Proton beam spot size and position measurements using a multi-strip ionization chamber.

PURPOSE: To develop and characterize a large-area multi-strip ionization chamber (MSIC) for efficient measurement of proton beam spot size and position at a synchrotron-based proton therapy facility. METHODS AND MATERIALS: A 420 mm x 320 mm MSIC was designed with 240 vertical strips and 180 horizontal strips at 1.75 mm pitch. The MSIC was characterized by irradiating a grid of proton spots across 17 energies from 73.5 MeV to 235 MeV and comparing to simultaneous measurements made with a reference Gafchromic EBT3 film. Beam profiles, spot sizes, and positions were analyzed. Short term measurement stability and sensitivity were evaluated. RESULTS: Excellent agreement was demonstrated between the MSIC and EBT3 film for both spot size and position measurements. Spot sizes agreed within ± 0.18 mm for all energies tested. Measured beam spot positions agreed within ± 0.17 mm. The detector showed good short term measurement stability and low noise performance. CONCLUSION: The large-area MSIC enables efficient and accurate proton beam spot characterization across the clinical energy range. The results indicate the MSIC is suitable for pencil beam scanning proton therapy commissioning and quality assurance applications requiring fast spot size and position quantification.

No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields.

The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research. In this study, we investigated the non-targeted effects on the regulation of the cell cycle of human cervical carcinoma (HeLa) cells with imperfect p53 function that express the FUCCI (HeLa-FUCCI cells). The possible effects on the cell-cycle phases via soluble factors were analyzed following exposure to different field configurations, which were delivered using a 150 kVp X-ray irradiator. In addition, using synchrotron-generated, 5.35 keV monochromatic X-ray microbeams, high-precision 200 µm-slit microbeam irradiation was performed to investigate the possible impacts on the cell-cycle phases via cell-cell contacts. Collectively, we could not detect the intercellular regulation of the cell cycle in HeLa-FUCCI cells, which suggested that the unregulated cell growth was a malignant tumor. Our findings indicated that there was no significant intercellular control system of the cell cycle in malignant tumors during or after radiotherapy, highlighting the differences between normal tissue and tumor characteristics.

Tracking biochemical changes induced by iron loading in AML12 cells with synchrotron live cell, time-lapse infrared microscopy.

Hepatocytes are essential for maintaining the homeostasis of iron and lipid metabolism in mammals. Dysregulation of either iron or lipids has been linked with serious health consequences, including non-alcoholic fatty liver disease (NAFLD). Considered the hepatic manifestation of metabolic syndrome, NAFLD is characterised by dysregulated lipid metabolism leading to a lipid storage phenotype. Mild to moderate increases in hepatic iron have been observed in ∼30% of individuals with NAFLD; however, direct observation of the mechanism behind this increase has remained elusive. To address this issue, we sought to determine the metabolic consequences of iron loading on cellular metabolism using live cell, time-lapse Fourier transform infrared (FTIR) microscopy utilising a synchrotron radiation source to track biochemical changes. The use of synchrotron FTIR is non-destructive and label-free, and allowed observation of spatially resolved, sub-cellular biochemical changes over a period of 8 h. Using this approach, we have demonstrated that iron loading in AML12 cells induced perturbation of lipid metabolism congruent with steatosis development. Iron-loaded cells had approximately three times higher relative ester carbonyl concentration compared with controls, indicating an accumulation of triglycerides. The methylene/methyl ratio qualitatively suggests the acyl chain length of fatty acids in iron-loaded cells increased over the 8 h period of monitoring compared with a reduction observed in the control cells. Our findings provide direct evidence that mild to moderate iron loading in hepatocytes drives de novo lipid synthesis, consistent with a role for iron in the initial hepatic lipid accumulation that leads to the development of hepatic steatosis.

A commercial treatment planning system with a hybrid dose calculation algorithm for synchrotron radiotherapy trials.

Synchrotron Radiotherapy (SyncRT) is a preclinical radiation treatment which delivers synchrotron x-rays to cancer targets. SyncRT allows for novel treatments such as Microbeam Radiotherapy, which has been shown to have exceptional healthy tissue sparing capabilities while maintaining good tumour control. Veterinary trials in SyncRT are anticipated to take place in the near future at the Australian Synchrotron's Imaging and Medical Beamline (IMBL). However, before veterinary trials can commence, a computerised treatment planning system (TPS) is required, which can quickly and accurately calculate the synchrotron x-ray dose through patient CT images. Furthermore, SyncRT TPS's must be familiar and intuitive to radiotherapy planners in order to alleviate necessary training and reduce user error. We have paired an accurate and fast Monte Carlo (MC) based SyncRT dose calculation algorithm with EclipseTM, the most widely implemented commercial TPS in the clinic. Using EclipseTM, we have performed preliminary SyncRT trials on dog cadavers at the IMBL, and verified calculated doses against dosimetric measurement to within 5% for heterogeneous tissue-equivalent phantoms. We have also performed a validation of the TPS against a full MC simulation for constructed heterogeneous phantoms in EclipseTM, and showed good agreement for a range of water-like tissues to within 5%-8%. Our custom EclipseTM TPS for SyncRT is ready to perform live veterinary trials at the IMBL.

Proton FLASH: passive scattering or pencil beam scanning?

This study focused on a direct comparison of dose delivery efficiency between two proton FLASH delivery modes: passive scattering and pencil beam scanning (PBS). Monte-Carlo simulation of the beamline was performed using the Geant4 package. Two proton energies (63 and 230 MeV) were selected, targeting for shallow and deep-seated tumors, respectively. Two irradiation field sizes were selected: 13 × 13 mm2 and 50 × 50 mm2. For each delivery mode, two cases were investigated: shoot-through and Bragg peak, yielding a total of 4 delivery scenarios. For the passive scattering mode, the impact on dose rate by multiple components along the beamline were investigated, including ridge-filter, scatterer, range shifter and collimator. A quantitative comparison among four scenarios was made in terms of field size, dose, dose rate and treatment plan quality (dose volume histogram). For the 230 MeV case, the dose rate (for 1 nA current) is 0.05 Gy s-1 (passive with Bragg peak, field size: 50 × 50 mm2) and 2.6 Gy s-1 (PBS with shoot-through). Dose rate comparison is made between passive scattering and PBS as the delivery changes from spot-layer to shoot-through. In conclusion, the study successfully established a benchmark reference for dose rate performance for different scenarios, taking into account components along the beamline, field size and beam current. The results allow us to predict and compare the required beam current to yield a dose rate sufficiently high, above the threshold of the FLASH effect.

Synchrotron FTIR microspectroscopy revealed apoptosis-induced biomolecular changes of cholangiocarcinoma cells treated with ursolic acid.

BACKGROUND: Ursolic acid (UA) is a natural triterpenoid which possesses anti-cancer activity. However, little is known regarding the activity and molecular mechanism of UA in cholangiocarcinoma (CCA). Thus, we investigated the effects of UA on growth inhibition and apoptosis induction through biomolecular changes in KKU-213 and KKU-055 CCA cell lines. METHODS: The anti-proliferative effect of UA against CCA cells was evaluated using SRB assay. Changes in biomolecules were assessed by SR-FTIR microspectroscopy combined with PCA and conventional methods (i.e., Annexin V-FITC/PI staining for lipid alteration and apoptosis induction; Western blot analysis and caspase-3/7 activity assay for apoptotic protein detection). RESULTS: UA suppressed the proliferation of CCA cells in a dose- and time-dependent manner. SR-FTIR data revealed a significant alteration in lipids attributable to changes in apoptotic cell membranes, confirmed by Annexin V-FITC/PI staining. SR-FTIR data showed that UA promoted changes in the protein secondary structure. Elevated expression of Bax and decreased expression of Bcl-2 and survivin/BIRC5 along with augmented caspase-3/7 activity supported alterations in apoptosis-related proteins. CONCLUSIONS: SR-FTIR microspectroscopy was successfully used as a label-free technique to monitor apoptosis-induced biomolecular changes in UA-treated CCA cells. UA exerted the cytotoxic and apoptotic activities in CCA cells through alterations in membrane lipids and apoptotic proteins. UA could be a potential anti-CCA candidate and a chemical starting point for the discovery of novel anti-cancer agents. SIGNIFICANCE: Our present study showed the first evidence that UA exhibited the anti-proliferative and pro-apoptotic activities toward CCA cells through changes in biomolecules, notably lipids and proteins.

Semiconductor dosimetry in modern external-beam radiation therapy.

Semiconductor dosimeters are ubiquitous in modern external-beam radiation therapy. They possess key features. The response, electronically available in real time, is stable and linear with absorbed dose for given irradiation conditions; the radiation-sensitive volume can be rather small in size, while retaining mechanical strength and high sensitivity. We describe three common semiconductor dosimeters: diodes, metal-oxide-semiconductor field-effect transistors and diamonds. We discuss in detail their operation principles and applications in modern external-beam radiation therapy, primarily with megavoltage photon beams. We also explore their use in proton and heavy ion therapy, and in experimental radiotherapy techniques such as synchrotron-based micro-beam radiation therapy.

Single-shot K-edge subtraction x-ray discrete computed tomography with a polychromatic source and the Pixie-III detector.

K-edge subtraction (KES) imaging is a technique able to map a specific element such as e.g. a contrast agent within the tissues, by exploiting the sharp rise of its absorption coefficient at the K-edge energy. Whereas mainly explored at synchrotron radiation sources, the energy discrimination properties of modern x-ray photon counting detectors (XPCDs) pave the way for an implementation of single-shot KES imaging with conventional polychromatic sources. In this work we present an x-ray CT imaging system based on the innovative Pixie-III detector and discrete reconstruction. The results reported here show that a reliable automatic localization of Barium (above a certain concentration) is possible with a few dozens of tomographic projections for a volume having an axial slice of 512 [Formula: see text] 512 pixels. The final application is a routine high-fidelity 3D mapping of a specific element ready for further morphological quantification by means of x-ray CT with potential promising applications in vivo.

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron.

Microbeam Radiation Therapy (MRT) is an emerging cancer treatment modality characterised by the use of high-intensity synchrotron-generated x-rays, spatially fractionated by a multi-slit collimator (MSC), to ablate target tumours. The implementation of an accurate treatment planning system, coupled with simulation tools that allow for independent verification of calculated dose distributions are required to ensure optimal treatment outcomes via reliable dose delivery. In this article we present data from the first Geant4 Monte Carlo radiation transport model of the Imaging and Medical Beamline at the Australian Synchrotron. We have developed the model for use as an independent verification tool for experiments in one of three MRT delivery rooms and therefore compare simulation results with equivalent experimental data. The normalised x-ray spectra produced by the Geant4 model and a previously validated analytical model, SPEC, showed very good agreement using wiggler magnetic field strengths of 2 and 3 T. However, the validity of absolute photon flux at the plane of the Phase Space File (PSF) for a fixed number of simulated electrons was unable to be established. This work shows a possible limitation of the G4SynchrotronRadiation process to model synchrotron radiation when using a variable magnetic field. To account for this limitation, experimentally derived normalisation factors for each wiggler field strength determined under reference conditions were implemented. Experimentally measured broadbeam and microbeam dose distributions within a Gammex RMI457 Solid Water® phantom were compared to simulated distributions generated by the Geant4 model. Simulated and measured broadbeam dose distributions agreed within 3% for all investigated configurations and measured depths. Agreement between the simulated and measured microbeam dose distributions agreed within 5% for all investigated configurations and measured depths.

Image quality comparison between a phase-contrast synchrotron radiation breast CT and a clinical breast CT: a phantom based study.

In this study we compared the image quality of a synchrotron radiation (SR) breast computed tomography (BCT) system with a clinical BCT in terms of contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), noise power spectrum (NPS), spatial resolution and detail visibility. A breast phantom consisting of several slabs of breast-adipose equivalent material with different embedded targets (i.e., masses, fibers and calcifications) was used. Phantom images were acquired using a dedicated BCT system installed at the Radboud University Medical Center (Nijmegen, The Netherlands) and the SR BCT system at the SYRMEP beamline of Elettra SR facility (Trieste, Italy) based on a photon-counting detector. Images with the SR setup were acquired mimicking the clinical BCT conditions (i.e., energy of 30 keV and radiation dose of 6.5 mGy). Images were reconstructed with an isotropic cubic voxel of 273 µm for the clinical BCT, while for the SR setup two phase-retrieval (PhR) kernels (referred to as "smooth" and "sharp") were alternatively applied to each projection before tomographic reconstruction, with voxel size of 57 × 57 × 50 µm3. The CNR for the clinical BCT system can be up to 2-times higher than SR system, while the SNR can be 3-times lower than SR system, when the smooth PhR is used. The peak frequency of the NPS for the SR BCT is 2 to 4-times higher (0.9 mm-1 and 1.4 mm-1 with smooth and sharp PhR, respectively) than the clinical BCT (0.4 mm-1). The spatial resolution (MTF10%) was estimated to be 1.3 lp/mm for the clinical BCT, and 5.0 lp/mm and 6.7 lp/mm for the SR BCT with the smooth and sharp PhR, respectively. The smallest fiber visible in the SR BCT has a diameter of 0.15 mm, while for the clinical BCT is 0.41 mm. Calcification clusters with diameter of 0.13 mm are visible in the SR BCT, while the smallest diameter for the clinical BCT is 0.29 mm. As expected, the image quality of the SR BCT outperforms the clinical BCT system, providing images with higher spatial resolution and SNR, and with finer granularity. Nevertheless, this study assesses the image quality gap quantitatively, giving indications on the benefits associated with SR BCT and providing a benchmarking basis for its clinical implementation. In addition, SR-based studies can provide a gold-standard in terms of achievable image quality, constituting an upper-limit to the potential clinical development of a given technique.

Contrast-enhanced spectral mammography with a compact synchrotron source.

For early breast cancer detection, mammography is nowadays the commonly used standard imaging approach, offering a valuable clinical tool for visualization of suspicious findings like microcalcifications and tumors within the breast. However, due to the superposition of anatomical structures, the sensitivity of mammography screening is limited. Within the last couple of years, the implementation of contrast-enhanced spectral mammography (CESM) based on K-edge subtraction (KES) imaging helped to improve the identification and classification of uncertain findings. In this study, we introduce another approach for CESM based on a two-material decomposition, with which we expect fundamental improvements compared to the clinical procedure. We demonstrate the potential of our proposed method using the quasi-monochromatic radiation of a compact synchrotron source-the Munich Compact Light Source (MuCLS)-and a modified mammographic accreditation phantom. For direct comparison with the clinical CESM approach, we also performed a standard dual-energy KES at the MuCLS, which outperformed the clinical CESM images in terms of contrast-to-noise ratio (CNR) and spatial resolution. However, the dual-energy-based two-material decomposition approach achieved even higher CNR values. Our experimental results with quasi-monochromatic radiation show a significant improvement of the image quality at lower mean glandular dose (MGD) than the clinical CESM. At the same time, our study indicates the great potential for the material-decomposition instead of clinically used KES to improve the quantitative outcome of CESM.

Optimization of motion management parameters in a synchrotron-based spot scanning system.

PURPOSE: To quantify the effects of combining layer-based repainting and respiratory gating as a strategy to mitigate the dosimetric degradation caused by the interplay effect between a moving target and dynamic spot-scanning proton delivery. METHODS: An analytic routine modeled three-dimensional dose distributions of pencil-beam proton plans delivered to a moving target. Spot positions and weights were established for a single field to deliver 100 cGy to a static, 15-cm deep, 3-cm radius spherical clinical target volume with a 1-cm isotropic internal target volume expansion. The interplay effect was studied by modeling proton delivery from a clinical synchrotron-based spot scanning system and respiratory target motion, patterned from surrogate patient breathing traces. Motion both parallel and orthogonal to the beam scanning direction was investigated. Repainting was modeled using a layer-based technique. For each of 13 patient breathing traces, the dose from 20 distinct delivery schemes (combinations of four gate window amplitudes and five repainting techniques) was computed. Delivery strategies were inter-compared based on target coverage, dose homogeneity, high dose spillage, and delivery time. RESULTS: Notable degradation and variability in plan quality were observed for ungated delivery. Decreasing the gate window reduced this variability and improved plan quality at the expense of longer delivery times. Dose deviations were substantially greater for motion orthogonal to the scan direction when compared with parallel motion. Repainting coupled with gating was effective at partially restoring dosimetric coverage at only a fraction of the delivery time increase associated with very small gate windows alone. Trends for orthogonal motion were similar, but more complicated, due to the increased severity of the interplay. CONCLUSIONS: Layer-based repainting helps suppress the interplay effect from intra-gate motion, with only a modest penalty in delivery time. The magnitude of the improvement in target coverage is strongly influenced by individual patient breathing patterns and the tumor motion trajectory.

Chemotherapeutic Targets in Osteosarcoma: Insights from Synchrotron-MicroFTIR and Quasi-Elastic Neutron Scattering.

This study aimed at the development of improved drugs against human osteosarcoma, which is the most common primary bone tumor in children and teenagers with a low prognosis. New insights into the impact of an unconventional Pd(II) anticancer agent on human osteosarcoma cells were obtained by synchrotron radiation-Fourier transform infrared microspectroscopy and quasi-elastic neutron scattering (QENS) experiments from its effect on the cellular metabolism to its influence on intracellular water, which can be regarded as a potential secondary pharmacological target. Specific infrared biomarkers of drug action were identified, enabling a molecular-level description of variations in cellular biochemistry upon drug exposure. The main changes were detected in the protein and lipid cellular components, namely, in the ratio of unsaturated-to-saturated fatty acids. QENS revealed reduced water mobility within the cytoplasm for drug-treated cells, coupled to a disruption of the hydration layers of biomolecules. Additionally, the chemical and dynamical profiles of osteosarcoma cells were compared to those of metastatic breast cancer cells, revealing distinct dissimilarities that may influence drug activity.

CM01: a facility for cryo-electron microscopy at the European Synchrotron.

Recent improvements in direct electron detectors, microscope technology and software provided the stimulus for a `quantum leap' in the application of cryo-electron microscopy in structural biology, and many national and international centres have since been created in order to exploit this. Here, a new facility for cryo-electron microscopy focused on single-particle reconstruction of biological macromolecules that has been commissioned at the European Synchrotron Radiation Facility (ESRF) is presented. The facility is operated by a consortium of institutes co-located on the European Photon and Neutron Campus and is managed in a similar fashion to a synchrotron X-ray beamline. It has been open to the ESRF structural biology user community since November 2017 and will remain open during the 2019 ESRF-EBS shutdown.

Clinical implementation of respiratory-gated spot-scanning proton therapy: An efficiency analysis of active motion management.

PURPOSE: The aim of this work is to describe the clinical implementation of respiratory-gated spot-scanning proton therapy (SSPT) for the treatment of thoracic and abdominal moving targets. The experience of our institution is summarized, from initial acceptance and commissioning tests to the development of standard clinical operating procedures for simulation, motion assessment, motion mitigation, treatment planning, and gated SSPT treatment delivery. MATERIALS AND METHODS: A custom respiratory gating interface incorporating the Real-Time Position Management System (RPM, Varian Medical Systems, Inc., Palo Alto, CA, USA) was developed in-house for our synchrotron-based delivery system. To assess gating performance, a motion phantom and radiochromic films were used to compare gated vs nongated delivery. Site-specific treatment planning protocols and conservative motion cutoffs were developed, allowing for free-breathing (FB), breath-holding (BH), or phase-gating (Ph-G). Room usage efficiency of BH and Ph-G treatments was retrospectively evaluated using beam delivery data retrieved from our record and verify system and DICOM files from patient-specific quality assurance (QA) procedures. RESULTS: More than 70 patients were treated using active motion management between the launch of our motion mitigation program in October 2015 and the end date of data collection of this study in January 2018. During acceptance procedures, we found that overall system latency is clinically-suitable for Ph-G. Regarding room usage efficiency, the average number of energy layers delivered per minute was <10 for Ph-G, 10-15 for BH and ≥15 for FB, making Ph-G the slowest treatment modality. When comparing to continuous delivery measured during pretreatment QA procedures, the median values of BH treatment time were extended from 6.6 to 9.3 min (+48%). Ph-G treatments were extended from 7.3 to 13.0 min (+82%). CONCLUSIONS: Active motion management has been crucial to the overall success of our SSPT program. Nevertheless, our conservative approach has come with an efficiency cost that is more noticeable in Ph-G treatments and should be considered in decision-making.

Bacteriorhodopsin: Structural Insights Revealed Using X-Ray Lasers and Synchrotron Radiation.

Directional transport of protons across an energy transducing membrane-proton pumping-is ubiquitous in biology. Bacteriorhodopsin (bR) is a light-driven proton pump that is activated by a buried all-trans retinal chromophore being photoisomerized to a 13-cis conformation. The mechanism by which photoisomerization initiates directional proton transport against a proton concentration gradient has been studied by a myriad of biochemical, biophysical, and structural techniques. X-ray free electron lasers (XFELs) have created new opportunities to probe the structural dynamics of bR at room temperature on timescales from femtoseconds to milliseconds using time-resolved serial femtosecond crystallography (TR-SFX). Wereview these recent developments and highlight where XFEL studies reveal new details concerning the structural mechanism of retinal photoisomerization and proton pumping. We also discuss the extent to which these insights were anticipated by earlier intermediate trapping studies using synchrotron radiation. TR-SFX will open up the field for dynamical studies of other proteins that are not naturally light-sensitive.

Resolving polymorphs and radiation-driven effects in microcrystals using fixed-target serial synchrotron crystallography.

The ability to determine high-quality, artefact-free structures is a challenge in micro-crystallography, and the rapid onset of radiation damage and requirement for a high-brilliance X-ray beam mean that a multi-crystal approach is essential. However, the combination of crystal-to-crystal variation and X-ray-induced changes can make the formation of a final complete data set challenging; this is particularly true in the case of metalloproteins, where X-ray-induced changes occur rapidly and at the active site. An approach is described that allows the resolution, separation and structure determination of crystal polymorphs, and the tracking of radiation damage in microcrystals. Within the microcrystal population of copper nitrite reductase, two polymorphs with different unit-cell sizes were successfully separated to determine two independent structures, and an X-ray-driven change between these polymorphs was followed. This was achieved through the determination of multiple serial structures from microcrystals using a high-throughput high-speed fixed-target approach coupled with robust data processing.

An Alternative Approach to Estimating Instrument Decision Thresholds for Clearance of Personal Property From Accelerator Facilities.

Personal property exposed to particle beams and stray radiation at high-energy particle accelerators may contain induced volumetric radioactivity. At both the Brookhaven National Laboratory's (BNL) Collider-Accelerator and National Synchrotron Light Source II Facilities this radioactivity contains both gamma-emitting and beta-emitting radionuclides. The US Department of Energy (US DOE) recently published Technical Standard 6004-2016. This standard provides radionuclide-specific volumetric screening levels (Bq g) below which accelerator materials are eligible for clearance and release from radiological control. The standard also establishes several approaches for decision-making relative to the clearance process implemented, one of which is the "Indistinguishable from Background" (IFB) approach. BNL implements the IFB approach for survey of potentially activated accelerator materials. Radiological control technicians perform on-contact measurements using portable scintillators that are sensitive to gamma and x-ray radiation. Instrument decision thresholds are usually estimated by measuring total background counts over a pre-determined counting interval using an integrating count-rate instrument and then applying an appropriate confidence level factor. Measurement results obtained in a low background area are then directly compared to these detection thresholds. This paper presents an alternative statistical approach using logistic regression for estimating instrument decision thresholds for small-mass items using the IFB method and compares them to established release criteria. On-contact Micro-R meter measurements are correlated with analytical data obtained for activated materials weighing 0.3 kg to 3 kg. Analytical sample results show that Co and Na accounted for more than 90% of total sample radioactivity. Co and Na emit high-energy gamma rays and are both group one radionuclides as defined in DOE-6004-2016. For this size material the results show that the probability of detecting residual volumetric radioactivity at the Group One screening level concentration of 0.11 Bq g under normal field conditions is about 68%. This increases to 95% at 0.16 Bq g. The 95% confidence interval is 0.09 Bq g to 0.23 Bq g. Grouping low-mass items during the survey process could mitigate this concern if all items are expected to have similar activity concentrations.

Oblique raster scanning: an ion dose delivery procedure with variable energy layers.

In ion therapy accelerator complexes the dose is delivered 'actively' by subdividing the target in equal energy layers (EELs), which are scanned by a beam spot visiting in sequence the planned spots, previously defined by the treatment planning system. Synchrotrons-based complexes have three problems: (i) the switching from the energy needed to scan one Equal Energy Layer to the next takes time, an effect that is more relevant for the very short treatment times now often required; (ii) the unavoidable 'ripples' of the quadrupoles and bending magnets currents produce large erratic time variations of the extracted current complicating the dose delivery; (iii) in case of superconducting synchrotrons, it is difficult to rapidly change the magnetic field because of the power dumped in the cold masses. These problems are mitigated in the proposed Qblique Raster Scanning procedure, in which the magnet currents of the beamlines vary in synchrony and a beam spot of continuously varying energy moves at a constant velocity in the beam direction scanning layers that are not perpendicular to it. In this paper it is shown that, even for a 13.5 s irradiation of a 0.5 l target, the B-field rates can be as low as dB/dt = 0.1 T s-1 and that the best procedures to follow 0.5 l moving targets, which combines 3D feedback systems with a five-fold rescanning, can be applied by accelerating in the synchrotron about 1010 carbon ions. ORS can be used in combination with respiratory gating,and is advantageous also for (synchro)cyclotrons-based centres: the variable energy beam can be produced with a slowly rotating absorber and a superconducting energy acceptance beamline/gantry system (with ΔE/E = ±1.5%) can substitute the more expensive beam transport systems which have ten times larger energy acceptance (ΔE/E ⩾ ±15%).

Technical Note: Relative proton stopping power estimation from virtual monoenergetic images reconstructed from dual-layer computed tomography.

PURPOSE: The objective of this technical note was to investigate the accuracy of proton stopping power relative to water (RSP) estimation using a novel dual-layer, dual-energy computed tomography (DL-DECT) scanner for potential use in proton therapy planning. DL-DECT allows dual-energy reconstruction from scans acquired at a single x-ray tube voltage V by using two-layered detectors. METHODS: Sets of calibration and evaluation inserts were scanned at a DL-DECT scanner in a custom phantom with variable diameter D (0 to 150 mm) at V of 120 and 140 kV. Inserts were additionally scanned at a synchrotron computed tomography facility to obtain comparative linear attenuation coefficients for energies from 50 to 100 keV, and reference RSP was obtained using a carbon ion beam and variable water column. DL-DECT monoenergetic (mono-E) reconstructions were employed to obtain RSP by adapting the Yang-Saito-Landry (YSL) method. The method was compared to reference RSP via the root mean square error (RMSE) over insert mean values obtained from volumetric regions of interest. The accuracy of intermediate quantities such as the relative electron density (RED), effective atomic number (EAN), and the mono-E was additionally evaluated. RESULTS: The lung inserts showed higher errors for all quantities and we report RMSE excluding them. RMSE for µ from DL-DECT mono-E was below 1.9%. For the evaluation inserts at D = 150 mm and V = 140 kV, RED RMSE was 1.0%, while for EAN it was 2.9%. RSP RMSE was below 0.8% for all D and V, which did not strongly affect the results. CONCLUSIONS: In this investigation of RSP accuracy from DL-DECT, we have shown that RMSE below 1% can be achieved. It was possible to adapt the YSL method for DL-DECT and intermediate quantities RED and EAN had comparable accuracy to previous publications.