scintillation from an orthovoltage unit (50 kVp, 30 mA) was visualized with a relatively short exposure time (10 s) and showed an inverse falloff (r(2) = 0.89). Electron beams were also imaged. For a fixed exposure time (100 s), air scintillation was proportional to dose rate (r(2) = 0.9998). As energy increased, the divergence of the electron beam decreased and the penumbra improved. By irradiating a transparent phantom, the authors also showed that Cherenkov luminescence did not interfere with the detection of air scintillation. In a final illustration of the capabilities of this new technique, the authors visualized air scintillation produced during a total skin irradiation treatment.Air scintillation can be measured to monitor a radiation beam in an inexpensive and nonperturbing manner. This physical phenomenon could be useful for dosimetry of therapeutic radiation beams or for online detection of gross errors during fractionated treatments.

Irradiation of a moving target with a scanning beam requires a comprehensive understanding of organ motion as well as a robust dose error mitigation technique. The authors studied the effects of intrafractional respiratory motion for carbon-ion pencil beam scanning with phase-controlled rescanning on dose distributions for lung tumors. To address density variations, they used 4DCT data.Dose distributions for various rescanning methods, such as simple layer rescanning (LR), volumetric rescanning, and phase-controlled rescanning (PCR), were calculated for a lung phantom and a lung patient studies. To ensure realism, they set the scanning parameters such as scanning velocity and energy variation time to be similar to those used at our institution. Evaluation metrics were determined with regard to clinical relevance, and consisted of (i) phase-controlled rescanning, (ii) sweep direction, (iii) target motion (direction and amplitude), (iv) respiratory cycle, and (v) prescribed dose. Spot weight maps were calculated by using a beam field-specific target volume, which takes account of range variations for respective respiratory phases. To emphasize the impact of intrafractional motion on the dose distribution, respiratory gating was not used. The accumulated dose was calculated by applying a B-spline-based deformable image registration, and the results for phase-controlled layered rescanning (PCRL) and phase-controlled volumetric rescanning (PCRV) were compared.For the phantom study, simple LR was unable to improve the dose distributions for an increased number of rescannings. The phase-controlled technique without rescanning (1×PCRL and 1×PCRV) degraded dose conformity significantly due to a reduced scan velocity. In contrast, 4×PCRL or more significantly and consistently improved dose distribution. PCRV showed interference effects, but in general also improved dose homogeneity with higher numbers of rescannings. Dose distributions with single PCRL∕PCRV with a sweep direction perpendicular to motion direction showed large hot∕cold spots; however, this effect vanished with higher numbers of rescannings for both methods. Similar observations were obtained for the other dose metrics, such as target motion (SI∕AP), amplitude (6-22 mm peak-to-peak) and respiratory period (3.0-5.0 s). For four or more rescannings, both methods showed significantly better results, albeit that volumetric PCR was more affected by interference effects, which lead to severe degradation of a few dose distributions. The clinical example showed the same tendencies as the phantom study. Dose assessment metrics (D95, Dmax∕Dmin, homogeneity index) were improved with an increasing number of PCRL∕PCRV, but with PCRL being more robust.PCRL requires a longer treatment time than PCRV for high numbers of rescannings in the NIRS scanning system but is more robust. Although four or more rescans provided good dose homogeneity and conformity, the authors prefer to use more rescannings for clinical cases to further minimize dose degradation effects due to organ motion.

In this experimental study, the authors explored the possibility to deliver the dose for proton therapy with fast uniform scanning on a gantry primarily designed for the delivery of conformal beam scanning and IMPT. The uniform scanning submode has been realized without equipment modifications by using the same small pencil beam used for conformal scanning, resulting in reduced realization costs. Uniform scanning has recently been adopted in a few proton therapy centers, as a basic beam delivery solution, and as an alternative to the use of scattering foils. The option to use such a mode to mimic scattering on a full-fledged scanning gantry could be of interest for treating some specific indications and as a possible solution for treating moving targets.Uniform iso-energy dose layers were painted by fast magnetic scanning alternated with fast energy changes with the gantry beam line. The layers were stacked and repainted appropriately to produce homogeneous three-dimensional dose distributions. A collimator∕compensator was used to adjust the dose to coincide laterally∕distally with the target volume. In addition, they applied volumetric repainting, since they are confident that this will further mitigate the effects of organ motion as compared with the presently used clinical scanning solutions. With the approach presented in this paper, they can profit from the higher flexibility of the scanning system to obtain additional advantages. For instance the shape of the energy layers can be adjusted to the projected target shape in order to reduce treatment time and neutrons produced in the collimator. The shape of the proximal layers can be shrunk, according to the cross section of the target at the corresponding range. This provides variable range modulation (proximal conformity) while standard scattering only provides fixed range modulation with unnecessary 100% dose proximal to the target. The field-specific hardware for a spherical target volume was mounted on the Gantry 2 nozzle. One field with proximal field size shrinking and one without, each of 1 Gy, were delivered. The dose distributions at different depths were recorded as CCD images of a scintillating screen.The time to scan the volume once was about 4 s and the total delivery time was approximately 30 s. For the field with proximal conformity, dose sparing of up to 25% was measured in the region proximal to the target. A repainting capability of 48 times was achieved on the most distal layer. The proximal layers were repainted more due to the contribution of the plateau dose from the deeper layers.The flexibility of a fast scanning gantry with very fast energy changes can easily provide beam delivery by uniform layer stacking with a significant degree of volumetric repainting and with the benefit of a dose reduction proximal to the target volume.

Purpose: Radiation therapy errors are rare but potentially catastrophic. Recent fatal incidents could have been avoided by utilizing real-time methods of monitoring delivery of radiation during treatment. However, few existing methods are practical enough to be used routinely. The study presents the first experimental demonstration of a novel non-perturbing method of monitoring radiation therapy through the phenomena of air scintillation. Methods: Monitoring of radiation delivery was devised by leveraging the phenomena of nitrogen excitation in air by ionizing radiation. The excitation induced weak luminescence in the 300–400 nm range, a process called air scintillation. An electron-multiplication charge-coupled device camera (f/0.95 lens; 440 nm shortpass) was set-up in a clinical treatment vault and was used to capture air scintillation images of kilovoltage and megavoltage beams. Monte Carlo simulations were performed to determine the correlation of radiation dose to air scintillation. Results: Megavoltage beams from a Varian Clinac 21EX and kilovoltage beams from an orthovoltage unit (50 kVp, 30 mA) were visualized with a relatively short exposure time (10 s). Cherenkov luminescence produced in a plastic transparent phantom did not interfere with detection of air scintillation. The image intensity displayed an inverse intensity falloff (r2 = 0.89) along the central axis and was proportional to dose rate (r2 = 0.9998). As beam energy increased, the divergence of the imaged beam decreased. Last, air scintillation was visualized during a simulated total skin irradiation electron treatment. Conclusion: Air scintillation can be clinically detected to monitor a radiation beam in an inexpensive and non-perturbing manner. This new method is advantageous in monitoring for gross delivery and uniquely capable of wide area in a single acquisition, such as the case for online verification of total body / skin / lymphoid irradiation treatments.

Purpose: Atherosclerosis is a progressive inflammatory condition that underlies coronary artery disease (CAD)—the leading cause of death in the USA. Thus, understating the metabolism of inflammatory cells can be a valuable tool for investigating CAD. To the best of our knowledge, we are the first to successfully investigate the pharmacokinetics of [18F]fluoro-deoxyglucose (18F-FDG) uptake in a single macrophages and compared with induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) with a novel imaging technique, radioluminescence microscopy, initially developed for cancer imaging. Methods: Live cells were cultured sparsely on Matrigel in a glass-bottom dish and starved for 1 hour before incubation with 250 microCi of 18F-FDG for 45 minutes. Excess radiotracer was removed using DMEM medium without glucose. Before imaging, DMEM (1 mL) was added to the cell culture and a 100 microm-thin CdWO4 scintillator plate was placed on top of the cells. Light produced following beta decay was imaged with a highly sensitive inverted microscope (LV200, Olympus) fitted with a 40x/1.3 high-NA oil objective, and an EM-CCD camera. The images were collected over 18,000 frames with 4×4 binning (1200 MHz EM Gain, 300ms exposure). Custom-written software was developed in MATLAB for image processing (Figure 1). For statistical analysismore » 10 different region-of-interests (ROIs) were selected for each cell type. Results: Figures 2A–2B show bright-field/fusion images for all three different cell types. The relationship between cell-to-cell comparisons was found to be linear for macrophages unlike iPSCs and MSCs, which were best fitted with moving or rolling average (Figure 2C). The average observed decay of 18F-FDG in a single cell of MSCs per second (0.067) was 20% and 36% higher compared to iPSCs (0.054) and macrophages (0.043), respectively (Figure 2D). Conclusion: MSCs was found to be 2–3x more sensitive to glucose molecule despite constant parameters for each cell type examined.« less

Purpose: To assess whether air scintillation produced during standard radiation treatments can be visualized and used to monitor a beam in a nonperturbing manner. Methods: Air scintillation is caused by the excitation of nitrogen gas by ionizing radiation. This weak emission occurs predominantly in the 300–430 nm range. An electron-multiplication charge-coupled device camera, outfitted with an f/0.95 lens, was used to capture air scintillation produced by kilovoltage photon beams and megavoltage electron beams used in radiation therapy. The treatment rooms were prepared to block background light and a short-pass filter was utilized to block light above 440 nm. Results: Air scintillation from an orthovoltage unit (50 kVp, 30 mA) was visualized with a relatively short exposure time (10 s) and showed an inverse falloff (r2 = 0.89). Electron beams were also imaged. For a fixed exposure time (100 s), air scintillation was proportional to dose rate (r2 = 0.9998). As energy increased, the divergence of the electron beam decreased and the penumbra improved. By irradiating a transparent phantom, the authors also showed that Cherenkov luminescence did not interfere with the detection of air scintillation. In a final illustration of the capabilities of this new technique, the authors visualized air scintillation produced during a total skin irradiation treatment. Conclusions: Air scintillation can be measured to monitor a radiation beam in an inexpensive and nonperturbing manner. This physical phenomenon could be useful for dosimetry of therapeutic radiation beams or for online detection of gross errors during fractionated treatments.